Analgesic and anti-inflammatory plaster and preparation method thereof

Abstract

The invention relates to the field of traditional Chinese medicine preparations, in particular to an analgesic and anti-inflammatory patch and a preparation method thereof.The patch comprises, by weight, 30 parts of gentiana macrophylla, 15 parts of frankincense, 15 parts of myrrh, 15 parts of ligusticum wallichii, 15 parts of angelica sinensis, 10 parts of notopterygium roots, 10 parts of radix angelicae pubescentis, 10 parts of garden balsam stems, 8 parts of ground beetles, 8 parts of carthamus tinctorius, 5 parts of borneol, 3 parts of menthol and 3 parts of liquorice. The radix gentianae macrophyllae is used as a monarch drug and is matched with the medicinal materials such as the frankincense, the myrrh and the ligusticum wallichii to form a scientific and reasonable compound compatibility, the components are in synergistic interaction, and the analgesic and anti-inflammatory effects of the application are remarkably improved. Gentiana macrophylla alkali A in gentiana macrophylla and boswellic acid and gallic acid in frankincense and myrrh have a synergistic effect, cyclooxygenase can be inhibited, prostaglandin synthesis can be reduced, capillary permeability can be reduced, inflammation exudation can be relieved, and therefore the multi-target analgesic and anti-inflammatory effects are achieved.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine preparations, in particular to an analgesic and anti-inflammatory patch and a preparation method thereof, which is suitable for treating pain symptoms caused by rheumatoid arthritis, rheumatoid arthritis, trauma, sprains and the like. Background Art

[0002] Traditional Chinese medicine patch therapy is an important component of traditional Chinese medicine, boasting advantages such as definite efficacy, ease of use, and minimal side effects. In recent years, with the modernization of Traditional Chinese Medicine, TCM patch formulations have gained widespread application and rapid growth. However, current analgesic and anti-inflammatory patches on the market still have some drawbacks, such as short duration of efficacy, low transdermal absorption efficiency, and high local irritation.

[0003] By searching relevant patent information, the following comparative documents are found that are relatively close to the present invention:

[0004] Chinese patent application CN118903293A discloses a traditional Chinese medicine formula for treating rheumatoid arthritis and its preparation method. The formula contains ingredients such as Gentiana macrophylla and Ligusticum chuanxiong, and is mainly used to promote blood circulation and remove blood stasis, dispel wind and dampness, and relieve numbness and pain. However, its extraction process is relatively traditional and its transdermal absorption efficiency is limited.

[0005] In addition, in the article "Therapeutic Effect of Qinjilisan Oral Liquid on Acute Gouty Arthritis Model Mice" (Medical Herald, 2018), it was confirmed that Qinji extract has significant anti-inflammatory and analgesic effects on gouty arthritis, but the study was limited to oral preparations and did not involve transdermal delivery systems.

[0006] The analgesic and anti-inflammatory dressings in the prior art mainly have the following deficiencies:

[0007] 1. The compatibility of medicinal materials is not reasonable and the synergistic effect is not obvious;

[0008] 2. The extraction process is inefficient and the content of active ingredients is unstable;

[0009] 3. The transdermal absorption efficiency is low and the duration of drug effect is short;

[0010] 4. The scope of indications is narrow and cannot meet the treatment needs of various pain symptoms.

[0011] Therefore, the development of an analgesic and anti-inflammatory patch with scientific and reasonable ingredient combination, advanced extraction technology, high transdermal absorption efficiency, and a wide range of indications has important clinical value and market prospects. Summary of the Invention

[0012] The purpose of the present invention is to overcome the shortcomings of the existing technology and provide an analgesic and anti-inflammatory patch with gentiana as the main ingredient and in combination with Chinese medicinal materials such as frankincense, myrrh, and ligusticum chuanxiong, and a preparation method thereof. The patch has the advantages of scientific and reasonable ingredient combination, advanced extraction technology, high transdermal absorption efficiency, and a wide range of indications.

[0013] To achieve the above object, the present invention provides the following technical solutions:

[0014] The invention discloses an analgesic and anti-inflammatory patch, comprising the following components by weight: 30 parts of gentiana macrophylla, 15 parts of frankincense, 15 parts of myrrh, 15 parts of ligusticum chuanxiong, 15 parts of angelica sinensis, 10 parts of notopterygium wilfordii, 10 parts of pubescens, 10 parts of scutellaria baicalensis, 8 parts of earthworm, 8 parts of safflower, 5 parts of borneol, 3 parts of menthol, and 3 parts of liquorice. The components are prepared by extracting and then compounding with a matrix.

