Treatment patch for activating blood of feet and preparation method of treatment patch

Abstract

The invention provides a treatment patch for promoting blood circulation of feet and a preparation method thereof, and relates to the technical field of treatment patches, the treatment patch for promoting blood circulation of feet comprises the following components by weight: 10-30 parts of red sage root, 5-20 parts of tree peony bark, 10-30 parts of Ligusticum wallichii, 10-25 parts of achyranthes root, 10-30 parts of Chinese angelica, 10-25 parts of pseudo-ginseng, 10-30 parts of thermal spring water, and 5-15 parts of ginger. According to the invention, the thermal spring water is used as a natural solvent rich in mineral substances, so that the dissolution of effective components of the medicinal materials is promoted, and the microcirculation and absorption capacity of local skin are assisted and enhanced due to the warm property of the thermal spring water and the mineral substances. Borneolum syntheticum and azone are combined for use to form a dual transdermal absorption promoting system, the borneol guides medicinal permeation by means of the aromatic resuscitation inducing characteristic, and azone is used as a high-efficiency chemical accelerant to improve the permeability of skin cuticle and opens up a channel for macromolecular herbal components to enter deep tissues together.

Description

Technical Field

[0001] The present invention relates to the technical field of therapeutic patches, and in particular to a therapeutic patch for promoting blood circulation in the foot and a preparation method thereof. Background Art

[0002] The field of therapeutic patch technology, generally referring to a sub-category of transdermal drug delivery systems, or pharmaceutical patches, focuses on the design and manufacture of flexible formulations capable of adhering to the skin surface. This technical field integrates knowledge from multiple disciplines, including polymer materials science, pharmaceutical formulations, skin physiology, and precision manufacturing engineering. Its basic structure typically consists of a backing layer for protection and support, a matrix layer (or drug reservoir layer) that stores and controls the release rate of the active ingredient, a pressure-sensitive adhesive layer that ensures the patch's secure adherence to the skin, and a protective release layer that is removed before use.

[0003] The preparation of traditional therapeutic patches generally adopts a one-pot decoction extraction method. This method is difficult to take into account the extraction conditions of the active ingredients in different medicinal materials. For example, long-term high-temperature decoction to fully extract the water-soluble phenolic acid in Salvia miltiorrhiza will inevitably lead to a large amount of volatile oil in ginger and borneol being lost, and the overall yield of the active ingredients is low. When this mixed extract is subsequently concentrated, a large amount of invalid impurities such as starch, protein, and tannin will be concentrated together, resulting in a dark color and strong odor of the final paste. More importantly, these impurities are the main potential factors causing skin allergies or discomfort. In the mixing stage of the matrix and the drug, conventional simple melt stirring is difficult to solve the compatibility problem of water-soluble and fat-soluble components, often resulting in uneven distribution of the drug, forming aggregation or separation of drug particles, which may cause irritation to the user due to excessive local drug concentration when applying the patch. Summary of the Invention

[0004] The purpose of the present invention is to solve the shortcomings of the prior art and to propose a therapeutic patch for promoting blood circulation in the foot and a preparation method thereof.

[0005] In order to achieve the above object, the present invention adopts the following technical solution: a therapeutic patch for promoting blood circulation in the foot, the therapeutic patch for promoting blood circulation in the foot comprising the following components in parts by weight:

[0006] 10-30 parts of Salvia miltiorrhiza, 5-20 parts of Moutan Bark, 10-30 parts of Chuanxiong, 10-25 parts of Achyranthes bidentata, 10-30 parts of Angelica sinensis, 10-25 parts of Panax notoginseng, 10-30 parts of hot spring water, 5-15 parts of ginger, 5-15 parts of hawthorn, 3-10 parts of Piper methysticum, 5-15 parts of Rubia cordifolia, 5-15 parts of Pollen Typhae, 3-10 parts of Cyperus rotundus, 5-15 parts of Perennial Herb, 10-25 parts of Astragalus, 10-25 parts of Poria, 0.5-3 parts of borneol, and 100-200 parts of pressure-sensitive ointment base.

[0007] Furthermore, the pressure-sensitive paste matrix is ​​prepared by mixing 80-150 parts of polyacrylate, 20-50 parts of hydrogenated rosin glycerol ester, 5-20 parts of white oil and 1-8 parts of azone.

[0008] The present invention also provides a method for preparing a therapeutic patch for promoting blood circulation in the foot, comprising the following steps:

[0009] S1, dynamic extraction of medicinal materials by graded extraction: the medicinal materials are divided into two groups, A and B, and extracted to obtain subcritical extract of group A and hot spring water extract of group B;

[0010] S2, extract two-phase refining and concentration; the subcritical extract of group A and the hot spring water extract of group B are treated separately to obtain a thick paste of medicinal materials in phase B and an essential oil in phase A;

[0011] S3, matrix pre-activation treatment: the pressure-sensitive paste matrix is ​​placed in a jacketed reactor and stirred to obtain a pre-activated pressure-sensitive adhesive matrix;

[0012] S4, compatibility and emulsification of the medicinal components; transferring the obtained phase B medicinal material paste to an emulsifier for emulsification to obtain an oil-in-water medicinal emulsion;

[0013] S5, low temperature negative pressure mixing; cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank and stirring under negative pressure to obtain a homogeneous bubble-free ointment;

[0014] S6, precise feedback control coating; transporting the homogeneous bubble-free ointment through the insulation pipe to the feed tank of the coating head and starting coating to obtain a wet coating patch;

[0015] S7, gradient combined drying; the wet coated patch is conveyed by a mesh belt and sequentially passes through a three-stage combined drying tunnel to obtain a dried and shaped patch;

[0016] S8, irradiation shaping and sterilization; the dried and shaped patch is subsequently treated by irradiation at a dose of 8-15 kGy to obtain a finished product of a therapeutic patch for promoting blood circulation in the foot.

