Plaster for treating pain in neck, shoulders, waist and legs

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, and discloses a plaster for treating pain in neck, shoulders, waist and legs, which comprises a volatile and heat-sensitive medicinal material group, a heat-resistant medicinal material group with toxic components, a floating medicinal material group, sesame oil, a composite micro-coating matrix and a physical activator. During preparation, volatile and heat-sensitive medicinal materials are pretreated by adopting a composite micro-coating matrix, and toxic medicinal materials are subjected to micro-wetting treatment by adopting a physical exciting agent; and putting the mixed powder to be fed into high-temperature sesame oil at one time for reaction, then transferring to a closed mechanical forming cavity, and forming through a warm-pressure coupling process of medium-temperature normal pressure, high-temperature positive-pressure intense permeation and medium-temperature negative-pressure sudden drop. According to the invention, the degradation of toxic diester-type alkaloid and the retention of thermosensitive components are synchronously realized by utilizing the phase change heat insulation of the coating substrate and the vaporization and micro-boiling mechanism of the exciting agent, and the physical topological structure of the plaster is remolded through temperature-pressure coupling, so that the leaching amount of effective components, the transdermal release efficiency and the product forming stability are improved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically a plaster for treating neck, shoulder, back and leg pain. Background Technology

[0002] Traditional Chinese medicine plasters are commonly used to treat bone and joint diseases such as neck, shoulder, back, and leg pain. Their traditional preparation process typically relies on high-temperature oil-phase media for decocting, extracting, and fusing the medicinal herbs with a matrix. The standard formulation of plasters usually includes both heat-resistant and primarily analgesic toxic herbs, such as Aconitum carmichaelii and Aconitum kusnezoffii, and herbs rich in volatile and heat-sensitive active ingredients, such as Ephedra sinica and Angelica sinensis. This presents a clear thermodynamic process contradiction in actual production. The main toxic components in the toxic herbs are diester alkaloids, which require hydrolysis and bond breaking at around 200 degrees Celsius to transform into less toxic monoester or alcoholamine alkaloids. However, the volatile and heat-sensitive components are highly susceptible to irreversible thermal degradation and phase transition vaporization under these high-temperature conditions.

[0003] To avoid this contradiction, conventional preparation processes often employ a distribution method where toxic medicinal materials are added first, followed by cooling to allow volatile medicinal materials to disseminate. However, in actual high-viscosity, high-temperature sesame oil systems, directly adding dried medicinal powders easily leads to severe agglomeration, as the high-viscosity fluid medium struggles to overcome surface tension and penetrate the powder's interior. The low heat and mass transfer efficiency at the solid-liquid interface results in a significant temperature gradient within the powder agglomerates, leading to insufficient hydrolysis activation energy for diester alkaloids. This results in incomplete thermal detoxification, and some low-boiling-point pyrolysis products remain trapped in the viscous medium, unable to effectively escape the reaction system. Furthermore, continuous heating and stirring in an open-system hot oil environment causes heat accumulation. Even with reduced feeding temperatures in the later stages of the process, the volatile gas-liquid exchange interface remains exposed, resulting in significant loss of heat-sensitive and volatile components over prolonged mass transfer.

[0004] Furthermore, existing plaster molding methods largely rely on physical cooling and curing under normal pressure. The plaster formed during normal pressure cooling has a highly dense and homogeneous internal structure, lacking interconnected channels. This increases the resistance to drug molecule migration to the skin interface, resulting in low macroscopic transdermal release efficiency of the final product. Simply relying on normal pressure temperature control to form a solid-liquid physical fusion interface has limited cohesion. Under long-term storage or heating conditions, plaster products are prone to matrix phase separation and oil seepage, leading to decreased mechanical bonding properties and poor molding stability. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a plaster for treating neck, shoulder, back, and leg pain. It solves the thermodynamic contradiction between the need for high-temperature detoxification of heat-resistant toxic medicinal materials and the need for retention of volatile and heat-sensitive active ingredients during the high-temperature decoction preparation process of traditional Chinese medicine plasters. Furthermore, direct feeding of dry powder can easily lead to encapsulation and agglomeration, resulting in low heat and mass transfer efficiency, low transdermal release rate, and poor molding stability.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A plaster for treating neck, shoulder, back, and leg pain is made from the following ingredients by weight: a herbal group providing volatile and heat-sensitive active ingredients, including Ephedra 30g, Angelica sinensis 20g, Safflower 10g, Saposhnikovia divaricata 20g, Frankincense 30g, and Myrrh 30g; and a herbal group providing heat-resistant and primarily analgesic but toxic components, including Aconitum carmichaelii 30g, Aconitum kusnezoffii 30g, Arisaema heterophyllum 30g, Pinellia ternata 20g, Eupolyphaga sinensis 30g, Eucommia ulmoides 30g, Sparganium stoloniferum 20g, Curcuma zedoaria 20g, Lycopodium clavatum 50g, and Angelica pubescens. 100g; 60 to 100g of floating medicinal materials for bone penetration and blood circulation promotion and stiffness removal, including white mustard seed, clematis root, chicken blood vine, and clematis root; 1140 to 2700g of sesame oil for providing extraction solvent and molding base; 7 to 14g of composite micro-coated matrix for forming a physical heat insulation buffer layer in high temperature environment; and 18.6 to 60.8g of physical activator for inducing internal fluid phase change vaporization and micro-boiling effect.

[0007] By adopting the above technical solution, and by using pre-selected excipients to differentiate and pre-treat medicinal powders with different properties, and by implementing a one-time high-temperature feeding process in subsequent steps, the technical effect of simultaneously and thoroughly degrading toxic components while retaining a high proportion of heat-sensitive and volatile effective components is achieved. The innovative principle and reaction mechanism of this invention are specifically carried out according to the following steps: The first step involves endothermic phase change and thermodynamic physical isolation. The surface of the medicinal herb particles containing volatile and heat-sensitive active ingredients is coated with a composite micro-encapsulated matrix. When this material is added to a high-temperature sesame oil medium, the composite micro-encapsulated matrix, which is solid at room temperature, undergoes a physical phase change from solid to liquid under thermal shock. This phase change process absorbs a large amount of latent heat from the extraction system, forming a transient physical insulation layer at the solid-liquid interface of the volatile and heat-sensitive medicinal powder particles. This physical insulation layer cuts off the direct heat conduction path from the high-temperature heat source to the pores inside the particles, maintaining a relatively low temperature inside the particles during the extremely high-temperature initial stage of feeding. This prevents the thermal degradation reaction of ephedrine hydrochloride and reduces the phase change vaporization rate of easily volatile, low-boiling-point components, thereby locking the volatile and heat-sensitive components within the microstructure of the plant tissue.

