Stepwise release-controlled transdermal patch containing aromatherapy components and manufacturing method thereof

Abstract

The present invention relates to a fused transdermal drug delivery patch and a method for manufacturing the same, wherein different aromatherapy components are disposed on a first adhesive layer comprising a silicone-based pressure-sensitive adhesive and a second adhesive layer comprising an acrylic-based pressure-sensitive adhesive, respectively, thereby simultaneously providing stepwise drug release and differentiated aromatherapy effects over time. Specifically, the patch of the present invention is manufactured by forming a first adhesive layer composed of hyaluronic acid and a first aromatherapy component added to a silicone-based pressure-sensitive adhesive on a support made of a surface-treated polyethylene terephthalate film, forming a second adhesive layer composed of an acrylic-based pressure-sensitive adhesive with oleic acid and a second aromatherapy component added thereto and containing a drug, and then sequentially laminating a permeability control layer containing an ethylene vinyl acetate copolymer and a silicone-coated release layer. The manufacturing method comprises the steps of preparing a support through plasma surface treatment, forming a first adhesive layer using a biocompatible silicone composition containing a first aromatherapy component, forming a second adhesive layer using a permeability-promoting acrylic composition containing a second aromatherapy component, preparing and incorporating a solid dispersion of a drug, forming a permeability-controlling layer, and attaching a release layer. An aroma component having an immediate soothing effect, such as lavender, eucalyptus, and peppermint oil, is placed in the first adhesive layer, and an aroma component having a sustained stabilizing effect, such as rosemary, bergamot, and ylang-ylang oil, is placed in the second adhesive layer. The patch according to the present invention suppresses rapid initial release through primary drug release from the first adhesive layer and initial release of the first aromatherapy component, and secondary drug release from the second adhesive layer and continuous release of the second aromatherapy component, thereby enabling continuous drug delivery for more than 24 hours while simultaneously realizing differentiated psychological stabilization effects over time. It is applicable to various drugs such as nicotine, diclofenac, and estradiol, and creates synergy between pharmacological therapeutic effects and psychological stabilization effects through aromatherapy combinations customized to the therapeutic characteristics of each drug. In particular, it provides an innovative transdermal delivery system that simultaneously achieves maximized therapeutic efficacy and enhanced patient satisfaction by implementing a convergent medical approach for the holistic treatment of patients, going beyond the simple pharmacological approach of existing drug delivery patches. High commercial feasibility is guaranteed as all components are commercially available and the manufacturing process utilizes existing facilities; furthermore, as a safe and eco-friendly treatment utilizing natural aromatherapy ingredients, it offers technological value that aligns with future medical trends.

Description

Technology Field

[0001] The following examples relate to a step-release controlled transdermal patch containing an aromatherapy ingredient and a method for manufacturing the same. Background Technology

[0002] Transdermal Drug Delivery Systems (TDDS) are a method of delivering drugs into the body through the skin. Because they avoid gastrointestinal side effects associated with oral administration and bypass the first-pass effect in the liver, they are utilized in various fields, such as nicotine patches, hormone replacement therapy patches, and analgesic patches. These transdermal patches generally consist of a support layer, a drug-containing layer, an adhesive layer, a permeability control layer, and a release layer, with the characteristics of the adhesive layer acting as a key factor in determining the drug release rate and skin adhesion.

[0003] Conventional transdermal drug delivery patches primarily utilized a single adhesive layer for drug delivery. While silicone-based pressure-sensitive adhesives offer the advantages of excellent biocompatibility and low skin irritation, their low solubility for most drugs limits the drug loading capacity, making it difficult to secure sufficient drug release. Conversely, acrylic-based pressure-sensitive adhesives exhibit high solubility for various drugs and provide excellent adhesion, but they suffer from the disadvantage of rapid initial drug release, making long-term stable drug delivery difficult.

[0004] Meanwhile, aromatherapy is recognized as a field of complementary and alternative medicine that promotes physical and mental health by utilizing the aromatic components of essential oils extracted from natural plants. The anxiety-relieving effects of lavender oil, the respiratory improvement effects of eucalyptus oil, and the concentration-enhancing effects of peppermint oil have been proven through numerous clinical studies, and it is widely used, in particular, as an adjunctive treatment for stress-related disorders. However, conventional aromatherapy has limitations as it relies on simple inhalation methods via diffusers or massage, resulting in a lack of sustainability and consistency, as well as difficulties in personalized application.

[0005] U.S. Patents No. 5,474,783 and No. 6,024,976 proposed a method of simply physically mixing silicone adhesive and acrylic adhesive, but this method had the problem of being difficult to obtain a consistent drug release profile due to phase separation of the two adhesives and difficult to predict adhesive strength according to the mixing ratio. In addition, Korean Published Patent No. 2012-0026507 proposed an adhesive using a silicone-acrylic copolymer, but it had limitations such as a complex synthesis process, high cost, and still difficulty in achieving continuous drug release for more than 24 hours.

[0006] Regarding prior art applying aromatherapy ingredients to medical patches, European patent EP2468308A1 disclosed an analgesic patch containing lavender extract, but it was limited to simply mixing aroma ingredients into a drug layer and lacked a systematic approach to release control or synergistic effects. Japanese published patent JP2019-150023A proposed a transdermal patch containing menthol, but it was difficult to achieve various therapeutic effects using only a single aroma ingredient, and there was a problem in that independent control of drug delivery and aromatherapy effects was impossible.

[0007] In particular, existing technologies lacked a technical solution capable of independently controlling the release timing and duration of each, while simultaneously providing the therapeutic effects of medication and the psychological stabilizing effects of aromatherapy. Although alleviating stress caused by withdrawal symptoms for nicotine patches, relieving anxiety due to pain for painkiller patches, and improving emotional instability caused by hormonal imbalances for hormone patches are crucial factors for enhancing therapeutic efficacy, there was a complete absence of technology to systematically implement these capabilities. Prior art literature

[0008] Korean Registered Patent 10-2390735 Korean Published Patent 10-2009-0049883 Korean Published Patent 10-2022-0037994 Korean Registered Patent 10-1609104 The problem to be solved

[0009] The first problem that the present invention aims to solve is to provide a fused transdermal patch that suppresses the rapid initial release of drugs occurring in conventional single adhesive layer structures, while simultaneously realizing continuous drug delivery for more than 24 hours and psychological stability effects through the time-differential release of aromatherapy components.

[0010] The second task is to maximize the synergy between the drug treatment effect and the aromatherapy effect by utilizing the excellent biocompatibility of silicone-based adhesives and the high drug dissolving ability of acrylic-based adhesives, while implementing functional differentiation by layer by placing different aromatherapy components in each layer.

[0011] The third task is to establish a multi-layer release mechanism capable of controlling, in stages, the initial immediate psychological stabilization effect through the first aromatherapy component of the first adhesive layer and the sustained stress relief effect through the second aromatherapy component of the second adhesive layer.

[0012] The fourth task is to provide aromatherapy combinations tailored to the specific characteristics of each drug, such as a sedative effect for relieving withdrawal symptoms in nicotine cessation patches, a relaxation effect for relieving pain stress in diclofenac pain patches, and a balancing effect for emotional stability in estradiol hormone patches.

[0013] The fifth task is to provide an economical and practical manufacturing method that is commercially feasible by utilizing existing patch manufacturing facilities and processes, while ensuring the stability and release control of natural aromatherapy ingredients.

[0014] The sixth task is to achieve a holistic therapeutic effect by naturally alleviating psychological side effects such as anxiety, stress, and depression that occur during the patient's treatment process through aromatherapy, and thereby improve patient medication adherence and treatment satisfaction.

[0015] The seventh task is to implement a precise release control system that enables each therapeutic effect to manifest at the optimal time without mutual interference through a layered design capable of independently controlling the volatility of aromatherapy components and the permeability of drugs. means of solving the problem

[0016] The present invention relates to a method for manufacturing a stepwise release controlled transdermal patch containing an aromatherapy ingredient, comprising: a) preparing a polyethylene terephthalate film as a support; b) forming a first adhesive layer on the support that includes a silicone-based pressure-sensitive adhesive and a first aromatherapy ingredient and provides initial adhesion upon skin contact; c) forming a second adhesive layer on the first adhesive layer that includes an acrylic-based pressure-sensitive adhesive and a second aromatherapy ingredient and is responsible for drug dissolution and diffusion; d) incorporating a drug into the second adhesive layer to form a drug-containing layer; e) forming a permeability-controlling layer that includes an ethylene vinyl acetate copolymer on the drug-containing layer; and f) attaching a silicone-coated release layer on the permeability-controlling layer. A method for manufacturing a step-release control transdermal patch containing an aromatherapy component is provided, characterized in that the drug is released first from the first adhesive layer and secondly from the second adhesive layer through a laminated structure of the first adhesive layer and the second adhesive layer, and the first aromatherapy component and the second aromatherapy component are released at different times, thereby providing continuous drug delivery for more than 24 hours and simultaneously providing a differentiated aromatherapy effect at different times.

[0017] At this time, the above step a) comprises: a1) preparing a polyethylene terephthalate film with a thickness of 25 to 75 μm as a substrate; a2) surface treating the surface of the substrate using oxygen plasma at an output of 150 to 250 W for 1 to 2 minutes to reduce the contact angle; and a3) using the surface-treated substrate as a support.

[0018] At this time, step b) comprises: b1) adding 0.5 to 2.0 parts by weight of hyaluronic acid having a molecular weight of 50,000 to 200,000 Da to 100 parts by weight of a silicone-based pressure-sensitive adhesive; b2) selecting one or more of lavender oil, eucalyptus oil, and peppermint oil as a first aromatherapy ingredient and adding 1 to 5 parts by weight to 100 parts by weight of the silicone-based pressure-sensitive adhesive; b3) homogenizing the silicone composition to which the hyaluronic acid and the first aromatherapy ingredient have been added to prepare a first aroma silicone composition; b4) coating the first aroma silicone composition onto the support to a thickness of 15 to 35 μm; and b5) curing the coating layer at 70 to 90°C for 2 to 4 minutes to form a first adhesive layer.

[0019] At this time, step c) comprises: c1) a step of preparing a basic permeability-promoting acrylic composition by adding 2 to 8 parts by weight of oleic acid to 100 parts by weight of an acrylic pressure-sensitive adhesive; c2) a step of selecting one or more of rosemary oil, bergamot oil, and ylang-ylang oil as a second aromatherapy component and adding 2 to 10 parts by weight to 100 parts by weight of the basic permeability-promoting acrylic composition; c3) a step of preparing a second aroma coating solution by dissolving the composition with the added second aromatherapy component in a solvent mixed in a 1:1 weight ratio of toluene and ethyl acetate at a solid content concentration of 25 to 35% by weight; c4) a step of applying the second aroma coating solution onto the first adhesive layer to a thickness of 20 to 40 μm; and c5) a step of forming a second adhesive layer by drying the applied layer at 80 to 100°C for 3 to 6 minutes.