[0017] Furthermore, the step S1 is specifically as follows: the medicinal materials are divided into two groups, A and B, wherein the medicinal materials of group A include ginger, pepper, chuanxiong, peony bark and angelica, and the medicinal materials of group B include salvia miltiorrhiza, astragalus, cyperus, panax notoginseng, hawthorn, madder, pollen, stachys chinensis, lantern grass and poria, the medicinal materials of group A are pretreated, crushed to 40-60 mesh, loaded into a subcritical fluid extraction kettle, and liquefied butane is used as the extraction solvent, and the mixture is stirred at a temperature of 30-50°C and 0.5-1 Under the pressure of 0.5MPa, 3-5 cycles of extraction are carried out, each cycle lasting 40-60 minutes. The medicinal materials of group B are crushed into 20-40 mesh and put into the extraction tank. 10-30 parts of hot spring water are added. First, soak and circulate at 50-60℃ for 30-45 minutes, then heat to 70-80℃ and extract for 60-90 minutes, and finally heat to 90-98℃ and maintain for 45-60 minutes. During this period, the circulating pump is at 1.5-3.0m 3 The flow rate was continuously operated at 1 / h to obtain group A subcritical extract and group B hot spring water extract.

[0018] Furthermore, the S2 step is specifically as follows: the subcritical extract of group A and the hot spring water extract of group B are treated separately, the hot spring water extract of group B is pumped into a ceramic membrane with a pore size of 0.1-0.5 microns for filtration, insoluble particles, macromolecular proteins and starch are filtered out at an operating pressure of 0.2-0.4 MPa, and the filtered clear night is transported to a thin film evaporator, and reduced pressure concentration is carried out at a vacuum degree of -0.07 to -0.09 MPa and a jacket heating temperature of 60-75°C until the relative density of the liquid reaches 1.20-1.35 g / cm 3 The subcritical extract of group A is subjected to reduced pressure distillation at 50-65° C. to recover the butane solvent to obtain a thick paste of medicinal materials of phase B and essential oil of phase A.

[0019] Furthermore, the S3 step is specifically as follows: placing the pressure-sensitive paste matrix into a reactor equipped with a jacket, introducing 130-150°C heat transfer oil into the jacket, stirring at a speed of 80-120RPM for 40-60 minutes to completely melt the matrix, introducing 5-15°C cooling water into the jacket, lowering the colloid temperature to 65-75°C and maintaining it for 1-2 minutes, then switching to 110-120°C heat transfer oil, heating the colloid and keeping it warm for 15-20 minutes to obtain a preactivated pressure-sensitive adhesive matrix.

[0020] Furthermore, the S4 step is specifically as follows: transferring the obtained phase B medicinal material thick paste to an emulsifying kettle, heating the jacket to 55-65°C as the water phase, adding the obtained phase A essential oil as the oil phase within 10-15 minutes through a metering pump under the shear state of 3000-5000RPM in the emulsifying kettle, and continuing emulsification for 20-30 minutes to obtain an oil-in-water medicinal emulsion.

[0021] Furthermore, the S5 step is specifically as follows: cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank to 55-65°C, pumping the pressure in the tank to a negative pressure state of -0.08 to -0.095MPa, pumping the water-in-oil type medicinal emulsion into the tank within 25-40 minutes, and at the same time, sucking the borneol powder through the vacuum suction port, setting the planetary stirring paddle to a revolution speed of 20-40RPM and a rotation speed of 50-70RPM for mixing for 60-90 minutes to obtain a homogeneous bubble-free ointment.

[0022] Furthermore, the S6 step is specifically as follows: transporting the homogeneous bubble-free ointment to the feed tank of the coating head through an insulated pipe, maintaining the temperature at 50-60°C, starting the coating production line, and feeding the non-woven backing material to the bottom of the coating head at a speed of 10-20 m / min. The ointment is squeezed to the coating head and evenly coated on the surface of the backing material to obtain a wet coating patch.

[0023] Furthermore, the S7 step is specifically as follows: the wet coated patch is conveyed by a mesh belt and sequentially passed through a three-section combined drying tunnel, the first zone is a far-infrared radiation drying zone with a length of 3-5 meters, the surface temperature of the far-infrared heating plate is controlled at 120-150°C, and the surface of the patch is gently radiated and heated for 3-5 minutes, the second zone is a hot air convection drying zone with a length of 8-12 meters, and the circulating fan blows 50-60°C hot air at a wind speed of 2-4 meters / second, and dries for 8-12 minutes, the third zone is a forced air cooling and shaping zone with a length of 2-3 meters, and the patch is cooled with air at 15-25°C for 2-3 minutes to obtain a dried and shaped patch.