[0008] The second step involves phase change expansion and fluid shear dispersion. The heat-resistant and toxic medicinal materials contain pre-adsorbed physical activators within their internal pores. Upon contact with the high-temperature oil phase, the liquid physical activators absorb heat from the surrounding medium, undergoing a rapid liquid-to-gas phase change and vaporization. The sudden volume increase resulting from this phase change triggers high-frequency micro-boiling in the local oil phase fluid. The continuous generation and collapse of vapor bubbles generate hydrodynamic shearing, completely disintegrating the solid-phase agglomeration structure of the dry powder material within the viscous ointment from a mechanical dynamic perspective. This hydrodynamic shearing forces the solid powder particles into a monodisperse suspension in the liquid medium, eliminating local hot spots and temperature gradients, and maximizing the solid-liquid heat transfer surface area.

[0009] The third step involves high-temperature hydrolysis and bond breaking, followed by detoxification and impurity removal through vapor extraction. Under monodisperse suspension and efficient heat transfer conditions, the heat-resistant and toxic components of the medicinal material are uniformly heated. The main toxic substances present within, aconitine, mesonaconitine, and hypoaconitine, undergo hydrolysis and thermal decomposition reactions under high temperature and with the participation of polar molecules. The acetyl group at C8 and the aromatic acyl ester bond at C14 in the diester alkaloid molecular skeleton undergo thermodynamic breakage. Specifically, the reaction dissociation process is as follows: the diester alkaloid hydrolyzes to remove one molecule of acetic acid, transforming into a less toxic monoester alkaloid; the monoester alkaloid continues to hydrolyze, removing one molecule of aromatic acid, transforming into an alkanolamine alkaloid. Simultaneously, the vapor generated by the phase change vaporization of the physical activator, as it escapes and dissipates towards the liquid phase surface, generates an upward vapor extraction force within the system. This air stripping process forcibly carries away the volatile small-molecule toxic substances and impurities generated by the pyrolysis of alkaloids from the oil phase reaction system, breaks through the surface tension of the fluid, and discharges them into the external environment, thus completing the internal purification and deep detoxification of the oil phase medium.

[0010] This invention provides a plaster for treating neck, shoulder, back, and leg pain. It has the following beneficial effects: 1. This invention achieves a one-time high-temperature feeding process by pretreating volatile and heat-sensitive medicinal materials with a composite micro-coating matrix and micro-wetting toxic medicinal materials with a physical activator. During feeding, the coating matrix undergoes a phase change and melts, absorbing heat and forming a heat insulation layer on the particle surface to protect volatile and heat-sensitive components from high-temperature damage. At the same time, the activator in the toxic powder vaporizes upon heating, initiating micro-boiling, breaking down the powder agglomeration, enhancing solid-liquid heat transfer efficiency, promoting the hydrolysis and bond breaking of diester-type alkaloids, and removing them from the system through steam stripping. In the same reaction system, the degradation of toxic substances and the retention of heat-sensitive active ingredients are achieved simultaneously.

[0011] 2. This invention improves the extraction and transdermal release of active ingredients by introducing a temperature-pressure coupling process in a closed molding cavity. In the high-temperature positive pressure strong penetration stage, the positive absolute pressure forces the low-viscosity oil phase medium to overcome pore resistance and penetrate into the deep tissue of the herbal powder, driving the internal active ingredients to dissolve and transfer to the fluid phase. In the subsequent medium-temperature negative pressure rapid drop stage, the sudden drop in environmental pressure forces the residual gas in the system to expand and precipitate outward. During the process of the ointment cooling and thickening, it washes out interlaced interconnected pores, increasing the macroscopic specific surface area of ​​the ointment and providing a fluid channel for the diffusion of drug molecules to the skin contact interface.

[0012] 3. This invention enhances the physical molding stability of plaster products and reduces oil seepage rate by combining composite matrix materials with pressure-changing processes. The alternating operation of positive pressure penetration and negative pressure shaping allows the powder to be fully encapsulated by the oil phase and polymer materials. The physical process of cooling and depressurization at the end blocks the thermal oxidation of components and promotes the composite matrix to complete phase change curing within the preset temperature range. The rapid shrinkage and shaping of the matrix locks the internal solid-liquid cross-linking system, cuts off the macroscopic migration path of the free oil phase in the plaster, and enables the final molded product to have continuous mechanical bonding properties, overcoming the matrix phase separation defect of traditional plasters under heating conditions. Detailed Implementation

[0013] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the embodiments and comparative examples. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0014] Preparation Examples 1-3: Preparation Example 1: This preparation example provides a method for preparing a composite micro-coated matrix, including the following steps: 50g of beeswax and 10g of stearic acid were placed in a reactor with a heating jacket and heated to 75°C until completely melted. In the molten state, 40g of polyethylene glycol 4000 solid particles were added. Mechanical stirring was started at 300 rpm and stirred at a constant temperature of 75°C for 15 minutes to ensure uniform mixing of the three components to form a homogeneous oil phase system. The mixture was then cooled to 45°C to obtain a composite micro-coated matrix in a semi-fluid state.

[0015] Preparation Example 2: This preparation example provides a method for preparing a composite micro-coated matrix, including the following steps: 55g of beeswax and 10g of stearic acid were placed in a reactor with a heating jacket and heated to 80°C to melt them completely. 35g of polyethylene glycol 4000 solid particles were added while the mixture was still molten. Mechanical stirring was started at 400 rpm and stirred at a constant temperature of 80°C for 22 minutes to ensure uniform mixing of the three components and the formation of a homogeneous oil phase system. The mixture was then cooled to 50°C to obtain a composite micro-coated matrix in a semi-fluid state.

[0016] Preparation Example 3: This preparation example provides a method for preparing a composite micro-coated matrix, including the following steps: 60g of beeswax and 5g of stearic acid were placed in a reactor with a heating jacket and heated to 85°C until completely melted. 35g of polyethylene glycol 4000 solid particles were added while the mixture was still molten. Mechanical stirring was started at 500 rpm and stirred at a constant temperature of 85°C for 30 minutes to ensure uniform mixing of the three components and the formation of a homogeneous oil phase system. The mixture was then cooled to 55°C to obtain a composite micro-coated matrix in a semi-fluid state.

