A formula of a stomach-warming and abdomen-soothing patch

Abstract

The application relates to the technical field of traditional Chinese medicine external preparation, and discloses a formula of a stomach-warming and abdomen-soothing plaster, which comprises 16 kinds of traditional Chinese medicine micro-powder such as Piper longum, Evodia rutaecarpa, Alpinia officinarum Hance, Corydalis tuber, Poria cocos, Aucklandia lappa Decne and Gekko japonicus. A hot melt adhesive matrix is composed of styrene-isoprene-styrene block copolymer, hydrogenated rosin glyceride and medical white oil. The preparation method involves traditional Chinese medicine ultra-micro grinding, matrix melting, and adding active ingredients under the condition of 100-110 DEG C for closed high-speed shearing homogenization, and finally coating and forming. The warm and hot effect generated by capsaicin stimulating microcirculation is synergized with the keratin layer lipid disturbance effect of azone, a warm and hot penetration carrier is constructed, and the transdermal speed of the medicine is improved. In combination with the modified hot melt adhesive matrix and the high-temperature homogenization process, the problems of heavy metal residues, easy flow and medicine aggregation of traditional plasters are solved, and the plaster has the characteristics of quick effect, strong adhesion and good biocompatibility.

Description

Technical Field

[0001] This invention relates to the field of external preparations of traditional Chinese medicine, specifically a formula for a stomach-warming and abdominal-soothing patch. Background Technology

[0002] In modern society, due to improper dietary habits, excessive consumption of raw and cold foods, and a fast-paced lifestyle, symptoms such as stomach pain, abdominal distension, and loss of appetite caused by spleen and stomach deficiency and blood stasis are becoming increasingly common. Compared to oral preparations, which have a first-pass effect and potential irritation to the gastrointestinal mucosa, topical application of traditional Chinese medicine is widely used in clinical practice for the conditioning and treatment of chronic gastrointestinal diseases because of its direct route of administration, fewer side effects, and high compliance.

[0003] Currently, commercially available gastrointestinal patch preparations mainly include traditional black plasters, rubber plasters, and novel gel plasters. Traditional black plasters are mostly made by high-temperature polymerization of lead oxide and vegetable oil. Although they have good adhesion, the residual lead and other heavy metal ions in the matrix pose a safety hazard with long-term skin contact. Furthermore, this type of matrix is ​​dark black in color and easily stains clothing. Its rheological properties are significantly affected by ambient temperature, often resulting in cracking and peeling in winter and flowing when heated in summer. In addition, traditional preparation processes usually require prolonged high-temperature oil refining, which can easily lead to a significant loss of volatile active ingredients in the formula, thereby reducing efficacy.

[0004] To overcome the shortcomings of traditional black plasters, modern processes often use rubber or hot melt adhesives as the matrix. However, conventional hot melt adhesive matrices are mostly strongly hydrophobic polymers, while Chinese herbal extracts or powders often have a certain degree of hydrophilicity. When preparing plasters with high drug loading, hydrophilic powders are prone to agglomeration in the hydrophobic matrix, making uniform dispersion difficult. This not only leads to uneven drug distribution in the finished product, but the agglomerated powder particles can also irritate the skin. Simultaneously, the polymer matrix has a strong encapsulation effect on drug molecules; without an effective release mechanism, the drug cannot be released from the matrix and penetrate the dense stratum corneum barrier, resulting in a slow transdermal absorption rate. Often, even several hours after application, patients do not experience significant symptom relief, failing to meet the clinical need for rapid pain relief. While some existing heating patches utilize iron powder oxidation to generate physical heat, they only provide a surface warmth sensation and lack therapeutic drug effects, failing to eradicate deep lesions. Meanwhile, simple medicated patches often suffer from low penetration efficiency due to a lack of thermal dynamics. Therefore, developing a compound topical formulation that can solve the problem of dispersing high-solids-content drug powders and achieve rapid efficacy through heat and chemical penetration mechanisms is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a formula for a stomach-warming and abdominal-soothing patch, which solves the problems of discontinuous control trajectory, static and unadjustable emotion mapping, lack of user feedback loop, weak adaptive ability, and insufficient fusion of multi-dimensional control information in existing technologies.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A formula for a stomach-warming and abdominal-soothing patch is made from the following ingredients in parts by weight: The ingredients are: Piper longum 6-12 parts, Evodia rutaecarpa 5-10 parts, Alpinia officinarum 8-15 parts, Corydalis yanhusuo 8-15 parts, Poria cocos 10-20 parts, Aucklandia lappa 6-12 parts, Gallus gallus domesticus gizzard lining 8-15 parts, Salvia miltiorrhiza 6-12 parts, Glycyrrhiza uralensis 5-10 parts, Amomum villosum 5-10 parts, Amomum cardamomum 5-10 parts, Paeonia lactiflora 8-15 parts, Bletilla striata 6-12 parts, Rehmannia glutinosa 8-15 parts, Panax notoginseng 3-8 parts, Foeniculum vulgare 5-10 parts; and hot melt adhesive matrix 30-50 parts, capsaicin 0.1-0.5 parts, azone 1-3 parts, camphor 2-6 parts, and clove oil 1-3 parts. The hot melt adhesive matrix, together with capsaicin, azone, camphor, and clove oil, forms a warm and permeation-enhancing carrier to carry and release the above-mentioned Chinese herbal ingredients.

[0007] By adopting the above technical solution, and utilizing the synergistic effect of the pre-proportioned traditional Chinese medicine components and the warm and heat-enhancing carrier, rapid onset of action and deep penetration of the drug are achieved. The mechanism of action and effects are as follows: First, a thermo-induced active transport pathway was established. Capsaicin in the formula, as a specific agonist of transient receptor potential vanillic acid subtype 1 (TRPV1), activates TRPV1 receptors at sensory nerve endings upon skin contact, triggering the release of neuropeptides (such as substance P and calcitonin gene-related peptide), leading to local capillary dilation and increased blood flow, producing a significant thermogenic effect. This physiological thermogenic effect raises local skin temperature and increases the fluidity of lipids in the stratum corneum.