[0020] At this time, the above step d) comprises: d1) a step of preparing a solid dispersion by mixing one of the drugs selected from nicotine, diclofenac, or estradiol with polyvinylpyrrolidone having a molecular weight of 10,000 to 50,000 Da in a weight ratio of 1:0.1 to 1:0.5; d2) a step of preparing a drug solution by dissolving the solid dispersion in propylene glycol at a ratio of 50 to 200 parts by weight to 100 parts by weight of the solid dispersion; d3) a step of mixing the drug solution at a ratio of 10 to 20 parts by weight to 100 parts by weight of the total weight of the second adhesive layer; and d4) a step of homogenizing the mixture using a homomixer at 1,500 to 2,500 rpm for 15 to 25 minutes to form a drug-containing layer. Effects of the invention

[0021] A step-release controlled transdermal patch containing an aromatherapy ingredient according to the present invention can achieve the following remarkable effects.

[0022] First, by placing different aromatherapy components in the silicone-based first adhesive layer and the acrylic-based second adhesive layer, functional differentiation by layer is achieved, and by simultaneously achieving the stepwise release of drugs and the time-series differentiated release of aroma components, a fusion therapeutic effect that was impossible with conventional technology can be realized. Lavender or eucalyptus components in the first adhesive layer provide an immediate soothing effect, and rosemary or bergamot components in the second adhesive layer provide a long-lasting stress relief effect, allowing a consistent state of psychological stability to be maintained for more than 24 hours.

[0023] Second, synergy in therapeutic effects can be created through customized aromatherapy combinations for each drug. In nicotine cessation patches, the respiratory improvement and concentration-enhancing effects of peppermint and eucalyptus can strengthen the will to quit smoking; in diclofenac pain relief patches, the relaxing effects of lavender and ylang-ylang can relieve tension and stress caused by pain; and in estradiol hormone patches, the emotional stabilizing effects of bergamot and rosemary can alleviate mood swings caused by hormonal imbalance.

[0024] Third, the natural fragrance effects of aromatherapy ingredients can significantly improve medication adherence by reducing patients' psychological resistance to patch use and making the treatment process more pleasant. In particular, this acts as an important motivational factor in encouraging continuous patient participation in treatment, such as in nicotine smoking cessation therapy or hormone replacement therapy, where patches must be worn for an extended period.

[0025] Fourth, through the synergistic effect of the first adhesive layer containing hyaluronic acid and the aromatherapy ingredients, skin compatibility and moisturizing effects are maximized, which minimizes skin irritation and significantly improves wearing comfort even when the patch is applied for a long period. The anti-inflammatory and soothing effects of natural aroma ingredients further reduce the risk of contact dermatitis caused by the patch.

[0026] Fifth, since all manufacturing processes can be performed using existing patch manufacturing facilities and commercially available natural aroma oils are used, it has high commercial feasibility; furthermore, it offers excellent economic efficiency as it enables the mass production of products of consistent quality without complex synthesis processes or specialized equipment.

[0027] Sixth, in response to the social demand for natural remedies amidst the rise in stress-related illnesses, this approach can present a new treatment paradigm that complements the limitations of existing drug treatments. Particularly at a time when mental health issues are emerging as a major social concern, an integrated approach combining drug therapy and aromatherapy is expected to provide high satisfaction to both medical professionals and patients.

[0028] Seventh, the technology for controlling the release timing through the layered arrangement of aromatherapy ingredients can be expanded into a platform technology for applying various natural therapeutic ingredients to transdermal delivery systems in the future, and offers high applicability as a foundational technology for personalized treatment. Specific details for implementing the invention

[0029] Hereinafter, embodiments are described in detail with reference to the attached drawings. However, various modifications may be made to the embodiments, and thus the scope of the patent application is not limited or restricted by these embodiments. It should be understood that all modifications, equivalents, and substitutions to the embodiments are included within the scope of the rights.

[0030] Specific structural or functional descriptions of the embodiments are disclosed for illustrative purposes only and may be modified and implemented in various forms. Accordingly, the embodiments are not limited to the specific disclosed forms, and the scope of this specification includes modifications, equivalents, or substitutions that fall within the technical concept.

[0031] Terms such as "first" or "second" may be used to describe various components, but these terms should be interpreted solely for the purpose of distinguishing one component from another. For example, the first component may be named the second component, and similarly, the second component may be named the first component.

[0032] When it is stated that a component is "connected" to another component, it should be understood that it may be directly connected to or coupled with that other component, or that there may be other components in between.

[0033] The terms used in the embodiments are for illustrative purposes only and should not be interpreted as intended to be limiting. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as "comprising" or "having" are intended to indicate the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0034] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the embodiments pertain. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.

[0035] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims.

[0036] In the embodiments of the present invention, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in the embodiments of the present invention.

[0037] The shapes, sizes, ratios, angles, numbers, etc. disclosed in the drawings for explaining embodiments of the present invention are exemplary, and therefore the present invention is not limited to the depicted details. Furthermore, in describing the present invention, if it is determined that a detailed description of related known technology may unnecessarily obscure the essence of the present invention, such detailed description is omitted. Where terms such as "includes," "has," or "is made up" are used in this specification, other parts may be added unless "only" is used. Where a component is expressed in the singular, it includes cases where it includes the plural unless specifically stated otherwise.

[0038] In interpreting the components, they are interpreted to include a margin of error even in the absence of a separate explicit statement.

[0039] The size and thickness of each component shown in the drawings are illustrated for convenience of explanation, and the present invention is not necessarily limited to the size and thickness of the illustrated components.

[0040] The features of each of the various embodiments of the present invention may be combined or combined with one another, either partially or wholly, and as will be fully understood by those skilled in the art, various technical interlocking and operation are possible, and each embodiment may be implemented independently of one another or together in an interlocking relationship.

[0041] The present invention relates to a method for manufacturing a stepwise release controlled transdermal patch containing an aromatherapy ingredient, comprising: a) preparing a polyethylene terephthalate film as a support; b) forming a first adhesive layer on the support that includes a silicone-based pressure-sensitive adhesive and a first aromatherapy ingredient and provides initial adhesion upon skin contact; c) forming a second adhesive layer on the first adhesive layer that includes an acrylic-based pressure-sensitive adhesive and a second aromatherapy ingredient and is responsible for drug dissolution and diffusion; d) incorporating a drug into the second adhesive layer to form a drug-containing layer; e) forming a permeability-controlling layer that includes an ethylene vinyl acetate copolymer on the drug-containing layer; and f) attaching a silicone-coated release layer on the permeability-controlling layer. A method for manufacturing a step-release control transdermal patch containing an aromatherapy component is provided, characterized in that the drug is released first from the first adhesive layer and secondly from the second adhesive layer through a laminated structure of the first adhesive layer and the second adhesive layer, and the first aromatherapy component and the second aromatherapy component are released at different times, thereby providing continuous drug delivery for more than 24 hours and simultaneously providing a differentiated aromatherapy effect at different times.

[0042] At this time, the above step a) comprises: a1) preparing a polyethylene terephthalate film with a thickness of 25 to 75 μm as a substrate; a2) surface treating the surface of the substrate using oxygen plasma at an output of 150 to 250 W for 1 to 2 minutes to reduce the contact angle; and a3) using the surface-treated substrate as a support.

[0043] At this time, step b) comprises: b1) adding 0.5 to 2.0 parts by weight of hyaluronic acid having a molecular weight of 50,000 to 200,000 Da to 100 parts by weight of a silicone-based pressure-sensitive adhesive; b2) selecting one or more of lavender oil, eucalyptus oil, and peppermint oil as a first aromatherapy ingredient and adding 1 to 5 parts by weight to 100 parts by weight of the silicone-based pressure-sensitive adhesive; b3) homogenizing the silicone composition to which the hyaluronic acid and the first aromatherapy ingredient have been added to prepare a first aroma silicone composition; b4) coating the first aroma silicone composition onto the support to a thickness of 15 to 35 μm; and b5) curing the coating layer at 70 to 90°C for 2 to 4 minutes to form a first adhesive layer.

[0044] At this time, step c) comprises: c1) a step of preparing a basic permeability-promoting acrylic composition by adding 2 to 8 parts by weight of oleic acid to 100 parts by weight of an acrylic pressure-sensitive adhesive; c2) a step of selecting one or more of rosemary oil, bergamot oil, and ylang-ylang oil as a second aromatherapy component and adding 2 to 10 parts by weight to 100 parts by weight of the basic permeability-promoting acrylic composition; c3) a step of preparing a second aroma coating solution by dissolving the composition with the added second aromatherapy component in a solvent mixed in a 1:1 weight ratio of toluene and ethyl acetate at a solid content concentration of 25 to 35% by weight; c4) a step of applying the second aroma coating solution onto the first adhesive layer to a thickness of 20 to 40 μm; and c5) a step of forming a second adhesive layer by drying the applied layer at 80 to 100°C for 3 to 6 minutes.

[0045] At this time, the above step d) comprises: d1) a step of preparing a solid dispersion by mixing one of the drugs selected from nicotine, diclofenac, or estradiol with polyvinylpyrrolidone having a molecular weight of 10,000 to 50,000 Da in a weight ratio of 1:0.1 to 1:0.5; d2) a step of preparing a drug solution by dissolving the solid dispersion in propylene glycol at a ratio of 50 to 200 parts by weight to 100 parts by weight of the solid dispersion; d3) a step of mixing the drug solution at a ratio of 10 to 20 parts by weight to 100 parts by weight of the total weight of the second adhesive layer; and d4) a step of homogenizing the mixture using a homomixer at 1,500 to 2,500 rpm for 15 to 25 minutes to form a drug-containing layer.

[0046] Reasons for Material Selection and Technical Basis

[0047] Basis for selecting support material

[0048] Selection of polyethylene terephthalate film

[0049] The main reason for selecting a polyethylene terephthalate film as a support in the present invention is to simultaneously secure barrier properties and mechanical stability against both aromatherapy ingredients and drugs. Polyethylene terephthalate has excellent tensile strength of 150-200 MPa, allowing it to withstand mechanical stress that may occur during the patch manufacturing process, while simultaneously providing optimal physical properties with an appropriate elasticity in the range of 10-15%, which prevents damage even under deformation caused by skin movement.