[0017] Examples 1-3: Example 1: This example provides a plaster for treating neck, shoulder, back and leg pain, including the following preparation steps: Ephedra 30g, Angelica sinensis 20g, Carthamus tinctorius 10g, Saposhnikovia divaricata 20g, Boswellia carterii 30g, and Commiphora myrrha 30g were weighed out as the volatile and heat-sensitive medicinal materials group. Aconitum carmichaelii 30g, Aconitum kusnezoffii 30g, Arisaema heterophyllum 30g, Pinellia ternata 20g, Eupolyphaga sinensis 30g, Eucommia ulmoides 30g, Sparganium stoloniferum 20g, Curcuma zedoaria 20g, Lycopodium clavatum 50g, Angelica pubescens 100g, Sinapis alba 60g, Clematis chinensis 60g, Spatholobus suberectus 80g, and Clematis chinensis 60g were weighed out as the heat-resistant and toxic medicinal materials group.

[0018] The volatile and heat-sensitive medicinal materials were pulverized to 100 mesh, and 7g of the composite micro-coated matrix obtained in Preparation Example 1, which was in a semi-fluid state at 45°C, was added. The mixture was stirred at 50 rpm for 10 min and then naturally cooled to 20°C to solidify the coating matrix and obtain pretreated powder A.

[0019] Heat-resistant and toxic medicinal materials were pulverized to 80 mesh, and 18.6g of rice wine was sprayed in. The mixture was stirred at 40 rpm for 10 minutes to slightly moisten the powder, resulting in pretreated powder B. Pretreated powder A and pretreated powder B were mixed at 30 rpm for 10 minutes to obtain the final mixed powder to be added. 1140g of sesame oil was placed in a refining pot and heated to a constant temperature of 190℃. The final mixed powder to be added was poured into the refining pot all at once, and the fluid temperature inside the pot was maintained at 180℃ for 3 minutes to obtain the primary oil-medicinal mixture.

[0020] The primary oil-powder mixture is transferred into a sealed mechanical forming chamber. The chamber temperature is adjusted to 85°C and maintained at 0.1 MPa for 5 minutes. The chamber temperature is then increased to 130°C, and nitrogen is injected simultaneously to raise the absolute pressure to 0.3 MPa and maintain this pressure for 10 minutes. The chamber temperature is then rapidly reduced to 60°C, and a vacuum pump is simultaneously activated to evacuate the chamber to -0.05 MPa and maintain this vacuum for 5 minutes. The vacuum is then released to restore normal pressure, and the outlet is opened to obtain the final product.

[0021] Example 2: This example provides a plaster for treating neck, shoulder, back, and leg pain, comprising the following preparation steps: 30g of Ephedra, 20g of Angelica sinensis, 10g of Carthamus tinctorius, 20g of Saposhnikovia divaricata, 30g of Frankincense, and 30g of Myrrh were weighed out as the volatile and heat-sensitive medicinal materials group. 30g each of Aconitum carmichaelii, Aconitum kusnezoffii, Arisaema heterophyllum, Pinellia ternata, Eupolyphaga sinensis, Eucommia ulmoides, Sparganium stoloniferum, Curcuma zedoaria, Lycopodium clavatum, Angelica pubescens, Sinapis alba, Clematis chinensis, Spatholobus suberectus, and Clematis chinensis were weighed out as the heat-resistant and toxic medicinal materials group.

[0022] The volatile and heat-sensitive medicinal materials were pulverized to 110 mesh, and 10.5 g of the composite micro-coated matrix obtained in Preparation Example 2, which was in a semi-fluid state at 50°C, was added. The mixture was stirred at 65 rpm for 15 min, and then naturally cooled to 22°C to solidify the coating matrix, thus obtaining pretreated powder A. The heat-resistant and toxic medicinal materials were pulverized to 90 mesh, and 38 g of rice wine was sprayed in. The mixture was stirred at 50 rpm for 12 min to slightly wet the powder, thus obtaining pretreated powder B.

[0023] Pretreated powder A and pretreated powder B were mixed at 40 rpm for 12 minutes to obtain the final mixed powder to be fed. 1867.5g of sesame oil was placed in a refining pot and heated to a constant temperature of 205℃. The final mixed powder to be fed was poured into the refining pot all at once, and the fluid temperature in the pot was maintained at 190℃ for 5 minutes to obtain the primary oil-medicine mixture fluid.

[0024] The primary oil-powder mixture is transferred into a sealed mechanical forming chamber. The chamber temperature is adjusted to 92°C and maintained at 0.1 MPa for 7 minutes. The chamber temperature is then increased to 140°C while nitrogen is injected to raise the absolute pressure to 0.4 MPa and maintained for 15 minutes. The chamber temperature is then rapidly reduced to 68°C while a vacuum pump is activated to evacuate the chamber to -0.06 MPa and maintained for 10 minutes. The vacuum is then released to restore normal pressure, and the outlet is opened to obtain the final product.

[0025] Example 3: This example provides a plaster for treating neck, shoulder, back, and leg pain, comprising the following preparation steps: 30g of Ephedra, 20g of Angelica sinensis, 10g of Carthamus tinctorius, 20g of Saposhnikovia divaricata, 30g of Frankincense, and 30g of Myrrh were weighed out as the volatile and heat-sensitive medicinal materials group. 30g each of Aconitum carmichaelii, Aconitum kusnezoffii, Arisaema heterophyllum, Pinellia ternata, Eupolyphaga sinensis, Eucommia ulmoides, Sparganium stoloniferum, Curcuma zedoaria, Lycopodium clavatum, Angelica pubescens, Sinapis alba, Clematis chinensis, Spatholobus suberectus, and Clematis chinensis were weighed out as the heat-resistant and toxic medicinal materials group.

[0026] The volatile and heat-sensitive medicinal materials were pulverized to 120 mesh, and 14g of the composite micro-coated matrix obtained in Preparation Example 3, which was in a semi-fluid state at 55°C, was added. The mixture was stirred at 80 rpm for 20 min, and then naturally cooled to 25°C to solidify the coating matrix, thus obtaining pretreated powder A. The heat-resistant and toxic medicinal materials were pulverized to 100 mesh, and 60.8g of rice vinegar was sprayed in. The mixture was stirred at 60 rpm for 15 min to slightly wet the powder, thus obtaining pretreated powder B.