[0015] Preferably, the matrix consists of 10 parts of hydroxypropyl methylcellulose, 5 parts of polyvinyl alcohol, 2 parts of glycerol, and 83 parts of purified water.

[0016] Furthermore, the active ingredient indicators in the patch are: gentianine A content is not less than 0.5 mg / g, ferulic acid content is not less than 1.0 mg / g, and ligustrazine content is not less than 0.8 mg / g.

[0017] The present invention also provides a method for preparing the analgesic and anti-inflammatory patch, comprising the following steps:

[0018] (1) Raw material pretreatment: crush the Radix Gentianae, Radix Notopterygii, Radix Angelicae Pubescentis, Herba Tougucao, Rhizoma Chuanxiong, Radix Angelicae Sinensis, and Carthamus Tinctorius to 80 mesh size; crush the Frankincense, Myrrha, and Eupolyphaga Eupolyphaga to 100 mesh size;

[0019] (2) Extraction of active ingredients: water extraction and alcohol extraction respectively;

[0020] (3) Matrix preparation: Prepare a transparent gel matrix;

[0021] (4) Compounding of medicinal materials with matrix: mixing the extract with the matrix;

[0022] (5) Patch molding: coating, drying, cutting, and packaging.

[0023] The water extraction in step (2) comprises: mixing Gentiana macrophylla, Notopterygium wilfordii, Angelica pubescens, Herba striatae radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis and Carthamus tinctorius, adding 10 times the amount of purified water and soaking for 4 hours, decocting twice, the first time for 90 minutes and the second time for 60 minutes, combining the decoctions, concentrating to a relative density of 1.20-1.25, and controlling the temperature at 60°C.

[0024] The alcohol extraction in step (2) comprises: mixing frankincense, myrrh, and earthworm, adding 8 times the amount of 75% ethanol, soaking for 12 hours, performing ultrasonic-assisted extraction at a power of 300 W and a frequency of 40 kHz for 30 minutes, filtering, decompressing the filtrate to recover ethanol until there is no alcohol smell, concentrating to a relative density of 1.15-1.20, and controlling the temperature at 60°C.

[0025] Furthermore, the matrix preparation in step (3) includes: taking 10 parts of hydroxypropyl methylcellulose, 5 parts of polyvinyl alcohol, 2 parts of glycerol, and 83 parts of purified water, adding the hydroxypropyl methylcellulose and polyvinyl alcohol to 80°C hot water and stirring until dissolved, when the temperature drops to 50°C, adding glycerol and continuing to stir for 30 minutes until uniform, and standing to degas to obtain a transparent gel matrix.

[0026] The compounding of the medicinal material and the matrix in step (4) comprises: mixing the water extract concentrate and the alcohol extract concentrate in a ratio of 1:1, adding borneol and menthol powder, stirring until completely dissolved, and then mixing with the matrix in a ratio of 3:7, and stirring at 40-45°C for 2 hours until uniform.

[0027] Finally, the patch forming in step (5) includes: evenly coating the mixture on a non-woven fabric substrate with a thickness of 0.8-1.2 mm, drying in a 60°C oven for 2 hours, covering with release paper, cutting into 7 cm × 10 cm specifications, and packaging and sealing.

[0028] The present invention also provides the use of the analgesic and anti-inflammatory patch in the preparation of medicines for treating rheumatoid arthritis, rheumatoid arthritis, traumatic injuries, sprains, muscle strains, neuralgia and lumbago and leg pain.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] 1. The present invention uses Gentiana macrophylla as the main drug and is combined with other medicinal materials such as frankincense, myrrh, and Chuanxiong to form a scientific and reasonable compound compatibility. The components synergize and enhance each other's effectiveness, significantly improving the analgesic and anti-inflammatory effects of the application. Gentinoline A in Gentiana macrophylla works synergistically with boswellic acid and myrrh acid in frankincense and myrrh to inhibit cyclooxygenase and reduce prostaglandin synthesis, while also reducing capillary permeability and alleviating inflammatory exudation, thereby achieving multi-target analgesic and anti-inflammatory effects.

[0031] 2. The present invention utilizes a combination of water and alcohol extraction, along with ultrasound-assisted extraction technology, significantly improving the extraction rate of active ingredients. Compared to traditional extraction processes, the present invention improves extraction efficiency by approximately 25-30%, particularly for the fat-soluble components of frankincense and myrrh.

[0032] 3. The present invention uses a composite matrix of hydroxypropyl methylcellulose and polyvinyl alcohol, combined with borneol and menthol as transdermal absorption enhancers, significantly improving the drug's skin permeability and sustained release. Experiments have shown that the patch's efficacy lasts for 8-12 hours, significantly outperforming existing similar products.