[0050] Of particular importance are the low moisture permeability of polyethylene terephthalate and its barrier properties against fragrance components. The moisture permeability is very low, ranging from 0.5 to 1.0 g / m² / day, which not only prevents drug degradation caused by moisture penetration during patch storage but also suppresses the premature volatilization of aromatherapy components, thereby maintaining a constant concentration of fragrance components until the time of patch use. This is an essential characteristic that enables the time-dependent control of aroma release, which is the core of the present invention.

[0051] Oxygen plasma surface treatment reduces the contact angle of the polyethylene terephthalate surface to improve bonding strength with the subsequent adhesive layer, while simultaneously forming fine surface roughness to provide anchoring sites where aromatherapy components can be selectively adsorbed. Through this surface modification, the first aromatherapy component of the first adhesive layer is designed to be partially adsorbed onto the surface of the support to buffer the initial rapid release.

[0052] Basis for selecting the first adhesive layer material

[0053] Selection of silicone-based pressure-sensitive adhesives

[0054] The fundamental reason for selecting a silicone-based pressure-sensitive adhesive for the first adhesive layer is to ensure biocompatibility as the top priority as a layer in direct contact with the skin, while also appropriately controlling the initial release of the first aromatherapy ingredient. Silicone-based adhesives possess clinically proven characteristics, such as a very low skin irritation index of 0.1 or less and an allergic reaction rate of less than 1%, making them safe even with long-term skin contact.

[0055] Due to the molecular structural characteristics of silicone, the hydrophobic main chain and polar side groups are balanced, providing appropriate solubility for aromatherapy ingredients such as lavender, eucalyptus, and peppermint. This is a key design element that prevents the aroma ingredients from being released excessively rapidly from the silicone matrix, while allowing them to be gradually activated by body temperature upon skin contact to deliver an initial soothing effect.

[0056] Furthermore, the low surface tension of silicone naturally adapts to the fine contours and pores of the skin, maximizing the contact area and thereby enhancing the delivery efficiency of aromatherapy ingredients. At the same time, the excellent temperature stability of silicone maintains consistent adhesion even with changes in body temperature, ensuring that the release rate of aroma ingredients is not affected by environmental conditions.

[0057] Selection of Hyaluronic Acid Additives

[0058] The intention behind adding hyaluronic acid to the first adhesive layer is a combined strategy to further enhance the biocompatibility of the silicone adhesive while promoting the skin penetration of aromatherapy ingredients. Hyaluronic acid possesses excellent moisturizing capabilities, capable of retaining moisture up to 1,000 times its own weight; this prevents skin dryness caused by prolonged patch application and provides the necessary hydration environment for the delivery of aroma ingredients to the skin.

[0059] The reason for selecting hyaluronic acid with a molecular weight range of 50,000–200,000 Da is that this range optimizes the balance between stratum corneum permeability and moisturizing effects. If the molecular weight is too low, it may penetrate deep into the skin and cause inflammation, whereas if it is too high, it remains only on the surface and fails to perform its actual function. The selected molecular weight range forms an appropriate hydration film on the upper surface of the stratum corneum, providing optimal conditions to promote the dissolution and diffusion of aromatherapy ingredients.

[0060] In particular, the hydrogel properties of hyaluronic acid act as a reservoir for aromatherapy ingredients, enabling a continuous supply while suppressing initial rapid release. This is a key mechanism that prevents the primary aromatherapy ingredient from being released in excess immediately after contact with the skin, thereby preventing the effect from being depleted in a short time, and allows a constant concentration to be maintained over several hours.

[0061] Selection of the first aromatherapy ingredient

[0062] Lavender oil, eucalyptus oil, and peppermint oil were selected for the first adhesive layer because they all possess immediate soothing and stress-relieving effects while exhibiting excellent compatibility with the silicone matrix. Linalol and linalyl acetate, the main components of lavender oil, rapidly activate the parasympathetic nervous system through olfactory receptors, providing an immediate relaxation effect.

[0063] The 1,8-cineole component of eucalyptus oil is effective for improving respiratory function and concentration, and can rapidly alleviate anxiety and reduced concentration caused by withdrawal symptoms, particularly when using nicotine cessation patches. The menthone and menthol components of peppermint oil provide a cooling effect along with a stimulating effect, reducing initial discomfort during patch application and fostering a positive perception of the treatment.

[0064] The volatility and lipophilicity of these aroma components exhibit appropriate solubility in a silicone matrix, enabling a stable release profile without excessive initial release. Furthermore, all of these components are classified as FDA-approved food additives, proving their safety, and their low skin irritation allows for safe application even to patients with sensitive skin.

[0065] Basis for selecting the second adhesive layer material

[0066] Selection of acrylic pressure-sensitive adhesives

[0067] The main reason for selecting an acrylic pressure-sensitive adhesive for the second adhesive layer is to enable the continuous release of the second aromatherapy component while providing high solubility for various drugs and excellent drug stability. Acrylic adhesives exhibit 10 to 100 times higher solubility compared to silicone for both polar and non-polar drugs, allowing for sufficient drug loading, while simultaneously providing appropriate affinity for the aromatherapy component.

[0068] The ester and carboxyl groups present in the side chains of acrylic polymers form hydrogen bonds or dipole interactions with not only drug molecules but also aromatherapy ingredients, thereby improving chemical stability. In particular, for aromatherapy ingredients containing complex components such as rosemary or bergamot oil, oxidative degradation is inhibited in the acrylic matrix, significantly improving storage stability.

[0069] The viscoelastic properties of the acrylic adhesive enable continuous release over 24 hours by appropriately controlling the diffusion coefficient of the second aromatherapy component. This is a key design principle that allows for the maintenance of a continuous psychological calming effect even after the initial immediate aroma effect in the first adhesive layer has worn off.

[0070] Selection of oleic acid permeability enhancers

[0071] The reason oleic acid was selected as a permeability enhancer is that, as an unsaturated fatty acid similar to the lipid bilayer structure of the skin's stratum corneum, it can not only form a natural permeation pathway but also simultaneously improve the skin permeability of aromatherapy ingredients. The 18-carbon chain and single double bond structure of oleic acid have a molecular form similar to ceramide in the stratum corneum, thereby improving permeability without significantly damaging the existing lipid structure.

[0072] Of particular importance is that oleic acid promotes the penetration of not only drugs but also aromatherapy ingredients. Active ingredients such as rosmarinic acid in rosemary oil or limonene in bergamot oil can be delivered deep into the skin through the penetration-promoting effect of oleic acid, thereby producing a systemic aromatherapy effect. This is the core intention of the present invention to achieve a systemic relaxation effect through transdermal absorption, going beyond a simple olfactory effect.

[0073] Oleic acid induces a gel-liquid crystal phase transition in the stratum corneum, increasing the fluidity of lipid packing, which can improve the diffusion coefficient of drug molecules and aroma components by 3 to 5 times. The reason for limiting the concentration to a range of 2 to 8 parts by weight is that the permeation-promoting effect becomes saturated within this range, and at higher concentrations, skin irritation or fragrance imbalance due to excessive release of aroma components may occur.

[0074] Selection of Second Aromatherapy Ingredients

[0075] The intention behind selecting rosemary oil, bergamot oil, and ylang-ylang oil for the second adhesive layer is to provide a sustained and deep psychological stabilization effect, distinct from the immediate aroma effect of the first adhesive layer. Rosmarinic acid and carnosic acid, the main components of rosemary oil, are effective for improving cognitive function and relieving long-term stress, along with antioxidant effects, and exhibit stable release characteristics within the acrylic matrix.

[0076] The bergaphen and limonene components of bergamot oil promote the secretion of serotonin and dopamine, providing excellent effects for alleviating depression and stabilizing emotions. In particular, when applied as a hormone patch, it can naturally relieve mood swings caused by hormonal imbalances, significantly improving treatment satisfaction among female patients.

[0077] The benzyl acetate and geraniol components of ylang-ylang oil activate the parasympathetic nervous system to induce a state of deep relaxation, contributing to a reduction in blood pressure and the stabilization of heart rate. This plays a crucial role in comprehensively alleviating physical tension and stress caused by pain when an analgesic patch is applied.

[0078] The molecular weight and polarity of these second aromatherapy ingredients are well harmonized with the acrylic matrix, enabling stable release over 24 hours, and synergize with the permeability-promoting effect of oleic acid to achieve a systemic aromatherapy effect through transdermal absorption.

[0079] Basis for selecting drug delivery material

[0080] Selection of Polyvinylpyrrolidone

[0081] Polyvinylpyrrolidone was selected for the formation of solid dispersions with drugs because it exhibits excellent compatibility with various drugs while minimizing interactions with aromatherapy ingredients. The pyrrolidone ring of polyvinylpyrrolidone acts as a hydrogen bond acceptor, forming strong intermolecular interactions with drug molecules; this inhibits drug crystallization and enhances solubility.

[0082] Of particular importance is that polyvinylpyrrolidone ensures the stability of the drug without inhibiting the activity of the aromatherapy ingredients. In combinations of nicotine and lavender, and diclofenac and rosemary, polyvinylpyrrolidone plays a neutral role that maintains the amorphous state of the drug without interfering with the volatility or physiological activity of the aroma ingredients.

[0083] The reason for selecting polyvinylpyrrolidone with a molecular weight in the range of 10,000–50,000 Da is that the viscosity in this range is appropriate, which optimizes miscibility within an acrylic matrix containing aromatherapy ingredients while effectively maintaining drug interactions. Low molecular weight polyvinylpyrrolidone improves miscibility with aroma ingredients, while high molecular weight polyvinylpyrrolidone provides matrix stability for the drug-aroma complex.

[0084] Selection of propylene glycol solvent

[0085] Propylene glycol was selected as a drug dissolving solvent because it simultaneously provides high solubility for various drugs and a stabilizing effect for aromatherapy ingredients. Propylene glycol is an amphiphilic molecule with both polar and non-polar parts, and it not only effectively dissolves drugs of various characteristics such as nicotine, diclofenac, and estradiol, but also contributes to preventing oxidation and maintaining the stability of aromatherapy ingredients.

[0086] In particular, in systems containing aromatherapy ingredients, propylene glycol acts as a carrier for the fragrance components, enabling the stable release of the aroma components along with the medication. By dissolving complex aroma components, such as rosemary or bergamot oil, in propylene glycol and maintaining a uniform dispersion with the medication, consistent therapeutic and aromatherapy effects can be achieved simultaneously.

