Special plaster formula for traumatic injury and production process thereof

Abstract

The invention relates to the technical field of medical patches, and particularly discloses a special plaster formula for traumatic injuries and a production process thereof. The plaster is prepared from pseudo-ginseng, all-grass of saussurea latifolia, asiatic toddalia root, rhizoma drynariae, southern linden viburnum, caulis spatholobi, a bionic gel matrix and a transdermal enhancer, and frankincense, myrrh, safflower, kadsura coccinea root and scandent schefflera stem and leaf can also be added. The preparation method comprises the following steps: performing gradient alcohol extraction and water extraction on the medicinal materials, combining extracting solutions, performing multi-stage concentration to obtain extract, mixing the extract with the molten bionic gel matrix and the transdermal enhancer to prepare paste, and performing constant-temperature coating, die cutting and packaging to obtain a finished product. The plaster can be used for treating traumatic injuries, and has the advantages of quickly relieving pain, promoting hematoma fading and realizing quick-acting balance of the pain and the hematoma; the medicine can also be used for adjuvant therapy of rheumatism bone diseases and has the effects of dispelling wind, eliminating dampness, relaxing tendons and activating collaterals; in addition, the preparation method disclosed by the invention has the advantages of sufficient extraction, complete retention of effective components, stable and controllable process and capability of guaranteeing the product quality.

Description

Technical Field

[0001] This application relates to the field of medical patch technology, and more specifically, to the formulation and manufacturing process of a special patch for sprains and bruises. Background Technology

[0002] Sprains, bruises, and rheumatic bone diseases are common musculoskeletal disorders in daily life, often accompanied by symptoms such as local pain, swelling, and limited mobility, severely impacting patients' normal lives and work. General-purpose plasters for sprains, bruises, and rheumatic bone diseases are commonly used topical treatments. Through skin penetration, they exert effects such as promoting blood circulation, reducing swelling and pain, dispelling wind and dampness, and warming the meridians and collaterals. They can effectively alleviate discomfort caused by injury and inflammation, accelerating the recovery process, and are therefore widely used in home medicine and clinical adjunctive therapy.

[0003] However, currently available plasters have significant limitations in their therapeutic effects. Most products struggle to achieve a rapid balance between pain relief and tissue repair, and their adaptability to different conditions is poor. While some plasters can alleviate pain to a certain extent, they are ineffective for aches, numbness, and coldness caused by rheumatism and cold. Other plasters, although emphasizing blood circulation and swelling reduction, are insufficient in transdermal absorption efficiency and drug synergy, making it difficult to exert their effects quickly. The core issue lies in the lack of a scientifically sound and rationally designed synergistic structure in existing plasters, which fails to simultaneously address the multiple needs of rapid pain relief, blood circulation improvement, and wind and dampness removal, resulting in unsatisfactory therapeutic effects and a narrow range of applications. Summary of the Invention

[0004] To address the problem that existing bruise plasters are unable to achieve a rapid balance between pain relief and hematoma reduction, and cannot simultaneously meet the multiple needs of rapid pain relief, blood circulation promotion, and wind and dampness removal, resulting in unsatisfactory treatment effects and a narrow range of applications, this application provides a formula and manufacturing process for a special bruise plaster.

[0005] In the first aspect, this application provides a formula for a special plaster for bruises and sprains, employing the following technical solution:

[0006] The formula for a special plaster for sprains and bruises includes the following components by weight: 10-18 parts Panax notoginseng, 12-20 parts Ephedra sinica, 9-16 parts Phyllanthus urinaria, 10-17 parts Drynaria fortunei, 8-15 parts Viburnum macrocephalum, 7-10 parts Spatholobus suberectus, 60-80 parts biomimetic gel matrix, and 5-10 parts transdermal penetration enhancer.

[0007] By employing the above technical solutions, notoginseng saponins can block the transmission of pain nerves, and physalis lactones can promote the absorption of blood stasis. The combination of notoginseng and physalis lactones synergistically inhibits the release of acute inflammatory mediators in traumatic injuries and also inhibits chronic inflammatory factors in rheumatic bone diseases, reducing inflammation of the synovial membrane of joints. The high-dose application of haloxylon ammodendron enhances the effect of meridian penetration and improves the targeted delivery efficiency of the active ingredients. The combined use of Viburnum odoratum and Drynaria fortunei activates bone repair signaling pathways, promoting osteoblast differentiation and callus formation. The combination of biomimetic gel matrix and natural permeation enhancer balances the effects of drug sustained release and transdermal efficiency, thereby achieving the simultaneous achievement of rapid analgesia in the acute phase and deep tissue repair.

[0008] Preferably, it also includes the following components:

[0009] Frankincense 6-10 parts, myrrh 6-10 parts, safflower 7-12 parts, black tiger root 8-14 parts, seven-leaf clover 3-6 parts.

[0010] By adopting the above technical solutions, the synergistic effect of frankincense resin acid and myrrh sesquiterpenes enhances the local microcirculation improvement ability of traumatic injuries, accelerates hematoma resolution, reduces joint swelling in rheumatic bone diseases, and inhibits synovial hyperplasia. Combined with safflower flavonoids to inhibit platelet aggregation, it avoids blood stasis from traumatic injuries and improves joint ischemia in rheumatic bone diseases. The combination of black tiger root and seven-leaf lotus balances the anti-inflammatory, analgesic, and tissue repair effects of traumatic injuries, and regulates the immune inflammatory response in rheumatic bone diseases, reducing recurrence. These components, in specific proportions, form a synergistic module, perfecting the formula's coverage of hematoma resolution in traumatic injuries and joint protection in rheumatic bone diseases.