[0027] Pretreated powder A and pretreated powder B were mixed at 50 rpm for 15 minutes to obtain the final mixed powder to be added. 2700g of sesame oil was placed in a refining pot and heated to a constant temperature of 220℃. The final mixed powder to be added was poured into the refining pot all at once, and the fluid temperature in the pot was maintained at 200℃ for 8 minutes to obtain the primary oil-medicine mixture.

[0028] The primary oil-powder mixture is transferred into a sealed mechanical forming chamber. The chamber temperature is adjusted to 100℃ and maintained at 0.1MPa for 10 minutes. The chamber temperature is then increased to 150℃ while nitrogen is injected to raise the absolute pressure to 0.5MPa and maintained for 20 minutes. The chamber temperature is then rapidly reduced to 75℃ while a vacuum pump is activated to evacuate the chamber to -0.08MPa and maintained for 15 minutes. The vacuum is then released to restore normal pressure, and the outlet is opened to obtain the final product.

[0029] Comparative Examples 1-4: Comparative Example 1: Compared with Example 2, the difference is that the volatile and heat-sensitive medicinal materials were not coated with the composite micro-coating matrix. Instead, they were pulverized and directly mixed with the pretreated medicinal powder B as the final mixed powder to be fed into the system. All other aspects are the same.

[0030] Comparative Example 2: Compared with Example 2, the difference is that the heat-resistant and toxic medicinal materials were not sprayed with rice wine for micro-wetting treatment. Instead, they were crushed and directly mixed with pretreated powder A as the final mixed powder to be added. All other aspects are the same.

[0031] Comparative Example 3: Compared with Example 2, the difference is that no powder pretreatment and one-time feeding steps were performed. Instead, a traditional distribution processing technology was used. After heating the sesame oil to 205°C, the powdered heat-resistant and toxic medicinal materials were first added and boiled for 5 minutes. Then, the powdered volatile and heat-sensitive medicinal materials were added and mixed. The rest were the same.

[0032] Comparative Example 4: Compared with Example 2, the difference is that only the temperature is adjusted in the closed mechanical forming cavity. Nitrogen is not injected to increase the absolute pressure, nor is a vacuum pump turned on to extract negative pressure. The internal pressure of the cavity is always kept at a normal pressure of 0.1 MPa. Everything else is the same.

[0033] Test Examples 1-5: Test Example 1: Feasibility Test for Degradation of Toxic Components Accurately weigh 2.0 g of each of the products obtained in Examples 1 to 3, place them in stoppered conical flasks, add 2 mL of ammonia test solution, mix well and let stand for 20 minutes to moisten.

[0034] Add 50 mL of diethyl ether-chloroform mixed solvent to the conical flask, weigh it, place it in an ultrasonic cleaner for 40 minutes, remove it, let it cool, weigh it again, replenish the lost weight with the above mixed solvent, shake well, and filter it with filter paper.

[0035] Accurately measure 25 mL of the filtrate and place it in an evaporating dish. Evaporate to dryness in a water bath. Dissolve the residue in a mixed solvent of isopropanol and dichloromethane. Transfer the solution to a 10 mL volumetric flask and make up to volume. Shake well and filter through a 0.45 μm microporous membrane. Use the filtrate as the test solution.

[0036] Accurately weigh appropriate amounts of aconitine, mesaccharine, and hypoaconitine reference standards, dissolve them in isopropanol-dichloromethane mixed solvent and dilute to volume to prepare a mixed reference solution containing approximately 10g of each of aconitine, mesaccharine, and hypoaconitine per 1mL.

[0037] An octadecylsilane-bonded silica gel column was used, with acetonitrile-tetrahydrofuran as mobile phase A and 0.1 mol / L ammonium acetate solution as mobile phase B for gradient elution. The detection wavelength was set at 235 nm, the column temperature at 40 °C, and the flow rate at 1.0 mL / min.

[0038] Inject 10 L each of the test solution and the reference solution into the liquid chromatograph, record the chromatograms, and calculate the content of the three diester alkaloids in each sample by peak area using the external standard method. The results are expressed in mg / kg.

[0039] Test results: Table 1. Results of diester-type alkaloid residue determination in Examples 1-3 Group Aconitine residue (mg / kg) aconitine residue (mg / kg) aconitine residue (mg / kg) Total diester alkaloids (mg / kg) Example 1 0.142 0.315 0.208 0.665 Example 2 0.098 0.241 0.173 0.512 Example 3 0.115 0.287 0.194 0.596 Results analysis: According to the data in Table 1, the residues of aconitine, mesonaconitine, and hypoaconitine in the products prepared in Examples 1 to 3 were all at low levels, with the highest total residue of the three diester alkaloids being 0.665 mg / kg. Diester alkaloids are the main toxic components of Aconitum carmichaelii and Aconitum kusnezoffii in the formulation, and their molecular structure is thermally unstable.

[0040] In the preparation process, the powder containing toxic medicinal materials is pre-wetted with rice wine or rice vinegar. When this powder mixture is added to high-temperature sesame oil at 190°C to 220°C, the liquid activator adsorbed inside the powder undergoes a rapid phase change and vaporization upon heating. The volume expansion caused by the phase change triggers violent physical turbulence within the fluid system, disrupting powder agglomeration and increasing the contact area and heat transfer efficiency between the solid medicinal powder and the high-temperature oil phase. The high-temperature environment induces hydrolytic cleavage of the C8 acetyl group and C14 aromatic acyl group in the diester-type alkaloid structure, transforming it into a less toxic monoester-type alkaloid or an alcoholamine-type alkaloid. The outward diffusion of vapor from the vaporization of the activator carries some of the volatile small-molecule toxic substances produced by thermal decomposition to the liquid surface.

[0041] The test data of Examples 1 to 3 cover the upper and lower limits and median of the raw material ratio and process parameters defined in this invention, and all show a stable removal effect of diester-type alkaloids, indicating that the combination mechanism of powder wetting pretreatment and high-temperature feeding operation can stably achieve the degradation and removal of toxic components.

[0042] Test Example 2: Macroscopic Physical Properties and Molding Stability Test The softening point of the products obtained in Examples 1 to 3 was determined using the ring and ball method. After the sample was heated and softened, it was placed in a brass ring of a specified size, cooled and the surface was scraped flat, and then placed in a constant temperature water bath. The temperature was increased at a constant rate of 5°C per minute, and the temperature of the bottom plate when the standard steel ball penetrated the sample layer and fell to a specified distance was recorded. This was repeated 3 times and the average value was taken.

