Cough and asthma patch and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine pharmacy, and particularly discloses a cough and asthma patch and a preparation method thereof. The cough and asthma patch is prepared from active ingredients and a matrix, the active ingredients are prepared from folium eriobotryae, almonds, elaeagnus pungens, actinidia chinensis roots, thyme, polygala japonica, elephantopus scaber, gynura bicolor, veronica didyma, borneol and mentholum, and the matrix is bionic polymeric gel. The preparation method comprises the following steps: S1, preparing the extract; s2, colloid melting: melting the bionic polymer gel; s3, mixing to prepare paste: adding the extract obtained in S1, borneol and mentholum into the molten colloid obtained in S2, and stirring and mixing; and S4, forming. The cough and asthma patch can be used for relieving cough and asthma symptoms caused by asthma and chronic bronchitis, and has the advantages of being rapid in effect taking and lasting in medicine effect; in addition, the preparation method of the cough and asthma patch has the advantages of improving the transfer rate of the active ingredients, the homogeneity of the paste and the low-temperature stability.

Description

Technical Field

[0001] This application relates to the field of traditional Chinese medicine pharmaceutical technology, and more specifically, it relates to a cough and asthma patch and its preparation method. Background Technology

[0002] Traditional Chinese medicine (TCM) pharmaceutical manufacturing is a technical system that uses traditional Chinese medicine theories as guidance and follows the standards and processes of Chinese herbal medicine processing to process medicinal materials into pharmaceutical preparations suitable for clinical use. It encompasses the processing of medicinal materials, preparation formation, and quality control. In the processing stage, methods such as cleaning, cutting, and roasting are used to reduce toxicity, enhance efficacy, moderate medicinal properties, or facilitate preparation. In the preparation stage, based on the desired efficacy and route of administration, the processed medicinal materials are made into various dosage forms such as decoctions, pills, powders, ointments, and injections. Emphasis is placed on the "combination of medicine and excipients," such as using excipients like honey and vinegar to enhance efficacy or improve drug properties. For example, external patches are often used to treat asthma.

[0003] Related asthma topical patches relieve bronchospasm through local administration of a single active ingredient, but cannot simultaneously address complications such as airway mucosal edema, thick sputum, and secondary infections, resulting in poor efficacy and short duration of action. Summary of the Invention

[0004] To address the problem that related asthma topical patches, which relieve bronchospasm through local administration of a single active ingredient, have poor efficacy and short duration of effect, this application provides a cough and asthma patch and its preparation method.

[0005] In the first aspect, this application provides a cough and asthma patch, which adopts the following technical solution:

[0006] A cough and asthma patch is composed of active ingredients and a matrix. The active ingredients are made from raw materials containing the following parts by weight: 10-25 parts loquat leaves, 8-20 parts almonds, 12-30 parts Elaeagnus angustifolia, 5-15 parts kiwifruit root, 3-12 parts thyme, 6-18 parts ginseng, 4-10 parts gentiana, 7-22 parts purple-backed achyranthes bidentata, 5-15 parts veronica var. gracilis, 1-5 parts borneol, and 0.5-3 parts menthol. The matrix is ​​30-60 parts biomimetic polymeric gel.

[0007] By employing the above technical solution, the use of loquat leaves and apricot kernels allows the triterpenoids in loquat leaves to reduce mucosal edema by inhibiting the release of airway inflammatory factors, while amygdalin in apricot kernels relaxes bronchial smooth muscle by regulating cyclic adenosine monophosphate levels. Additionally, Elaeagnus pungens and Actinidia chinensis root are used as adjuvants. The flavonoids in Elaeagnus pungens enhance airway ciliary movement and promote sputum expectoration, while the triterpenoids in Actinidia chinensis root inhibit bronchospasm by blocking histamine H1 receptors. Thyme, Panax notoginseng, and Eleutherococcus senticosus are used as adjuvants. Thyme volatile oil inhibits the proliferation of respiratory pathogens by penetrating bacterial cell membranes, while Panax notoginseng saponins improve ventilation by reducing alveolar surface tension. Finally, Ardisia japonica and Granny Smith are added. The drug contains sodium, and the alkaloids of *Achyranthes bidentata* promote mucus thinning by activating TRPV1 channels, while the iridoids of *Veronica tenuifolia* reduce nerve sensitivity by inhibiting the cough center. Due to the permeation-enhancing effects of borneol and menthol, the borneol structure of borneol enhances drug penetration by altering the lipid arrangement of the stratum corneum, and the menthol in menthol dilates capillaries by stimulating cold receptors in the skin. Finally, under the controlled-release matrix formed by the biomimetic polymeric gel, the three-dimensional network structure of the gel achieves sustained drug release through intermolecular hydrogen bonds. Furthermore, the gel relies on its thermal melting properties to regulate the phase transition temperature to ensure the stability of the active ingredients. Therefore, the drug achieves rapid onset and prolonged duration of action, simultaneously reducing cough frequency, sputum viscosity, and wheezing intensity.

[0008] Preferably, the weight ratio of loquat leaves to Elaeagnus pungens is 1:(1.2-2.4).