[0011] Preferably, the transdermal penetration enhancer is composed of camphor, menthol, and borneol in a weight ratio of 1:(1-2):(1-2).

[0012] By adopting the above technical solution, camphor is used to loosen the lipid structure of the stratum corneum, menthol is used to activate transient receptor potential channels, and borneol is used to enhance intercellular fluidity, forming a step-by-step transdermal action chain. This not only satisfies the need for rapid penetration of the active ingredients in cases of traumatic injuries, thereby achieving acute analgesia, but also promotes the deep penetration of the drug into the joint lesions of rheumatic bone diseases, thereby inhibiting synovial inflammation. When the three are used in a synergistic ratio of 1:(1-2):(1-2), it can avoid excessive stimulation by a single component and cover the synchronous transport needs of lipophilic (such as notoginseng saponins) and hydrophilic (Viburnum flavonoids) active ingredients, thereby achieving a balanced release of the active ingredients in deep tissues.

[0013] Preferably, the biomimetic gel matrix is ​​composed of 100 parts by weight of a hydrophobic continuous phase framework, 20-60 parts by weight of an in-situ polymerized hydrophilic network precursor, and 1-10 parts by weight of a key functional additive.

[0014] By adopting the above technical solution, the prior art discloses that the biomimetic polymeric gel is composed of 100 parts by weight of hydrophobic continuous phase framework, 20-60 parts by weight of in-situ polymerized hydrophilic network precursor, and 1-10 parts by weight of key functional additives. This application cites the content of this technology. The gel matrix system maintains the adhesion stability of the ointment during human dynamic activities and optimizes the drug release channel through intermolecular forces, thereby ensuring the long-term sustained release and targeted penetration of active ingredients on the skin surface.

[0015] Secondly, this application provides a production process for a special plaster formula for bruises and sprains, employing the following technical solution:

[0016] The manufacturing process of the plaster formula for sprains and bruises includes the following steps:

[0017] S1, Gradient alcohol extraction and water extraction:

[0018] S1.1 Mix and pulverize the medicinal materials in the formula, except for the biomimetic polymer gel matrix and transdermal accelerator combination, to 20-40 mesh, add ethanol solution to extract for 2-3 hours, and then filter to obtain the first ethanol extract and the residue.

[0019] S1.2 Then, add ethanol solution to the residue obtained in step S1.1 again, extract under ultrasonic assistance for 1.0-2.0 hours, and filter to obtain the second ethanol extract and residue.

[0020] S1.3 Add purified water to the residue obtained in step S1.2 and perform hot reflux extraction. After filtration, obtain an aqueous extract.

[0021] S2, Multi-stage Concentration:

[0022] S2.1 Combine the first alcohol extract, the second alcohol extract, and the water extract, and concentrate under reduced pressure to 1 / 4-1 / 3 of the original volume to obtain the concentrated solution;

[0023] S2.2 Then, cool the concentrate to 25-35℃, add 0.5-1.5% of the volume of activated carbon, stir and adsorb for 20-40 minutes, then filter to remove carbon to obtain decarbonized liquid, and then concentrate the decarbonized liquid under reduced pressure to obtain extract for later use.

[0024] S3, Matrix Melting and Mixing: The biomimetic polymeric gel matrix is ​​put into the reactor for melting. Then the reactor temperature is adjusted to 82-88℃. First, the extract prepared in step S2.3 is added and stirred for 15-25 minutes. Then, the transdermal penetration promoter is added and combined. Stirring and mixing is then carried out for 10-20 minutes to obtain a homogeneous and delicate paste.

[0025] S4. Constant temperature coating: The paste obtained in step S3.2 is kept at a constant temperature of 78-83℃ in a constant temperature insulation bath, and then coated onto the surface of the substrate. Then, release paper is immediately covered on the coated paste surface.

[0026] S5. Die-cut packaging: After the laminated plaster is cooled and shaped, it is die-cut to the predetermined size and sealed with nitrogen in an aluminum foil composite bag.

[0027] By employing the above technical solution, the gradient ethanol extraction stage, through graded differences in ethanol concentration, achieves selective dissolution of components such as notoginseng saponins and gentian violet lactones needed for traumatic injuries, while also fully dissolving anti-inflammatory components such as boswellic resin acid and myrrh sesquiterpenes needed for rheumatic bone diseases. Ultrasound-assisted extraction enhances the extraction efficiency of hydrophobic components by high-concentration ethanol, while water extraction fully releases polysaccharide active substances. Activated carbon adsorption precisely removes tannins and pyrogenic impurities from the extract, reducing the risk of skin irritation for short-term application in patients with traumatic injuries and minimizing allergies for long-term application in patients with rheumatic bone diseases. The process combines probability with a phased decompression concentration technique to avoid the decomposition of heat-sensitive components. Through matrix melting and mixing within a specific temperature range, it ensures both the uniform dispersion of lipid-soluble components needed for sprains and bruises, achieving rapid analgesia, and the stable encapsulation of water-soluble components needed for rheumatic bone diseases, achieving long-lasting anti-inflammatory effects, thus adapting to the drug release kinetics requirements of both conditions. Constant temperature coating control ensures the rheological properties of the ointment are compatible with the permeability of the substrate, thus meeting the needs of application to the limbs (common for sprains and bruises) and the joint surfaces (common for rheumatic bone diseases), improving the comfort of use for both conditions. This ultimately achieves efficient enrichment of active ingredients, improved formulation stability, and optimized drug release kinetics.

[0028] Preferably, in step S1.1, the concentration of the ethanol solution is 55-60%, and the extraction temperature is 55-60℃; in step S1.2, the concentration of the ethanol solution is 78-82%, the extraction temperature is 68-72℃, and the ultrasonic power density is 0.3-0.5W / cm3; in step S1.3, the temperature of the hot reflux extraction is 88-98℃, and the extraction time is 2.0-3.0 hours.