[0043] The products obtained in Examples 1 to 3 were cut to standard sizes and laid flat on a stainless steel test plate with an inclination angle of 30 degrees for initial tack testing. A series of standard steel balls with increasing volumes were allowed to roll freely from a specified position at the top of the inclined plane, and the number of the largest steel ball that could stop completely within its test area was recorded. The test was repeated 3 times and the average value was taken.

[0044] Cut a product sample with a contact area of ​​25mm x 25mm and attach it to a clean standard stainless steel test plate. Roll the sample back and forth three times with a standard pressure roller at the specified pressure. After standing at room temperature for 20 minutes, suspend the steel plate vertically on the test frame and attach a 1kg standard weight to the bottom of the sample. Record the time it takes for the sample to completely slide off the surface of the steel plate and fall. Repeat the measurement three times and take the average value.

[0045] Cut a product sample with a surface area of ​​10 square centimeters, accurately weigh its initial weight, and place it flat in the center of a pre-weighed quantitative filter paper. Place the filter paper and the sample together in a constant temperature incubator set at 60°C for 48 hours. Remove the sample and allow it to return to room temperature. Remove the main sample, accurately weigh the filter paper after absorbing the exudate, and calculate the percentage of the exudate oil phase mass to the initial sample mass, which is the oil exudation rate.

[0046] Test results: Table 2. Results of macroscopic physical properties and molding stability measurements of Examples 1-3 Group Softening point (°C) Initial tack (maximum steel ball size) Holding power (min) Oil penetration rate (%) Example 1 64.3 11 178 1.62 Example 2 67.8 14 224 0.75 Example 3 70.1 12 191 1.28 Results analysis: According to the data in Table 2, the softening points of the products obtained in Examples 1 to 3 ranged from 64.3℃ to 70.1℃, the initial tack strength was between 11 and 14 steel ball numbers, the holding power was maintained between 178 and 224 minutes, and the oil penetration rate under accelerated aging conditions was all below 1.7%. The test results indicate that the cohesive force of the product matrix and the interfacial adhesion with the substrate have reached a stable state, the matrix phase separation degree is low under high temperature conditions, and it possesses good molding stability. The formation mechanism of these macroscopic physical properties originates from the thermo-pressure coupling operation within the closed mechanical molding cavity.

[0047] In the middle stage of molding, a high temperature of 130℃ to 150℃ combined with a system positive pressure of 0.3MPa to 0.5MPa alters the rheological properties of the internal mixed fluids, significantly reducing the surface tension of the high-viscosity oil phase. The mechanical positive pressure forcibly drives the oil phase fluid to penetrate into the internal pores of the solid powder and the microstructure of the broken plant cells, forming a highly uniform solid-liquid co-linked system. In the subsequent locking-in stage, the system temperature rapidly drops to 60℃ to 75℃, simultaneously superimposed with a negative pressure environment of -0.05MPa to -0.08MPa. The instantaneous reversal of the environmental pressure causes the residual gas in the system to expand outward and be extracted, while the composite matrix completes phase change curing within this temperature range. The cooling and depressurization physical process, while blocking the thermal oxidation of the components, promotes the shrinkage and shaping of the overall paste network and generates uniform permeable pores. The alternating coupling of positive high-pressure infiltration and negative cooling and shaping allows the powder particles to be tightly wrapped and locked by the oil phase and polymer materials, blocking the macroscopic migration path of the free oil phase in the matrix, thereby significantly reducing the oil penetration rate and giving the final molded product continuous and stable mechanical bonding properties.

[0048] Test Example 3: Comparative Test of Retention Rate of Volatile Active Ingredients Accurately weigh 5.0g of each of the products obtained in Example 2, Comparative Example 1 and Comparative Example 3, cut them into small pieces and place them in a 250mL stoppered conical flask. Add 100mL of petroleum ether (boiling range 60℃ to 90℃) and weigh the total weight.

[0049] Place the conical flask in a constant temperature water bath ultrasonic extractor and ultrasonically treat it for 45 minutes at room temperature. Remove it and let it cool to room temperature before weighing it again. Add petroleum ether of the same specification to make up for the weight loss. Shake well and filter it through a 0.45 μm organic phase microporous membrane. Take the filtrate and place it in a rotary evaporator. Concentrate it under reduced pressure in a 40°C water bath to about 2 mL. Transfer it to a 5 mL volumetric flask and dilute it to volume with petroleum ether to obtain the test solution for the determination of total volatile oil.

[0050] Separately, accurately weigh 3.0 g of each of the above-mentioned products, place them in a Soxhlet extractor, add methanol and reflux continuously for 4 hours, concentrate the extract under reduced pressure to dryness, dissolve the residue in 0.1% phosphoric acid aqueous solution (by volume) and transfer to a 10 mL volumetric flask and make up to volume, filter, and take the filtrate as the test solution for the determination of ephedrine hydrochloride.

[0051] Accurately weigh an appropriate amount of ephedrine hydrochloride reference standard, dissolve it in methanol to prepare a reference standard stock solution containing 0.5 mg per 1 mL; separately take appropriate amounts of the stock solution to prepare standard working solutions of gradient concentrations.

[0052] The total volatile oil content was determined using a gas chromatograph equipped with a flame ionization detector (FID). The chromatographic column was a polyethylene glycol capillary column (30m x 0.25mm, 0.25m); the injection port temperature was 250℃, and the detector temperature was 260℃. The temperature program was as follows: initial temperature 60℃, held for 2 minutes; increased to 150℃ at a rate of 5℃ / min; then increased to 240℃ at a rate of 10℃ / min, held for 10 minutes. High-purity nitrogen was used as the carrier gas at a flow rate of 1.0 mL / min; the split ratio was set to 10:1. 2L of each sample was injected, and the chromatograms were recorded. The total volatile oil content was calculated using the area normalization method and converted to its mass fraction in the product matrix.

[0053] The determination of ephedrine hydrochloride was performed using the same gas chromatography system, but the column was replaced with a 5% phenyl-95% methyl polysiloxane capillary column. The absolute content of ephedrine hydrochloride in the sample was calculated using the external standard method combined with the peak area, and the retention rate was calculated in combination with the theoretical input of raw materials.