[0033] 4. The patch of the present invention is suitable for the treatment of various pain symptoms, including rheumatoid arthritis, traumatic injury, sprain, muscle strain, neuralgia and low back pain, etc., and has a wide range of clinical application value. DETAILED DESCRIPTION

[0034] The present invention will be further described in detail below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto.

[0035] The pharmacological mechanisms of action of the components of the present invention are as follows:

[0036] Gentiana macrophylla, as the main herb, contains active ingredients such as gentianine A, which has the effects of dispelling rheumatism, clearing away heat and detoxifying, and promoting blood circulation and removing blood stasis. Modern pharmacological studies have shown that gentianine A has a clear analgesic effect in rats. Although the effect is short-lived, it is significantly enhanced when combined with other herbs. Furthermore, gentianine A can significantly reduce capillary permeability, alleviate inflammatory exudation, and stimulate the pituitary gland through the nervous system, promoting increased secretion of adrenocortical hormones, exerting anti-inflammatory effects similar to those of glucocorticoids.

[0037] Frankincense and myrrh, as auxiliary herbs, complement each other when used together. Frankincense primarily contains boswellic acid and boswellol, which promote blood circulation and qi, reduce swelling and relieve pain; myrrh, primarily containing bisabolol and myrrhic acid, promotes blood circulation, dissipates blood stasis, and promotes tissue regeneration. Modern pharmacological research indicates that the boswellic acid and myrrhic acid in frankincense and myrrh can inhibit cyclooxygenase and reduce prostaglandin synthesis, thereby exerting anti-inflammatory and analgesic effects. When used together, frankincense favors qi circulation, while myrrh favors blood stasis dispersal, creating a mutually beneficial effect that enhances the analgesic and anti-inflammatory effects.

[0038] Chuanxiong and Angelica sinensis are both adjuvant herbs, commonly used to promote blood circulation and dissipate blood stasis. Chuanxiong contains components such as ligustrazine, which has the effects of promoting blood circulation, promoting qi, dispelling wind and relieving pain; while Angelica sinensis contains components such as ferulic acid, which has the effects of nourishing blood, promoting blood circulation, regulating menstruation and relieving pain. Modern pharmacological research has shown that ligustrazine can dilate blood vessels, improve blood circulation, and relieve pain caused by ischemia; while Angelica sinensis can inhibit platelet aggregation and improve microcirculation. The synergistic effect of these two ingredients significantly enhances the blood circulation and analgesic effects of the application.

[0039] Qianghuo, Duhuo, and Tougucao are used as adjuvants, which have the effects of removing rheumatism, unblocking meridians, promoting blood circulation and reducing swelling, and relieving menstruation and pain. When used in combination with the main and auxiliary drugs, they further enhance the analgesic and anti-inflammatory effects of the plaster.

[0040] Borneol and menthol, as adjuvant drugs, not only have the effects of clearing away heat and relieving exterior symptoms, promoting blood circulation and unblocking collaterals, but can also serve as percutaneous absorption promoters, enhancing the skin permeability of other drugs and improving the bioavailability of the patch.

[0041] Licorice, as a guiding drug, has the effect of harmonizing various drugs, can alleviate the irritation of other drugs, and also has a certain anti-inflammatory effect.

[0042] In terms of matrix materials, the composite application of hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) not only ensures the adhesion of the dressing, but also provides good drug sustained-release performance. The addition of glycerol further improves the flexibility and comfort of the dressing.

[0043] The present invention is described in detail below through specific embodiments:

[0044] Example 1

[0045] The invention discloses an analgesic and anti-inflammatory dressing, comprising the following components by weight: 30 parts of gentiana macrophylla, 15 parts of frankincense, 15 parts of myrrh, 15 parts of ligusticum chuanxiong, 15 parts of angelica sinensis, 10 parts of notopterygium wilfordii, 10 parts of pubescens, 10 parts of scutellaria baicalensis, 8 parts of earthworm, 8 parts of safflower, 5 parts of borneol, 3 parts of menthol and 3 parts of liquorice.

[0046] The preparation method comprises the following steps:

[0047] (1) Raw material pretreatment: Grind the Radix Gentianae, Radix Notopterygii, Radix Angelicae Pubescentis, Herba Tougucao, Rhizoma Chuanxiong, Radix Angelicae Sinensis, and Carthamus Tinctorius to 80 mesh size; Grind the frankincense and myrrh to 100 mesh size; Stir-fry the Eupolyphaga sinensis and grind to 100 mesh size; Set aside borneol and menthol.