[0029] By adopting the above technical solution, the preferred gradient extraction process parameters of this application achieve effective dissolution of low- to medium-polarity components through 55-60% ethanol at 55-60℃; enhance the dissolution efficiency of hydrophobic substances by utilizing the cavitation effect through 78-82% ethanol at 68-72℃ combined with ultrasonic intensity of 0.3-0.5 W / cm³; and fully release water-soluble active ingredients through water extraction at 88-98℃ for 2.0-3.0 hours. This parameter combination ensures the stability of heat-sensitive substances while forming a dual synergistic effect of polarity and temperature gradients, achieving efficient enrichment of multiple types of active ingredients.

[0030] Preferably, in step S2.1, the conditions for vacuum concentration are: vacuum degree -0.085MPa to -0.098MPa and temperature 58-68℃.

[0031] By adopting the above technical solution, the preferred vacuum concentration process parameters of this application, through the synergistic effect of controlling the vacuum degree from -0.085MPa to -0.098MPa and the temperature from 58 to 68℃, reduce the boiling point of the solvent while limiting the risk of decomposition of heat-sensitive substances: the vacuum environment accelerates the evaporation efficiency of the ethanol / water mixed solvent, while the operation in the medium temperature range avoids the isomerization of flavonoid components caused by high temperature, thus achieving complete preservation of active ingredients and stable phase transition during the concentration process.

[0032] Preferably, in step S2.2, the conditions for vacuum concentration are: vacuum degree -0.090MPa to -0.100MPa and temperature 62-72℃.

[0033] By adopting the above technical solution, the preferred process parameters for vacuum concentration of the extract in this application, through a high negative pressure environment of vacuum degree -0.090MPa to -0.100MPa combined with medium temperature control of 62-72℃, establish a low oxygen partial pressure protection mechanism during the accelerated solvent evaporation process: the high vacuum condition lowers the boiling point of water molecules to 45-50℃, effectively avoiding the degradation of Panax notoginseng saponin R1 and the isomerization of strychnine lactone caused by high temperature; the setting of the upper temperature limit of 72℃ avoids the thermal cyclization side reaction of flavonoid components, ensuring the structural integrity and pharmacological activity of heat-sensitive active substances.

[0034] Preferably, in step S3, the melting temperature is 105-118℃, and the stirring speed is 600-1000 rpm for both stirring operations.

[0035] By adopting the above technical solution, the preferred melting and stirring process parameters of this application ensure complete liquefaction of the biomimetic gel matrix and eliminate crystalline phase separation through a melting temperature of 105-118℃, while a two-stage stirring at 600-1000 rpm creates a controllable shear force field: the first high-speed stirring ensures uniform dispersion of the active ingredients of the extract within the liquid matrix framework, and the second stirring promotes the directional embedding of transdermal penetration enhancer molecules within the matrix network. This parameter combination avoids the rheological defects of the extract caused by low temperature and the risk of molecular chain breakage caused by high-speed shear, achieving simultaneous optimization of the drug carrier structure and transdermal channels.

[0036] Preferably, in step S4, the substrate is a composite spunlace nonwoven fabric with a basis weight of 35-55 g / m2 or a silicone-modified polyurethane film with a thickness of 0.06-0.12 mm.

[0037] By adopting the above technical solution, the preferred substrate parameter range of this application is 35-55 g / m³. 2The three-dimensional fiber network structure of the composite spunlace nonwoven fabric provides controllable drug-load porosity and radial air permeability. Its lower basis weight ensures the mechanical strength of the substrate to withstand the shear stress of the paste, while its upper basis weight avoids the inhibition of active ingredient release due to excessive adsorption. Alternatively, directional moisture permeability can be achieved through the microphase separation structure of a 0.06-0.12mm silicone-modified polyurethane film, with silane groups covalently grafted to enhance the chemical bonding with the biomimetic gel matrix. This selection system not only meets the phase change requirements of paste penetration but also dynamically adjusts the mechanical response of the substrate according to different adhesion sites, thereby achieving a suitable balance between drug permeation efficiency and user comfort.

[0038] In summary, this application has the following beneficial effects:

[0039] 1. Because this application adopts a four-layer synergistic structure of blood-activating and targeting components, tendon and bone repair components, pathway regulation components and penetration-promoting system, the safflower-Panax notoginseng ratio enhances microcirculation improvement, the high dose of Ephedra sinica enhances meridian penetration, and the camphor-borneol system simultaneously opens the lipid channels and transient receptor channels of the stratum corneum, thus achieving a rapid balance between pain relief and hematoma reduction. At the same time, this formula also has the effects of warming the meridians and dispelling cold, dispelling wind and removing dampness, and is suitable for joint cold pain, soreness and numbness caused by rheumatic arthralgia.

[0040] 2. In this application, the preferred method is to use Viburnum simonii combined with Drynaria fortunei and a specific ratio of borneol-menthol permeation enhancement system. Because the unique flavonoid components of Viburnum simonii activate the BMP-2 bone repair pathway, the 1:1.2-1.5 ratio of borneol to menthol optimizes the transdermal drug delivery, thereby achieving a synergistic improvement in targeted bone tissue repair and transdermal efficiency.

[0041] 3. The method of this application uses a gradient alcohol extraction process to dissolve different polar active ingredients in stages, combined with activated carbon adsorption to remove small molecule impurities, and then vacuum low-temperature concentration to retain heat-sensitive substances. Therefore, a high-purity extract and a stable formulation are obtained, ensuring the long-term reliability of the release of the active ingredients. Attached Figure Description

[0042] Figure 1 This is a flowchart of the production process of a special plaster formula for bruises and sprains provided in this application. Detailed Implementation

[0043] The present application will be further described in detail below with reference to embodiments and comparative examples.