[0008] Secondly, it achieves a dual penetration-enhancing effect through physicochemical synergy. Based on the warming effect that activates skin microcirculation, azone, camphor, and clove oil exert a synergistic penetration-enhancing effect. Azone primarily acts on the intercellular lipids of the stratum corneum, disrupting the orderly arrangement of the lipid bilayer; camphor and clove oil, with their high volatility and lipid solubility, can carry drug molecules to dissolve and penetrate the sebum membrane. This tertiary penetration-enhancing mechanism increases the transdermal penetration rate of macromolecular alkaloid drugs (such as long pepperamide and corydaline).

[0009] Third, the comprehensive formula achieves both symptomatic and root-cause treatment. The pungent and warm herbs such as Piper longum, Alpinia galanga, and Evodia rutaecarpa dispel cold and relieve pain, while Corydalis yanhusuo, Salvia miltiorrhiza, and Panax notoginseng invigorate blood and remove blood stasis. With the assistance of a warm and permeation-promoting carrier, the medicinal components quickly reach the lesions in the stomach, relieving smooth muscle spasms, improving gastric mucosal blood perfusion, and resolving cold pain and indigestion caused by spleen and stomach deficiency.

[0010] Preferably, the hot melt adhesive matrix is ​​composed of the following components in parts by weight: 25-45 parts of styrene-isoprene-styrene block copolymer, 40-50 parts of hydrogenated rosin glycerol ester, and 15-25 parts of medical white oil. By employing the above technical solution, the styrene-isoprene-styrene block copolymer serves as the backbone material, providing excellent cohesion and elasticity; the hydrogenated rosin glycerol ester acts as a tackifier, improving the initial adhesion of the matrix to the skin; and the medical white oil acts as a softener, regulating the rheological properties of the system. The three components work together to construct a physically cross-linked polymer network structure. This structure locks in the drug at room temperature to prevent exudation, softens moderately at body temperature to facilitate the diffusion and release of drug molecules, and is free of heavy metals, exhibiting good biocompatibility.

[0011] Preferably, the hot melt adhesive matrix is ​​prepared through the following steps: Medical white oil and hydrogenated rosin glycerol ester are mixed and heated to 120-125°C while stirring until completely melted; the temperature is then raised to 155-165°C, and styrene-isoprene-styrene block copolymer is added. The mixture is then stirred continuously at 150-170°C for 60-120 minutes until a transparent system without unmelted particles is formed. Cooling yields the final product. By employing the above technical solution, the segmented temperature control process ensures full plasticization and fusion of each component, avoids oxidative degradation of the polymer at high temperatures, and guarantees the physical stability of the matrix.

[0012] Preferably, the following ingredients are ultrafine powders: Piper longum, Evodia rutaecarpa, Alpinia galanga, Corydalis yanhusuo, Poria cocos, Aucklandia lappa, Gallus gallus domesticus gizzard lining, Salvia miltiorrhiza, Glycyrrhiza uralensis, Amomum villosum, Amomum cardamomum, Paeonia lactiflora, Bletilla striata, Rehmannia glutinosa, Panax notoginseng, and Foeniculum vulgare. These powders are processed using ultrafine pulverization, with a particle size passing through an 80-120 mesh sieve. By adopting the above technical solution, the raw materials of traditional Chinese medicine are processed into 80-120 mesh powders, increasing the specific surface area of ​​the drugs, improving the uniformity of drug dispersion and dissolution rate in the matrix, and facilitating the migration of drug components from the matrix to the skin interface.

[0013] Preferably, the weight ratio of hydrogenated rosin glyceryl ester to medical white oil in the hot melt adhesive matrix is ​​1.8:1-3.0:1; and the weight ratio of capsaicin to azone is 1:5-1:12. By adopting the above technical solution, the ratio of thickener to softener is controlled, balancing the peel strength and tack of the paste, avoiding the problems of the paste being too hard and not sticky or too soft and leaving residue; controlling the ratio of capsaicin to azone ensures the speed of warming effect while avoiding skin burning or redness and allergies caused by excessive capsaicin concentration, keeping the warming sensation within a comfortable range.

[0014] Preferably, the stomach-warming and abdominal-soothing patch is prepared by a method comprising the following steps: mixing various Chinese herbal raw materials and then grinding and ultra-fine pulverizing them so that all the raw materials pass through an 80-120 mesh sieve to obtain Chinese herbal micro powder; heating and melting a hot melt adhesive matrix, adding the Chinese herbal micro powder, and stirring to initially impregnate the Chinese herbal micro powder with the hot melt adhesive matrix; adding capsaicin, azone, camphor, and clove oil to the mixture containing the hot melt adhesive matrix and the Chinese herbal micro powder, raising the temperature, and performing closed high-speed stirring to obtain a medicinal adhesive mixture; coating, cooling, and cutting the medicinal adhesive mixture. More preferably, the temperature of heating and melting the hot melt adhesive matrix is ​​controlled at 80-85℃, and stirring is performed until the hot melt adhesive matrix is ​​liquid; the temperature after adding capsaicin, azone, camphor, and clove oil is controlled at 100-110℃, and the closed high-speed stirring time is 20-35 minutes.

[0015] By adopting the above technical solution, especially the high-temperature homogenization stirring process at 100-110℃, the technical problem of dispersing high-solids-content traditional Chinese medicine micropowders in hydrophobic hot melt adhesive matrices has been solved. The microscopic dispersion mechanism is as follows: Step 1: Matrix softening and wetting. During the preheating stage at 80-85℃, the hot melt adhesive matrix softens, initially contacting and wetting the surface of the Chinese herbal medicine powder.

[0016] Step 2: Viscosity Reduction and Interface Modification. When the temperature is increased to 100-110℃, the molecular chain segment movement of the styrene-isoprene-styrene block copolymer intensifies, the matrix melt viscosity decreases, and the optimal rheological state is reached. At this time, the added azone and volatile oil components not only serve as active ingredients but also act as compatibilizers, reducing the interfacial tension between the hydrophilic Chinese medicine powder and the hydrophobic matrix.