[0054] Test results: Table 3. Results of retention rate determination of volatile active ingredients in Example 2 and Comparative Examples 1 and 3 Group Ephedrine hydrochloride content (mg / g) Ephedrine hydrochloride retention rate (%) Total volatile oil content (mg / g) Total volatile oil retention rate (%) Example 2 1.84 86.42 21.35 81.17 Comparative Example 1 0.37 17.38 4.62 17.56 Comparative Example 3 1.15 54.01 13.88 52.75 Results analysis: According to the data in Table 3, in Example 2, the retention rate of ephedrine hydrochloride reached 86.42%, and the retention rate of total volatile oil reached 81.17%, both of which are at a high retention level. In Comparative Example 1, without the pretreatment step of the composite micro-coating matrix, the retention rates of ephedrine hydrochloride and total volatile oil dropped to 17.38% and 17.56%, respectively. Comparative Example 3 used a traditional distribution processing technology of adding toxic medicinal materials first and then volatile medicinal materials, and its ephedrine hydrochloride retention rate was 54.01%, and the total volatile oil retention rate was 52.75%. In Comparative Example 1, the powder was not coated with the beeswax and polyethylene glycol 4000 composite material. The exposed volatile and heat-sensitive medicinal material powder directly contacted the high-temperature sesame oil at 205°C. The heat-sensitive alkaloids underwent high-temperature degradation, and the low-boiling-point volatile oil components vaporized in large quantities upon contact and escaped the reaction system with the hot airflow, resulting in irreversible loss of the effective components.

[0055] The composite micro-coated matrix introduced in Example 2 is in a solidified state at room temperature, tightly encapsulating the volatile drug powder. When the powder suspension is fed into the high-temperature oil phase in one go, the surface beeswax and polyethylene glycol undergo a solid-liquid phase transition. The phase transition melting process absorbs a large amount of latent heat within the system, forming a transient physical heat-insulating buffer layer on the surface of the volatile drug powder particles, blocking the direct conduction of high heat above 200°C to the particle interior. At this time, accompanied by the micro-boiling effect generated by the vaporization of another set of powder surface activators, the drug powder is rapidly dispersed in the hot oil, avoiding localized overheating areas.

[0056] Although Comparative Example 3 reduced the feeding temperature in the later stages of the process to protect volatile components, the continuous heating and stirring of the open hot oil system still caused heat accumulation and continuous exposure of the volatile interface. Volatile substances gradually dissipated into the air due to prolonged mass transfer. In Example 2, after a brief period of high-temperature mixing, the fluid was rapidly transferred to a closed mechanical molding cavity for the subsequent temperature-pressure coupling process. The vacuum negative pressure combined with the 68°C medium-temperature rapid cooling operation cut off the gas-liquid exchange interface between the high-temperature grease and the external environment, forcibly sealing the incompletely dissipated volatile components in the micro-network formed by the shrinkage of the grease, thus inhibiting the continuous volatilization and oxidation reaction during the cooling stage. The phase change endothermic mechanism of the composite micro-coated matrix and the negative pressure drop mechanism of the closed molding system are linked, maintaining the overall one-time high-temperature feeding and rapid detoxification reaction while constructing a thermodynamic isolation barrier and a physically enclosed space for heat-sensitive and volatile molecules.

[0057] Test Example 4: Comparison Test of Toxicity Degradation Efficiency Accurately weigh 2.5g of each of the products obtained in Example 2 and Comparative Example 2, place them in 50mL stoppered centrifuge tubes, add 2.5mL of ammonia test solution, vortex to mix evenly, and let stand for 30 minutes to allow for full alkalization.

[0058] Add 25 mL of diethyl ether-chloroform mixed solvent to a centrifuge tube, weigh the initial total weight, place it in a CNC ultrasonic cleaner, and ultrasonically extract at room temperature for 45 minutes. Remove the tube, let it cool to room temperature, weigh it again, add the same proportion of mixed solvent to make up the lost weight, shake well, centrifuge at 4000 rpm for 10 minutes, and collect the supernatant.

[0059] Accurately measure 15 mL of the supernatant into a round-bottom flask, connect it to a rotary evaporator, and evaporate it to dryness under reduced pressure in a 35°C water bath. Add isopropanol-dichloromethane mixed solvent to the residue and dissolve it by sonication. Transfer the solution to a 5 mL volumetric flask, filter it using a 0.45 μm polytetrafluoroethylene microporous membrane, discard the initial filtrate, and use the subsequent filtrate as the test solution.

[0060] Accurately weigh appropriate amounts of aconitine, mesaccharine, and hypoaconitine reference standards, dissolve and dilute them in isopropanol-dichloromethane mixed solvent to prepare a mixed reference standard stock solution containing 8.5 g of aconitine, 11.2 g of mesaccharine, and 9.6 g of hypoaconitine per 1 mL.

[0061] An octadecylsilane-bonded silica gel column was used. Mobile phase A was acetonitrile-tetrahydrofuran, and mobile phase B was 0.1 mol / L ammonium acetate solution. Gradient elution was performed according to the set program. The detection wavelength was 235 nm, the column temperature was kept constant at 40 °C, and the flow rate was set to 1.0 mL / min.

[0062] Inject 10 L each of the test solution and the reference solution into the high performance liquid chromatograph, record the elution chromatograms, and calculate the absolute residue of the three diester alkaloids in each sample by integrating the peak area using the external standard method. The results are expressed in mg / kg.

[0063] Test results: Table 4. Results of the determination of diester-type alkaloid residues in Example 2 and Comparative Example 2 Group Aconitine residue (mg / kg) aconitine residue (mg / kg) aconitine residue (mg / kg) Total diester alkaloids (mg / kg) Example 2 0.098 0.241 0.173 0.512 Comparative Example 2 1.254 2.871 1.946 6.071 Results analysis: According to the data in Table 4, the total amount of diester alkaloids in the product prepared in Example 2 was 0.512 mg / kg, while the total amount of diester alkaloids in the product of Comparative Example 2 was as high as 6.071 mg / kg, showing a difference of orders of magnitude. In Comparative Example 2, without the pretreatment of micro-wetting with rice wine, the heat-resistant and toxic medicinal materials were directly added to high-temperature sesame oil in a dry powder state. The surface tension of the high-viscosity oil phase system made it difficult for the surface of the dry powder particles to be rapidly wetted, resulting in severe agglomeration of the powder in the oil phase. Heat conduction relied solely on slow penetration at the solid-liquid interface, and a significant temperature gradient existed within the powder agglomerates. The activation energy supply for the hydrolysis reaction of the diester alkaloids was insufficient, leading to a very incomplete thermal detoxification reaction.