[0024] 1. Compared with the prior art, in the present invention, hot spring water, as a natural solvent rich in minerals, not only promotes the dissolution of the active ingredients of medicinal materials, but its warm properties and the minerals themselves also assist in enhancing the microcirculation and absorption capacity of the local skin. The combined use of borneol and azone constitutes a dual transdermal absorption promotion system. Borneol guides the penetration of medicinal properties with its aromatic and rejuvenating properties, while azone acts as an efficient chemical accelerator to enhance the permeability of the skin's stratum corneum, jointly opening up channels for large-molecule herbal ingredients to enter deep tissues. The precise ratio of polyacrylate, hydrogenated rosin glycerol ester and white oil in the pressure-sensitive cream matrix gives the therapeutic patch excellent adhesion, flexibility and biocompatibility, ensuring that it can fit closely to the feet with frequent activities and complex contours. During the long-term wearing process, it can not only ensure the continuous and stable release of the medicinal effect, but also will not fall off due to stiffness or insufficient viscosity, thereby improving the convenience of use and the compliance of treatment.

[0025] 2. Compared to existing technologies, this invention achieves maximum retention of volatile, heat-sensitive components such as ginger and borneol by classifying medicinal materials based on their physical and chemical properties and extracting them using a combination of subcritical fluid and programmed hot spring water heating and dynamic circulation. This method also improves the dissolution rate of water-soluble saponins and polysaccharides in salvia miltiorrhiza and astragalus. The resulting biphasic extract is then subjected to membrane filtration and cryogenic concentration, removing macromolecular impurities at the source. This results in a purer, more pleasing medicinal component with better color and odor, reducing the risk of skin sensitization. The pressure-sensitive adhesive matrix undergoes a pre-activation treatment by chilling and reheating, physically creating a loose, porous microstructure that provides a foundation for efficient drug loading and the creation of an excellent sustained-release channel. A water-soluble thick paste and a fat-soluble essential oil are combined under high shear to form a stable oil-in-water medicinal emulsion. Mixing the medicinal emulsion with the pre-activated matrix in a low-temperature, negative-pressure environment not only protects the active ingredients but also achieves homogenization, degassing, and antioxidant properties in a single step, improving process efficiency and product stability. Precision coating with feedback control using an integrated laser thickness gauge ensures accurate and standardized product dosage. A gradient drying method simulates the natural evaporation process, preventing surface crusting and ensuring uniform drying from the inside out and the integrity of the sustained-release structure. The final irradiation treatment not only sterilizes the ointment but also forms a breathable protective film on the surface, enhancing product cleanliness and user experience.

[0026] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0028] Figure 1 The present invention provides a preparation step diagram of a method for preparing a therapeutic patch for promoting blood circulation in the foot. DETAILED DESCRIPTION

[0029] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0030] Example 1, see Figure 1, providing a therapeutic patch for promoting blood circulation in the foot, the therapeutic patch for promoting blood circulation in the foot comprises the following components in parts by weight:

[0031] 10 parts of Salvia miltiorrhiza, 5 parts of Paeonia suffruticosa, 10 parts of Ligusticum chuanxiong, 10 parts of Achyranthes bidentata, 10 parts of Angelica sinensis, 10 parts of Panax notoginseng, 10 parts of hot spring water, 5 parts of ginger, 5 parts of Crataegus, 3 parts of Piper nigrum, 5 parts of Rubia cordifolia, 5 parts of Pollen Typhae, 3 parts of Ligusticum wallichii, 5 parts of Perennis grandis, 10 parts of Astragalus, 10 parts of Poria, 0.5 part of Borneolum, and 100 parts of pressure-sensitive plaster base.

[0032] In this embodiment, the pressure-sensitive paste matrix is ​​a mixture of 80 parts of polyacrylate, 20 parts of hydrogenated rosin glycerol ester, 5 parts of white oil and 1 part of azone.

[0033] This embodiment also provides a method for preparing a therapeutic patch for promoting blood circulation in the foot, comprising the following steps:

[0034] S1, dynamic extraction of medicinal materials by graded extraction: the medicinal materials are divided into two groups, A and B, and extracted to obtain subcritical extract of group A and hot spring water extract of group B;

[0035] S2, extract two-phase refining and concentration; the subcritical extract of group A and the hot spring water extract of group B are treated separately to obtain a thick paste of medicinal materials in phase B and an essential oil in phase A;

[0036] S3, matrix pre-activation treatment: the pressure-sensitive paste matrix is ​​placed in a jacketed reactor and stirred to obtain a pre-activated pressure-sensitive adhesive matrix;

[0037] S4, compatibility and emulsification of the medicinal components; transferring the obtained phase B medicinal material paste to an emulsifier for emulsification to obtain an oil-in-water medicinal emulsion;

[0038] S5, low temperature negative pressure mixing; cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank and stirring under negative pressure to obtain a homogeneous bubble-free ointment;

[0039] S6, precise feedback control coating; transporting the homogeneous bubble-free ointment through the insulation pipe to the feed tank of the coating head and starting coating to obtain a wet coating patch;

[0040] S7, gradient combined drying; the wet coated patch is conveyed by a mesh belt and sequentially passes through a three-stage combined drying tunnel to obtain a dried and shaped patch;

[0041] S8, irradiation shaping and sterilization; the dried and shaped patch is subsequently treated and irradiated with a dose of 8 kGy to obtain a finished product of a therapeutic patch for promoting blood circulation in the foot.

[0042] In this embodiment, the S1 step is specifically as follows: the medicinal materials are divided into two groups, A and B. The medicinal materials in group A include ginger, pepper, Chuanxiong, peony bark and angelica, and the medicinal materials in group B include salvia miltiorrhiza, astragalus, Achyranthes bidentata, Panax notoginseng, hawthorn, madder, pollen, stachys scabra, lantern grass and Poria cocos. The medicinal materials in group A are pretreated, crushed to 40 mesh, and loaded into a subcritical fluid extraction kettle. Liquefied butane is used as the extraction solvent. Under the conditions of a temperature of 30°C and a pressure of 0.5MPa, 3 cycles of extraction are performed, each cycle lasting 40 minutes. The medicinal materials in group B are crushed to 20 mesh, put into an extraction tank, and hot spring water is added. They are first soaked and circulated at 50°C for 30 minutes, then heated to 70°C for extraction for 60 minutes, and finally heated to 90°C and maintained for 45 minutes. During this period, the circulating pump is operated at 1.5m 3 The flow rate was continuously operated at 1 / h to obtain group A subcritical extract and group B hot spring water extract.