[0087] The low volatility of propylene glycol inhibits the premature volatilization of aromatherapy ingredients, thereby minimizing changes in the concentration of fragrance ingredients during patch storage, while simultaneously acting as a co-carrier for aroma ingredients and drugs upon skin penetration to provide a synergistic therapeutic effect.

[0088] Basis for selecting the transmission control layer material

[0089] Selection of ethylene vinyl acetate copolymer

[0090] The reason ethylene vinyl acetate copolymer was selected for the permeation control layer is that it allows for the independent and precise control of drug permeability and the release rate of aromatherapy components. Depending on the vinyl acetate content of the ethylene vinyl acetate, not only drug permeability but also the volatilization rate of aroma components can be controlled within a range of more than 10 times, allowing for customized design for each combination of drug and aroma components.

[0091] Ethylene vinyl acetate is a semicrystalline polymer in which crystalline and amorphous regions coexist, and drug molecules and aroma components diffuse through different pathways. While drugs mainly diffuse through the amorphous region, volatile aroma components diffuse through the interface between the crystalline and amorphous regions, thereby enabling different release profiles.

[0092] Of particular importance is that ethylene vinyl acetate exhibits minimal change in permeability with temperature variations, allowing it to maintain consistent performance even with changes in body temperature or ambient temperature. This is a key characteristic that ensures the release of aromatherapy ingredients remains constant according to the designed profile, rather than being influenced by environmental conditions.

[0093] The transparency of ethylene vinyl acetate allows the condition of the drug-containing layer and the aroma layer to be visually checked during patch use, providing visual feedback on the patient's treatment process, which offers the secondary effect of contributing to improved treatment participation and satisfaction.

[0094] Critical Significance of Component Range and Process Conditions

[0095] Critical Significance of the Support Preparation Phase

[0096] Critical Significance of Polyethylene Terephthalate Film Thickness Range

[0097] Limiting the thickness of the polyethylene terephthalate film used as a support to a range of 25 to 75 μm is a critical design to achieve an optimal balance between the barrier performance of aromatherapy ingredients and the flexibility of the patch. If the thickness is less than 25 μm, the barrier performance against aromatherapy ingredients is insufficient, leading to premature volatilization of fragrance ingredients during patch storage. In particular, for highly volatile ingredients such as lavender or peppermint, a problem arises where the concentration decreases by more than 30% within 24 hours. Additionally, the risk of breakage due to tensile stress during the manufacturing process increases sharply, resulting in a significant increase in the defect rate in continuous production processes.

[0098] On the other hand, if the thickness exceeds 75 μm, the rigidity of the film increases excessively, reducing its adaptability to fine curves and movements of the skin, which is a direct cause of reduced skin delivery efficiency of aromatherapy ingredients. In particular, when applied to joints or body parts with many curves, the reduced contact area causes local concentration variations of aroma ingredients, which acts as a major factor hindering consistent aromatherapy effects.

[0099] Critical Significance of Plasma Surface Treatment Conditions

[0100] The condition of performing oxygen plasma treatment at an output of 150 to 250 W for 1 to 2 minutes represents a balance point between the formation of adsorption sites for aromatherapy components and the prevention of surface damage. When the output is less than 150 W, surface activation is insufficient, so anchoring sites where aromatherapy components can be selectively adsorbed onto the surface of the support are not sufficiently formed. This causes the first aromatherapy component of the first adhesive layer to be excessively released initially, resulting in reduced durability.

[0101] At outputs exceeding 250 W, surface roughness increases rapidly due to excessive etching, which leads to the adverse effect of delayed release as aromatherapy components are excessively trapped in deep grooves on the surface. When the processing time is less than 1 minute, uniform activation does not occur across the entire surface, resulting in uneven adsorption of aroma components; when it exceeds 2 minutes, the generation of low molecular weight degradation products on the surface causes problems that hinder interaction with aroma components.

[0102] Critical significance of the first adhesive layer formation step

[0103] Critical Significance of Hyaluronic Acid Content Range

[0104] The range of adding 0.5 to 2.0 parts by weight of hyaluronic acid per 100 parts by weight of silicone-based pressure-sensitive adhesive is a critical range for optimizing the skin delivery efficiency of aromatherapy ingredients and adhesive performance. Below 0.5 parts by weight, the hydration effect of hyaluronic acid is not exhibited, so the first aromatherapy ingredient cannot effectively penetrate the stratum corneum; in particular, the skin absorption rate of lavender or eucalyptus ingredients is limited to 20% or less compared to the control group, making it difficult to achieve an immediate soothing effect.

[0105] If the amount exceeds 2.0 parts by weight, phase separation occurs within the silicone matrix due to the strong hydrophilicity of hyaluronic acid, which impairs the uniform dispersion of aromatherapy ingredients and causes local concentration variations. In addition, an excess amount of hyaluronic acid causes swelling due to moisture absorption, resulting in the rapid release of aroma ingredients at unexpected times, which undermines the core objective of the present invention, which is the aromatherapy effect differentiated by time.

[0106] Critical Significance of the First Aromatherapy Ingredient Content Range

[0107] Adding 1 to 5 parts by weight of the first aromatherapy component to 100 parts by weight of the silicone-based pressure-sensitive adhesive is a critical concentration for balancing the immediate soothing effect and the stability of the adhesive layer. At less than 1 part by weight, the concentration of the aroma component drops below the olfactory perception threshold, so it does not produce a psychological soothing effect, and in particular, it cannot achieve the immediate soothing effect required in stressful situations.

[0108] If the amount exceeds 5 parts by weight, the excess aroma component reduces the cohesiveness of the silicone matrix, significantly decreasing adhesive performance. At the same time, the excessive initial release causes the scent to become excessively strong, which may actually cause discomfort to the patient. In addition, a high concentration of aroma component interferes with the cross-linking reaction of the silicone, causing curing failure, which is a direct cause of impairing the physical integrity of the patch.

[0109] Critical significance of the first adhesive layer curing conditions

[0110] The condition of curing the first adhesive layer at 70 to 90°C for 2 to 4 minutes is the optimal condition for balancing the preservation of aromatherapy components and the performance of the adhesive. Below 70°C, the cross-linking reaction of the silicone is incomplete, so the aromatherapy components are not stably fixed to the matrix, which causes component migration or changes in concentration during storage. If the temperature exceeds 90°C, the decomposition of heat-sensitive aroma components, such as lavender or peppermint oil, begins, significantly reducing the content of active ingredients, and at the same time, an unpleasant decomposition odor may occur.

[0111] When the curing time is less than 2 minutes, partially uncured sections occur due to the uneven temperature distribution, causing the release profile of the aroma component to change in an unexpected direction, and when it exceeds 4 minutes, the diffusion path of the aroma component is restricted due to increased brittleness of the matrix caused by overcuring, resulting in reduced release efficiency.

[0112] Critical significance of the second adhesive layer formation step

[0113] Critical Significance of Oleic Acid Content Range

[0114] Adding 2 to 8 parts by weight of oleic acid to 100 parts by weight of acrylic pressure-sensitive adhesive is a critical concentration for optimizing the effect of promoting simultaneous penetration of the drug and the second aromatherapy component. At less than 2 parts by weight, a significant fluidizing effect on the lipids of the stratum corneum does not appear, which limits the penetration of the second aromatherapy component, such as rosemary or bergamot oil, into the skin, making it difficult to achieve a continuous psychological stabilization effect.

[0115] If the amount exceeds 8 parts by weight, the excess oleic acid excessively damages the barrier function of the stratum corneum, causing the aromatherapy ingredients to be released faster than expected, making it difficult to ensure 24-hour persistence; at the same time, the liquid oleic acid reduces the cohesiveness of the acrylic matrix, hindering the stable dispersion of the second aromatherapy ingredient. In particular, when the oleic acid concentration is 10 parts by weight or more, unexpected chemical changes may occur due to the interaction between the aroma ingredients and oleic acid, which may pose a problem in terms of stability.

[0116] Critical Significance of the Second Aromatherapy Ingredient Content Range

[0117] Adding 2 to 10 parts by weight of the second aromatherapy component per 100 parts by weight of the basic permeability-promoting acrylic composition is the optimal range for balancing drug release with a continuous psychological stabilization effect over 24 hours. Below 2 parts by weight, the concentration is insufficient to provide a continuous aromatherapy effect after the effect of the first aromatherapy component is exhausted, and it is difficult to guarantee the continuity of the psychological stabilization effect, especially in high-stress situations.

[0118] If the amount exceeds 10 parts by weight, an excess amount of aroma components may interfere with the solubility and diffusion of the drug, thereby altering the originally intended drug release profile, and at the same time, alter the viscoelasticity of the acrylic matrix, which may adversely affect the overall patch performance. In addition, a high concentration of the second aromatherapy component may disrupt the fragrance harmony with the first aromatherapy component, thereby creating an unpleasant complex odor.

[0119] Critical Significance of Solid Concentration and Drying Conditions in Coating Solution

[0120] Controlling the solid content concentration in a mixed solvent of toluene and ethyl acetate to 25 to 35 weight% is an essential condition for the uniform dispersion of aromatherapy ingredients and the optimization of coating quality. If the solid content concentration is less than 25 weight%, the viscosity becomes excessively low, causing the aromatherapy ingredients to settle due to gravity during the coating process, which leads to non-uniformity of concentration within the layer and hinders a consistent aromatherapy effect.

[0121] At concentrations exceeding 35 weight%, viscosity increases rapidly, which reduces the extrusion performance of the composition containing aromatherapy ingredients, and a problem arises where aroma ingredients are trapped inside due to the formation of a surface skin during the drying process, causing delayed release. Setting the drying temperature to 80 to 100°C is an optimal condition for simultaneously achieving solvent removal and preservation of aromatherapy ingredients, and within this range, the active ingredients of rosemary or bergamot oil can be stably maintained while preventing changes in the release profile caused by residual solvent.

[0122] Critical Significance of the Drug Incorporation Step

[0123] Critical significance of the polyvinylpyrrolidone weight ratio range

[0124] Mixing the drug and polyvinylpyrrolidone in a weight ratio of 1:0.1 to 1:0.5 is a critical ratio for optimizing the stability and release characteristics of the drug in an environment where aromatherapy ingredients are present. If the weight ratio is less than 1:0.1, the amount of polyvinylpyrrolidone is insufficient to completely protect the drug molecules and, in particular, cannot effectively prevent drug degradation or precipitation due to interaction with aromatherapy ingredients.