[0048] (2) Extraction of active ingredients:

[0049] a. Water extraction: Mix Gentiana macrophylla, Notopterygium wilfordii, Angelica pubescens, Herba Tougucao, Ligusticum chuanxiong, Angelica sinensis, and Carthamus tinctorius according to the formula ratio, add 10 times the amount of purified water, soak for 4 hours, decoct twice, the first time for 90 minutes and the second time for 60 minutes, combine the decoctions, and concentrate to a relative density of 1.20 (60℃).

[0050] b. Alcohol extraction: Mix frankincense, myrrh, and earthworm according to the formula ratio, add 8 times the amount of 75% ethanol, soak for 12 hours, and extract with ultrasonic assistance for 30 minutes (power 300W, frequency 40kHz), filter, and recover ethanol by decompressing the filtrate until there is no alcohol smell, and concentrate to a relative density of 1.15 (60℃).

[0051] (3) Matrix preparation: Take 10 parts of hydroxypropyl methylcellulose (HPMC, viscosity 4000-6000 mPa·s, Dow Chemical Company, USA), 5 parts of polyvinyl alcohol (PVA, degree of polymerization 1700±100, China Bluestar Chemical New Materials Co., Ltd.), 2 parts of glycerol (analytical grade, Sinopharm Chemical Reagent Co., Ltd.), and 83 parts of purified water. Add HPMC and PVA to 80℃ hot water and stir until dissolved. When the temperature drops to 50℃, add glycerol and continue stirring for 30 minutes until uniform. Let it stand to degas, and a transparent and uniform gel matrix is ​​obtained.

[0052] (4) Compounding of medicinal materials and matrix: Mix the water extract concentrate and the alcohol extract concentrate in a ratio of 1:1, stir evenly, add borneol and menthol powder, stir until completely dissolved, mix the mixture with the matrix in a ratio of 3:7, control the temperature at 42°C, and stir for 2 hours until uniform.

[0053] (5) Patch molding: The mixture was evenly coated on a non-woven fabric substrate (80 g / m², Nantong Baicao Pharmaceutical Co., Ltd.) with a thickness of 1.0 mm. The patch was dried in an oven at 60 °C for 2 h, covered with release paper, cut into 7 cm × 10 cm sizes, and packaged and sealed.

[0054] Example 2

[0055] The invention discloses an analgesic and anti-inflammatory dressing, comprising the following components by weight: 25 parts of gentiana macrophylla, 12 parts of frankincense, 12 parts of myrrh, 12 parts of ligusticum chuanxiong, 12 parts of angelica sinensis, 8 parts of notopterygium wilfordii, 8 parts of pubescens, 8 parts of scutellaria baicalensis, 6 parts of earthworm, 6 parts of safflower, 4 parts of borneol, 2.5 parts of menthol and 2.5 parts of liquorice.

[0056] The preparation method is basically the same as that of Example 1, except that:

[0057] (2) Extraction of active ingredients:

[0058] a. Water extraction: Concentrate to a relative density of 1.22 (60°C).

[0059] b. Alcohol extraction: Concentrate to a relative density of 1.17 (60°C).

[0060] (4) Compounding of medicinal materials and matrix: The mixed solution and matrix were mixed in a ratio of 2.5:7.5, and the temperature was controlled at 40°C.

[0061] (5) Patch molding: The thickness was controlled at 0.9 mm, the oven temperature was adjusted to 55 °C, and the drying time was extended to 2.5 h.

[0062] Example 3

[0063] The invention discloses an analgesic and anti-inflammatory dressing, comprising the following components by weight: 35 parts of gentiana macrophylla, 18 parts of frankincense, 18 parts of myrrh, 18 parts of ligusticum chuanxiong, 18 parts of angelica sinensis, 12 parts of notopterygium wilfordii, 12 parts of pubescens, 12 parts of scutellaria baicalensis, 10 parts of earthworm, 10 parts of safflower, 6 parts of borneol, 3.5 parts of menthol and 3.5 parts of liquorice.

[0064] The preparation method is basically the same as that of Example 1, except that:

[0065] (1) Raw material pretreatment: Grind the Radix Gentianae, Radix Notopterygii, Radix Angelicae Pubescentis, Herba Tougucao, Rhizoma Chuanxiong, Radix Angelicae Sinensis, and Carthamus Tinctorius to 70 mesh size; Grind the Frankincense, Myrrha, and Eupolyphaga Scolopendra to 90 mesh size.

[0066] (2) Extraction of active ingredients:

[0067] a. Water extraction: Add 9 times the amount of purified water, soak for 5 hours, decoct twice, the first time for 100 minutes, the second time for 70 minutes, and concentrate to a relative density of 1.25 (60℃).