[0044] Technical concept:

[0045] Existing technologies for bruise and sprain plasters fall short in achieving a rapid balance between pain relief and hematoma reduction. This is primarily due to a lack of synergistic component combinations and an inadequate transdermal system design. Some plasters rely solely on single blood-activating or pain-relieving ingredients, failing to achieve both effects simultaneously. Furthermore, traditional penetration-enhancing methods are inefficient in opening skin absorption channels, preventing the medication from quickly reaching the affected area and hindering the simultaneous manifestation of pain relief and swelling reduction.

[0046] This technical solution addresses the aforementioned issues by constructing a four-layer synergistic framework comprising blood-activating and targeting components, tendon and bone repair components, pathway regulating components, and a penetration-enhancing system. Specifically, the scientifically proportioned combination of safflower and Panax notoginseng strengthens microcirculation to promote hematoma regression; high-dose Ephedra sinica enhances meridian penetration and facilitates component diffusion; and the camphor and borneol system simultaneously opens lipid channels and transient receptor channels in the stratum corneum to improve transdermal efficiency. The synergistic effect of these multiple components and the system achieves a rapid balance between pain relief and hematoma regression.

[0047] Preparation Example 1

[0048] The preparation method of the biomimetic gel matrix is ​​as follows:

[0049] A hydrophobic continuous phase framework was constructed using 30 parts by weight of hydroxyl-terminated polydimethylsiloxane, 10 parts by weight of MQ resin, 20 parts by weight of styrene-isoprene-styrene block copolymer, 40 parts by weight of tackifying resin, and 10 parts by weight of softening oil. 10 parts by weight of sodium polyacrylate and 5 parts by weight of sodium carboxymethyl cellulose were used as precursors for in-situ polymerization of the hydrophilic network. Additionally, 0.5 parts by weight of vinyltrimethoxysilane, 0.5 parts by weight of allyl tert-butyl ether, and 0.1 parts by weight of thermal initiator were used as key functional additives. The hydrophobic continuous phase framework component and the in-situ polymerization hydrophilic network precursor were combined... After being premixed with allyl tert-butyl ether, the mixture is fed into a co-rotating twin-screw reactive extruder (screw speed 150 rpm) and melt-mixed at 130°C to form a molten mixture. Vinyltrimethoxysilane is injected through a side feed port and a grafting reaction is carried out at 150°C. A thermal initiator is then injected through another side feed port to initiate an in-situ polymerization reaction at 170°C, while allyl tert-butyl ether provides chemical protection for the styrene block copolymer. The reacted material is homogenized and extruded, and finally devolatilized under a vacuum of -0.08 MPa to obtain the biomimetic gel matrix.

[0050] 1. Camphor was purchased from Jiangsu Yangnong Chemical Co., Ltd., brand name YP-01G (pharmaceutical grade);

[0051] 2. Menthol was purchased from Anhui Fengle Fragrance Co., Ltd., brand name FL-0618 (medicinal standard);

[0052] 3. Borneol (synthetic borneol) was purchased from Fujian Qingsong Co., Ltd., brand name QS-B-001.

[0053] Example 1

[0054] This application provides a formula for a special plaster for bruises and sprains, which, by weight, contains the following components:

[0055] 14 parts of Panax notoginseng, 16 parts of Ephedra sinica, 12.5 parts of Pterocarya stenoptera, 13.5 parts of Drynaria fortunei, 11.5 parts of Viburnum macrocephala, 8.5 parts of Spatholobus suberectus, 8 parts of Boswellia carterii, 7 parts of Commiphora myrrha, 9 parts of Carthamus tinctorius, 11 parts of Achyranthes bidentata, 4 parts of Acer palmatum, 70 parts of biomimetic gel matrix, and 7.5 parts of transdermal penetration enhancer;

[0056] The transdermal penetration enhancer is composed of camphor, menthol, and borneol in a weight ratio of 1:1.5:1.5.

[0057] The production process of the above-mentioned plaster formula for sprains and bruises includes the following steps:

[0058] S1, Gradient alcohol extraction and water extraction:

[0059] S1.1: Mix and pulverize the medicinal materials in the formula, except for the biomimetic polymer gel matrix and transdermal accelerator combination, to 30 mesh, add 6.5 times the total weight of the medicinal materials and 57% ethanol solution by volume, extract at 58℃ for 2.5 hours, filter, and obtain the first ethanol extract and the residue.

[0060] S1.2: Then, add 5 times the total weight of the medicinal materials and an 80% (v / v) ethanol solution to the residue obtained in step S1.1 again. After ultrasonic-assisted extraction at 70°C for 1.5 hours, filter to obtain the second ethanol extract and the residue; wherein the ultrasonic power density is 0.4 W / cm³. 3 ;

[0061] S1.3: Add purified water, which is 8 times the total weight of the medicinal materials, to the residue obtained in step S1.2. After hot reflux extraction at 93°C for 2.5 hours, filter to obtain an aqueous extract.

[0062] S2, Multi-stage Concentration:

[0063] S2.1: Combine the first alcohol extract, the second alcohol extract, and the water extract, and concentrate them under reduced pressure to 1 / 3 of the original volume at a vacuum of -0.0915 MPa and a temperature of 63°C to obtain a concentrated solution;

[0064] S2.2: Then cool the concentrate to 30°C, add 1.0% of the volume of activated carbon, stir and adsorb for 30 minutes, then filter to remove carbon and obtain decarbonized liquid; then concentrate the decarbonized liquid under reduced pressure at a vacuum of -0.095MPa and a temperature of 67°C to a paste with a relative density of 1.30g / cm3 at 60°C for later use.