[0017] Step 3: Shear Dispersion and Deagglomeration. Under the dual action of low viscosity and high-speed shear force, the agglomerates of traditional Chinese medicine powder are broken down and encapsulated by a monolayer of polymer matrix, forming a uniform and stable polymer filler suspension system. This process avoids powder agglomeration and paste stratification caused by low-temperature stirring, while the sealed environment prevents the loss of volatile active ingredients.

[0018] This invention provides a formula for a stomach-warming and abdominal-soothing patch. It has the following beneficial effects: 1. This invention improves the onset speed and bioavailability of drugs by constructing a warm and penetrating carrier system. The trace amount of capsaicin in the formula stimulates the expansion of local microcirculation, and the azone's disturbance effect on the lipid structure of the stratum corneum overcomes the skin barrier's obstruction of macromolecular drugs. Combined with the traditional Chinese medicine components that dispel cold, relieve pain, and promote blood circulation, it achieves the simultaneous exertion of physical warming effect and drug therapeutic effect, solving the problems of low transdermal penetration rate and slow onset of action of traditional plasters.

[0019] 2. This invention uses a modified hot melt adhesive matrix to replace the traditional lead oxide or rubber matrix, eliminating the risk of heavy metal residue and improving aging resistance. The matrix utilizes the physical cross-linking network of styrene-isoprene-styrene block copolymer to give the plaster suitable cohesive force and peel strength, ensuring firmness during application and painless removal. At the same time, the matrix can maintain structural stability in high-temperature environments, overcoming the defects of traditional black plasters that are easily affected by body temperature or ambient temperature, resulting in dripping, oil seepage, and staining of clothing.

[0020] 3. This invention utilizes a high-temperature homogenization preparation process to solve the problem of dispersing high-solids-content traditional Chinese medicine micropowders in a hydrophobic matrix. By raising the mixing temperature to a preset range and applying high-speed shear force, the viscosity of the matrix melt is reduced and the interfacial wetting ability of solid particles is enhanced, thereby breaking down micropowder agglomerates. This allows the drug particles to be uniformly suspended in a monodisperse state within the matrix, ensuring the uniformity of drug content in each plaster and avoiding local differences in efficacy or skin irritation caused by powder agglomeration. Detailed Implementation

[0021] 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.

[0022] It should be noted that the parts by weight mentioned in the claims and specification of this invention represent the mass ratio between the components and are not limited to a specific unit of measurement. In specific embodiments and examples, for ease of laboratory preparation and measurement, grams (g) are used as the specific unit of weight, i.e., 1 part by weight is equivalent to 1 gram (g). In actual industrial production or large-scale preparation, this unit of weight can be replaced with other units of mass such as kilograms (kg) or tons (t) according to the production scale requirements, as long as the ratio between the components remains within the weight ratio range defined in the claims, it falls within the protection scope of this invention.

[0023] Preparation Examples 1-3: Preparation Example 1: This preparation example provides a method for preparing a general-purpose hot melt adhesive matrix, including the following steps: Accurately weigh 200g of medical white oil and 450g of hydrogenated rosin glycerol ester and place them into a reaction vessel equipped with a heating and stirring device; Turn on the heating device and raise the temperature to 120°C. Turn on the stirring paddle and stir at a speed of 40 rpm until the hydrogenated rosin glycerol ester is completely melted and mixed evenly with the medical white oil to form a liquid mixture. Continue to raise the temperature to 160℃, slowly add 350g of weighed styrene-isoprene-styrene block copolymer (SIS), adjust the stirring speed to 60 rpm, and keep the temperature between 155-165℃ and continue stirring for 90 minutes until the system is transparent and there are no unmelted polymer particles. Stop heating and allow it to cool naturally to room temperature before removing it to obtain a block-shaped general-purpose hot melt adhesive matrix.

[0024] Preparation Example 2: This preparation example provides a method for preparing a high-cohesion hot melt adhesive matrix, including the following steps: Accurately weigh 150g of medical white oil and 400g of hydrogenated rosin glycerol ester and place them into a reaction vessel equipped with a heating and stirring device; Turn on the heating device and raise the temperature to 125°C. Turn on the agitator and stir at a speed of 40 rpm until the hydrogenated rosin glycerol ester is completely melted. Raise the temperature to 165℃, add 450g of weighed styrene-isoprene-styrene block copolymer (SIS) in batches, adjust the stirring speed to 80 rpm, and keep the temperature between 160-170℃ and continue stirring for 120 minutes to ensure that the high content of elastomer is completely plasticized and dispersed. Stop heating, discharge and cool the material to obtain a block-shaped, high-cohesion hot melt adhesive matrix.

[0025] Preparation Example 3: This preparation example provides a method for preparing a high initial tack hot melt adhesive matrix, including the following steps: Accurately weigh 250g of medical white oil and 500g of hydrogenated rosin glycerol ester and place them into a reaction vessel equipped with a heating and stirring device; Turn on the heating device to raise the temperature to 115℃, and turn on the agitator to stir at a speed of 30 rpm to obtain a low-viscosity mixture. Raise the temperature to 155℃, add 250g of weighed styrene-isoprene-styrene block copolymer (SIS), adjust the stirring speed to 50 rpm, and keep the temperature between 150-160℃ and stir continuously for 60 minutes. Stop heating, discharge and cool the material to obtain a block-shaped high initial tack hot melt adhesive matrix.

[0026] Examples 1-5; Example 1: This example provides a formula for a stomach-warming and abdominal-soothing patch, including the following steps: First, prepare and pre-treat the raw materials. Weigh out 9g of Piper longum, 8g of Evodia rutaecarpa, 12g of Alpinia officinarum, 12g of Corydalis yanhusuo, 15g of Poria cocos, 9g of Aucklandia lappa, 12g of chicken gizzard lining, 9g of Salvia miltiorrhiza, 8g of Glycyrrhiza uralensis, 8g of Amomum villosum, 8g of Amomum cardamomum, 12g of Paeonia lactiflora, 9g of Bletilla striata, 12g of Rehmannia glutinosa, 5g of Panax notoginseng, and 8g of Foeniculum vulgare. Mix the above sixteen Chinese herbs and process them using a grinding method and ultra-micro pulverization technology, so that all of them pass through a 100-mesh sieve. Continue grinding until they present a fine micro-powder paste for later use.