[0043] In this embodiment, the S2 step is specifically as follows: the subcritical extract of group A and the hot spring water extract of group B are treated separately, the hot spring water extract of group B is pumped into a ceramic membrane with a pore size of 0.1 micron for filtration, insoluble particles, macromolecular proteins and starch are filtered out at an operating pressure of 0.2 MPa, and the filtered clear night is transported to a thin film evaporator, and reduced pressure concentration is performed at a vacuum degree of -0.07 MPa and a jacket heating temperature of 60°C until the relative density of the liquid reaches 1.20 g / cm 3 The subcritical extract of group A is subjected to reduced pressure distillation at 50°C to recover the butane solvent to obtain a thick paste of medicinal materials of phase B and essential oil of phase A.

[0044] In this embodiment, the S3 step is specifically as follows: the pressure-sensitive paste matrix is ​​placed in a reactor equipped with a jacket, 130°C heat transfer oil is introduced into the jacket, and the mixture is stirred at a speed of 80RPM for 40 minutes to completely melt the matrix. 5°C cooling water is introduced into the jacket to reduce the colloid temperature to 65°C and maintain it for 1 minute, and then the heat transfer oil is switched to 110°C, and the colloid is heated and kept warm for 15 minutes to obtain a preactivated pressure-sensitive adhesive matrix.

[0045] In this embodiment, the S4 step is specifically as follows: the obtained phase B medicinal material thick paste is transferred to an emulsifying kettle, the jacket is heated to 55° C. as the water phase, and the obtained phase A essential oil is added as the oil phase within 10 minutes through a metering pump under a shear state of 3000 RPM in the emulsifying kettle, and emulsification is continued for 20 minutes to obtain an oil-in-water medicinal emulsion.

[0046] In this embodiment, the S5 step is specifically as follows: cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank to 55°C, pumping the pressure in the tank to a negative pressure state of -0.08MPa, pumping the water-in-oil type medicinal emulsion into the tank within 25 minutes, and at the same time, sucking the borneol powder through the vacuum suction port, setting the planetary stirring paddle to a revolution speed of 20RPM and a rotation speed of 50RPM for mixing for 60 minutes to obtain a homogeneous bubble-free ointment.

[0047] In this embodiment, the S6 step is specifically as follows: the homogeneous bubble-free ointment is transported to the feed tank of the coating head through an insulated pipe, the temperature is maintained at 50°C, the coating production line is started, and the non-woven backing material is fed to the bottom of the coating head at a speed of 10 m / min. The ointment is squeezed to the coating head and evenly coated on the surface of the backing material to obtain a wet coating patch.

[0048] In this embodiment, the S7 step is specifically as follows: the wet coated patch is conveyed by a mesh belt and sequentially passed through a three-section combined drying tunnel. The first zone is a far-infrared radiation drying zone with a length of 3 meters. The surface temperature of the far-infrared heating plate is controlled at 120°C, and the surface of the patch is gently radiated and heated for 3 minutes. The second zone is a hot air convection drying zone with a length of 8 meters. The circulating fan blows 50°C hot air at a wind speed of 2 meters / second and dries for 8 minutes. The third zone is a forced air cooling and shaping zone with a length of 2 meters. The patch is cooled with air at 15°C for 2 minutes to obtain a dried and shaped patch.

[0049] Example 2, see Figure 1 , providing a therapeutic patch for promoting blood circulation in the foot, the therapeutic patch for promoting blood circulation in the foot comprises the following components in parts by weight:

[0050] 30 parts of Salvia miltiorrhiza, 20 parts of Paeonia suffruticosa, 30 parts of Ligusticum chuanxiong, 25 parts of Achyranthes bidentata, 30 parts of Angelica sinensis, 25 parts of Panax notoginseng, 30 parts of hot spring water, 15 parts of ginger, 15 parts of Crataegus, 10 parts of Piper japonica, 15 parts of Rubia cordifolia, 15 parts of Pollen Typhae, 10 parts of Ligusticum chuanxiong, 15 parts of Herba Astragali, 25 parts of Poria, 0.3 part of Borneolum, and 200 parts of pressure-sensitive plaster base.

[0051] In this embodiment, the pressure-sensitive paste matrix is ​​a mixture of 150 parts of polyacrylate, 50 parts of hydrogenated rosin glycerol ester, 20 parts of white oil and 8 parts of azone.