[0009] By adopting the above technical solution, loquat leaves and Elaeagnus pungens are added at a weight ratio of 1:(1.2-2.4). The triterpenoids in loquat leaves exert an anti-inflammatory effect by inhibiting the synthesis of leukotrienes, an inflammatory mediator in the airways, while the tannins in Elaeagnus pungens reduce inflammatory exudation by enhancing the bronchial mucosal epithelial barrier function. When the amount of loquat leaves is fixed, an amount of Elaeagnus pungens less than 1.2 times the amount will result in insufficient protective effect of tannins on the mucosa to synergize with the anti-inflammatory effect of triterpenoids. Conversely, an amount of Elaeagnus pungens exceeding 2.4 times the amount will result in insufficient tannin content and a poor synergistic effect with the loquat leaves. The protein components in the extract combine to form precipitates, reducing the dissolution rate of active ingredients during the extraction process. This ratio range maintains the dissolution balance of polar components in the two medicinal materials, avoiding the formation of large molecular complexes during the alcohol extraction process and ensuring that the active ingredients are fully transferred to the extract. At the same time, the tannin-triterpene acid complex formed under this ratio forms a nanoscale molecular sieve structure in the gel matrix through hydrogen bonding, which slows down the drug release rate. Therefore, it achieves the effects of synergistic effect of inflammation control and mucosal repair, improved solid-liquid separation efficiency in the extraction process, and extended sustained-release time of the patch.

[0010] Preferably, the weight ratio of borneol to menthol is (2:1) to (4:1), and the total weight of the two does not exceed 8% of the total weight of the active ingredients.

[0011] By adopting the above technical solution, the weight ratio of borneol to menthol is controlled between 2:1 and 4:1. Borneol, containing dextrorotatory borneol, acts on the intercellular lipids of the stratum corneum, reducing the orderliness of the lipid bilayer to improve drug penetration efficiency. Menthol, containing menthol, instantaneously activates the skin's TRPM8 cold receptors, promoting capillary dilation to accelerate the increase in local drug concentration. Simultaneously, since the total weight of both does not exceed 8% of the total weight of the active ingredients, this upper limit balances the concentration threshold of terpene penetration enhancers with the risk of skin irritation, avoiding excessive menthol leading to intercellular edema and subsequent patch peeling residue. Furthermore, this ratio range allows for the formation of a borneol-menthol co-crystal structure through intermolecular hydrogen bonds during the mixing and ointment preparation process, thereby enhancing the thermal stability of volatile components. Therefore, the effects of increased transdermal absorption rate and reduced incidence of adverse skin contact reactions are achieved.

[0012] Preferably, it also includes a penetration enhancer, which is at least one of azone or ethyl oleate, and the amount added is 0.1% to 2% of the weight of the biomimetic polymer gel.

[0013] By employing the above technical solution, using azone or ethyl oleate as a penetration enhancer and controlling its addition amount to 0.1%–2% of the biomimetic polymer gel weight, azone increases lipid fluidity and reduces drug diffusion resistance by acting on the hydrocarbon chain structure of intercellular lipids in the stratum corneum; while ethyl oleate expands polar channels by inserting into the intercellular lipid bilayer to promote the penetration of aqueous components. This concentration range is controlled by temperature during the colloidal melting process to ensure uniform dispersion of the penetration enhancer in the gel network, avoiding crystallization caused by excessively high local concentrations. Simultaneously, this addition amount ensures that the penetration enhancer molecules form a stable π-π conjugated system with borneol-menthol, enhancing the sustained-release performance of volatile components. Therefore, the effect of increasing the transdermal penetration rate of small molecule active ingredients is achieved.

[0014] Preferably, the biomimetic polymeric gel is made from raw materials comprising the following parts by weight: 40-60 parts of hydroxyl-terminated polydimethylsiloxane, 15-25 parts of MQ resin, 10-20 parts of styrene-butadiene-styrene block copolymer, 5-15 parts of tackifying resin, and 5-15 parts of softening oil.

[0015] By adopting the above technical solution, hydroxyl-terminated polydimethylsiloxane is used as the base polymer. Its terminal active hydroxyl groups form Si-O-Si bridge bonds with the silanol groups of MQ resin through condensation reaction, constructing a three-dimensional cross-linked framework. At the same time, styrene-butadiene-styrene block copolymer strengthens the network toughness through physical entanglement. The phenolic structure of the tackifying resin enhances interfacial adhesion through π-π stacking. The softening oil reduces the glass transition temperature by swelling the styrene hard segments. The raw material ratio range synergistically regulates chemical reactions and physical effects. When the hydroxyl-terminated polydimethylsiloxane is less than 40 parts, the cross-linking density is insufficient, resulting in a decrease in tack. When it exceeds 60 parts, the extensibility of the paste is reduced due to excessive cross-linking. When the MQ resin is less than 15 parts, the bridge bond formation is incomplete. When it exceeds 25 parts, gel embrittlement occurs. Therefore, the patch achieves the effects of improved tack, no breakage in low-temperature environments, and no residue after skin peeling.

[0016] Secondly, this application provides a method for preparing a cough and asthma patch, which adopts the following technical solution:

[0017] A method for preparing a cough and asthma patch includes the following steps:

[0018] S1. Preparation of extract: Loquat leaf, apricot kernel, Elaeagnus pungens, kiwi root, thyme, ginseng, gentian, purple-backed aralia, and Veronica scabra are mixed and first subjected to two alcohol extractions, followed by one water extraction; then the alcohol extract and water extract are combined and the mixture is concentrated into an extract with a relative density of 1.15 to 1.25.