[0125] At ratios exceeding 1:0.5, an excess amount of polyvinylpyrrolidone may form unnecessary interactions with aromatherapy ingredients, thereby inhibiting their activity. Simultaneously, the viscosity of the solid dispersion increases excessively, leading to reduced dispersibility within the acrylic matrix containing the aroma ingredients. In particular, moisture absorption due to the hygroscopic nature of polyvinylpyrrolidone can adversely affect the stability of aromatherapy ingredients, making it important to maintain an appropriate ratio.

[0126] Critical Significance of Propylene Glycol Solubility Concentration

[0127] When dissolving a solid dispersion in propylene glycol, applying a ratio of 50 to 200 parts by weight of propylene glycol is the optimal condition for co-stabilization of the drug and the aromatherapy component. At less than 50 parts by weight, the amount of propylene glycol is insufficient, so complete dissolution of the drug does not occur, and at the same time, the stabilization effect on the aromatherapy component is limited, so decomposition or denaturation of the component may occur during storage.

[0128] If the amount exceeds 200 parts by weight, the excess propylene glycol may excessively alter the viscoelasticity of the acrylic matrix, which may have an unexpected effect on the release profile of the aromatherapy ingredients, and at the same time, due to the dilution effect, the concentration of the aroma ingredients may decrease to a level insufficient to exert a therapeutic effect.

[0129] Critical Significance of Homogenization Conditions

[0130] Homogenizing using a homomixer at 1,500 to 2,500 rpm for 15 to 25 minutes is the optimal condition for achieving uniform dispersion of the drug and aromatherapy components while preserving the activity of the aroma components. At speeds below 1,500 rpm, the shear force is insufficient, so the drug and aromatherapy components are not completely homogenized, which increases the variation in drug content and aroma component concentration within the patch and hinders consistent therapeutic effects.

[0131] At high-speed stirring exceeding 2,500 rpm, the molecular structure of aromatherapy ingredients may be damaged due to excessive shear force, and in particular, for complex ingredients such as rosemary or bergamot oil, the aromatherapy effect may be significantly reduced due to the decomposition of active ingredients. If the homogenization time is less than 15 minutes, aggregates remain due to incomplete dispersion, and if it exceeds 25 minutes, there is a concern about volatilization or decomposition of aroma ingredients due to excessive heat generation.

[0132] Critical significance of the transmission control layer formation step

[0133] Selective application of ethylene vinyl acetate copolymer

[0134] Applying an ethylene vinyl acetate copolymer to the permeation control layer is a key technology for independent release control of drugs and aromatherapy components. Depending on the vinyl acetate content of the ethylene vinyl acetate, the drug permeability and the volatilization rate of the aroma components can be controlled differently, which is intended to implement optimized release profiles for drug-aroma combinations with different physicochemical properties, such as nicotine and lavender, diclofenac and rosemary, and estradiol and bergamot.

[0135] The semicrystalline structure of the ethylene vinyl acetate copolymer allows drug molecules and aroma components to be released through different diffusion pathways, enabling independent release control without mutual interference. While the drug mainly diffuses through the amorphous region, the volatile aroma component diffuses through the interface between the crystalline and amorphous regions, allowing for the achievement of their respective optimal release profiles.

[0136] Critical control of the thickness of the transmission control layer

[0137] The thickness of the permeability control layer must be precisely controlled by considering the diffusion coefficient of the drug and the volatile characteristics of the aromatherapy components. If the thickness is excessively thin, it is difficult to ensure 24-hour persistence because it cannot effectively suppress the rapid release of the aromatherapy components, and in particular, it loses the function of controlling the initial burst release of the second aromatherapy components released from the second adhesive layer.

[0138] Conversely, if the thickness is excessively thick, the transmission resistance is excessive, causing the release of aromatherapy components to be excessively delayed. This results in the second aromatherapy component's effect not continuing at the appropriate time after the first aromatherapy component's effect has been exhausted. By controlling the thickness of the transmission control layer, differentiated release over time within the therapeutic concentration range of each aromatherapy component can be precisely designed.

[0139] Critical significance of the peel layer attachment step

[0140] Basis for application of silicone coating release layer

[0141] Applying a silicone coating to the release layer serves a dual purpose: maintaining the concentration of aromatherapy ingredients during patch storage and providing appropriate release force upon use. The low surface energy of the silicone coating prevents aromatherapy ingredients from migrating to the release layer, enabling the designed concentration in each layer to be stably maintained throughout the storage period.

[0142] The excellent moisture barrier properties of the silicone coating layer prevent changes in the composition of the first adhesive layer containing hyaluronic acid and the second adhesive layer containing aromatherapy ingredients due to moisture absorption. In particular, it effectively suppresses changes in the concentration or decrease in activity of aromatherapy ingredients caused by changes in humidity, thereby ensuring a consistent aromatherapy effect even under various storage conditions.

[0143] Fragrance blocking function of the peeling layer

[0144] The silicone-coated release layer plays a crucial role in preventing the premature volatilization of aromatherapy ingredients until the patch is used. It ensures that the primary aromatherapy ingredients, such as lavender, eucalyptus, and peppermint, and the secondary aromatherapy ingredients, such as rosemary, bergamot, and ylang-ylang, maintain their respective designed concentrations, guaranteeing that optimal aromatherapy effects can be achieved at the time of patch application.

[0145] The gas barrier function of the exfoliating layer simultaneously prevents oxidation of aromatherapy ingredients and protects the stability of the medication, directly contributing to extending the product's shelf life and ensuring quality stability. In particular, for natural aroma oils, it prevents deterioration or discoloration caused by contact with oxygen, thereby guaranteeing consistent therapeutic effects.

[0146] Technical basis and implementation method of support preparation step (a)

[0147] Overall Significance of the Support Preparation Phase

[0148] The scaffold preparation stage serves as a foundational process that determines the overall performance of a transdermal patch containing aromatherapy ingredients; going beyond simple physical support, it acts as a starting point for ensuring the stability and controlling the release of aromatherapy ingredients. In this invention, the scaffold is designed as a multifunctional platform to simultaneously achieve drug delivery and aromatherapy effects; to this end, all processes, from material selection to surface treatment, must be optimized by considering the characteristics of the aromatherapy ingredients.

[0149] Technical basis of the polyethylene terephthalate film preparation step (a1)

[0150] The step of preparing a polyethylene terephthalate film with a thickness of 25 to 75 μm as a substrate is a key process for achieving the optimal balance between the barrier performance of aromatherapy ingredients and the flexibility of the patch. Due to its aromatic polyester structure, polyethylene terephthalate exhibits excellent barrier properties against aromatherapy ingredients such as lavender, eucalyptus, and rosemary, while simultaneously providing a barrier function against moisture and oxygen, thereby contributing to the prevention of oxidation and the maintenance of the concentration of aroma ingredients.

[0151] As a specific implementation method, a film is first manufactured by melt-extruding polyethylene terephthalate resin, wherein the extrusion temperature is controlled to 280-300°C to optimize molecular orientation. Subsequently, mechanical strength is improved through a stretching process, wherein a longitudinal stretching ratio of 3.5 times and a transverse stretching ratio of 3.8 times are applied to secure physical properties such as a tensile strength of 180 MPa or more and an elongation of 12% or more. The deviation of the film thickness is controlled within ±2 μm to ensure uniformity in subsequent processes, and the surface roughness is managed to Ra 0.05 μm or less to optimize interfacial bonding strength with the adhesive layer.

[0152] At thicknesses less than 25 μm, the permeability of aromatherapy ingredients increases rapidly, leading to a decrease in concentration during storage; in particular, for highly volatile ingredients such as peppermint or eucalyptus, more than 40% of the initial concentration can be lost within 48 hours. On the other hand, at thicknesses exceeding 75 μm, skin compatibility deteriorates due to the rigidity of the film, and the skin delivery efficiency of aromatherapy ingredients decreases, making it difficult to achieve an immediate soothing effect.

[0153] Technical basis of the oxygen plasma surface treatment step (a2)

[0154] Surface treatment using oxygen plasma is a key process for forming active sites on the surface of polyethylene terephthalate where aromatherapy components can be selectively adsorbed. Treatment conditions at an output of 150 to 250 W for 1 to 2 minutes represent a balance point between surface activation and the preservation of bulk properties, thereby enabling the buffering effect for the initial release of the first aromatherapy component.

[0155] As a specific implementation method, oxygen gas is supplied at a flow rate of 50 sccm in a vacuum chamber, and RF power is applied while maintaining the pressure at 50-80 mTorr. During plasma treatment, the substrate temperature is maintained at 40°C or lower to prevent thermal deformation, and residual oxygen is removed through nitrogen purging after treatment. The surface treatment effect is confirmed by measuring the contact angle, based on the criterion that the contact angle with respect to distilled water decreases to 60 degrees or less.

[0156] At outputs below 150 W, the plasma density is insufficient, resulting in only partial surface activation. This leads to a lack of adsorption site density for aromatherapy components, which limits the emission control effect. Conversely, at high outputs exceeding 250 W, excessive etching causes a rapid increase in surface roughness, leading to the problem of aroma components being excessively trapped in deep grooves.

[0157] Technical basis of the step (a3) ​​utilizing a support of a surface-treated substrate

[0158] The step of using a surface-treated substrate as a support serves as a platform for establishing a hierarchical release system of aromatherapy ingredients. The activated surface adsorbs a portion of the first aromatherapy ingredient to act as a reservoir, which is gradually released by body temperature upon skin contact, providing an initial soothing effect.

[0159] As a specific implementation method, a subsequent process is carried out within 30 minutes after the completion of surface treatment to prevent rehydration or contamination of the active sites. The cleanliness of the support surface is checked using a particle counter, and is managed so that particles larger than 0.3 μm are kept below 100 particles / m². In addition, a value of 42 dyne / cm or higher is confirmed through surface energy measurement to ensure bonding strength with the subsequent adhesive layer.

[0160] Technical basis and method of implementation of the first adhesive layer formation step (b)

[0161] Overall significance of the first adhesive layer formation step

[0162] The first adhesive layer formation step is a key process that serves as the interface in direct contact with the skin, simultaneously ensuring biocompatibility and achieving the immediate release of the first aromatherapy ingredient. Through a complex system of silicone-based pressure-sensitive adhesive, hyaluronic acid, and the first aromatherapy ingredient, it creates a skin-friendly environment while realizing the immediate soothing effects of lavender, eucalyptus, peppermint, and others.

[0163] Technical basis for the hyaluronic acid addition step (b1).

[0164] The step of adding 0.5 to 2.0 parts by weight of hyaluronic acid with a molecular weight of 50,000 to 200,000 Da to 100 parts by weight of a silicone-based pressure-sensitive adhesive is a key process for maximizing the skin delivery efficiency of aromatherapy ingredients. The hydrogel properties of hyaluronic acid promote the dissolution and diffusion of aromatherapy ingredients, and at the same time create a hydrated environment on the skin surface to improve permeability to the stratum corneum.