[0064] Some of the low-boiling-point products that have undergone pyrolysis are trapped in the viscous hot oil medium and cannot effectively overcome the surface tension to escape the reaction system. In Example 2, the liquid activator adsorbed by the powder undergoes a violent phase change and vaporization upon contact with sesame oil at 205°C. The sudden increase in volume caused by the transformation from liquid to gas phase triggers a high-frequency micro-boiling phenomenon within the system. The rapid generation and collapse of bubbles generate strong fluid shear forces, forcibly disintegrating the powder agglomeration structure from a mechanical dynamics perspective, causing the solid particles to suspend in a monodisperse state in the liquid medium, thus expanding the heat transfer surface area. The uniform and instantaneous high thermal shock forces the ester bonds in the diester-type alkaloid molecular structure to break completely. A large amount of vaporized vapor generates a lift-off effect as it overflows to the liquid surface, rapidly carrying away the volatile toxic substances produced by the thermal decomposition of the alkaloids from the oil medium.

[0065] Micro-wetting pretreatment alters the initial interfacial tension of solid powders and introduces an endogenous phase change driving force for the high-temperature feeding stage. This constructs a detoxification mass transfer kinetic system that integrates powder dispersion, enhanced heat transfer, and gas phase exfoliation, with a toxicity degradation efficiency significantly superior to the traditional dry powder direct feeding process.

[0066] Test Example 5: Comparison Test of Macroscopic Extraction and Transdermal Release of Active Ingredients Accurately weigh 5.0 g of each of the products obtained in Example 2 and Comparative Example 4, and place them in stoppered conical flasks. Add 50 mL of methanol and weigh the total weight. Place the conical flasks in a constant temperature water bath ultrasonic extractor and ultrasonically extract at room temperature for 60 minutes. Remove and cool to room temperature, then weigh again. Make up the weight loss with methanol, shake well, and filter through quantitative filter paper.

[0067] Accurately measure 10 mL of the filtrate and place it in an evaporating dish. Evaporate to dryness in a water bath. Dissolve the residue in methanol and transfer it to a 5 mL volumetric flask. Make up to volume, shake well, and filter through a 0.45 μm microporous membrane. Use the filtrate as the test solution for macroscopic extract determination.

[0068] Separately, accurately weigh appropriate amounts of paeoniflorin and ferulic acid reference standards, dissolve them in methanol, and dilute to a final volume to prepare a mixed reference solution containing 42g of paeoniflorin and 26g of ferulic acid per 1mL.

[0069] An octadecylsilane-bonded silica gel column was used with acetonitrile as mobile phase A and 0.1% phosphoric acid aqueous solution as mobile phase B for gradient elution. The detection wavelength was set to a dual-wavelength switching mode of 230 nm and 320 nm, the column temperature was kept constant at 30℃, and the flow rate was set at 1.0 mL / min. 10 μL each of the test solution and the reference solution were injected into the liquid chromatograph. The total leaching content of paeoniflorin and ferulic acid in the sample was calculated based on peak area using the external standard method, and the results were expressed as mg / g.

[0070] Transdermal release assays were performed using a modified Franz diffusion cell apparatus. A hydrophilic polycarbonate microporous membrane was used as the permeation barrier, and the effective transdermal area of ​​the supply cell was 3.14 square centimeters. The receiving cell was filled with physiological saline containing 20% ​​ethanol as the receiving medium, and the temperature of the constant-temperature water bath jacket was maintained at 37°C, with a constant magnetic stirring speed of 300 rpm.

[0071] Each product sample, with an area of ​​3.14 square centimeters, was taken and tightly adhered to the surface of the permeable membrane, and then flattened and fixed between the supply cell and the receiving cell. At the 24-hour mark of the experiment, 2 mL of receiving medium was precisely extracted from the sampling port of the receiving cell, and an equal volume of blank receiving medium at the same temperature was immediately added to the receiving cell.

[0072] The extracted transdermal receiving fluid was filtered through a 0.45 μm microporous membrane and then directly injected under the above-described liquid chromatography conditions to determine the concentration of ferulic acid. The cumulative transdermal release per unit area over 24 hours was calculated, and the results were expressed as g / cm³. 2 count.

[0073] Test results: Table 5. Results of comparison of extractable amount and transdermal release of active ingredients between Example 2 and Comparative Example 4 Group Paeoniflorin extraction amount (mg / g) Ferulic acid extraction amount (mg / g) <![CDATA[Cumulative percutaneous release amount of ferulic acid in 24 hours (g / cm 2 ) <!-- 9 -->]]> Example 2 12.37 4.86 83.15 Comparative Example 4 5.41 1.92 27.63 Results analysis: According to the data in Table 5, the macroscopic leaching amounts of paeoniflorin and ferulic acid in the product prepared in Example 2 were 12.37 mg / g and 4.86 mg / g, respectively, and the cumulative transdermal release of ferulic acid reached 83.15 g / cm³ after 24 hours. In Comparative Example 4, which maintained a constant atmospheric pressure of 0.1 MPa throughout the molding cavity, the leaching amounts of paeoniflorin and ferulic acid were only 5.41 mg / g and 1.92 mg / g, respectively, and the cumulative transdermal release of ferulic acid was as low as 27.63 g / cm³ after 24 hours. 2 .

[0074] Comparative Example 4 relies on physical fusion through thermal conduction and free diffusion under normal pressure. The spreading of the high-viscosity base oil phase and composite micro-coated matrix on the surface of the medicinal powder particles is constrained by capillary resistance and surface tension, making it difficult for the fluid medium to penetrate the deep microstructure exposed after the plant cell walls are broken. Insufficient solid-liquid wetting prevents the effective components inside the medicinal material from being effectively dissolved and transferred to the oil phase medium. The physical cooling and solidification process under normal pressure results in a highly dense and homogeneous internal structure of the final paste. The lack of interconnected media channels within the formed product increases the resistance to drug molecule migration to the contact interface, leading to low macroscopic transdermal release efficiency.

[0075] Example 2 introduces a temperature-pressure coupling process within a closed molding cavity. During the mid-stage high-temperature, positive-pressure, strong-permeation phase, an ambient heat source of 140°C significantly reduces the viscosity of the mixed oil phase system. The 0.4 MPa absolute positive pressure generated by the synchronously injected inert gas overcomes the inherent capillary resistance within the material, forcibly squeezing the low-viscosity fluid into the deep pores and network of the solid powder. This fluid-mechanical-based forced permeation mechanism creates a large solid-liquid contact surface area, disrupting the mass transfer resistance of the solid-liquid boundary layer and promoting efficient dissolution and transfer of components such as paeoniflorin and ferulic acid into the fluid phase.