[0019] S2, Colloidal Melting: The biomimetic polymeric gel is heated at 110-130℃ until it is completely melted;

[0020] S3. Mixing and preparing the paste: Add the extract obtained in S1, borneol and menthol to the molten colloid obtained in S2, and stir and mix at 70-85°C for 20-40 minutes.

[0021] S4. Molding: First, the mixed paste obtained in S3 is applied to the substrate, then covered with release film or release paper, and then sliced ​​and packaged to obtain the finished product.

[0022] By employing the above technical solution, which combines two-stage gradient ethanol extraction with one-stage water extraction, the first ethanol extraction uses 65%–70% ethanol to disrupt the lipid layer structure of plant cell walls and promote the dissolution of triterpenoids. The second ethanol extraction uses 50%–55% ethanol to regulate the polar environment and enhance the solubility of flavonoid glycosides. The subsequent water extraction drives the release of water-soluble polysaccharides and alkaloids through osmotic pressure difference. This avoids protein denaturation and coagulation caused by high concentrations of ethanol, which would encapsulate active ingredients, and also prevents excessive hydrolysis of tannins in the acidic water extraction environment. In the concentration process, the mixed extract is controlled at 60°C with a relative density of 1.15–1.25. This density range ensures that small molecule volatile components are not destroyed by high temperatures, while maintaining sufficient viscosity to prevent subsequent melting and gelation. Phase separation occurs during mixing; simultaneously, during the colloidal melting stage, the biomimetic polymer gel is heated to 110–130°C, allowing the sodium polyacrylate molecular chains to fully extend and form a continuous network framework. Meanwhile, aluminum ions from the ionization of aluminum hydroxyaluminate are thermodynamically driven and uniformly distributed at the cross-linking sites between polymer chains. In the ointment-making process, the extract and penetration-enhancing components are added at 70–85°C. This temperature window maintains the plasticizing effect of glycerol to prevent the crystallization of borneol, while also ensuring that menthol molecules are embedded into the gaps in the gel network through diffusion. Finally, during coating, the ointment temperature is controlled within the range of 45–50°C, utilizing the temperature gradient to induce the ordered arrangement of polymer chains to form a stable three-dimensional structure. Therefore, the effects of increased active ingredient transfer rate, reduced ointment phase separation rate, and improved sustained-release rate of effective ingredients are achieved.

[0023] Preferably, the alcohol extraction uses 50% to 70% ethanol, the solid-liquid ratio is 1:8 to 1:12 for each extraction, the extraction temperature is 60 to 80°C, and each extraction lasts for 1 to 2 hours.

[0024] By employing the above technical solution, the use of 50%–70% ethanol for extraction allows for the adjustment of solvent polarity to balance the solubility of terpenes, flavonoids, and alkaloids. 50% ethanol preferentially dissociates small molecule flavonoid glycosides by weakening hydrogen bonding, while 70% ethanol enhances hydrophobicity to promote the release of triterpene acids. Simultaneously, the solid-liquid ratio is controlled within the range of 1:8–1:12, ensuring the solvent fully penetrates the intercellular spaces of the medicinal material to create an osmotic pressure difference. A solid-liquid ratio below 1:8 prevents complete penetration of the dense tissue structure of the medicinal material, leading to a decrease in dissolution rate; a ratio above 1:12 results in excessive dilution of the extract, increasing energy consumption in subsequent concentration processes. Maintaining the extraction temperature at 60–80°C accelerates the transmembrane diffusion of active ingredients. Controlling the extraction time to 1–2 hours ensures a dynamic equilibrium in mass transfer; extractions shorter than 1 hour cannot fully release intracellular solutes, while extractions exceeding 2 hours cause hydrolysis of some glycosides due to prolonged heat exposure. Therefore, the effect of improved active ingredient transfer rate is achieved.

[0025] Preferably, the water extraction solid-liquid ratio is 1:10 to 1:15, the water extraction temperature is 90 to 100°C, and the water extraction time is controlled at 1.5 to 3 hours.

[0026] By adopting the above technical solution, the solid-liquid ratio of water extraction is controlled at 1:10 to 1:15. This ratio balances the solvent osmotic pressure and the mass transfer efficiency of the active ingredients, allowing hydrogen bonds to break and the cellulose structure of plant cell walls to disintegrate in hot water at 90-100℃, thus promoting the dissolution of water-soluble polysaccharides and alkaloid salts. At the same time, maintaining the extraction temperature at 90-100℃ utilizes the thermal kinetic energy of water molecules to enhance the solubility of polar substances, while controlling the water extraction time at 1.5-3 hours to complete the phase transfer process of macromolecular polysaccharides from the cytoplasm to the solvent. Therefore, the effect of highly efficient dissolution of medicinal substances is achieved.

[0027] Preferably, the stirring speed is controlled at 200-400 rpm during mixing, and the extract is added in two parts: first, 70% of the total extract is added and mixed for 10 minutes, then the remaining extract, borneol, and menthol are added.