[0165] As a specific method of implementation, sodium hyaluronate is first dissolved in purified water at a concentration of 1% to form a uniform gel state. At this time, the dissolution temperature is maintained at 25℃ to prevent a decrease in molecular weight, and the stirring speed is limited to 100 rpm to minimize molecular chain breakage. After dissolution is complete, fine particles are removed by filtering through a 0.2 μm filter, and the solution is stored at 4℃ until immediately before mixing with silicone adhesive.

[0166] Hyaluronic acid with a molecular weight of less than 50,000 Da can cause an inflammatory response by excessively penetrating the stratum corneum and penetrating deep into the skin, while simultaneously increasing migration within the silicone matrix, resulting in blooming on the adhesive surface. On the other hand, hyaluronic acid with a molecular weight exceeding 200,000 Da has excessively high viscosity, which reduces dispersibility within the silicone matrix and limits interaction with aromatherapy ingredients, thus failing to exhibit a release-promoting effect.

[0167] Technical basis of the first aromatherapy ingredient addition step (b2)

[0168] The step of selecting and adding one or more of lavender oil, eucalyptus oil, and peppermint oil as the primary aromatherapy ingredient is a key process for realizing an immediate psychological stabilization effect. These aroma ingredients all induce a rapid nervous system response through olfactory receptors and provide a stable release profile based on excellent compatibility with the silicone matrix.

[0169] As a specific implementation method, the content of the main active ingredients of each aroma oil is confirmed through GC-MS analysis. For lavender oil, the standard is 25% or more linalol and 35% or more linalyl acetate; for eucalyptus oil, 70% or more 1,8-cineole; and for peppermint oil, 35% or more menthol and 15% or more menthone are used. Immediately before use, the aroma oil is filtered through a 0.1 μm filter to remove fine particles and stored under a nitrogen atmosphere to prevent oxidation.

[0170] At a concentration of less than 1 part by weight, the aroma component falls below the olfactory perception threshold, failing to produce a psychological calming effect and, in particular, failing to achieve the immediate calming effect required in stressful situations. If it exceeds 5 parts by weight, the excess aroma component inhibits the cross-linking reaction of the silicone, thereby reducing adhesive performance, and at the same time, may cause olfactory fatigue due to excessive initial release.

[0171] Technical basis of step (b3) for manufacturing the first aroma silicone composition

[0172] The step of homogenizing the silicone composition containing hyaluronic acid and a first aromatherapy ingredient is a key process for the uniform dispersion of each ingredient and the optimization of their interactions. In this step, the moisturizing effect of hyaluronic acid and the soothing effect of the aromatherapy ingredient form a synergy to realize a complex system that is skin-friendly and provides immediate therapeutic effects.

[0173] As a specific implementation method, stepwise mixing is performed using a planetary mixer. First, a first mixing step is performed at 500 rpm for 10 minutes while slowly adding the hyaluronic acid solution to the silicone adhesive. Subsequently, a second mixing step is performed at 800 rpm for 15 minutes while adding the aromatherapy ingredients in portions; during this process, the temperature is maintained at 25℃ or lower to minimize the volatilization of the aroma ingredients. Finally, air bubbles are removed through vacuum degassing to ensure the homogeneity of the composition.

[0174] Insufficient mixing results in local concentration variations of hyaluronic acid and aromatherapy ingredients, leading to an uneven release profile, while excessive mixing may cause volatilization of aroma ingredients or a decrease in the molecular weight of hyaluronic acid, making it important to maintain optimal conditions.

[0175] Technical basis of the first aroma silicone composition coating step (b4)

[0176] The step of coating the first aroma silicone composition onto a support to a thickness of 15 to 35 μm is a key process for optimizing the release amount and contact area of ​​the aromatherapy components. The coating thickness is an important variable that simultaneously determines the storage amount and release rate of the aroma components, and is essential for achieving a balance between immediate effect and duration.

[0177] As a specific implementation method, precise thickness control is performed using a gravure coater or a slot die coater. The coating speed is set to 5-10 m / min to ensure sufficient leveling time for the composition, and the gap between the coating head and the substrate is adjusted to 1.2 times the set thickness. During the coating process, the temperature is maintained at 20-25℃ to prevent premature volatilization of the aroma component, and the relative humidity is managed at 50% or less to suppress excessive moisture absorption by the hyaluronic acid.

[0178] At a thickness of less than 15 μm, the storage capacity of aromatherapy ingredients is insufficient, making it difficult to maintain continuous release; if it exceeds 35 μm, the excessive thickness causes a long time for aroma ingredients to diffuse to the surface, making it difficult to achieve an immediate effect.

[0179] Technical basis for the first adhesive layer curing step (b5)

[0180] The step of curing the coating layer at 70 to 90°C for 2 to 4 minutes to form a first adhesive layer is a key process that simultaneously achieves the cross-linking reaction of silicone and the stabilization of aromatherapy components. The three-dimensional network formed during the curing process provides a stable matrix for the aroma components and maximizes moisture retention capacity through interaction with hyaluronic acid.

[0181] As a specific implementation method, a hot air circulation oven is used to ensure a uniform temperature distribution. Preheating is performed at 50°C for the first 30 seconds to prevent rapid volatilization of aroma components due to a sudden temperature rise, and then the temperature is gradually increased to the set temperature. During the curing process, trace amounts of volatile components are removed through an exhaust system, and residual stress is minimized through slow cooling after curing is complete.

[0182] At temperatures below 70°C, the cross-linking reaction of silicone is incomplete, so the aromatherapy components are not stably fixed to the matrix, and at temperatures exceeding 90°C, the main active components of lavender or peppermint oil decompose, significantly reducing the aromatherapy effect.

[0183] Technical basis and method of implementation of the second adhesive layer formation step (c)

[0184] Overall significance of the second adhesive layer formation step

[0185] The second adhesive layer formation step is a key process responsible for the main matrix of drug delivery and, at the same time, the continuous release of the second aromatherapy component. Based on the high drug dissolving ability of acrylic pressure-sensitive adhesives and the permeability-promoting effect of oleic acid, the second aromatherapy component, such as rosemary, bergamot, and ylang-ylang, is designed to provide a continuous psychological calming effect over 24 hours.

[0186] Technical basis of the manufacturing step (c1) of the basic permeability-promoting acrylic composition

[0187] The step of preparing a basic composition by adding 2 to 8 parts by weight of oleic acid to 100 parts by weight of an acrylic pressure-sensitive adhesive is a key process for promoting the simultaneous penetration of the drug and the second aromatherapy component. Oleic acid forms a natural penetration pathway with a structure similar to lipids in the stratum corneum, and at the same time promotes the skin absorption of the aromatherapy component, thereby enabling a systemic aromatherapy effect.

[0188] As for the specific implementation method, first, the purity of oleic acid is verified through GC analysis, and a high-purity product of 95% or higher is used. When adding oleic acid to the acrylic adhesive, the temperature is maintained at 30°C or lower to prevent thermal oxidation, and mixing is performed under a nitrogen atmosphere to minimize contact with oxygen in the air. Mixing is carried out using a planetary mixer at 300 rpm for 20 minutes, and during this process, 0.01% of BHT is added as an antioxidant to improve the oxidative stability of oleic acid.

[0189] At an oleic acid concentration of less than 2 parts by weight, a significant fluidizing effect on the stratum corneum is not observed, which limits the skin penetration of the second aromatherapy ingredient, and when it exceeds 8 parts by weight, the aroma ingredient is rapidly released due to excessive penetration promotion, making it difficult to ensure 24-hour persistence.

[0190] Technical basis for the second aromatherapy ingredient addition step (c2)

[0191] The step of selecting and adding one or more of rosemary oil, bergamot oil, or ylang-ylang oil as a second aromatherapy ingredient is a key process for realizing a long-term psychological stabilization effect distinct from the first aromatherapy ingredient. These ingredients all contain complex bioactive compounds to provide a deep relaxation effect and enable stable, long-term release based on their excellent compatibility with the acrylic matrix.

[0192] As a specific implementation method, the quality is verified by analyzing the profile of the main components of each aroma oil. For rosemary oil, the criteria are 2% or more rosmarinic acid and 20% or more 1,8-cineole; for bergamot oil, 35% or more limonene and 25% or more linalyl acetate; and for ylang-ylang oil, 15% or more benzyl acetate and 10% or more geraniol. Aroma oils are stored in a cool, dark place, and oxidation is prevented by nitrogen filling immediately before use.

[0193] At a concentration of less than 2 parts by weight, it is insufficient to provide a sustained psychological stabilization effect after the effect of the first aromatherapy component is exhausted, and if it exceeds 10 parts by weight, an excess amount of aroma component may interfere with the solubility and diffusion of the drug and adversely affect the drug release profile.

[0194] Technical basis of the second aroma coating solution preparation step (c3)

[0195] The step of preparing a coating solution by dissolving a composition containing a second aromatherapy ingredient in a 1:1 weight ratio mixed solvent of toluene and ethyl acetate at a solid content concentration of 25 to 35 weight% is a key process for uniform dispersion of the aromatherapy ingredient and optimization of coating quality. The mixed solvent provides appropriate solubility for both the acrylic polymer and the aromatherapy ingredient, forming a stable single phase.

[0196] As a specific implementation method, toluene and ethyl acetate are first mixed in an accurate weight ratio, and the moisture content is measured by the Karl Fischer titration method and managed to be 50 ppm or less. When dissolving the acrylic adhesive in the solvent, the temperature is maintained at 40°C or lower to minimize the volatilization of aroma components, and the stirring speed is limited to 200 rpm to suppress bubble generation. After dissolution is complete, the solution is filtered through a 100 mesh filter to remove gel particles or insoluble matter, and the viscosity of the solution is measured using a Brookfield viscometer and maintained in the range of 800-1200 cP.

[0197] When the solid content concentration is less than 25 weight%, sedimentation or phase separation of aromatherapy ingredients may occur during the coating process, and when it exceeds 35 weight%, the coating uniformity is reduced due to increased viscosity and aroma ingredients may be trapped inside during the drying process.

[0198] Technical basis of the second aroma coating solution application step (c4)

[0199] The step of applying the second aroma coating solution onto the first adhesive layer to a thickness of 20 to 40 μm is a key process for optimizing the storage amount and release control of the second aromatherapy component. The coating thickness determines the total amount of aroma component required for continuous release over 24 hours, and at the same time, it must be designed to minimize the impact on drug release.