[0027] Start the prescription plaster mixing machine, set the heating temperature to 80°C, and add 40g of the general-purpose hot melt adhesive matrix prepared in Preparation Example 1 into the mixing chamber. Start slow stirring until the matrix is ​​completely melted into a liquid state. After the matrix melts, accurately add the pre-treated Chinese herbal powder paste into the mixing chamber through the quantitative feeding module, and maintain stirring to allow the powder to be initially impregnated and coated by the matrix.

[0028] Then, add 0.3g capsaicin, 2g azone, 4g camphor, and 2g clove oil to the container in sequence. Immediately adjust the temperature control system of the mixing machine to 110℃ and switch to high-speed stirring mode. Stir continuously for 25 minutes in a closed environment. Use high temperature and shear force to fully dissolve capsaicin and transdermal agent into the matrix, while ensuring that the Chinese medicine powder is evenly dispersed.

[0029] After stirring, turn on the discharge mode to evenly coat the molten medicinal adhesive mixture onto the non-woven fabric backing, control the coating thickness, cover with release paper after natural cooling, and cut to obtain the final product.

[0030] Example 2: This example provides a formula for a stomach-warming and abdominal-soothing patch, including the following steps: Weigh out 6g of Piper longum, 5g of Evodia rutaecarpa, 8g of Alpinia officinarum, 8g of Corydalis yanhusuo, 10g of Poria cocos, 6g of Aucklandia lappa, 8g of chicken gizzard lining, 6g of Salvia miltiorrhiza, 5g of Glycyrrhiza uralensis, 5g of Amomum villosum, 5g of Amomum cardamomum, 8g of Paeonia lactiflora, 6g of Bletilla striata, 8g of Rehmannia glutinosa, 3g of Panax notoginseng, and 5g of Foeniculum vulgare. Grind them into a fine powder of 100 mesh and set aside.

[0031] Preheat the mixing machine to 80°C, add 50g of the general-purpose hot melt adhesive matrix prepared in Preparation Example 1, and after it is completely melted, add the above-mentioned fine powder of traditional Chinese medicine for preliminary mixing.

[0032] Next, add 0.1g capsaicin, 1g azone, 2g camphor, and 1g clove oil to the mixture, raise the temperature to 100℃, and stir for 30 minutes in a sealed state to ensure that the low content of active ingredients is evenly distributed in the high proportion of matrix.

[0033] Finally, the homogenized paste is extracted, spread on a cotton cloth backing, cooled, and sliced.

[0034] Example 3: This example provides a formula for a stomach-warming and abdominal-soothing patch, including the following steps: Weigh out 12g of Piper longum, 10g of Evodia rutaecarpa, 15g of Alpinia officinarum, 15g of Corydalis yanhusuo, 20g of Poria cocos, 12g of Aucklandia lappa, 15g of chicken gizzard lining, 12g of Salvia miltiorrhiza, 10g of Glycyrrhiza uralensis, 10g of Amomum villosum, 10g of Amomum cardamomum, 15g of Paeonia lactiflora, 12g of Bletilla striata, 15g of Rehmannia glutinosa, 8g of Panax notoginseng, and 10g of Foeniculum vulgare. Grind them into a fine powder of 100 mesh for later use.

[0035] Given the large total amount of drug powder in this embodiment, a matrix with stronger cohesive force was selected. The mixing machine was heated to 85°C, and 30g of the high cohesive hot melt adhesive matrix prepared in Preparation Example 2 was added and stirred until completely melted. Subsequently, the above-mentioned ultrafine Chinese medicine powder was added in batches to prevent the powder from agglomerating, while maintaining continuous stirring.

[0036] After all the drug powder was added, 0.5g of capsaicin, 3g of azone, 6g of camphor, and 3g of clove oil were added. The process temperature was set to 110℃, and the high-speed stirring time was extended to 35 minutes. The high cohesive properties of the matrix in Preparation Example 2 were used to strongly encapsulate a high proportion of the drug powder.

[0037] After discharging and applying a thick layer, observe the surface of the paste after cooling. If the paste surface is smooth and there is no powder falling off, then a high-drug-loaded plaster is obtained.

[0038] Example 4: This example provides a formula for a stomach-warming and abdominal-soothing patch, including the following steps: Adjust the proportions of ingredients according to the pre-set clinical protocol. Weigh out 12g of Piper longum, 15g of Alpinia officinarum (to enhance warming and dispersing cold stagnation), 15g of Corydalis yanhusuo, 12g of Salvia miltiorrhiza, and 8g of Panax notoginseng (to enhance blood circulation and remove blood stasis). The remaining ingredients are 8g of Evodia rutaecarpa, 15g of Poria cocos, 9g of Aucklandia lappa, 12g of Gallus gallus domesticus gizzard lining, 8g of Glycyrrhiza uralensis, 8g of Amomum villosum, 8g of Amomum cardamomum, 12g of Paeonia lactiflora, 9g of Bletilla striata, 12g of Rehmannia glutinosa, and 8g of Foeniculum vulgare to maintain the optimal ratio. Grind all the medicinal materials together into a fine powder of 100 mesh.

[0039] Start the mixing machine to 80°C, add 40g of the general-purpose hot melt adhesive matrix prepared in Preparation Example 1 to melt, and then add the adjusted Chinese herbal powder as described above and mix.

[0040] Then add 0.3g capsaicin, 2g azone, 4g camphor, and 2g clove oil, adjust the temperature to 105℃, and stir in a sealed container for 25 minutes.

[0041] After coating, a personalized stomach-warming and abdominal-soothing patch is obtained, specifically for severe blood stasis and cold coagulation type.

[0042] Example 5: This example provides a formula for a stomach-warming and abdominal-soothing patch, including the following steps: The Chinese medicine components and proportions are completely consistent with those in Example 1, and are processed into a 100-mesh fine powder paste.

[0043] The mixing machine was heated to 80°C, and 40g of the high initial tack hot melt adhesive matrix prepared in Preparation Example 3 was added. This matrix contains a high proportion of tackifying resin and softener, resulting in a fast melting speed. After melting, the herbal powder was added.