[0028] By adopting the above technical solution, the stirring speed is controlled at 200-400 rpm, which creates a uniform shear force field through the critical state of laminar and turbulent flow. Simultaneously, the extract is added in two stages. The first addition allows the high-viscosity extract to be fully dispersed in the hot-melt gel, forming a continuous phase carrier network. The mixing time is controlled at 10 minutes to ensure that the sodium polyacrylate molecular chains establish hydrogen bonds with the extract polysaccharides. Subsequently, the remaining extract, borneol, and menthol are added. The concentration gradient difference formed by the two additions drives the diffusion of terpene molecules into the gaps in the gel network. The later addition of borneol and menthol avoids loss due to prolonged heating and volatilization. Furthermore, the control of the stirring speed combined with the stepwise addition sequence suppresses local crystallization caused by abrupt changes in melting temperature of borneol. Therefore, the effects of homogenization of the extract and enhanced drug stability are achieved.

[0029] Preferably, the coating thickness is 0.8 to 1.5 mm, the substrate is non-woven fabric or polyethylene film, and after coating, it is cured by cold air at 10 to 15°C for 5 to 10 minutes.

[0030] By adopting the above technical solution, the coating thickness is controlled between 0.8 and 1.5 mm. A thickness of 0.8 mm ensures that the drug concentration per unit area reaches the minimum effective concentration threshold, while the upper limit of 1.5 mm avoids edge curling of the patch due to stress concentration. This thickness range balances the effective drug diffusion area and skin adhesion. Regarding the substrate selection, non-woven fabric promotes uniform distribution of the ointment through fiber capillary action, while polyethylene film reduces drug migration and adsorption due to its low-energy surface properties. Applying cold air at 10–15°C for 5–10 minutes after coating, a temperature window slightly higher than the crystallization point of the glycerol-water system, accelerates the decay of polymer chain kinetic energy. Curing time less than 5 minutes results in unbalanced molecular chain orientation, while curing time exceeding 10 minutes leads to surface cracking due to excessive dehydration. Maintaining an air velocity of 2–5 m / s creates a laminar flow field, preventing turbulent disturbances from disrupting the self-balance of the ointment's surface tension. Therefore, the application reliability, drug utilization rate, and environmental adaptability of the cough and asthma patch are improved.

[0031] In summary, this application has the following beneficial effects:

[0032] 1. Because this application uses a specific ratio of active ingredients such as loquat leaf, almond, and oleaster fruit, the triterpenoid acid components of loquat leaf, in conjunction with amygdalin of almond, reduce mucosal edema and relax bronchial smooth muscle by inhibiting the release of airway inflammatory factors and regulating cyclic adenosine monophosphate levels, respectively. At the same time, oleaster fruit and kiwi root promote sputum expectoration and inhibit bronchospasm by enhancing ciliary movement and blocking histamine receptors. Thyme and guaiac seeds are added to inhibit the proliferation of pathogenic bacteria and improve alveolar ventilation. Finally, under the permeation-enhancing effect of borneol and menthol, the drug is released sustainably through the biomimetic polymeric gel matrix, thereby achieving the effect of simultaneously reducing cough frequency, sputum viscosity and wheezing intensity, and prolonging the duration of drug efficacy.

[0033] 2. In this application, loquat leaves and oleaster seeds are preferably combined in a weight ratio of 1:1.2 to 2.4. This ratio balances the anti-inflammatory effect of triterpenic acids and the mucosal protective function of tannins, avoiding insufficient mucosal repair due to a low ratio or precipitation caused by a high ratio. At the same time, this ratio maintains the dissolution balance of polar components during alcohol extraction, ensuring efficient transfer of active ingredients and forming a nanoscale molecular sieve structure in the gel matrix, thereby enhancing anti-inflammatory and mucosal repair capabilities, improving extraction efficiency, and prolonging the sustained-release time of the patch.

[0034] 3. The preparation method of this application adopts a process of two gradient alcohol extractions combined with one water extraction. The first alcohol extraction breaks down the lipid layer of the cell wall to promote the dissolution of lipid-soluble components. The second alcohol extraction optimizes the polar environment to dissolve flavonoid glycosides. The water extraction drives the release of water-soluble polysaccharides and alkaloids, avoiding component loss caused by a single solvent. At the same time, the extract is added in two gradients during the mixing and ointment stage. The first addition establishes a continuous phase carrier network, and the second addition drives the diffusion of terpene molecules. The low temperature cold air solidification is controlled to regulate the polymer chain arrangement, thereby achieving the effects of improving the transfer rate of active ingredients, the homogeneity of the ointment and the sustained-release stability of the drug. Attached Figure Description

[0035] Figure 1 This is a flowchart illustrating a method for preparing a cough and asthma patch as proposed in this application. Detailed Implementation

[0036] The present application will be further described in detail below with reference to the accompanying drawings and embodiments.

[0037] Related asthma topical patches relieve bronchospasm through local administration of a single active ingredient, but cannot simultaneously address complications such as airway mucosal edema, thick sputum, and secondary infections, thus requiring patients to use multiple medications in combination. At the same time, due to insufficient matrix controlled-release capacity and defects in permeation technology, the duration of efficacy of traditional patches is generally less than 4 hours, forcing patients to frequently change patches and causing the risk of skin irritation.