[0068] b. Alcohol extraction: Add 7 times the amount of 80% ethanol, soak for 15 hours, and perform ultrasonic-assisted extraction for 40 minutes (power 350W, frequency 45kHz), and concentrate to a relative density of 1.20 (60℃).

[0069] (4) Compounding of medicinal materials and matrix: The mixed solution and matrix were mixed in a ratio of 3.5:6.5, and the temperature was controlled at 45°C.

[0070] Example 4

[0071] The invention discloses an analgesic and anti-inflammatory dressing, comprising the following components by weight: 30 parts of gentiana macrophylla, 15 parts of frankincense, 15 parts of myrrh, 15 parts of ligusticum chuanxiong, 15 parts of angelica sinensis, 10 parts of notopterygium wilfordii, 10 parts of pubescens, 10 parts of scutellaria baicalensis, 8 parts of earthworm, 8 parts of safflower, 5 parts of borneol, 3 parts of menthol and 3 parts of liquorice.

[0072] The preparation method is basically the same as that of Example 1, except that:

[0073] (3) Matrix preparation: Take 12 parts of hydroxypropyl methylcellulose, 6 parts of polyvinyl alcohol, 2.5 parts of glycerol, and 79.5 parts of purified water.

[0074] (5) Patch molding: The mixture was evenly coated on a non-woven fabric substrate with a thickness of 1.2 mm and dried in an oven at 58 °C for 2.2 h.

[0075] In order to verify the technical effect of the present invention, the following comparative examples were designed:

[0076] Comparative Example 1

[0077] The preparation method is basically the same as that of Example 1, but does not contain Gentiana macrophylla, that is, the components are: 15 parts of frankincense, 15 parts of myrrh, 15 parts of Chuanxiong, 15 parts of angelica, 10 parts of Notopterygium wilfordii, 10 parts of Duhuo, 10 parts of Polygonum multiflorum, 8 parts of Eupolyphaga sinensis, 8 parts of Carthamus tinctorius, 5 parts of borneol, 3 parts of menthol, and 3 parts of liquorice.

[0078] Comparative Example 2

[0079] The preparation method is basically the same as that of Example 1, but does not contain frankincense and myrrh, that is, the components are: 30 parts of Gentiana macrophylla, 15 parts of Chuanxiong, 15 parts of Angelica sinensis, 10 parts of Notopterygium wilfordii, 10 parts of Angelica dahurica, 10 parts of Radix Angelicae Pubescentis, 10 parts of Herba Polygoni Multiflori, 8 parts of Eupolyphaga sinensis, 8 parts of Carthamus tinctorius, 5 parts of Borneolum Syntheticum, 3 parts of menthol, and 3 parts of Licorice.

[0080] Comparative Example 3

[0081] The preparation method is basically the same as that of Example 1, but instead of using ultrasonic-assisted extraction technology, a traditional reflux extraction method is used: frankincense, myrrh, and earthworm are added to 8 times the amount of 75% ethanol, and reflux extraction is repeated for 2 hours. The extracts are combined, and the ethanol is recovered under reduced pressure until there is no alcohol taste, and then concentrated to a relative density of 1.15 (60°C).

[0082] Comparative Example 4

[0083] The preparation method is basically the same as that of Example 1, but the matrix does not contain polyvinyl alcohol and is composed only of 15 parts of hydroxypropyl methylcellulose, 2 parts of glycerol, and 83 parts of purified water.

[0084] In order to evaluate the analgesic and anti-inflammatory effects of the dressing of the present invention, the following experiments were performed:

[0085] Experiment 1: Evaluation of analgesic activity

[0086] The analgesic activity of each patch was evaluated using a writhing test. The experimental method was as follows: 60 healthy Kunming mice weighing 18-22 g, half male and half female, were randomly divided into six groups, with 10 mice in each group. These groups included a blank control group, a positive control group (Yunnan Baiyao Patch, Yunnan Baiyao Group Co., Ltd.), Example 1 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group.

[0087] Each patch was applied to the abdomen of mice, covering an area of ​​approximately 1 cm². Four hours after application, 0.6% acetic acid solution (0.1 mL / 10 g) was injected intraperitoneally. The number of writhings in the mice was observed over 15 minutes, and the analgesic rate was calculated. Analgesic rate = (number of writhings in the control group - number of writhings in the treatment group) / number of writhings in the control group × 100%.

[0088] Experiment 2: Evaluation of anti-inflammatory activity

[0089] The anti-inflammatory activity of each patch was evaluated using a mouse paw swelling test. The experimental method was as follows: 60 healthy Kunming mice weighing 18-22 g, half male and half female, were randomly divided into six groups of 10 mice each. These groups included a blank control group, a positive control group (Yunnan Baiyao patch), Example 1 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group.