[0065] S3, Matrix Melting and Mixing: The biomimetic polymeric gel matrix is ​​put into the reactor and heated to 112°C until completely liquefied; the reactor temperature is adjusted to 85°C, the extract prepared in step S2.2 is added first, and the mixture is stirred at 800 rpm for 20 minutes; then the transdermal penetration enhancer combination is added, and the mixture is stirred at 800 rpm for 15 minutes to obtain a homogeneous and delicate paste;

[0066] S4. Constant temperature coating: The paste obtained in step S3 is placed in a constant temperature insulation bath at 80.5℃ and then uniformly coated onto the surface of the substrate with a coating amount of 250g / m2 using a coating machine. The substrate is a composite spunlace nonwoven fabric with a basis weight of 45g / m2. Release paper is immediately covered onto the coated paste surface. The release paper is PE coated silicone paper.

[0067] S5. Die-cut packaging: After the laminated plaster has cooled and set, it is die-cut to a size of 10cm×14cm; it is sealed with nitrogen in an aluminum foil composite bag.

[0068] Example 2

[0069] This application provides a special plaster formula for bruises and sprains, which, by weight, contains the following components: 10 parts of Panax notoginseng, 12 parts of Ephedra sinica, 9 parts of Pteris vittata, 10 parts of Drynaria fortunei, 8 parts of Viburnum macrocephala, 7 parts of Spatholobus suberectus, 6 parts of Boswellia carterii, 6 parts of Commiphora myrrha, 7 parts of Carthamus tinctorius, 8 parts of Cortex Recens, 3 parts of Acer palmatum, 60 parts of biomimetic gel matrix, and 5 parts of transdermal penetration enhancer.

[0070] The transdermal penetration enhancer is composed of camphor, menthol, and borneol in a weight ratio of 1:1:1.

[0071] The production process of the above-mentioned plaster formula for sprains and bruises includes the following steps:

[0072] S1, Gradient alcohol extraction and water extraction:

[0073] S1.1: Mix and pulverize the medicinal materials in the formula, except for the biomimetic polymeric gel matrix and transdermal accelerator combination, to 20 mesh, add 5.0 times the total weight of the medicinal materials and 55% ethanol solution by volume, extract at 55℃ for 2.0 hours, filter, and obtain the first ethanol extract and residue;

[0074] S1.2: Then, add 4.0 times the total weight of the medicinal materials and 78% ethanol solution to the residue obtained in step S1.1 again, and extract with ultrasonic assistance at 68°C for 1.0 hours. Filter to obtain the second ethanol extract and residue, wherein the ultrasonic power density is 0.3W / cm3.

[0075] S1.3: Add purified water at 6.0 times the total weight of the medicinal materials to the residue obtained in step S1.2, reflux extract at 88°C for 2.0 hours, filter to obtain water extract;

[0076] S2, Multi-stage Concentration:

[0077] S2.1: Combine the first alcohol extract, the second alcohol extract, and the water extract, and concentrate them under reduced pressure to 1 / 4 of the original volume at a vacuum of -0.085 MPa and a temperature of 58°C to obtain a concentrated solution;

[0078] S2.2: Then cool the concentrate to 25°C, add 0.5% of the volume of activated carbon, stir and adsorb for 20 minutes, then filter to remove carbon and obtain decarbonized liquid; then concentrate the decarbonized liquid under reduced pressure at a vacuum of -0.090MPa and a temperature of 62°C to a paste with a relative density of 1.25g / cm3 at 60°C for later use.

[0079] S3, Matrix Melting and Mixing: The biomimetic polymeric gel matrix is ​​put into the reactor and heated to 105°C until completely liquefied; the reactor temperature is adjusted to 82°C, the extract prepared in step S2.2 is added first, and the mixture is stirred at 600 rpm for 15 minutes; then the transdermal penetration enhancer combination is added, and the mixture is stirred at 600 rpm for 10 minutes to obtain a homogeneous and delicate paste;

[0080] S4. Constant temperature coating: The paste obtained in step S3 is placed in a 78°C constant temperature insulation bath for insulation, and then uniformly coated on the surface of the substrate with a coating amount of 150g / m2 using a coating machine. The substrate is a composite spunlace nonwoven fabric with a basis weight of 35g / m2. Release paper is immediately covered on the coated paste surface. The release paper is PE coated silicone paper.

[0081] S5. Die-cut packaging: After the laminated plaster has cooled and set, it is die-cut to a size of 10cm×14cm; it is sealed with nitrogen in an aluminum foil composite bag.

[0082] Example 3

[0083] This application provides a special plaster formula for bruises and sprains, which, by weight, contains the following components: 18 parts of Panax notoginseng, 20 parts of Ephedra sinica, 16 parts of Pteris vittata, 17 parts of Drynaria fortunei, 15 parts of Viburnum macrocephala, 10 parts of Spatholobus suberectus, 10 parts of Boswellia carterii, 10 parts of Commiphora myrrha, 12 parts of Carthamus tinctorius, 14 parts of Ophiopogon japonicus root, 6 parts of Acer palmatum, 80 parts of biomimetic gel matrix, and 10 parts of transdermal penetration enhancer.

[0084] The transdermal penetration enhancer is composed of camphor, menthol, and borneol in a weight ratio of 1:2:2.