[0038] This application discloses a cough and asthma patch and its preparation method. The cough and asthma patch is composed of active ingredients and a matrix. The active ingredients are made from the following raw materials: loquat leaf, almond, oleaster fruit, kiwi root, thyme, purslane, gentian root, purple-backed achyranthes, fine-leaved speedwell, borneol, and menthol. The matrix is ​​a biomimetic polymeric gel. The preparation method is as follows: S1, extract preparation; S2, colloid melting: melting the biomimetic polymeric gel; S3, mixing and ointment preparation: adding the extract obtained in S1, borneol, and menthol to the molten colloid obtained in S2 and stirring and mixing; S4, molding.

[0039] This application employs a specific ratio of active ingredients such as loquat leaf, almond, and oleaster fruit. The triterpenoid acid components of loquat leaf, in conjunction with amygdalin of almond, reduce mucosal edema and relax bronchial smooth muscle by inhibiting the release of airway inflammatory factors and regulating cyclic adenosine monophosphate levels. Meanwhile, oleaster fruit and kiwi root promote sputum expectoration and inhibit bronchospasm by enhancing ciliary movement and blocking histamine receptors. Thyme and guaiac seeds are added to inhibit the proliferation of pathogenic bacteria and improve alveolar ventilation. Finally, with the permeation-enhancing effects of borneol and menthol, the drug is released sustainably through a biomimetic polymeric gel matrix, thereby simultaneously reducing cough frequency, sputum viscosity, and wheezing intensity, and prolonging the duration of the drug's effect.

[0040] Loquat leaf, apricot kernel, oleaster fruit, kiwi root, thyme, cinnamon bark, gentian root, purple-backed achyranthes root, and fine-leaved speedwell: purchased from China National Pharmaceutical Group Co., Ltd., and conforming to the standards of Part I of the 2020 edition of the Chinese Pharmacopoeia;

[0041] Borneol: Purchased from Shanghai Maclean Biochemical Technology Co., Ltd., brand name B817812;

[0042] Peppermint ice: Purchased from Shanghai Maclean Biochemical Technology Co., Ltd., brand name M813109;

[0043] Azone: Purchased from Nanjing Shuguang Chemical Group Co., Ltd., brand name AZONE-HP;

[0044] Ethyl oleate: purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., grade O806022;

[0045] Ethanol: Purchased from Sinopharm Chemical Reagent Co., Ltd., grade 64-17-5;

[0046] Hydroxyl-terminated polydimethylsiloxane: purchased from Dow Corning, Inc., brand name Sylgard 184;

[0047] MQ resin: purchased from Wacker Chemie, brand name ResinMK;

[0048] Styrene-butadiene-styrene block copolymer: purchased from Kronen Polymers, grade G1650;

[0049] Tackifying resin: Purchased from Eastman Chemical Company, brand name Regalite TM R1100;

[0050] Softening oil: purchased from Shell, brand name Shellflex 371;

[0051] Non-woven fabric: purchased from Zhejiang Jin Sanfa Sanitary Materials Technology Co., Ltd., brand name JSW-30;

[0052] Polyethylene film: purchased from Shandong Taipeng Environmental Protection Materials Co., Ltd., grade TP-PE08;

[0053] Release film / release paper: purchased from Jiangsu Shuangxing Color Plastic New Material Co., Ltd., grade SS-2.0.

[0054] Example 1

[0055] This embodiment provides a cough and asthma patch, which is composed of active ingredients and a matrix. The active ingredients are made from the following raw materials in parts by weight: 10 parts loquat leaf, 8 parts almond, 12 parts Elaeagnus pungens, 5 parts kiwi root, 3 parts thyme, 6 parts purslane, 4 parts gentian, 7 parts purple-backed achyranthes, 5 parts veronica, 1 part borneol, and 0.5 parts menthol. The matrix is ​​30 parts biomimetic polymeric gel. The weight ratio of loquat leaf to Elaeagnus pungens is 1:0.8; the weight ratio of borneol to menthol is 2:1, and the total weight of the two accounts for 3% of the total weight of the active ingredients. It also contains azone as a penetration enhancer, which is added at 0.1% of the weight of the biomimetic polymeric gel. The biomimetic polymeric gel is made from the following raw materials in parts by weight: 40 parts hydroxyl-terminated polydimethylsiloxane, 20 parts MQ resin, 20 parts styrene-butadiene-styrene block copolymer, 10 parts tackifying resin, and 10 parts softening oil.

[0056] The preparation method of the above cough and asthma patch is as follows:

[0057] S1. Extract Preparation: Loquat leaves, apricot kernels, Elaeagnus pungens, kiwi root, thyme, Panax notoginseng, Elaeagnus pungens, Ardisia crenata, and Veronica persica were mixed and subjected to two alcohol extractions: the first extraction used 50% ethanol with the following parameters: solid-liquid ratio 1:8, temperature 60℃, time 1 hour; the second extraction used 50% ethanol with the following parameters: solid-liquid ratio 1:8, temperature 60℃, time 1 hour; followed by a water extraction with the following parameters: solid-liquid ratio 1:10, temperature 90℃, time 1.5 hours; the alcohol and water extracts were then combined and the mixture was concentrated to an extract with a relative density of 1.15.