[0044] Add 0.3g capsaicin, 2g azone, 4g camphor, and 2g clove oil. Set the stirring temperature to 100℃ (the temperature should not be too high because the substrate is soft) and stir for 20 minutes to achieve homogenization.

[0045] After the material is discharged and coated, and cooled, the initial tack of the paste surface increases, thus obtaining a high-viscosity stomach-warming and abdominal-soothing patch.

[0046] Comparative Examples 1-4; Comparative Example 1: Compared with Example 1, the difference is that capsaicin and azone are removed from the formula, while the types, amounts and preparation process parameters of the other raw materials are the same.

[0047] This comparative example aims to reverse-engineer the principles of the above formulation: capsaicin, camphor, clove oil, and azone synergistically promote transdermal absorption, accelerate onset of action, and enhance the local warming sensation.

[0048] Comparative Example 2: Compared with Example 1, the difference is that Piper longum and Alpinia galanga were removed from the formula, while the types, amounts and preparation process parameters of the other raw materials are the same.

[0049] This comparative study aims to reverse-engineer the core pharmacological mechanism by which Piper longum, Evodia rutaecarpa, Alpinia galanga, and Foeniculum vulgare warm the middle jiao, promote qi circulation, dispel cold, and relieve pain, thereby directly improving the state of spleen and stomach deficiency and cold.

[0050] Comparative Example 3: Compared with Example 1, the difference lies in the homogenization mixing temperature in the preparation process: In this comparative example, after the addition of excipients, the stirring temperature was always maintained at 80°C, and it was not raised to 100°C-110°C for high-temperature homogenization. All other aspects were the same.

[0051] This comparative example aims to reverse-engineer the technical effect of the above preparation principle: by using a high-temperature environment of 100℃-110℃ and mechanical shear force, the fat-soluble excipients (capsaicin, azone, camphor, clove oil) and the hot melt adhesive matrix are fully miscible, while the Chinese medicine powder is uniformly suspended in the colloidal system, forming a uniform and stable medicated paste.

[0052] Comparative Example 4: Compared with Example 1, the difference lies in the matrix carrier: the hot melt adhesive matrix prepared in Example 1 was replaced with an equal amount of traditional lead oxide and sesame oil black plaster matrix, while the proportions of other drugs remained the same, and the process adopted was the traditional black plaster hot spreading method.

[0053] This comparative example aims to reverse-engineer the advantages of the above formulation principle: hot melt adhesive, as the base of the plaster, ensures the adhesion and stability of the plaster and avoids the destruction of effective ingredients caused by traditional high-temperature cooking.

[0054] Test Examples 1-4: Test Example 1: Physical and Mechanical Properties and Aging Stability Test of Paste Experimental steps: Sample preparation: Take the finished plasters prepared in Examples 1, 2, 3, and 5, as well as Comparative Examples 3 and 4, remove the edge portions, and cut them into samples with a width of 25 mm and a length conforming to the requirements of the Adhesion Determination Method in General Chapter 0952 of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Place all samples in a constant temperature and humidity environment (temperature 23±2℃, relative humidity 50±5%) for 24 hours to condition them.

[0055] Initial tack test (rolling ball method): Fix the sample with the adhesive side facing up on an inclined plate at a 30° angle, with a run-up length of 100 mm. Select steel balls of different sizes and release them from rest at the top of the run-up section. Record the largest steel ball size that can adhere to the central area of ​​the sample's adhesive surface and roll a distance not exceeding the specified range. Perform three parallel tests on each group of samples and take the average value.

[0056] Holding power test (weight method): The adhesive surface of the sample is adhered to a standard stainless steel test plate, with an adhesion area of ​​25mm × 25mm. A 2kg standard pressure roller is used to roll the sample back and forth three times at a speed of 300mm / min. After 20 minutes, a 1kg weight is suspended from the end of the sample, and the time required for the sample to completely detach from the steel plate is recorded. If the sample does not detach within 120 minutes, it is recorded as >120min.

[0057] Peel strength test (180° peel method): The sample is attached to a stainless steel plate, rolled with a pressure roller, and then peeled along the 180° direction at a tensile speed of 300 mm / min using an electronic tensile testing machine. The average force value during the peeling process is recorded, and the peel strength (N / 25 mm) is calculated.

[0058] Heat resistance aging test: The sample is placed in a 60℃ constant temperature forced air drying oven and suspended vertically for 168 hours (7 days). Observe whether the paste flows, seeps oil or the backing penetrates. After cooling to room temperature, check whether there is obvious residual glue when touched with a finger.

[0059] Test results: Table 1. Physical and mechanical properties and aging resistance test results of each group of samples. ; Results analysis: According to the data in Table 1, Example 1 exhibits a good balance in various physical properties. The initial tack reaches that of a No. 22 steel ball, the holding power exceeds 120 minutes, and the peel strength remains within a suitable range of 16.42 N / 25 mm, indicating that the formulation ensures strong adhesion while minimizing mechanical damage to the skin during peeling.

[0060] Comparing the data differences between Example 1 and Comparative Example 3 verifies the crucial role of the high-temperature homogenization process. Comparative Example 3, prepared at 80°C, exhibited a holding power of only 41 minutes and a lower peel strength than Example 1 (8.56 vs 16.42 N / 25 mm), and showed powder agglomeration. This is because the block copolymer (SIS) in the hot melt adhesive matrix had not yet reached a sufficient rheological state at 80°C, failing to fully impregnate and encapsulate the 100-mesh herbal powder. The unimpregnated powder agglomerates formed stress concentration points and physical defects within the adhesive layer, leading to a significant decrease in cohesion and causing the paste to become brittle and easily detach. In contrast, Example 1 employed a high-temperature shearing process at 100°C-110°C, ensuring that the polymer chains fully extended and formed a tight interfacial bond with the powder particles, thus constructing a stable polymer-filler composite system.

[0061] Compared with Comparative Example 4 (traditional black plaster), Comparative Example 4 exhibited severe flow and oil seepage during the heat aging test. This is because the traditional lead oxide and sesame oil matrix has high thermorheological sensitivity and a low softening point. In contrast, the hot melt adhesive matrix used in this invention utilizes the physical cross-linking network of SIS block copolymers, maintaining structural integrity even at 60°C. This solves the problem of traditional plasters easily staining clothing and leaving adhesive residue in summer or when body temperature is high.