[0090] Each patch was applied to the plantar surface of the right hind paw of mice, covering an area of ​​approximately 0.5 cm². Four hours after application, a 1% carrageenan solution (0.05 mL / mouse) was subcutaneously injected into the plantar surface of the right hind paw. The left hind paw served as a control. Three hours after injection, the volume of both paws was measured using a foot volume meter, and the swelling rate and inhibition rate were calculated. Swelling rate = (right paw volume - left paw volume) / left paw volume × 100%; inhibition rate = (control group swelling rate - treatment group swelling rate) / control group swelling rate × 100%.

[0091] Experiment 3: Transdermal Permeability Evaluation

[0092] The transdermal permeability of each patch was evaluated using a Franz diffusion cell method. The experimental method was as follows: Fresh pigskin (ear skin, approximately 0.8 mm thick) was cleaned and set aside. A 2.0 cm² patch was applied to the pigskin and placed in a Franz diffusion cell containing a pH 7.4 phosphate buffer solution. At 37 ± 0.5°C, samples were collected at 1, 2, 4, 6, 8, 10, and 12 hours, and the cumulative permeation of gentianine A, ferulic acid, and ligustrazine in the receiving solution was determined.

[0093] Experiment 4: Stability Evaluation

[0094] The sealed packages of the patches from Example 1, Example 3, Comparative Example 3, and Comparative Example 4 were stored at 25°C / 60% relative humidity (normal temperature) and 40°C / 75% relative humidity (accelerated storage). Samples were collected at 0, 1, 3, and 6 months, and the contents of gentianine A, ferulic acid, and ligustrazine were determined. The content retention rates were calculated.

[0095] The experimental results and analysis are as follows:

[0096] Table 1 Analgesic activity evaluation results

[0097] Group Number of twists (times) Analgesia rate (%) Blank control group 38.6±5.2 - Positive control group 19.4±3.8 49.7 Example 1 group 15.8±3.2 59.1 Example 3 group 14.3±2.9 62.9 Comparative Example 1 25.6±4.1 33.7 Comparative Example 2 28.2±4.3 26.9

[0098] Table 2 Anti-inflammatory activity evaluation results

[0099] Group Swelling rate (%) Inhibition rate (%) Blank control group 52.3±6.8 - Positive control group 29.5±4.2 43.6 Example 1 group 23.8±3.7 54.5 Example 3 group 21.6±3.5 58.7 Comparative Example 1 37.2±4.9 28.9 Comparative Example 2 35.4±4.6 32.3

[0100] Table 3 Transdermal permeability evaluation results (12-hour cumulative permeation, μg / cm²)

[0101] Group Gentianine A Ferulic acid Ligustrazine Example 1 group 12.5±1.8 28.3±3.2 19.7±2.6 Example 3 group 14.2±2.0 31.5±3.5 22.4±2.9 Comparative Example 3 8.6±1.4 18.7±2.5 13.2±2.1 Comparative Example 4 10.3±1.6 22.6±2.8 16.5±2.3

[0102] Table 4 Stability evaluation results (content retention after 6 months, %)

[0103] Group condition Gentianine A Ferulic acid Ligustrazine Example 1 group normal temperature 96.3±1.5 95.7±1.4 97.2±1.6 Example 1 group accelerate 92.5±1.7 91.8±1.6 93.6±1.8 Example 3 group normal temperature 95.8±1.4 94.9±1.3 96.8±1.5 Example 3 group accelerate 91.9±1.6 90.7±1.5 92.9±1.7 Comparative Example 3 normal temperature 92.1±1.8 90.3±1.7 93.5±1.9 Comparative Example 3 accelerate 85.4±2.0 83.6±1.9 87.2±2.1 Comparative Example 4 normal temperature 94.7±1.6 93.8±1.5 95.9±1.7 Comparative Example 4 accelerate 89.2±1.8 88.3±1.7 90.6±1.9

[0104] As can be seen from the results in Tables 1 and 2, both Example 1 and Example 3 of the present invention demonstrated superior analgesic and anti-inflammatory activity to the positive control and comparative groups. The analgesic and anti-inflammatory inhibition rates in Example 3 reached 62.9% and 58.7%, respectively, significantly higher than those in the other groups. This demonstrates the scientific and rational compatibility of the medicinal materials used in the patch of the present invention, demonstrating a significant synergistic effect between the components.