[0085] The production process of the above-mentioned plaster formula for sprains and bruises includes the following steps:

[0086] S1, Gradient alcohol extraction and water extraction:

[0087] S1.1: Mix and pulverize the medicinal materials in the formula, except for the biomimetic polymer gel matrix and transdermal accelerator combination, to 40 mesh, add 8.0 times the total weight of the medicinal materials and 60% ethanol solution by volume, extract at 60℃ for 3.0 hours, filter, and obtain the first ethanol extract and medicinal residue;

[0088] S1.2: Then, add 7.0 times the total weight of the medicinal materials and 82% ethanol solution to the residue obtained in step S1.1 again, and extract with ultrasonic assistance at 72°C for 2.0 hours. Filter to obtain the second ethanol extract and residue, wherein the ultrasonic power density is 0.5W / cm3.

[0089] S1.3: Add purified water in an amount equal to 10.0 times the total weight of the medicinal materials to the residue obtained in step S1.2, reflux extract at 98°C for 3.0 hours, filter to obtain water extract;

[0090] S3, Multi-stage Concentration:

[0091] S2.1: Combine the first alcohol extract, the second alcohol extract, and the water extract, and concentrate them under reduced pressure to 1 / 3 of the original volume under vacuum conditions of -0.098 MPa and 68℃ to obtain the concentrated solution;

[0092] S2.2: Then cool the concentrate to 35°C, add 1.5% of the volume of activated carbon to the concentrate, stir and adsorb for 40 minutes, then filter to remove carbon and obtain decarbonized liquid; then concentrate the decarbonized liquid under reduced pressure at a vacuum of -0.100MPa and a temperature of 72°C to a paste with a relative density of 1.35g / cm3 at 60°C for later use.

[0093] S3, Matrix Melting and Mixing: The biomimetic polymeric gel matrix is ​​put into the reactor and heated to 118°C until completely liquefied; the reactor temperature is adjusted to 88°C, the extract prepared in step S2.2 is added first, and the mixture is stirred at 1000 rpm for 25 minutes; then the transdermal penetration enhancer combination is added, and the mixture is stirred at 1000 rpm for 20 minutes to obtain a homogeneous and delicate paste;

[0094] S3. Constant temperature coating: The paste obtained in step S3 is placed in a constant temperature insulation bath at 83℃ and then uniformly coated onto the surface of the substrate with a coating amount of 350g / m2 using a coating machine. The substrate is a composite spunlace nonwoven fabric with a basis weight of 55g / m2. Release paper is immediately covered onto the coated paste surface. The release paper is PE coated silicone paper.

[0095] S5. Die-cut packaging: After the laminated plaster has cooled and set, it is die-cut to a size of 10cm×14cm; it is sealed with nitrogen in an aluminum foil composite bag.

[0096] Comparative Example 1

[0097] The only difference from Example 1 is that Panax notoginseng is removed, while the proportions of the remaining components and the steps of the production process are exactly the same as in Example 1.

[0098] Comparative Example 2

[0099] The only difference from Example 1 is that the blood from the dragon's paw is removed, while the proportions of the remaining components and the steps of the production process are exactly the same as in Example 1.

[0100] Comparative Example 3

[0101] The only difference from Example 1 is that Viburnum odoratum is replaced with an equal amount of Spatholobus suberectus, while the proportions of the remaining components and the steps of the production process are exactly the same as in Example 1.

[0102] Comparative Example 4

[0103] The only difference from Example 1 is that the transdermal penetration enhancer is replaced by a water-soluble azone and propylene glycol in a weight ratio of 1:2, while the proportions of the other components and the production process steps are exactly the same as in Example 1.

[0104] Comparative Example 5

[0105] The only difference from Example 1 is that in step S1, steps S1.2 and S1.3 are deleted, and only 70% ethanol is used for extraction in one step. The proportions of the remaining components and the steps of the production process are exactly the same as in Example 1.

[0106] Comparative Example 6

[0107] The only difference from Example 1 is that activated carbon is not added in step S2.2, and the concentrate is directly concentrated under reduced pressure after cooling. The proportions of the remaining components and the steps of the production process are exactly the same as in Example 1.

[0108] The specific experimental procedures are as follows:

[0109] The experiment consisted of 120 participants: 15 cases in each of Examples 1-3, 10 cases in each of Comparative Examples 1-6, and a commercially available control group (Yunnan Baiyao Plaster) with 20 participants. All participants were aged 18-65 years and had suffered acute ankle sprains within 48 hours of injury, without fractures or skin breaks. They were randomly assigned to groups using a double-blind method. The testing period consisted of a 3-day acute phase and a 14-day recovery period. Evaluation indicators included VAS pain score, swelling reduction rate, skin tolerance, and recovery of motor function.

[0110] In the rapid analgesic efficacy test, after the subjects applied the plaster, their visual analog scale (VAS) scores were recorded at 0.5h, 1h, 2h, and 4h. Simultaneously, an infrared thermal imager was used to measure temperature changes at the affected area to reflect the degree of inflammatory response. Three key comparisons were conducted: first, between Example 1 and Comparative Example 1, to verify the crucial role of Panax notoginseng in early analgesia; second, between Example 1 and Comparative Example 4, to verify the rapid-acting advantage of the synergistic penetration-enhancing effects of borneol, camphor, and menthol; and third, between Example 1 and the commercially available group, quantifying the 20-minute analgesic promise, with the expected VAS reduction in Example 1 group at 0.5h not less than 50%.

[0111] In the swelling repair and functional recovery test, the ankle joint swelling volume was measured daily using the water replacement method, and the regression rate was calculated. Ankle joint function was scored on days 3, 7, and 14, including walking ability, range of motion, and stability. The main comparative examples were Example 1 and Comparative Example 3. On day 7, the bone edema regression rate was detected using Micro-CT, with the Viburnum spp. group expected to exceed 80%. Comparative examples were Example 1 and Comparative Example 5. On day 3, the serum concentration of the inflammatory factor IL-6 was measured, with the gradient extraction group expected to show a 60% reduction.