[0052] This embodiment also provides a method for preparing a therapeutic patch for promoting blood circulation in the foot, comprising the following steps:

[0053] S1, dynamic extraction of medicinal materials by graded extraction: the medicinal materials are divided into two groups, A and B, and extracted to obtain subcritical extract of group A and hot spring water extract of group B;

[0054] S2, extract two-phase refining and concentration; the subcritical extract of group A and the hot spring water extract of group B are treated separately to obtain a thick paste of medicinal materials in phase B and an essential oil in phase A;

[0055] S3, matrix pre-activation treatment: the pressure-sensitive paste matrix is ​​placed in a jacketed reactor and stirred to obtain a pre-activated pressure-sensitive adhesive matrix;

[0056] S4, compatibility and emulsification of the medicinal components; transferring the obtained phase B medicinal material paste to an emulsifier for emulsification to obtain an oil-in-water medicinal emulsion;

[0057] S5, low temperature negative pressure mixing; cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank and stirring under negative pressure to obtain a homogeneous bubble-free ointment;

[0058] S6, precise feedback control coating; transporting the homogeneous bubble-free ointment through the insulation pipe to the feed tank of the coating head and starting coating to obtain a wet coating patch;

[0059] S7, gradient combined drying; the wet coated patch is conveyed by a mesh belt and sequentially passes through a three-stage combined drying tunnel to obtain a dried and shaped patch;

[0060] S8, irradiation shaping and sterilization; the dried and shaped patch is subsequently treated and irradiated with a dose of 15 kGy to obtain a finished therapeutic patch for promoting blood circulation in the foot.

[0061] In this embodiment, the S1 step is specifically as follows: the medicinal materials are divided into two groups, A and B. The medicinal materials in group A include ginger, pepper, Chuanxiong, peony bark and angelica, and the medicinal materials in group B include salvia miltiorrhiza, astragalus, Achyranthes bidentata, Panax notoginseng, hawthorn, madder, pollen, stachybotrys, lantern grass and Poria. The medicinal materials in group A are pretreated, crushed to 60 mesh, and loaded into a subcritical fluid extraction kettle. Liquefied butane is used as the extraction solvent. Five cycles of extraction are performed at a temperature of 50°C and a pressure of 1.5MPa. Each cycle lasts for 60 minutes. The medicinal materials in group B are crushed to 40 mesh and put into an extraction tank. 30 parts of hot spring water are added. The medicinal materials are first soaked and circulated at 60°C for 45 minutes, then heated to 80°C for extraction for 90 minutes, and finally heated to 98°C and maintained for 60 minutes. During this period, the circulating pump is circulated at 3.0m 3 The flow rate was continuously operated at 1 / h to obtain group A subcritical extract and group B hot spring water extract.

[0062] In this embodiment, the S2 step is specifically as follows: the subcritical extract of group A and the hot spring water extract of group B are treated separately, the hot spring water extract of group B is pumped into a ceramic membrane with a pore size of 0.5 microns for filtration, insoluble particles, macromolecular proteins and starch are filtered out at an operating pressure of 0.4 MPa, and the filtered clear night is transported to a thin film evaporator, and reduced pressure concentration is performed at a vacuum degree of -0.09 MPa and a jacket heating temperature of 75°C until the relative density of the liquid reaches 1.35 g / cm 3 The subcritical extract of group A is subjected to reduced pressure distillation at 65°C to recover the butane solvent to obtain a thick paste of medicinal materials of phase B and essential oil of phase A.

[0063] In this embodiment, the S3 step is specifically as follows: the pressure-sensitive paste matrix is ​​placed in a reactor equipped with a jacket, 150°C heat transfer oil is introduced into the jacket, and the mixture is stirred at a speed of 120RPM for 60 minutes to completely melt the matrix. 15°C cooling water is introduced into the jacket to reduce the colloid temperature to 75°C and maintain it for 2 minutes, and then the heat transfer oil is switched to 120°C, the colloid is heated and kept warm for 20 minutes to obtain a preactivated pressure-sensitive adhesive matrix.

[0064] In this embodiment, the S4 step is specifically as follows: the obtained phase B medicinal material thick paste is transferred to an emulsifying kettle, the jacket is heated to 65° C. as the water phase, and under the shear state of the emulsifying kettle at 5000 RPM, the obtained phase A essential oil is added as the oil phase through a metering pump within 15 minutes, and emulsification is continued for 30 minutes to obtain an oil-in-water medicinal emulsion.

[0065] In this embodiment, the S5 step is specifically as follows: cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank to 65°C, pumping the pressure in the tank to a negative pressure state of -0.095MPa, pumping the water-in-oil type medicinal emulsion into the tank within 40 minutes, and at the same time, sucking the borneol powder through the vacuum suction port, setting the planetary stirring paddle to a revolution speed of 40RPM and a rotation speed of 70RPM for mixing for 90 minutes to obtain a homogeneous bubble-free ointment.

[0066] In this embodiment, the S6 step is specifically as follows: the homogeneous bubble-free ointment is transported to the feed tank of the coating head through an insulated pipe, the temperature is maintained at 60°C, the coating production line is started, and the non-woven backing material is fed to the bottom of the coating head at a speed of 20 m / min. The ointment is squeezed to the coating head and evenly coated on the surface of the backing material to obtain a wet coating patch.

[0067] In this embodiment, the S7 step is specifically as follows: the wet coated patch is conveyed by a mesh belt and sequentially passed through a three-section combined drying tunnel, the first zone is a far-infrared radiation drying zone with a length of 5 meters, the surface temperature of the far-infrared heating plate is controlled at 150°C, and the surface of the patch is gently radiated and heated for 5 minutes, the second zone is a hot air convection drying zone with a length of 12 meters, and the circulating fan blows 60°C hot air at a wind speed of 4 meters / second, and dries for 12 minutes, the third zone is a forced air cooling shaping zone with a length of 3 meters, and the patch is cooled with air at 25°C for 3 minutes to obtain a dried and shaped patch.