[0058] S2, Colloidal Melting: The biomimetic polymeric gel is heated at 110℃ until it is completely melted;

[0059] S3. Mixing and preparing the paste: Add the molten colloid obtained in S2 to the paste obtained in S1 in two batches: First, add 70% of the total paste and mix for 10 minutes while controlling the stirring speed at 200 rpm; then add the remaining paste, borneol, and menthol ice, and mix at 70°C for 20 minutes.

[0060] S4. Molding: First, the mixed paste obtained in S3 is coated on non-woven fabric with a thickness of 0.8mm. Then, a release film is covered and cured in cold air at 10℃ for 5 minutes. After curing, the product is sliced ​​and packaged to obtain the finished product.

[0061] Example 2

[0062] This embodiment provides a cough and asthma patch, which is composed of active ingredients and a matrix. The active ingredients are made from the following raw materials in parts by weight: 10 parts loquat leaf, 14 parts almond, 24 parts oleaster, 10 parts kiwi root, 7.5 parts thyme, 12 parts purslane, 7 parts gentian, 14.5 parts purple-backed achyranthes, 10 parts veronica, 3 parts borneol, and 1 part menthol. The matrix is ​​45 parts biomimetic polymeric gel. The weight ratio of borneol to menthol is 3:1, and their total weight accounts for 5.5% of the total weight of the active ingredients. It also contains ethyl oleate as a penetration enhancer, which is added at 1% of the weight of the biomimetic polymeric gel. The biomimetic polymeric gel is made from the following raw materials in parts by weight: 50 parts hydroxyl-terminated polydimethylsiloxane, 15 parts MQ resin, 15 parts styrene-butadiene-styrene block copolymer, 12 parts tackifying resin, and 8 parts softening oil.

[0063] The preparation method of the above cough and asthma patch is as follows:

[0064] S1. Extract Preparation: Loquat leaves, apricot kernels, Elaeagnus pungens, kiwi root, thyme, Panax notoginseng, Elaeagnus pungens, Ardisia crenata, and Veronica persica were mixed and subjected to two alcohol extractions: the first extraction used 60% ethanol with the following parameters: solid-liquid ratio 1:10, temperature 70℃, and time 1.5 hours; the second extraction used 60% ethanol with the same parameters: solid-liquid ratio 1:10, temperature 70℃, and time 1.5 hours. A third water extraction was then performed with the following parameters: solid-liquid ratio 1:12.5, temperature 95℃, and time 2.25 hours. The alcohol and water extracts were then combined and the mixture was concentrated to a paste with a relative density of 1.20.

[0065] S2, Colloidal Melting: The biomimetic polymeric gel is heated at 120°C until it is completely melted;

[0066] S3. Mixing and preparing the paste: Add the molten colloid obtained in S2 to the paste obtained in S1 in two batches: First, add 70% of the total paste and mix for 10 minutes while controlling the stirring speed at 300 rpm; then add the remaining paste, borneol, and menthol, and mix at 77.5℃ for 30 minutes.

[0067] S4. Molding: First, the mixed paste obtained in S3 is coated on a polyethylene film with a thickness of 1.15mm, then covered with release paper, and cured in cold air at 12.5℃ for 7.5 minutes. After curing, it is sliced ​​and packaged to obtain the finished product.

[0068] Example 3

[0069] This embodiment provides a cough and asthma patch, which is composed of active ingredients and a matrix. The active ingredients are made from the following raw materials in parts by weight: 25 parts loquat leaf, 20 parts almond, 30 parts oleaster, 15 parts kiwi root, 12 parts thyme, 18 parts purslane, 10 parts gentian, 22 parts purple-backed achyranthes, 15 parts veronica, 5 parts borneol, and 3 parts menthol. The matrix is ​​60 parts biomimetic polymeric gel. The weight ratio of borneol to menthol is 4:1, and their total weight accounts for 8% of the total weight of the active ingredients. It also contains azone and ethyl oleate as penetration enhancers, which are added at 2% of the weight of the biomimetic polymeric gel. The biomimetic polymeric gel is made from the following raw materials in parts by weight: 60 parts hydroxyl-terminated polydimethylsiloxane, 25 parts MQ resin, 10 parts styrene-butadiene-styrene block copolymer, 5 parts tackifying resin, and 15 parts softening oil.

[0070] The preparation method of the above cough and asthma patch is as follows:

[0071] S1. Extract Preparation: Loquat leaves, apricot kernels, Elaeagnus pungens, kiwi root, thyme, Panax notoginseng, Elaeagnus pungens, Ardisia crenata, and Veronica persica were mixed and subjected to two alcohol extractions: the first extraction used 70% ethanol with the following parameters: solid-liquid ratio 1:12, temperature 80℃, time 2 hours; the second extraction used 70% ethanol with the following parameters: solid-liquid ratio 1:12, temperature 80℃, time 2 hours; a third extraction was performed with water, with the following parameters: solid-liquid ratio 1:15, temperature 100℃, time 3 hours; the alcohol and water extracts were then combined and the mixture was concentrated to an extract with a relative density of 1.25.

[0072] S2, Colloidal Melting: The biomimetic polymeric gel is heated at 130℃ until it is completely melted;

[0073] S3. Mixing and preparing the paste: Add the molten colloid obtained in S2 to the paste obtained in S1 in two batches: First, add 70% of the total paste and mix for 10 minutes while controlling the stirring speed at 400 rpm; then add the remaining paste, borneol, and menthol ice, and mix at 85°C for 40 minutes.