[0076] During the later stage of medium-temperature negative pressure setting, the cavity temperature plummeted to 68℃, and the simultaneously applied -0.06MPa negative pressure caused the residual gaseous medium dissolved during deep penetration to expand and precipitate violently. The escape of gaseous substances to the surface eroded an interwoven macroscopic pore network within the cooling and thickening matrix. This solidification and retention of physical voids directly increased the macroscopic specific surface area of ​​the ointment, providing unobstructed fluid channels for the dissolution and diffusion of active ingredients during transdermal absorption. The alternating application of positive and negative pressure broke through the physical bottleneck of deep extraction and reshaped the physical topology of the formed product, resulting in significantly better macroscopic leaching levels and transdermal release kinetics than the ambient pressure temperature-controlled process.

Claims

1. A plaster for treating neck, shoulder, back, and leg pain, characterized in that, Made from raw materials comprising the following weights: The herbal formula containing volatile and heat-sensitive active ingredients is as follows: Ephedra 30g, Angelica sinensis 20g, Safflower 10g, Saposhnikovia divaricata 20g, Frankincense 30g, and Myrrh 30g. The following herbal group provides heat resistance and main analgesic effects but contains toxic components: Aconitum carmichaelii 30g, Aconitum kusnezoffii 30g, Arisaema heterophyllum 30g, Pinellia ternata 20g, Eupolyphaga sinensis 30g, Eucommia ulmoides 30g, Sparganium stoloniferum 20g, Curcuma zedoaria 20g, Lycopodium clavatum 50g, Angelica pubescens 100g. A floating herbal formula that provides bone penetration and promotes blood circulation to relieve stiffness: white mustard seed 60-100g, clematis root 60-100g, chicken blood vine 80-100g, clematis root 60-100g; Sesame oil used to provide extraction solvent and molding base: 1140-2700g; Composite micro-coated matrix for forming a physical thermal insulation buffer layer in high-temperature environments: 7-14g; Physical activator used to induce internal fluid phase change vaporization and micro-boiling effect: 18.6-60.8g.

2. The plaster for treating neck, shoulder, back and leg pain according to claim 1, characterized in that, The physical activator is rice wine with an alcohol content of 15%-20% by volume or rice vinegar with a total acidity of 5.0%-9.0%.

3. The plaster for treating neck, shoulder, back, and leg pain according to claim 1, characterized in that, The composite micro-coated matrix is ​​composed of beeswax, polyethylene glycol 4000 and stearic acid.

4. The plaster for treating neck, shoulder, back and leg pain according to claim 3, characterized in that, The weight ratio of the beeswax, polyethylene glycol 4000 and stearic acid is (50-60):(30-40):(5-10). The preparation method of the composite micro-coated matrix is ​​as follows: yellow wax and stearic acid are melted at 75-85℃, polyethylene glycol 4000 is added in the molten state, mechanical stirring is turned on and stirred at a constant temperature of 300-500 rpm for 15-30 min, and then cooled to 45-55℃ to obtain a matrix in a semi-fluid state.

5. A plaster for treating neck, shoulder, back and leg pain according to claim 1, characterized in that, In the preparation of the plaster, the medicinal materials that provide volatile and heat-sensitive active ingredients are pre-treated as follows: The medicinal materials containing the volatile and heat-sensitive active ingredients are pulverized to 100-120 mesh, and a composite micro-coated matrix in a semi-fluid state at 45-55℃ is added. The mixture is stirred at 50-80 rpm for 10-20 minutes and then naturally cooled to 20-25℃ to solidify the composite micro-coated matrix, thus obtaining pretreated powder A.

6. A plaster for treating neck, shoulder, back, and leg pain according to claim 5, characterized in that, In the preparation of the plaster, the medicinal material group that provides heat resistance and main analgesic effects but has toxic components, and the floating medicinal material group that provides bone penetration and promotes blood circulation and relieves stiffness, are pre-treated as follows: The two groups of medicinal materials are mixed and pulverized to 80-100 mesh, the physical activator is sprayed in, and the mixture is stirred at 40-60 rpm for 10-15 minutes to slightly wet the powder, thus obtaining pretreated powder B.

7. A plaster for treating neck, shoulder, back, and leg pain according to claim 6, characterized in that, In the preparation process of the plaster, pretreated powder A and pretreated powder B are mixed at a speed of 30-50 rpm for 10-15 minutes to obtain the final mixed powder to be added. Place the sesame oil in a refining pot and heat it at a constant temperature of 190-220℃. Pour the final mixed powder into the refining pot all at once and maintain the fluid temperature in the pot at 180-200℃ for 3-8 minutes to obtain the primary oil-medicine mixture fluid.

8. A plaster for treating neck, shoulder, back and leg pain according to claim 1, characterized in that, The primary oil-pharmaceutical mixture is transferred to a closed mechanical forming cavity, and forming is achieved through the following temperature-pressure coupling process parameters: Medium temperature and normal pressure procedure: Adjust the chamber temperature to 85-100℃ and maintain the pressure at 0.09-0.11MPa for 5-10 minutes; High-temperature positive pressure strong permeation step: Raise the temperature of the chamber to 130-150℃ and simultaneously inject nitrogen to increase the absolute pressure to 0.3-0.5MPa and maintain it for 10-20 minutes; Medium-temperature negative pressure drop procedure: The cavity temperature is dropped to 60-75℃ and the vacuum pump is turned on simultaneously to evacuate the vacuum to -0.05 to -0.08MPa and maintain it for 5-15 minutes.

9. A plaster for treating neck, shoulder, back and leg pain according to claim 1, characterized in that, The total residual amount of diester-type alkaloids in the finished plaster is controlled within the range of 0.512-0.665 mg / kg, and the diester-type alkaloids include aconitine, mesonaconitine and hypoaconitine.

10. A plaster for treating neck, shoulder, back and leg pain according to claim 1, characterized in that, The macroscopic physical properties of the finished plaster are controlled within the following ranges: the softening point is maintained at 64.3-70.1℃, and the oil penetration rate is 0.75%-1.62% after being placed at a constant temperature of 60-65℃ for 48-50 hours.