[0068] Experimental methods:

[0069] In vitro transdermal permeation experiment:

[0070] This experiment is intended to evaluate the ability of the active ingredient (with ferulic acid as an index component) in the treatment patch to penetrate the skin. The experiment is carried out using the Franz diffusion cell method. First, healthy male Wistar rats are taken, and their abdominal skin is taken after being killed, and subcutaneous fat and connective tissue are carefully removed to make an isolated full-thickness skin. The prepared mouse skin is fixed between the supply chamber and the receiving chamber of the Franz diffusion cell so that the stratum corneum is toward the supply chamber. The receiving chamber is filled with phosphate buffered saline (PBS, pH 7.4) preheated to 37 degrees Celsius as a receiving solution, and stirred at a constant speed with a magnetic stirrer to simulate blood circulation in the body. Then, the treatment patch to be tested (Comparative Example 1, Example 1, Example 2) is cut into a circular patch identical to the diffusion cell effective area, and is closely applied to the stratum corneum surface of the mouse skin to ensure that there is no bubble. At the set time point, such as 2, 4, 6, 8, 12 and 24 hours, a certain volume of receiving solution is drawn from the sampling port of the receiving chamber, and immediately supplemented with equal amounts, isothermal fresh PBS receiving solution. The collected samples were filtered through a microporous membrane and analyzed by high performance liquid chromatography (HPLC). The chromatographic conditions were: using an octadecylsilane bonded silica gel column, the mobile phase was methanol-0.1% phosphoric acid aqueous solution (volume ratio 35:65), the detection wavelength was set to 321nm, the column temperature was maintained at 30 degrees Celsius, and the flow rate was 1.0 ml per minute. By measuring the concentration of ferulic acid in the sample and calculating the cumulative permeation amount at each time point based on the sampling volume and dilution, the total cumulative permeation amount for 24 hours was finally divided by the initial total content of ferulic acid in the patch sample, and then multiplied by 100% to obtain the 24-hour cumulative transdermal permeability.

[0071] Adhesion performance test (initial adhesion, lasting adhesion, 180° peel strength):

[0072] This test comprehensively evaluates the adhesive properties of a therapeutic patch. The initial adhesion test utilizes the inclined ball rolling method. The patch is mounted with the adhesive side facing up on a test plate tilted at a 30-degree angle. A set of standard diameter steel balls (numbers 1 to 20) are selected and allowed to roll freely down from the top of the inclined surface at the same height. The number of the largest ball that remains stuck to the adhesive layer for more than 5 seconds is recorded; this number represents the initial adhesion test result; a larger number indicates stronger initial adhesion. The sustained adhesion test evaluates the patch's resistance to shear slippage. The patch is cut into a standard 25 mm by 25 mm size and adhered to a vertically suspended, polished stainless steel plate, with an adhesion area of ​​25 mm by 25 mm. A standard roller is used to roll the patch back and forth three times to ensure uniform adhesion. A 1 kg weight is suspended from the lower end of the patch, and the entire apparatus is placed in a constant temperature and humidity environment. The time (in hours) required from the time the weight is attached until the patch completely falls off the plate or slides a specified distance is recorded. If it has not fallen off after more than 24 hours, it will be recorded as greater than 24 hours. The 180-degree peel strength test is performed using an electronic tensile testing machine. Cut the therapeutic patch into 25mm wide strips, stick them on a standard stainless steel test plate, and roll them with a standard pressure roller. Fix the test plate on the lower fixture of the tensile machine, fold the free end of the patch 180 degrees and clamp it on the upper fixture. Start the tensile machine and peel it at a constant speed of 300 mm per minute. The computer system automatically records the force changes during the peeling process and calculates the average peel force. The final result is expressed in Newtons per 25 mm (N / 25mm).

[0073] Accelerated stability testing:

[0074] This experiment aims to investigate the quality stability of the therapeutic patch under harsh conditions. After the finished products of each group of therapeutic patches are sealed and packaged, they are placed in a constant temperature and humidity chamber, and the accelerated test conditions are set to a temperature of 40 degrees Celsius and a relative humidity of 75%. Samples are taken out at the 0th month, 1st month, 3rd month and 6th month after the start of the experiment. For the samples taken out, they are first accurately weighed, then cut into pieces and placed in a stoppered conical flask. An appropriate amount of methanol is added as the extraction solvent, and ultrasonic extraction is performed in an ultrasonic cleaner for 30 minutes to ensure that the active ingredient (in terms of ferulic acid) is completely dissolved. After the extract is cooled to room temperature, it is diluted to the scale with methanol, shaken, and filtered through a 0.45 micron filter membrane, and the filtrate is taken as the test solution. The ferulic acid content in the extract is determined using the same HPLC chromatographic conditions as in the transdermal penetration experiment. The content retention rate is calculated by comparing the active ingredient content measured in the 6th month with the initial content in the 0th month. The calculation method is: divide the content in the 6th month by the content in the 0th month, and then multiply by 100% to obtain the percentage of active ingredient content after accelerated stability testing.