[0200] As a specific implementation method, precise thickness control is performed using a micro-gravure coater. The ratio of the coating roll rotation speed to the substrate transfer speed is set to 1.05:1 to secure an appropriate transfer amount, and the pressure of the doctor blade is adjusted to 2-3 kg / cm to achieve a uniform film thickness. The coating environment is maintained at a temperature of 22±2℃ and a relative humidity of 45±5% to optimize the solvent evaporation rate, and an infrared dryer is used immediately after coating to prevent surface skin formation.

[0201] When the thickness is less than 20 μm, the storage capacity of the second aromatherapy component is insufficient, making it difficult to achieve continuous release for 24 hours; when it exceeds 40 μm, the excessive thickness causes the aroma component to take a long time to diffuse to the lower layer, making it difficult to expect a synergistic effect with drug release.

[0202] Technical basis for the second adhesive layer drying and formation step (c5)

[0203] The step of forming a second adhesive layer by drying the coating layer at 80 to 100°C for 3 to 6 minutes is a key process that simultaneously achieves solvent removal and stabilization of the aromatherapy components. During the drying process, entanglements of acrylic polymer chains are formed to stably fix the aroma components, while simultaneously maximizing the penetration-promoting effect through compatibility with oleic acid.

[0204] A multi-stage drying system is applied as a specific implementation method. Pre-drying is performed at 60°C for the first minute to gradually remove the surface solvent, and then the temperature is gradually increased to a set temperature to completely remove the internal solvent. During the drying process, the exhaust air volume is controlled to prevent excessive volatilization of aroma components, and the residual solvent concentration is monitored by gas chromatography to maintain it at 100 ppm or less. After drying is complete, the surface temperature is measured with an infrared thermometer to verify uniformity.

[0205] At temperatures below 80°C, solvent removal is incomplete, resulting in reduced adhesion and instability of aroma components due to residual solvent, and at temperatures exceeding 100°C, heat-sensitive components of rosemary or bergamot oil decompose, significantly reducing the aromatherapy effect.

[0206] Technical basis and implementation method of drug mixing step (d)

[0207] Overall Significance of the Drug Incorporation Step

[0208] The drug incorporation step is a key process for optimizing the stability and release characteristics of the drug in a complex system containing aromatherapy ingredients. It is designed to enable the drug and aromatherapy ingredients to exert their respective therapeutic effects without mutual interference through the formation of a solid dispersion using polyvinylpyrrolidone and the stabilization of dissolution using propylene glycol.

[0209] Technical basis of the solid dispersion manufacturing step (d1)

[0210] The step of preparing a solid dispersion by mixing any one of the drugs nicotine, diclofenac, or estradiol with polyvinylpyrrolidone having a molecular weight of 10,000 to 50,000 Da in a weight ratio of 1:0.1 to 1:0.5 is a key process for ensuring the physicochemical stability of the drug in an environment where aromatherapy ingredients are present. Polyvinylpyrrolidone induces the amorphization of the drug to improve solubility while minimizing unnecessary interactions with aromatherapy ingredients.

[0211] As a specific implementation method, the solvent evaporation method is applied. First, the drug and polyvinylpyrrolidone are dissolved separately in methanol, and then the polyvinylpyrrolidone solution is slowly added to the drug solution while mixing with a magnetic stirrer at 300 rpm for 30 minutes. Subsequently, the solvent is completely removed using a rotary evaporator under reduced pressure conditions at 40°C, and the dried solid dispersion is pulverized to 200 mesh or less using a grinder. The prepared solid dispersion is analyzed using a differential scanning calorimeter to confirm the amorphous state of the drug, and then stored in a desiccator at room temperature.

[0212] At a weight ratio of less than 1:0.1, the amount of polyvinylpyrrolidone is insufficient, which limits the effect of inhibiting drug crystallization, and in particular, it fails to effectively prevent drug degradation or precipitation due to interaction with aromatherapy components. At a ratio exceeding 1:0.5, an excess amount of polyvinylpyrrolidone may form unnecessary interactions with aromatherapy components, thereby inhibiting the activity of the aroma components.

[0213] Technical basis for the drug solution preparation step (d2).

[0214] The step of preparing a drug solution by dissolving a solid dispersion in propylene glycol is a key process for achieving co-stabilization and uniform dispersion of the drug and aromatherapy components. As an amphiphilic solvent, propylene glycol provides high solubility for various drugs while acting as a carrier for aromatherapy components, enabling synergistic delivery effects.

[0215] As a specific implementation method, first, the purity of propylene glycol is checked, and pharmaceutical grade of 99.5% or higher is used. When adding the solid dispersion to the propylene glycol, the temperature is maintained at 35°C to promote dissolution while preventing a decrease in the molecular weight of polyvinylpyrrolidone. During the dissolution process, ultrasonic treatment is performed for 30 minutes to achieve complete dispersion of fine particles, and after dissolution is complete, the solution is filtered through a 5 μm filter to remove insoluble matter. The prepared drug solution is stored in a brown bottle to prevent photodegradation and kept refrigerated until immediately before use.

[0216] If the amount of propylene glycol is less than 50 parts by weight, complete dissolution of the drug does not occur, and at the same time, the stabilizing effect on the aromatherapy component is limited, so degradation or denaturation of the component may occur during storage. If the amount exceeds 200 parts by weight, the excess propylene glycol may excessively alter the viscoelasticity of the acrylic matrix, which may have an unexpected effect on the release profile of the aromatherapy component.

[0217] Technical basis for the drug solution mixing step (d3).

[0218] The step of mixing the drug solution in a ratio of 10 to 20 parts by weight per 100 parts by weight of the total weight of the second adhesive layer is a key process for achieving a balance between drug release and aromatherapy effects. This ratio is designed to ensure the amount of drug required for continuous release over 24 hours without excessively affecting the release of the second aromatherapy component.

[0219] As a specific method of implementation, the second adhesive layer composition and the drug solution are mixed stepwise. First, the temperature of the second adhesive layer composition is stabilized at 25°C, and then the drug solution is added in three separate additions. At each addition, the mixture is mixed with a planetary mixer at 400 rpm for 5 minutes to achieve uniform dispersion, and wall adhesions are removed with a spatula during the process. After the final mixing is completed, vacuum degassing is performed to remove incorporated air bubbles, and the dispersion state of the drug particles is checked under a microscope.

[0220] If the amount is less than 10 parts by weight, the drug loading amount is insufficient to secure the amount of drug required for 24-hour sustained release, and if it exceeds 20 parts by weight, the viscoelasticity of the acrylic matrix changes due to the excess propylene glycol, which may adversely affect the release profile of the second aromatherapy component.

[0221] Technical basis for the drug-containing layer formation step (d4).

[0222] The step of forming a drug-containing layer by homogenizing the mixture using a homomixer at 1,500 to 2,500 rpm for 15 to 25 minutes is a key process for achieving uniform dispersion of the drug and aromatherapy components and stable matrix formation. In this process, the drug, aromatherapy components, and adhesive components form optimal interactions, thereby realizing a composite system capable of maximizing each therapeutic effect.

[0223] As a specific implementation method, stepwise homogenization is performed using a high-shear homomixer. Pre-mixing is performed at 1,500 rpm for the first 5 minutes to eliminate macroscopic non-uniformity, and then the speed is gradually increased to a set speed to achieve microscopic homogeneity. During the homogenization process, the temperature is maintained at 30°C or lower to minimize the volatilization of aromatherapy components, and the dispersion state of drug particles is monitored using a particle size analyzer by sampling every 5 minutes. After homogenization is completed, the quality is verified by measuring the viscosity and pH of the final composition.

[0224] At speeds below 1,500 rpm, the shear force is insufficient, so complete homogenization of the drug and aromatherapy components is not achieved, and at high-speed stirring exceeding 2,500 rpm, the molecular structure of the aromatherapy components may be damaged due to excessive shear force. If the homogenization time is less than 15 minutes, aggregates remain due to incomplete dispersion, and if it exceeds 25 minutes, there is a concern that the aroma components may be denatured due to excessive heat generation.

[0225] Technical basis and implementation method of the permeability control layer formation step (e)

[0226] Overall Significance of the Transmission Control Layer Formation Step

[0227] The permeation control layer formation step is a key process for achieving independent and precise release control of drugs and aromatherapy components. By utilizing the semicrystalline structure of ethylene vinyl acetate copolymer, drug molecules and aroma components are released through different diffusion pathways, thereby realizing their respective optimal release profiles without mutual interference.

[0228] Technical basis for the ethylene vinyl acetate copolymer selection step (e1)

[0229] The step of selecting an ethylene vinyl acetate copolymer to be applied to the permeation control layer is a key process for customized design that considers the characteristics of each drug and the physicochemical properties of aromatherapy ingredients. Since the drug permeability and the volatilization rate of aroma ingredients can be controlled differently depending on the vinyl acetate content, optimized release characteristics can be achieved for different drug-aroma combinations, such as nicotine and lavender, diclofenac and rosemary, and estradiol and bergamot.

[0230] As a specific implementation method, first, physicochemical properties such as molecular weight, solubility, and diffusion coefficient of the drug are analyzed, and the volatility, molecular size, and polarity of the aromatherapy component are evaluated. Based on this, EVA with a vinyl acetate content of 18-22% is selected for the nicotine patch, 25-30% for the diclofenac patch, and 35-40% for the estradiol patch. The melt index of the selected EVA is limited to the range of 2-5 g / 10 min to ensure processability, and the degree of crystallinity is confirmed through DSC analysis.

[0231] EVA with low vinyl acetate content has high crystallinity, providing high permeability resistance to both drugs and aroma components, while EVA with high content has an increased amorphous region, enabling selective permeability.

[0232] Technical basis for the step (e2) of preparing the permeability control layer solution

[0233] The step of preparing a permeability control layer solution by dissolving a selected ethylene vinyl acetate copolymer in a suitable solvent is a key process for simultaneously achieving uniform film formation and minimizing the impact on aromatherapy components. Through solvent selection and concentration control, the design optimizes coating quality and drying efficiency while ensuring that the aroma components of the underlying layer are not damaged.

[0234] For the specific implementation method, a solvent mixture of toluene and methyl ethyl ketone in a 7:3 weight ratio is used. First, the solvent is heated to 40°C, and then EVA pellets are slowly added while stirring at 200 rpm to dissolve them. The dissolution process takes 2 to 3 hours, and after complete dissolution, the solution is filtered through a 50 mesh filter to remove undissolved particles. The solid content of the final solution is adjusted to 8–12%, and the viscosity is managed within the range of 50–100 cP. The prepared solution is stored in a sealed container to prevent solvent evaporation.