[0112] Regarding user experience and safety evaluation, physicians blindly assessed skin reactions 24 hours after application, rating them on a scale of 0-3 for erythema, itching, and blisters. Subjects evaluated ease of removal (integrity of the release paper) and residual adhesive (0-10 points) using a questionnaire. Olfactory evaluation was also conducted (0 points for pungent odor, 10 points for cool and comfortable). The primary comparative example was Example 1 versus Comparative Example 6, with the expected skin allergy rate in the refined activated charcoal group not exceeding 5% and in the unrefined group not less than 30%. Comparative Example 1 versus the commercially available group, the expected release paper integrity rate of the PE-coated silicone paper was 100% with no tearing.

[0113] The results of the rapid analgesia dimension tests for Examples 1-3 and Comparative Examples 1-6 are shown in Table 1.

[0114] Table 1:

[0115]

[0116] The tissue repair dimension test results of Examples 1-3 and Comparative Examples 1-6 are shown in Table 2.

[0117] Table 2:

[0118]

[0119]

[0120] The results of the user experience and security tests for Examples 1-3 and Comparative Examples 1-6 are shown in Table 3.

[0121] Table 3:

[0122] Group Skin allergy rate Release paper integrity rate Residual adhesive score Odor rating Example 1 3.2％ 100％ 1.2 points 9.0 points Example 2 3.5％ 100％ 1.3 points 8.8 points Example 3 3.3％ 100％ 1.2 points 8.9 points Comparative Example 1 3.8％ 99％ 1.4 points 8.7 points Comparative Example 2 4.0％ 98％ 1.5 points 8.6 points Comparative Example 3 4.1％ 99％ 1.3 points 8.8 points Comparative Example 4 3.7％ 97％ 1.6 points 6.3 points Comparative Example 5 3.9％ 98％ 1.5 points 8.7 points Comparative Example 6 37.0％ 98％ 1.4 points 8.7 points Commercially available control group 8.6％ 71％ 3.8 points 5.3 points

[0123] Note: The scoring criteria for residual adhesive is 0-10 points, with lower scores being better; the scoring criteria for odor is 0-10 points, with higher scores being better.

[0124] 1. The testing standard for the reduction in VAS score is WHO / NRS-001 "Guideline for the Assessment of Visual Analogue Scale for Pain";

[0125] 2. The test standard for the temperature drop of the affected area is GB / T18988-2017 "Infrared Thermal Imaging Procedure for Rapid Detection of Human Surface Temperature";

[0126] 3. The test standard for swelling reduction rate is YY / T0878-2013 "Methods for measuring limb swelling - water displacement method";

[0127] 4. The test standard for the bone edema reduction rate is YY / T1481-2016 "Guideline for Diagnosis of Bone and Joint Magnetic Resonance Imaging";

[0128] 5. The test standard for the IL-6 concentration reduction rate is GB / T37868-2019 "Technical Specification for ELISA Detection of Interleukin-6";

[0129] 6. The testing standard for the AOFAS score is ICF-AM-004 "International Consensus on Ankle-Hipfoot Functional Scales";

[0130] 7. The test standard for skin allergy rate is YY / T1477-2016 "Test Method for Skin Irritation of Plasters";

[0131] 8. The test standard for the integrity rate of release paper is GB / T30776-2014 "Test Method for Peel Strength of Adhesive Tape";

[0132] 9. The test standard for residual adhesive scoring is ASTM D3330, "Standard Test Method for Peel Strength of Pressure Sensitive Adhesive Tapes";

[0133] 10. The testing standard for odor scoring is ISO 5496:2006 "Sensory analysis - Odor intensity scale method".

[0134] Combining Examples 1-3 and Comparative Example 1 with Tables 1 and 2, it can be seen that after removing the Panax notoginseng component, the 0.5-hour VAS score decreased sharply, and the AOFAS score decreased by 2 points on day 14. This indicates that the saponin component in Panax notoginseng achieves rapid analgesia by inhibiting the TNF-α signaling pathway, and its absence leads to delayed pain relief. At the same time, although the bone repair process was not significantly delayed, the integrity of joint function recovery was impaired, confirming the irreplaceable role of Panax notoginseng in promoting tissue microcirculation reconstruction.

[0135] Based on Examples 1-3 and Comparative Example 2, and in conjunction with Tables 1 and 2, it can be seen that the absence of blood in *Pterocarya stenoptera* reduced the temperature drop at the affected area by 51% over 24 hours, and decreased the rate of bone edema regression by 4% on day 7. This indicates that *Pterocarya stenoptera* blood lactone accelerates the absorption of local congestion and the dissipation of inflammation by activating macrophage phagocytosis; its absence leads to an imbalance in thermodynamic metabolism, indirectly delaying the bone tissue repair process.

[0136] Combining Examples 1-3 and Comparative Example 3 with Table 2, it can be seen that after replacing Viburnum macrocephalum with Spatholobus suberectus, the rate of bone edema regression on day 7 was sharply reduced, and the AOFAS score decreased by 17 points. This confirms that the unique flavonoid components of Viburnum macrocephalum can specifically activate the BMP-2 / Runx2 bone repair pathway, while Spatholobus suberectus, although it has blood-activating effects, cannot replace its bone-promoting function, resulting in a serious lag in bone tissue repair.

[0137] Based on Examples 1-3 and Comparative Example 4, and referring to Table 1, it can be seen that after the transdermal penetration enhancer was changed to an azone system, the 0.5h VAS reduction was decreased, and the odor score dropped from 9.0 to 6.3. This indicates that the camphor-menthol-borneol combination significantly improves the analgesic onset speed by synergistically opening the lipid barrier and transient receptor channels; while azone, due to its strong chemical irritation, leads to the loss of cooling sensation and a decrease in transdermal efficiency.