[0074] S4. Molding: First, the mixed paste obtained in S3 is coated on a polyethylene film with a thickness of 1.5mm. Then, a release film is covered and cured in cold air at 15℃ for 10 minutes. After curing, the product is sliced ​​and packaged to obtain the finished product.

[0075] Comparative Example 1

[0076] The comparative example is the same as in Example 1, except that the amount of Elaeagnus angustifolia is adjusted to 8 parts, and the rest is the same as in Example 1.

[0077] Comparative Example 2

[0078] The comparative example is the same as in Example 1, except that the amount of borneol is adjusted to 1 part and the amount of menthol ice is adjusted to 2 parts, and the rest is the same as in Example 1.

[0079] Comparative Example 3

[0080] The comparative example is the same as in Example 1, except that the proportions of the biomimetic polymer gel are adjusted to: 30 parts of hydroxyl-terminated polydimethylsiloxane, 30 parts of MQ resin, 25 parts of styrene-butadiene-styrene block copolymer, 5 parts of tackifying resin and 10 parts of softening oil; the rest are the same as in Example 1.

[0081] Comparative Example 4

[0082] This comparative example is based on Example 1, except that the alcohol extraction step uses 40% ethanol for extraction, while the rest is the same as in Example 1.

[0083] Comparative Example 5

[0084] The comparative example is the same as Example 1, except that the temperature of the water extraction step is adjusted to 85°C, and the rest is the same as Example 1.

[0085] Comparative Example 6

[0086] The comparative example is the same as in Example 1, except that the stirring speed in the mixing and paste-making step is adjusted to 100 rpm, and the rest is the same as in Example 1.

[0087] Performance testing

[0088] Sample preparation: Cough and asthma patch samples were prepared according to the formulation and process described in Examples 1-3 and Comparative Examples 1-6. Three batches were prepared for each group, with 10 patches in each batch. The average value was taken for subsequent testing. The ointment sampling was divided into ointment sampling and finished product sampling. For ointment sampling, 50g of ointment was evenly scraped from the downstream of the coating roller before curing after coating and packaged into light-proof sealed containers. For finished product sampling, 5 patches were randomly selected after packaging, and the ointment layer was taken after peeling off the release film.

[0089] 24-hour transdermal cumulative dose detection: First, fresh pig ear skin with a thickness of 0.8±0.1 mm was used as an ex vivo skin model. After hair removal and dissection of subcutaneous adipose tissue, it was rinsed with PBS buffer and frozen at -80℃; it was then thawed to 32℃ before use; subsequently, a Franz diffusion cell was installed, and a pH 7.4 phosphate buffer containing 0.01% sodium azide was injected into the receiving cell. The magnetic stirring speed was controlled at 300 rpm, and the temperature was kept constant at 32±0.5℃ in a water bath; the cough and asthma patch was then injected at 10 mg / cm³. 2 The administered dose was evenly applied to the surface of the stratum corneum of the skin and fixed in a diffusion cell. 0.5 mL of the receiving solution was collected at time points of 1, 2, 4, 8, 12, and 24 hours. An equal volume of fresh buffer was added after each sampling, and the peak area of ​​borneol in the receiving solution was determined by HPLC.

[0090] Crystallization rate detection of the ointment: First, the cough and asthma patch was evenly coated on the surface of a 10×10mm silicon wafer and cured at 10℃ for 10 minutes; then, a 10nm gold layer was sprayed onto the sample surface using a vacuum gold plating instrument; then, five fields of view were randomly scanned using a scanning electron microscope at an accelerating voltage of 5kV; finally, the percentage of borneol crystal area to the total field of view was calculated using image analysis software with a grayscale threshold range of 150-255.

[0091] FEV1 improvement rate test: Moderate asthma patients were selected as subjects and randomly divided into groups of 30. Subjects discontinued bronchodilators for 24 hours and applied cough and wheezing patches to the Tanzhong acupoint. FEV1 values ​​were measured 30 minutes later. The bronchodilator effect was calculated according to the formula "improvement rate = (FEV1 after application - baseline FEV1) / baseline FEV1 × 100%".

[0092] Clinical onset time detection: Subjects wore a respiratory plethysmography device to monitor cough frequency in real time; when the cough frequency decreased by 50% or more within 5 consecutive minutes, it was determined as the onset time point; independent observers used a double-blind method to time and record this time point.

[0093] The performance test results of Examples 1-3 and Comparative Examples 1-6 are shown in Table 1.

[0094] Table 1:

[0095]

[0096]

[0097] Example Conclusion:

[0098] Based on Examples 1-3 and Comparative Example 1, and in conjunction with Table 1, it can be seen that when the dosage of Elaeagnus pungens is maintained within a limited range, the synergistic effect of anti-inflammatory and mucosal repair is enhanced, enabling the cough and asthma patch to stably form a tannin-triterpene acid complex, thereby ensuring the continuous release of its bronchodilatory efficacy.

[0099] Combining Examples 1-3 and Comparative Example 2 with Table 1, it can be seen that: borneol and menthol, under a limited ratio, construct a borneol-menthol eutectic structure, optimize the thermal stability of terpene components, and maximize the transdermal penetration-enhancing function.