[0105] The analgesic and anti-inflammatory activities of Comparative Example 1 (excluding Gentiana macrophylla) and Comparative Example 2 (excluding frankincense and myrrh) were significantly lower than those of the Example group, indicating that Gentiana macrophylla, as the monarch herb, and frankincense and myrrh, as the assistant herb, play a key role in the present invention's patch. This also validates the scientific nature of the present invention's formulation design based on the "monarch, minister, assistant, and envoy" theory.

[0106] The results in Table 3 show that the transdermal permeability of the active ingredients in the Example group using ultrasound-assisted extraction technology was significantly superior to that of the Comparative Example 3 group using traditional reflux extraction. The 12-hour cumulative permeation rates of gentianine A, ferulic acid, and ligustrazine in the Example 3 group were 14.2, 31.5, and 22.4 μg / cm², respectively, representing 65.1%, 68.4%, and 69.7% higher than those in the Comparative Example 3 group, respectively. This demonstrates that ultrasound-assisted extraction technology can significantly improve the extraction efficiency and transdermal absorption performance of the active ingredients.

[0107] In addition, the transdermal permeability of the Example group containing polyvinyl alcohol is also better than that of the Comparative Example 4 group not containing polyvinyl alcohol, indicating that the composite matrix of hydroxypropyl methylcellulose and polyvinyl alcohol can effectively improve the skin permeability of drugs.

[0108] From the stability evaluation result of Table 4, embodiment group of the present invention all shows good stability under normal temperature and accelerated condition.Through 6 months storage, embodiment 1 group's content retention rate of each index component under normal temperature condition is all more than 95%, and also remains on more than 90% under accelerated condition.And 3 groups of comparative examples that adopt traditional extraction process, its stability is obviously poor, especially under accelerated condition, the content retention rate of ferulic acid is only 83.6%.This has further proved that extraction process of the present invention can effectively improve the stability of product.

[0109] Based on the above experimental results, Example 3 of the present invention showed the best analgesic and anti-inflammatory effects, transdermal permeability and stability, and was determined to be the best embodiment. Its formula composition is: 35 parts of Gentiana macrophylla, 18 parts of frankincense, 18 parts of myrrh, 18 parts of Chuanxiong, 18 parts of Angelica sinensis, 12 parts of Notopterygium wilfordii, 12 parts of Angelica pubescens, 12 parts of Radix Angelicae Pubescentis, 12 parts of Radix Scutellariae, 10 parts of Eupolyphaga sinensis, 10 parts of Carthamus tinctorius, 6 parts of Borneolum Syntheticum, 3.5 parts of menthol, and 3.5 parts of Licorice.

[0110] In a clinical observation conducted in the Rheumatology and Immunology Department of a tertiary hospital, 90 patients with rheumatoid arthritis were randomly divided into a treatment group (using the patch of Example 3 of the present invention) and a control group (using a commercially available brand of analgesic patch), with 45 patients in each group. The patch was changed once daily for 14 consecutive days. The results showed that the total effective rate in the treatment group was 91.1%, significantly higher than the 75.6% in the control group (P < 0.05); the pain relief time in the treatment group was 30.5 ± 8.2 minutes, significantly shorter than the 52.3 ± 10.6 minutes in the control group (P < 0.01); and the incidence of adverse reactions in the treatment group was 4.4%, significantly lower than the 13.3% in the control group (P < 0.05).

[0111] In addition, in clinical observations on other pain symptoms such as traumatic injuries and muscle strain, the patch of the present invention also showed significant therapeutic effects, with patient satisfaction reaching over 95%.

[0112] The analgesic and anti-inflammatory effects of the patch of the present invention are mainly achieved through the following mechanisms:

[0113] First, genus macrophylla (genus macrophylla) stimulates the pituitary gland through the nervous system, increasing the secretion of adrenocortical hormones and exerting an anti-inflammatory effect similar to that of glucocorticoids. At the same time, genus macrophylla can also significantly reduce capillary permeability and alleviate inflammatory exudation.

[0114] Secondly, the boswellic and myrrhic acids in frankincense and myrrh can inhibit cyclooxygenase and reduce prostaglandin synthesis, thereby exerting anti-inflammatory and analgesic effects. Frankincense tends to promote qi circulation, while myrrh tends to disperse blood stasis. The two complement each other when used together.

[0115] Third, Ligustrazine can dilate blood vessels, improve blood circulation, and relieve pain caused by ischemia; while Angelica sinensis can inhibit platelet aggregation and improve microcirculation. The two work synergistically to significantly enhance the blood-activating and analgesic effects of the patch.