[0062] Although Example 3 achieved the maximum drug loading capacity, resulting in a slight decrease in initial tack and peel strength compared to Example 1 (excessive powder filling interfered with the adhesive interface), its various indicators were still superior to Comparative Example 3. This demonstrates that, with a high-cohesive matrix and reasonable process parameters, the present invention can support a higher proportion of traditional Chinese medicine powder without disintegration. Example 5, by adjusting the matrix formulation, achieved extremely high initial tack (29 steel ball), verifying the feasibility of adapting this solution to different clinical needs (such as patients with dry skin) through matrix modification.

[0063] Test Example 2: Drug Content Uniformity and Dispersion Stability Test Experimental steps: Sample Collection: The finished plasters prepared in Examples 1, 3, and Comparative Example 3 were selected as test subjects. To comprehensively evaluate the component distribution of the plaster in different areas, a 2cm × 2cm sample was cut from each of the following locations on the coated surface of each batch of molded plaster: the upper left corner, the upper right corner, the lower left corner, the lower right corner, and the center. The weight was then accurately measured.

[0064] Preparation of the test solution: Place the shredded sample in a stoppered conical flask and accurately add 50 ml of methanol. Considering the encapsulation effect of the hot melt adhesive matrix, first heat the conical flask in a 40°C water bath for 20 minutes to soften the matrix, then sonicate it at 300 W and 40 kHz for 45 minutes to destroy the polymer backbone and completely extract the drug components. Remove and cool, shake well, filter through a 0.45 μm microporous membrane, and use the filtrate as the test solution.

[0065] Preparation of reference solution: Accurately weigh an appropriate amount of corydaline reference standard, dissolve and dilute it in methanol to prepare a solution containing 20 μg per ml, which is used as the reference solution. Corydaline was chosen as the indicator component because, as an alkaloid, its uniform distribution in the herbal powder can represent the overall dispersion state of the powder in a lipophilic matrix.

[0066] Chromatographic conditions: High-performance liquid chromatography (HPLC) was used for determination. The chromatographic column was an Octadecylsilane (ODS) C18 column (250 mm × 4.6 mm, 5 μm); the mobile phase was methanol-0.1% phosphoric acid solution (60:40); the flow rate was 1.0 mL / min; the detection wavelength was 280 nm; the column temperature was 30 °C; and the injection volume was 10 μL.

[0067] Data acquisition and calculation: The peak area of ​​each of the five sampling points in each group was measured. The content of corydaline in each gram of sample (mg / g) was calculated according to the external standard method. The relative standard deviation (RSD) of the five data points in each group was calculated. The uniformity of the paste was evaluated by using this value.

[0068] Test results: Table 2. Results of corydaline content determination and uniformity analysis in different parts of each group of samples. ; Results analysis: According to the data in Table 2, the RSD value of corydaline content at the five different sampling points in Example 1 was 1.63%, exhibiting extremely high uniformity. This indicates that at a process temperature of 110°C, the viscosity of the hot melt adhesive matrix decreased to a suitable rheological range. Combined with the shear stress provided by mechanical stirring, this was sufficient to overcome the van der Waals forces between the micronized powder particles of the traditional Chinese medicine, preventing the agglomeration of fine powder and ensuring that the drug particles were uniformly suspended in a monodisperse state within the polymer matrix.

[0069] In contrast, the data for Comparative Example 3 showed dramatic fluctuations, with an RSD value as high as 45.21%. The content at sampling points 2 and 5 was higher than the average, while sampling point 4 was only 0.198 mg / g. This extreme distribution difference confirms the defects of the low-temperature process: at 80℃, the SIS block copolymer was not completely unwrapped, resulting in excessively high system viscosity and an inability to effectively wet the large surface area of ​​the traditional Chinese medicine powder. The unwetted powder underwent severe physical agglomeration during mixing, leading to a random distribution of high-concentration powder clumps and almost drug-free pure adhesive areas within the ointment. This macroscopic inhomogeneity not only resulted in significant differences in efficacy at different application sites, but the agglomerated powder also directly irritated the skin due to the lack of matrix encapsulation.

[0070] Furthermore, in Example 3, despite a significant increase in drug loading (approaching the upper limit of the formulation), the RSD value was controlled at 4.78%. Although slightly higher than in Example 1, it remained within the pharmaceutically acceptable range (typically requiring RSD < 5%). This result further supports the rationality of the process parameters of this invention, demonstrating that appropriately increasing the stirring temperature and shear time can solve the problem of solid particle dispersion in high-solids-content systems (high-filling systems), ensuring drug uniformity and quality stability in high-drug-loading plasters.

[0071] Test Example 3: In vitro transdermal release performance test Experimental steps: Skin barrier preparation: Healthy male Kunming mice, weighing 20±2g, were euthanized by cervical dislocation. Abdominal villi were immediately shaved, and the abdominal skin was harvested. Subcutaneous adipose tissue and adhesions were carefully removed, and the skin was repeatedly rinsed with physiological saline. After confirming the skin surface was undamaged, it was immersed in physiological saline for later use. The preparation process was carried out at 4℃ to maintain skin bioactivity.

[0072] Diffusion apparatus setup: A modified Franz vertical diffusion cell apparatus was used. The receiving chamber volume was 15 ml, and the effective diffusion area was 2.8 cm². 2 The receiving solution is a physiological saline solution containing 20% ​​ethanol to ensure that the solubility of poorly soluble drug components in the receiving solution meets the requirements of the sink. The circulating water bath system is turned on, and the temperature of the receiving chamber is controlled at a constant 37±0.5℃. The receiving solution is continuously magnetically stirred at a speed of 300r / min.

[0073] Application and Sampling: The treated detached skin stratum corneum was fixed between the supply chamber and the receiving chamber with the stratum corneum facing upwards. The plaster samples from Example 1, Comparative Example 1, and Comparative Example 4 were taken, cut to the desired diffusion area, and tightly applied to the surface of the stratum corneum. At 2, 4, 8, 12, and 24 hours after the start of the experiment, 5 ml of receiving liquid was drawn from the sampling port, and an isothermal and equal-volume blank receiving liquid was immediately added.