[0100] Combining Examples 1-3 and Comparative Example 3 with Table 1, it can be seen that: the gel ratio regulates the crosslinking density of hydroxysiloxane and MQ resin, while balancing the toughening and tackifying effects of the styrene-butadiene-styrene block copolymer and the adhesive properties of the resin. When the hydroxysiloxane content is low, the crosslinking network is loose, weakening the penetration-promoting function, while when the MQ resin content is high, excessive crosslinking leads to brittleness of the ointment. At the same time, excessive styrene-butadiene-styrene block copolymer content reduces skin adhesion due to excessive toughening. This ratio range achieves a balance between transdermal channel stability and ointment flexibility, thereby ensuring drug sustained-release performance and clinical response efficiency.

[0101] Based on Examples 1-3 and Comparative Example 4, and in conjunction with Table 1, it can be seen that using 50% ethanol can disrupt the lignin barrier of the medicinal material's cell wall and selectively dissociate flavonoid glycoside bonds, thereby fully releasing the anti-inflammatory active ingredients.

[0102] Combining Examples 1-3 and Comparative Example 5 with Table 1, it can be seen that by using a water extraction temperature of 90°C to provide energy to break down the cellulose crystal zone, the alkaloid-organic acid ionic bonds are broken efficiently, ensuring that the bronchodilator substances are fully dissolved.

[0103] Combining Examples 1-3 and Comparative Example 6 with Table 1, it can be seen that by using a critical shear force of 200 rpm to establish a laminar-turbulent dynamic equilibrium, a uniform concentration gradient field is formed, thereby achieving the ideal diffusion distribution of terpene molecules in the gel network.

[0104] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A cough and asthma patch, characterized in that, It consists of active ingredients and a matrix, wherein the active ingredients are made from the following raw materials in parts by weight: 10-25 parts loquat leaves, 8-20 parts almonds, 12-30 parts Elaeagnus angustifolia, 5-15 parts kiwifruit root, 3-12 parts thyme, 6-18 parts ginseng, 4-10 parts gentiana, 7-22 parts purple-backed achyranthes bidentata, 5-15 parts veronica var. gracilis, 1-5 parts borneol, and 0.5-3 parts menthol, while the matrix is ​​100 parts biomimetic polymeric gel.

2. The cough and asthma patch according to claim 1, characterized in that, The weight ratio of loquat leaves to Elaeagnus pungens is 1:(1.2-2.4).

3. The cough and asthma patch according to claim 1, characterized in that, The weight ratio of borneol to menthol is (2:1) to (4:1), and the total weight of the two does not exceed 8% of the total weight of the active ingredients.

4. A cough and asthma patch according to claim 1, characterized in that, It also contains a penetration enhancer, which is at least one of azone or ethyl oleate, and the amount added is 0.1% to 2% of the weight of the biomimetic polymer gel.

5. A cough and asthma patch according to claim 1, characterized in that, The biomimetic polymer gel is made from the following raw materials in parts by weight: 40-60 parts of hydroxyl-terminated polydimethylsiloxane, 15-25 parts of MQ resin, 10-20 parts of styrene-butadiene-styrene block copolymer, 5-15 parts of tackifying resin, and 5-15 parts of softening oil.

6. A method for preparing a cough and asthma patch, characterized in that, A cough and asthma patch according to any one of claims 1-5 includes the following steps: S1. Preparation of extract: Loquat leaf, apricot kernel, Elaeagnus pungens, kiwi root, thyme, ginseng, gentian, purple-backed aralia, and Veronica scabra are mixed and first subjected to two alcohol extractions, followed by one water extraction; then the alcohol extract and water extract are combined and the mixture is concentrated into an extract with a relative density of 1.15 to 1.

25. S2, Colloidal Melting: The biomimetic polymeric gel is heated at 110-130℃ until it is completely melted; S3. Mixing and preparing the paste: Add the extract obtained in S1, borneol and menthol to the molten colloid obtained in S2, and stir and mix at 70-85°C for 20-40 minutes. S4. Molding: First, the mixed paste obtained in S3 is applied to the substrate, then covered with release film or release paper, and then sliced ​​and packaged to obtain the finished product.

7. The method for preparing a cough and asthma patch according to claim 6, characterized in that, In step S1, the alcohol extraction uses 50% to 70% ethanol, the solid-liquid ratio is 1:8 to 1:12 for each extraction, the extraction temperature is 60 to 80°C, and each extraction lasts for 1 to 2 hours.

8. The method for preparing a cough and asthma patch according to claim 6, characterized in that, In step S1, the water extraction solid-liquid ratio is 1:10 to 1:15, the water extraction temperature is 90 to 100℃, and the water extraction time is controlled between 1.5 and 3 hours.

9. The method for preparing a cough and asthma patch according to claim 6, characterized in that, In step S3, the stirring speed is controlled at 200-400 rpm during mixing, and the extract is added in two parts: first, add 70% of the total extract and mix for 10 minutes, then add the remaining extract, borneol, and menthol.

10. The method for preparing a cough and asthma patch according to claim 6, characterized in that, In step S4, the coating thickness is 0.8–1.5 mm, the substrate is non-woven fabric or polyethylene film, and after coating, it is cured with cold air at 10–15°C for 5–10 minutes.

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