[0075] Skin irritation test:

[0076] This experiment is used to evaluate the potential irritation of the therapeutic patch to the skin. Healthy New Zealand white rabbits were selected as experimental animals. 24 hours before the experiment, the hair on both sides of their back spine was cut off. The depilatory area was about 10 cm by 15 cm in size, and care was taken to avoid damaging the skin. The rabbits were randomly divided into three groups, and the therapeutic patches of Comparative Example 1, Example 1 and Example 2 were applied respectively. In the depilatory area of ​​each rabbit, one side was selected as the experimental area and the therapeutic patch of the corresponding group was affixed; the other side was used as the blank control area and was not treated in any way. The application site was fixed with non-irritating tape and gauze to prevent the rabbit from scratching. After the application lasted for 24 hours, the patch and fixture were carefully removed. The erythema and edema of the skin at the application site were observed and recorded at 1 hour, 24 hours, 48 ​​hours and 72 hours after removal. Scoring was performed according to the scoring criteria in the "Technical Specifications for Safety of Cosmetics" (erythema and edema were scored on a 0-4 scale, with 0 being no reaction and 4 being a severe reaction). The skin irritation score of each sample was calculated based on the scoring results of all animals at each observation time point. The mean irritation index is calculated by adding the sum of the erythema and edema scores for all animals at all observation time points, then dividing by the product of the total number of animals and the number of observations. The intensity of the irritation is determined based on the magnitude of the index.

[0077] The finished materials prepared in Examples 1-2 were tested, with Comparative Example 1 being the product prepared in Chinese Invention Patent Publication No. CN103271997B. The experimental results are as follows:

[0078] Table 1 Performance test data

[0079]

[0080] As can be seen from Table 1, Examples 1-2 have advantages over Comparative Example 1 in terms of transdermal absorption efficiency, adhesion performance, product stability and skin safety. This is due to a series of technical means adopted in the preparation process of the present invention. First, the graded dynamic extraction of step S1 is key, which separates the lipophilic medicinal materials rich in volatile oil (Group A) from the medicinal materials rich in water-soluble components (Group B). Using subcritical butane to extract Group A medicinal materials, lipophilic and heat-sensitive components such as ferulic acid, ligustilide, etc. in Chuanxiong and Angelica sinensis, and gingerol in ginger can be extracted with extremely high efficiency and low temperature. These components themselves are natural transdermal enhancers. At the same time, Group B medicinal materials are subjected to gradient temperature extraction using hot spring water to fully dissolve water-soluble active ingredients such as tanshinone and astragaloside IV. This graded treatment avoids the loss of volatile oil and the high-temperature degradation of some components during the traditional co-decoction process, laying a material foundation for subsequent high transdermal rate and high stability.

[0081] Secondly, the refining step in S2 and the emulsification step in S4 work synergistically to improve drug delivery efficiency. The extract in Group B is filtered through a ceramic membrane to remove large molecular impurities and reduce skin irritation. The essential oil in Phase A, obtained after solvent recovery from the extract in Group A, is then emulsified with the thick paste of Phase B medicinal materials through high shear in Step S4 to form an oil-in-water medicinal emulsion. This microemulsion structure tightly combines the essential oil as a transdermal enhancer with the water-soluble component of the main drug, increasing the dispersion and uniformity of the drug in the matrix and synergistically promoting drug penetration through the skin's hydration channels and lipid bilayer channels.

[0082] Furthermore, the matrix pre-activation of S3 and the low-temperature negative pressure mixing of S5 ensure the excellent adhesion performance and stability of the plaster. The pressure-sensitive plaster matrix undergoes a specific "heating-cooling-reheating" pre-activation treatment to optimize its rheological properties and molecular chain structure, so that it has excellent initial adhesion, lasting adhesion and peel strength. The mixing of medicinal emulsion and borneol under low-temperature negative pressure conditions not only avoids the volatilization and degradation of heat-sensitive components and ensures product stability, but also eliminates bubbles in the paste by vacuuming, making the coating more uniform and the contact between the paste and the skin closer, thereby enhancing the lasting adhesion and drug penetration. Finally, the combination of S7 gradient drying and S8 irradiation sterilization not only ensures that the active ingredients are not destroyed, but also realizes the sterilization of the product, further improving the safety of the product. In summary, the present invention achieves synergistic synergy between each component and each process by designing and combining a series of process links such as extraction, refining, emulsification, and mixing.

Claims

1. A therapeutic patch for promoting blood circulation in the foot, characterized in that: The therapeutic patch for promoting blood circulation in the foot comprises the following components in parts by weight: 10-30 parts of Salvia miltiorrhiza, 5-20 parts of Moutan Bark, 10-30 parts of Chuanxiong, 10-25 parts of Achyranthes bidentata, 10-30 parts of Angelica sinensis, 10-25 parts of Panax notoginseng, 10-30 parts of hot spring water, 5-15 parts of ginger, 5-15 parts of hawthorn, 3-10 parts of Piper methysticum, 5-15 parts of Rubia cordifolia, 5-15 parts of Pollen Typhae, 3-10 parts of Cyperus rotundus, 5-15 parts of Perennial Herb, 10-25 parts of Astragalus, 10-25 parts of Poria, 0.5-3 parts of borneol, and 100-200 parts of pressure-sensitive ointment base.

2. The therapeutic patch for promoting blood circulation in the foot according to claim 1, characterized in that: The pressure-sensitive paste matrix is ​​prepared by mixing 80-150 parts of polyacrylate, 20-50 parts of hydrogenated rosin glycerol ester, 5-20 parts of white oil and 1-8 parts of azone.