[0116] Fourth, adjuvants such as Qianghuo, Duhuo and Ligusticum chuanxiong further enhance the analgesic and anti-inflammatory effects of the patch, while borneol and menthol, as transdermal absorption enhancers, can significantly improve the skin permeability of other drugs.

[0117] These components, through complex synergistic effects, together form a multi-target, multi-pathway analgesic and anti-inflammatory network, enabling the patch of the present invention to effectively relieve a variety of pain symptoms.

[0118] In summary, the present invention provides an analgesic and anti-inflammatory patch with scientific and reasonable ingredient combination, advanced extraction technology, high transdermal absorption efficiency, and a wide range of indications, and a preparation method thereof, which has significant clinical application value and market prospects.

[0119] The foregoing is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are intended to fall within the scope of protection of the present invention.

Claims

1. An analgesic and anti-inflammatory patch, characterized in that: The dressing comprises the following components in parts by weight: 30 parts of Gentiana macrophylla, 15 parts of frankincense, 15 parts of myrrh, 15 parts of Chuanxiong, 15 parts of Chinese angelica, 10 parts of Notopterygium wilfordii, 10 parts of Angelica pubescens, 10 parts of Herba schizonepetae, 10 parts of Scolopendra subspinipes, 8 parts of Carthamus tinctorius, 5 parts of Borneolum Syntheticum, 3 parts of Menthol, and 3 parts of Licorice; The components are prepared by extracting and then compounding with a matrix.

2. The analgesic and anti-inflammatory patch according to claim 1, characterized in that: The matrix consists of 10 parts of hydroxypropyl methylcellulose, 5 parts of polyvinyl alcohol, 2 parts of glycerol and 83 parts of purified water.

3. The analgesic and anti-inflammatory patch according to claim 1, characterized in that: The indicators of the effective ingredients in the patch are: gentianine A content is not less than 0.5 mg / g, ferulic acid content is not less than 1.0 mg / g, and ligustrazine content is not less than 0.8 mg / g.

4. The preparation method of the analgesic and anti-inflammatory patch according to claim 1, characterized in that: The following steps are involved: 1) Raw material pretreatment: Grind Gentiana macrophylla, Notopterygium wilfordii, Angelica pubescens, Herba Tougucao, Rhizoma Chuanxiong, Angelica sinensis, and Carthamus tinctorius to 80 mesh; Grind Frankincense, Myrrh, and Eupolyphaga sinensis to 100 mesh; 2) Extraction of active ingredients: water extraction and alcohol extraction respectively; 3) Matrix preparation: Prepare a transparent gel matrix; 4) Compounding of medicinal materials and matrix: mixing the extract with the matrix; 5) Patch molding: coating, drying, cutting and packaging.

5. The preparation method according to claim 4, characterized in that The water extraction in step 2) includes: Mix Gentiana macrophylla, Notopterygium wilfordii, Angelica pubescens, Herba Tougucao, Rhizoma Chuanxiong, Radix Angelicae Sinensis and Safflower, add 10 times amount of purified water and soak for 4 hours, decoct twice, the first time for 90 minutes and the second time for 60 minutes, combine the decoctions, concentrate to a relative density of 1.20-1.25, and control the temperature at 60℃.

6. The preparation method according to claim 4, characterized in that The alcohol extraction in step 2) includes: Mix frankincense, myrrh, and earthworm, add 8 times the amount of 75% ethanol, soak for 12 hours, and extract with ultrasound at a power of 300 W and a frequency of 40 kHz for 30 minutes. Filter, and recover the ethanol from the filtrate under reduced pressure until there is no alcohol smell. Concentrate to a relative density of 1.15-1.20, and control the temperature at 60°C.

7. The preparation method according to claim 4, characterized in that The matrix preparation in step 3) includes: Take 10 parts of hydroxypropyl methylcellulose, 5 parts of polyvinyl alcohol, 2 parts of glycerin, and 83 parts of purified water. Add hydroxypropyl methylcellulose and polyvinyl alcohol to 80°C hot water and stir until dissolved. When the temperature drops to 50°C, add glycerin and continue stirring for 30 minutes until uniform. Let it stand to degas to obtain a transparent gel matrix.

8. The preparation method according to claim 4, characterized in that The combination of medicinal materials and matrix in step 4) includes: Mix the water extract concentrate and the alcohol extract concentrate in a ratio of 1:1, add borneol and menthol powder, stir until completely dissolved, then mix with the matrix in a ratio of 3:7, and stir at 40-45°C for 2 hours until uniform.

9. The preparation method according to claim 4, characterized in that The patch forming in step 5) includes: The mixture was evenly coated on a non-woven fabric substrate with a thickness of 0.8-1.2 mm in a 60°C oven.