[0074] Sample determination and calculation: The collected receiving liquid was filtered through a 0.45 μm microporous membrane, and the concentration of the indicator component, fumarate ethyl, was determined by high-performance liquid chromatography (HPLC). According to Fick's first law of diffusion, the cumulative permeate per unit area (Qn, μg / cm²) at each time point was calculated. 2 ) and steady-state transdermal rate (J, μg·cm) -2 ·h -1 ).

[0075] Test results: Table 3. Results of in vitro transdermal permeation and transdermal rate measurements for each group of samples. ; Results analysis: Based on the data in Table 3, the in vitro transdermal behavior of Example 1 exhibited rapid release and sustained penetration characteristics. In the initial stage of application (2 hours), the cumulative penetration amount of Example 1 reached 18.42 μg / cm³. 2 The values ​​are respectively Comparative Example 1 (3.12 μg / cm³). 2 The concentration of the novel coronavirus was 5.9 times that of the control group and 5.67 μg / cm³ of the control group. 2 The effect was 3.2 times greater than that of the previous formulation. This difference directly relates to the mechanism of action of this invention: the capsaicin and azone added to the formulation of Example 1 exerted a synergistic effect on penetration. Capsaicin dilates capillaries and increases the fluidity of stratum corneum lipids by stimulating skin receptors, and together with the perturbation effect of azone on the stratum corneum lipid bilayer, it opens the skin barrier channels, allowing drug molecules to quickly penetrate the stratum corneum and enter the subcutaneous tissue in a short time.

[0076] Comparative Example 1 and Comparative Example 1 (without transdermal agent) show the same matrix but significantly different penetration efficiencies (total amount over 24 hours: 231.55 vs 62.37 μg / cm³). 2 This indicates that relying solely on the occlusive effect of the hot melt adhesive matrix is ​​insufficient to drive efficient transdermal delivery of macromolecular drugs (such as alkaloids), and that the pre-defined transdermal activator combination in this protocol is necessary to overcome skin resistance.

[0077] Compared with Comparative Example 1 and Comparative Example 4 (traditional black plaster), the steady-state transdermal rate of Example 1 was 9.14 μg·cm⁻¹. -2 ·h -1 ) higher than traditional matrix (3.65 μg·cm -2 ·h -1This is because the traditional lead oxide and sesame oil matrix has a dense structure, and the polymerization of plant oils exerts a strong binding force on drug molecules, resulting in high resistance to drug release. In contrast, the hot melt adhesive matrix used in this invention, although solid at room temperature, undergoes microscopic relaxation of the polymer chains under body temperature (37°C) and the localized warming effect of capsaicin, increasing free volume and facilitating the diffusion and release of drug molecules. Furthermore, the hot melt adhesive matrix does not contain heavy metals such as lead oxide, avoiding the complexation reaction between heavy metal ions and alkaloid drugs, which could reduce the concentration of free drug and thus ensure higher bioavailability.

[0078] Test Example 4: Simulated Clinical Drug Efficacy and Thermosensitive Time-Effect Test Experimental steps: Subject selection: Following the diagnostic criteria for spleen and stomach deficiency-cold syndrome or cold-induced blood stasis syndrome in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," 100 volunteer subjects were selected. Inclusion criteria included: typical symptoms such as cold pain in the stomach, relief upon warming, abdominal distension, and poor appetite, and no use of related medications within the past week. Exclusion criteria included broken skin, pregnant women, and those allergic to capsaicin.

[0079] Grouping and Administration: Subjects were randomly divided into 5 groups: Example 1 (optimal formula), Example 4 (enhanced formula for severe cases), Comparative Example 1 (without transdermal and warming agents), Comparative Example 2 (without core medicinal flavor), and Comparative Example 4 (traditional black plaster matrix), with 20 subjects in each group. A double-blind application trial was conducted, with the Zhongwan and Shenque acupoints selected as application points. Before application, the skin was cleaned with 75% ethanol, dried, and then the corresponding plaster was applied for 24 hours.

[0080] Indicator observation and recording: Onset time determination: Timing starts from the moment of application. Subjects are required to record the time (min) immediately when they feel a significant warm or comfortable sensation at the application site.

[0081] Pain relief assessment: The degree of epigastric pain before and 24 hours after application of the patch was scored using the Visual Analogue Scale (VAS) (0 points for no pain, 10 points for severe pain), and the difference in VAS scores was calculated.

[0082] Skin tolerance assessment: Observe skin reaction 1 hour after removing the plaster, record the number of cases of erythema, edema or itching, and calculate the incidence of adverse reactions.

[0083] Test results: Table 4. Statistical table of warming sensation and analgesic effect of human body patch for each group of samples. ; Results analysis: According to the data in Table 4, both Example 1 and Example 4 groups showed advantages in terms of onset speed and therapeutic effect. The average onset time of the warming sensation in Example 1 was 23.4 minutes, verifying the technical indicator of rapid onset of effect within 30 minutes of this protocol.

[0084] Comparing the data from Example 1 and Comparative Example 1 reveals the synergistic mechanism of capsaicin and azone. Comparative Example 1, which removed capsaicin and azone, saw the vast majority of subjects report no significant warming sensation within 2 hours, and the VAS score reduction was only 1.34 points, indicating weak pain relief. This result confirms that without active warming components stimulating TRPV1 receptors and without transdermal agents opening the stratum corneum channels, simple traditional Chinese medicine powder is unlikely to penetrate the skin barrier and exert its therapeutic effect in a short time. This invention, by adding trace amounts of capsaicin to induce neurogenic warming feedback, not only provides subjective comfort (soothing warmth) but also accelerates the absorption of subsequent drug components through local hyperemia.