3. A method for preparing a therapeutic patch for promoting blood circulation in the foot, characterized in that: The following steps are involved: S1, dynamic extraction of medicinal materials by classification: the medicinal materials are divided into two groups, A and B, and extracted to obtain subcritical extract of group A and hot spring water extract of group B; S2, extract two-phase refining and concentration; the subcritical extract of group A and the hot spring water extract of group B are treated separately to obtain a thick paste of medicinal materials in phase B and an essential oil in phase A; S3, matrix preactivation treatment; The pressure-sensitive adhesive matrix is ​​placed in a jacketed reactor and stirred to obtain a pre-activated pressure-sensitive adhesive matrix; S4, compatibility and emulsification of the medicinal components; transferring the obtained phase B medicinal material paste to an emulsifier for emulsification to obtain an oil-in-water medicinal emulsion; S5, low temperature negative pressure mixing; cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirred tank and stirring under negative pressure to obtain a homogeneous bubble-free ointment; S6, precise feedback control coating; transporting the homogeneous bubble-free ointment through the insulation pipe to the feed tank of the coating head and starting coating to obtain a wet coating patch; S7, gradient combined drying; the wet coated patch is conveyed by a mesh belt and sequentially passes through a three-stage combined drying tunnel to obtain a dry and shaped patch; S8, irradiation shaping and sterilization; the dried and shaped patch is subsequently treated by irradiation at a dose of 8-15 kGy to obtain a finished product of a therapeutic patch for promoting blood circulation in the foot.

4. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The step S1 is specifically as follows: the medicinal materials are divided into two groups, A and B. The medicinal materials of group A include ginger, pepper, chuanxiong, moutan bark and angelica, and the medicinal materials of group B include salvia miltiorrhiza, astragalus, cyperus, panax notoginseng, hawthorn, madder, pollen, huarui stone, lantern grass and poria. The medicinal materials of group A are pretreated, crushed to 40-60 mesh, loaded into a subcritical fluid extraction kettle, and liquefied butane is used as the extraction solvent. The medicinal materials are extracted at a temperature of 30-50 ° C and 0.5-1.5 MPa pressure, perform 3-5 cycles of extraction, each cycle lasting 40-60 minutes, crush the medicinal materials in group B to 20-40 mesh, put them into the extraction tank, add 10-30 parts of hot spring water, first soak and circulate at 50-60℃ for 30-45 minutes, then heat to 70-80℃ and extract for 60-90 minutes, finally heat to 90-98℃ and maintain for 45-60 minutes, during which the circulating pump is at 1.5-3.0m 3 The flow rate was continuously operated at 1 / h to obtain group A subcritical extract and group B hot spring water extract.

5. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S2 step is specifically as follows: the subcritical extract of group A and the hot spring water extract of group B are treated separately, the hot spring water extract of group B is pumped into a ceramic membrane with a pore size of 0.1-0.5 microns for filtration, insoluble particles, macromolecular proteins and starch are filtered out at an operating pressure of 0.2-0.4 MPa, the filtered clear night is transported to a thin film evaporator, and reduced pressure concentration is carried out at a vacuum degree of -0.07 to -0.09 MPa and a jacket heating temperature of 60-75°C until the relative density of the liquid reaches 1.20-1.35 g / cm 3 The subcritical extract of group A is subjected to reduced pressure distillation at 50-65° C. to recover the butane solvent to obtain a thick paste of medicinal materials of phase B and essential oil of phase A.

6. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S3 step is specifically as follows: placing the pressure-sensitive paste matrix into a jacketed reactor, introducing 130-150°C heat transfer oil into the jacket, stirring at 80-120 RPM for 40-60 minutes to completely melt the matrix, introducing 5-15°C cooling water into the jacket, lowering the colloid temperature to 65-75°C and maintaining it for 1-2 minutes, then switching to 110-120°C heat transfer oil, heating the colloid and keeping it warm for 15-20 minutes to obtain a preactivated pressure-sensitive adhesive matrix.

7. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S4 step is specifically as follows: transferring the obtained phase B medicinal material thick paste to an emulsifying kettle, heating the jacket to 55-65°C as the water phase, adding the obtained phase A essential oil as the oil phase within 10-15 minutes through a metering pump under the shear state of 3000-5000RPM in the emulsifying kettle, and continuing emulsification for 20-30 minutes to obtain an oil-in-water medicinal emulsion.

8. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S5 step is specifically as follows: cooling the pre-activated pressure-sensitive adhesive matrix in the planetary stirring kettle to 55-65°C, reducing the pressure in the kettle to a negative pressure state of -0.08 to -0.095 MPa, pumping the oil-in-water medicinal emulsion into the kettle within 25-40 minutes, and at the same time, sucking borneol powder through a vacuum suction port, setting the planetary stirring paddle to a revolution speed of 20-40 RPM and a rotation speed of 50-70 RPM for mixing for 60-90 minutes to obtain a homogeneous bubble-free ointment.

9. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S6 step is specifically as follows: transporting the homogeneous bubble-free ointment to the feed tank of the coating head through an insulated pipe, maintaining the temperature at 50-60°C, starting the coating production line, and feeding the non-woven backing material to the bottom of the coating head at a speed of 10-20 m / min. The ointment is squeezed to the coating head and evenly coated on the surface of the backing material to obtain a wet coating patch.

10. The method for preparing the therapeutic patch for promoting blood circulation in the foot according to claim 3, characterized in that: The S7 step is specifically as follows: the wet coated patch is conveyed by a mesh belt and sequentially passes through a three-section combined drying tunnel, wherein the first zone is a far-infrared radiation drying zone with a length of 3-5 meters, the surface temperature of the far-infrared heating plate is controlled at 120-150°C, and the surface of the patch is gently radiated and heated for 3-5 minutes; the second zone is a hot air convection drying zone with a length of 8-12 meters, and a circulating fan blows hot air at 50-60°C at a wind speed of 2-4 m / s for drying for 8-12 minutes; the third zone is a forced air cooling and shaping zone with a length of 2-3 meters, and the patch is cooled with air at 15-25°C for 2-3 minutes to obtain a dried and shaped patch.

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