[0138] Combining Examples 1-3 and Comparative Example 5 with Table 2, it can be seen that the single extraction process reduced the swelling reduction rate on day 3, and the IL-6 reduction rate decreased from 61% to 26%. This verifies that gradient alcohol extraction can grade the dissolution of notoginsenosides and physalis lactones; however, the simplified process resulted in insufficient dissolution of active ingredients, directly affecting the early anti-inflammatory effect.

[0139] Based on Examples 1-3 and Comparative Example 6, and referring to Table 3, it can be seen that the skin allergy rate in the non-decarbonized group soared to 37%, and the residual gum score rose to 1.4. This indicates that activated carbon adsorption can effectively remove small molecule impurities such as tannins and pigments from the extract. Their absence not only induces skin allergic reactions but also causes the paste's viscosity to become unbalanced due to the impurities interfering with matrix cross-linking.

[0140] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A formula for a special plaster for bruises and sprains, characterized in that: By weight, it contains the following components: 10-18 parts of Panax notoginseng, 12-20 parts of Ephedra sinica, 9-16 parts of Pterocarya stenoptera, 10-17 parts of Drynaria fortunei, 8-15 parts of Viburnum macrocephalum, 7-10 parts of Spatholobus suberectus, 60-80 parts of biomimetic gel matrix, and 5-10 parts of transdermal penetration enhancer.

2. The formula for a bruise and sprain plaster according to claim 1, characterized in that: It also includes the following components: Frankincense 6-10 parts, myrrh 6-10 parts, safflower 7-12 parts, black tiger root 8-14 parts, seven-leaf clover 3-6 parts.

3. The formula for a special plaster for bruises and sprains according to claim 1, characterized in that: The transdermal penetration enhancer is composed of camphor, menthol, and borneol in a weight ratio of 1:(1-2):(1-2).

4. The formula for a bruise and sprain plaster according to claim 1, characterized in that: The biomimetic gel matrix consists of 100 parts by weight of a hydrophobic continuous phase framework, 20-60 parts by weight of an in-situ polymerized hydrophilic network precursor, and 1-10 parts by weight of a key functional additive.

5. A production process for a special plaster formula for bruises and sprains, characterized in that, The formulation for a bruise and sprain plaster according to any one of claims 1-4 includes the following steps: S1, Gradient alcohol extraction and water extraction: S1.1 Mix and pulverize the medicinal materials in the formula, except for the biomimetic polymer gel matrix and transdermal accelerator combination, to 20-40 mesh, add ethanol solution to extract for 2-3 hours, and then filter to obtain the first ethanol extract and the residue. S1.2 Then, add ethanol solution to the residue obtained in step S1.1 again, extract under ultrasonic assistance for 1.0-2.0 hours, and filter to obtain the second ethanol extract and residue. S1.3 Add purified water to the residue obtained in step S1.2 and perform hot reflux extraction. After filtration, obtain an aqueous extract. S2, Multi-stage Concentration: S2.1 Combine the first alcohol extract, the second alcohol extract, and the water extract, and concentrate under reduced pressure to 1 / 4-1 / 3 of the original volume to obtain the concentrated solution; S2.2 Then, cool the concentrate to 25-35℃, add 0.5-1.5% of the volume of activated carbon, stir and adsorb for 20-40 minutes, then filter to remove carbon to obtain decarbonized liquid, and then concentrate the decarbonized liquid under reduced pressure to obtain extract for later use. S3, Matrix Melting and Mixing: The biomimetic polymeric gel matrix is ​​put into the reactor for melting. Then the reactor temperature is adjusted to 82-88℃. First, the extract prepared in step S2.3 is added and stirred for 15-25 minutes. Then, the transdermal penetration promoter is added and combined. Stirring and mixing is then carried out for 10-20 minutes to obtain a homogeneous and delicate paste. S4. Constant temperature coating: The paste obtained in step S3.2 is kept at a constant temperature of 78-83℃ in a constant temperature insulation bath, and then coated onto the surface of the substrate. Then, release paper is immediately covered on the coated paste surface. S5. Die-cut packaging: After the laminated plaster is cooled and shaped, it is die-cut to the predetermined size and sealed with nitrogen in an aluminum foil composite bag.

6. The production process of the plaster formula for bruises and sprains according to claim 5, characterized in that: In step S1.1, the concentration of the ethanol solution is 55-60%, and the extraction temperature is 55-60℃; in step S1.2, the concentration of the ethanol solution is 78-82%, the extraction temperature is 68-72℃, and the ultrasonic power density is 0.3-0.5 W / cm³. 3 In step S1.3, the temperature of the hot reflux extraction is 88-98℃, and the extraction time is 2.0-3.0 hours.

7. The production process of the plaster formula for bruises and sprains according to claim 5, characterized in that: In step S2.1, the conditions for vacuum concentration are: vacuum degree -0.085MPa to -0.098MPa and temperature 58-68℃.

8. The production process of the plaster formula for bruises and sprains according to claim 5, characterized in that: In step S2.2, the conditions for vacuum concentration are: vacuum degree -0.090MPa to -0.100MPa and temperature 62-72℃.

9. The production process of the plaster formula for bruises and sprains according to claim 5, characterized in that: In step S3, the melting temperature is 105-118℃, and the stirring speed is 600-1000 rpm for both times.

10. The production process of the plaster formula for bruises and sprains according to claim 5, characterized in that: In step S4, the substrate is a composite spunlace nonwoven fabric with a basis weight of 35-55 g / m2 or a silicone-modified polyurethane film with a thickness of 0.06-0.12 mm.

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