[0085] Comparing the data from Example 1 and Comparative Example 2 highlights the pharmacological essence of the compound formulation. Although Comparative Example 2 retained capsaicin, its onset time (25.1 minutes) was similar to that of Example 1, indicating that the warming sensation mainly depends on capsaicin. However, the VAS score reduction value of Comparative Example 2 was only 1.63 points, far lower than the 5.27 points of Example 1. This indicates that simple heat stimulation cannot replace the therapeutic effects of core drugs such as long pepper and galangal. Example 1 combined physical heat with drug treatment through a hot melt adhesive matrix, using the heat effect as a precursor to promote the deep penetration of antispasmodic and analgesic components such as long pepper and galangal, thus achieving both symptomatic and root-cause treatment. If there is only a warming sensation without the core medicinal flavor (Comparative Example 2), it cannot effectively relieve the deep pain caused by gastrointestinal smooth muscle spasms.

[0086] Furthermore, Example 4 increased the proportion of blood-activating and stasis-removing drugs for critically ill patients, resulting in a VAS score reduction of 5.92 points, demonstrating stronger analgesic efficacy and verifying the feasibility of flexibly adjusting the formula according to the patient's condition. Regarding safety, Comparative Example 4 (traditional black plaster) had an adverse reaction rate as high as 35.0%, mainly manifested as contact dermatitis and itching, which is related to the poor breathability of the traditional matrix and lead oxide residue. In contrast, the SIS hot melt adhesive matrix used in the Example group has better biocompatibility and breathability, with an adverse reaction rate controlled at a low level of 5%, and no serious allergic reactions were observed, demonstrating the safety advantages of the novel matrix in clinical applications.

Claims

1. A formula for a stomach-warming and abdominal-soothing patch, characterized in that, Made from the following ingredients in parts by weight: Piper longum 6-12 parts, Evodia rutaecarpa 5-10 parts, Alpinia officinarum 8-15 parts, Corydalis yanhusuo 8-15 parts, Poria cocos 10-20 parts, Aucklandia lappa 6-12 parts, Gallus gallus domesticus gizzard lining 8-15 parts, Salvia miltiorrhiza 6-12 parts, Glycyrrhiza uralensis 5-10 parts, Amomum villosum 5-10 parts, Amomum cardamomum 5-10 parts, Paeonia lactiflora 8-15 parts, Bletilla striata 6-12 parts, Rehmannia glutinosa 8-15 parts, Panax notoginseng 3-8 parts, Foeniculum vulgare 5-10 parts, Hot melt adhesive matrix 30-50 parts, Capsaicin 0.1-0.5 parts, Azone 1-3 parts, Camphor 2-6 parts, Clove oil 1-3 parts; The hot melt adhesive matrix, together with capsaicin, azone, camphor, and clove oil, forms a warm-heat permeation-enhancing carrier.

2. The formula for a stomach-warming and abdominal-soothing patch according to claim 1, characterized in that, The hot melt adhesive matrix is ​​made of the following components in parts by weight: 25-45 parts of styrene-isoprene-styrene block copolymer, 40-50 parts of hydrogenated rosin glycerol ester, and 15-25 parts of medical white oil.

3. The formula for a stomach-warming and abdominal-soothing patch according to claim 2, characterized in that, The hot melt adhesive matrix is ​​prepared by the following steps: Mix medical white oil with hydrogenated rosin glycerol ester, heat to 120-125℃ and stir until completely melted; Heat to 155-165℃, add styrene-isoprene-styrene block copolymer, and stir continuously at 150-170℃ for 60-120 minutes until a transparent system without unmelted particles is formed. Cool to obtain the final product.

4. The formula for a stomach-warming and abdominal-soothing patch according to claim 1, characterized in that, The ingredients mentioned, including Piper longum, Evodia rutaecarpa, Alpinia galanga, Corydalis yanhusuo, Poria cocos, Aucklandia lappa, Gallus gallus domesticus gizzard lining, Salvia miltiorrhiza, Glycyrrhiza uralensis, Amomum villosum, Amomum cardamomum, Paeonia lactiflora, Bletilla striata, Rehmannia glutinosa, Panax notoginseng, and Foeniculum vulgare, are all ultra-fine powders that have been processed by ultra-fine grinding and have a particle size that passes through an 80-120 mesh sieve.

5. The formula for a stomach-warming and abdominal-soothing patch according to claim 1, characterized in that, The weight ratio of hydrogenated rosin glycerol ester to medical white oil in the hot melt adhesive matrix is ​​1.8:1-3.0:1; the weight ratio of capsaicin to azone is 1:5-1:

12.

6. The formula for a stomach-warming and abdominal-soothing patch according to claim 1, characterized in that, The stomach-warming and abdominal-soothing patch also includes a backing layer and a release paper covering the surface of the paste. The paste made from the raw materials is coated on the backing layer with a coating thickness of 0.5-1.5 mm.

7. The formula for a stomach-warming and abdominal-soothing patch according to claim 6, characterized in that, The backing layer is made of breathable non-woven fabric or cotton fabric.

8. The formula for a stomach-warming and abdominal-soothing patch according to claim 1, characterized in that, The stomach-warming and abdominal-soothing patch is prepared through the following steps: After mixing the various Chinese medicinal materials, they are ground and ultra-fine pulverized so that all the Chinese medicinal materials pass through an 80-120 mesh sieve to obtain Chinese medicinal powder. The hot melt adhesive matrix is ​​heated and melted, and the traditional Chinese medicine micro powder is added. The mixture is stirred so that the traditional Chinese medicine micro powder is initially impregnated by the hot melt adhesive matrix. Capsaicin, azone, camphor, and clove oil are added to a mixture containing the hot melt adhesive matrix and the traditional Chinese medicine powder. The temperature is increased and the mixture is stirred at high speed in a closed environment to obtain a medicinal adhesive mixture. The medicated adhesive mixture is coated, cooled, and cut.

9. The formula for a stomach-warming and abdominal-soothing patch according to claim 8, characterized in that, The temperature of the hot melt adhesive matrix is ​​controlled at 80-85℃, and it is stirred until the hot melt adhesive matrix is ​​liquid.

10. The formula for a stomach-warming and abdominal-soothing patch according to claim 8, characterized in that, After adding capsaicin, azone, camphor, and clove oil, the temperature is controlled at 100-110℃, and the high-speed stirring time is 20-35 minutes. The high-temperature shear force is used to dissolve capsaicin and transdermal agent into the hot melt adhesive matrix and to evenly disperse the Chinese medicine powder.