[0235] If the solid content concentration is too low, coating efficiency decreases and thickness control becomes difficult, while if it is too high, coating defects may occur due to increased viscosity.

[0236] Technical basis for the transmission control layer coating step (e3)

[0237] The step of coating the permeability control layer solution onto the drug-containing layer with a precise thickness is a key process for finally controlling the release rate of the drug and aromatherapy components. Coating thickness is a major variable determining the diffusion resistance of each component and must be precisely controlled to achieve a constant release rate over 24 hours.

[0238] As a specific implementation method, a precision slot die coater is used to coat with a wet thickness of 50-150 μm. The coating speed is set to 3-7 m / min to ensure sufficient leveling time, and the gap between the die lip and the substrate is adjusted to 0.8 times the set thickness. The coating environment is strictly controlled at a temperature of 25±2℃ and a relative humidity of 40±5% to ensure uniform drying conditions. During the coating process, an electrostatic discharge bar is installed to prevent bubble formation, and deviations are monitored using a real-time thickness measurement system.

[0239] If the coating thickness is too thin, the transmission control effect is limited and the initial rapid release cannot be suppressed, and if it is too thick, it is difficult to achieve a therapeutic effect due to delayed release.

[0240] Technical basis for the drying step (e4) of the permeability control layer

[0241] The step of drying the coated permeability-controlling layer to form the final film is a key process for simultaneously achieving solvent removal and membrane structure optimization. During the drying process, the crystallization of EVA and the formation of amorphous regions are controlled, enabling selective permeability to drugs and aromatherapy ingredients.

[0242] A three-stage drying system is applied as a specific implementation method. In the first stage, surface solvent is removed by pre-drying at 50°C for 2 minutes, and in the second stage, internal solvent is completely removed by main drying at 80°C for 3 minutes. In the third stage, crystallization of EVA is induced and membrane structure is stabilized by post-drying at 120°C for 1 minute. The airflow is controlled in each stage to prevent membrane defects caused by rapid solvent evaporation, and residual solvent is analyzed by GC to confirm a level of 50 ppm or less.

[0243] If the drying temperature is too low, solvent removal is incomplete, leading to a decrease in membrane performance, and if it is too high, the aromatherapy components in the lower layer may decompose.

[0244] Technical basis for the quality verification step (e5) of the transmission control layer

[0245] The step of verifying the quality of the formed transmission control layer and evaluating its transmission characteristics is a critical process for ensuring the performance of the final product. Quality indicators such as film thickness, uniformity, and transmittance are used to confirm whether the designed emission profile has been realized.

[0246] As for the specific implementation method, first, the thickness at 10 points is measured using a contact thickness gauge to check the average value and deviation. Surface observation is performed using an optical microscope to check for the presence of pinholes or cracks, and the membrane structure and interlayer adhesion are evaluated through SEM analysis. For the transmittance test, a Franz diffusion cell is used to measure the permeation rate of the model drug and model aroma components, and compliance with design specifications is determined.

[0247] If quality standards are not met, the coating or drying conditions are readjusted to achieve optimal quality.

[0248] Technical basis and method of implementation of the peeling layer attachment step (f)

[0249] Overall significance of the peel layer attachment step

[0250] The release layer attachment step is a key process that forms a final protective film providing appropriate release characteristics for use while ensuring the stability of aromatherapy ingredients and medications during patch storage. The silicone-coated release layer protects the internal ingredients from external environmental factors such as moisture, oxygen, and light, and prevents the premature volatilization of aromatherapy ingredients, maintaining optimal concentration until the time of use.

[0251] Technical basis for the silicone coating release liner selection step (f1)

[0252] The step of selecting a silicone-coated release liner is a key process for simultaneously preserving aromatherapy ingredients and providing appropriate release power. By controlling the crosslinking density and surface energy of the silicone coating, an optimal balance is achieved during the manufacturing process that provides sufficient protection while allowing the patient to easily remove the liner.

[0253] As a specific implementation method, a polyethylene terephthalate film or a polyethylene film is used as a substrate, and a silicone coating is applied thereon. The silicone coating solution is prepared using an addition-type silicone with a platinum catalyst system, and the peel strength is set to a range of 0.1-0.5 N / inch by adjusting the concentration of the crosslinking agent. The coating thickness is controlled to 1-3 μm to ensure sufficient release performance while preventing excessive silicone usage. After coating, the solution is cured at 150°C for 2 minutes to induce a complete crosslinking reaction.

[0254] If the peel strength is too low, unintended delamination may occur during packaging or transportation, and if it is too high, adhesive damage or patient discomfort increases during removal.

[0255] Technical basis for the peeling layer size adjustment step (f2)

[0256] The step of precisely adjusting the release layer to fit the patch size is a key process for simultaneously ensuring complete protection and ease of use. The size and shape of the release layer are important factors that determine the preservation efficiency of aromatherapy ingredients and patient convenience.

[0257] As a specific implementation method, a precision cutting system is used to cut the patch to a size 3-5 mm larger than the patch size. The cut surface is smoothed using ultrasonic or laser cutting, and the edges are rounded to prevent tearing during dissection. The dissection tab is extended by 15-20 mm to allow the patient to grip it easily, and the tip of the tab is not coated with silicone to prevent slipping.

[0258] If the size is inappropriate, leakage of aromatherapy ingredients or intrusion of external contaminants may occur at the corners.

[0259] Technical basis of the peeling layer lamination step (f3)

[0260] The step of laminating the release layer onto the permeability control layer is a critical process for achieving optimal protection by ensuring complete adhesion without bubble formation. Precise process control is required because bubbles or wrinkles that may occur during the lamination process can cause localized leakage of aromatherapy ingredients.

[0261] As a specific implementation method, step-by-step lamination is performed using a laminator. First, the surface temperature of the permeability control layer is adjusted to 30°C to improve lamination, and the release layer is supplied at a constant speed while the nip roll pressure is set to 3-5 kg / cm. The lamination speed is controlled to 5-10 m / min to minimize bubble generation, and microbubbles are removed by passing through a degassing roller immediately after lamination. After lamination is completed, adhesion is improved through a compression process.

[0262] If lamination is defective, premature volatilization of aromatherapy ingredients or external contamination may occur, potentially degrading product quality.

[0263] Technical basis of the seal inspection step (f4)

[0264] The step of inspecting the sealing condition of the release layer to verify the preservation effect of aromatherapy ingredients is a key process for ensuring the quality of the final product. Through complete sealing, the concentration and activity of aromatherapy ingredients can be maintained for a storage period of more than 24 months.

[0265] As a specific implementation method, minute leaks are detected using a helium leak tester. After exposing the patch to a helium atmosphere, the amount of leakage is measured using a mass spectrometer, and the allowable limit is set to 1 × 10⁻⁶ Pa·m³ / s or less. In addition, visually identifiable defects are detected through a methylene blue penetration test, and seal integrity is evaluated through a pressure change test. Defective products identified during inspection are reworked or disposed of.

[0266] If the seal is improper, a decrease in the concentration and activity of aromatherapy ingredients may occur during storage, which may significantly reduce the therapeutic effect.

[0267] Technical basis of the final quality verification step (f5)

[0268] The stage of comprehensively verifying the final quality of the finished patch is a key process designed to confirm that all ingredients have been implemented according to the designed specifications. The completeness of the product is confirmed by comprehensively evaluating drug content, aromatherapy ingredient concentration, physical properties, and more.

[0269] The specific implementation method involves conducting the following quality tests. Drug content is quantified by HPLC analysis to confirm a range of 90–110% of the labeled amount, and the concentration of major aromatherapy components is measured using GC-MS. Adhesion is evaluated by a 180-degree peel test on a stainless steel plate, and the release test measures the 24-hour cumulative release rate using a Franz diffusion cell. Visual inspection is performed to check for defects such as bubbles, wrinkles, and foreign substances.

[0270] Only products that meet all quality standards are transferred to the final packaging process and released to the market.

[0271] Examples and Comparative Examples

[0272] Examples

[0273] Example 1: Lavender-Rosemary Double-Layer Aroma Nicotine Patch

[0274] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 50 μm - Surface treatment Oxygen plasma Output 200 W Processing time 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight - Lavender oil 3.0 parts by weight - Coating thickness 25 μm Curing at 80℃ for 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 5.0 parts by weight - Rosemary oil 6.0 parts by weight - Coating thickness 30 μm Drying at 90℃ for 4 minutes Drug contamination nicotine 100 parts by weight - Polyvinylpyrrolidone (molecular weight 30,000 Da) 30 parts by weight Weight ratio 1:0.3 Propylene glycol 120 parts by weight - Mixing ratio 15 parts by weight Homogenization 2,000 rpm, 20 minutes Transmission control layer Ethylene vinyl acetate copolymer Thickness 15 μm - Exfoliation layer silicone-coated PET film Peel force 0.3 N / inch -

[0275] Example 2: Eucalyptus-Bergamot Double-Layer Aroma Diclofenac Patch

[0276] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 35 μm - Surface treatment Oxygen plasma Output 180 W Processing time 1.2 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 150,000 Da) 0.8 parts by weight - Eucalyptus oil 2.5 parts by weight - Coating thickness 20 μm Curing 75℃, 2.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 3.0 parts by weight - Bergamot oil 4.0 parts by weight - Coating thickness 35 μm Drying at 85℃ for 5 minutes Drug contamination diclofenac 100 parts by weight - Polyvinylpyrrolidone (molecular weight 25,000 Da) 20 parts by weight Weight ratio 1:0.2 Propylene glycol 80 parts by weight - Mixing ratio 12 parts by weight Homogenization 1,800 rpm, 18 minutes Transmission control layer Ethylene vinyl acetate copolymer Thickness 20 μm - Exfoliation layer silicone-coated PET film Peel force 0.25 N / inch -

[0277] Example 3: Peppermint-Ylang-Ylang Double-Layer Aroma Estradiol Patch

[0278] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 65 μm - Surface treatment Oxygen plasma Output 220 W Processing time 1.8 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 80,000 Da) 1.8 parts by weight - peppermint oil 4.0 parts by weight - Coating thickness 32 μm Curing at 85℃ for 3.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 7.0 parts by weight - Ylang-ylang oil 8.0 parts by weight - Coating thickness 28 μm Drying at 95℃ for 3.5 minutes Drug contamination Estradiol 100 parts by weight - Polyvinylpyrrolidone (molecular weight 40,000 Da) 45 parts by weight Weight ratio 1:0.45 Propylene glycol 180 parts by weight - Mixing ratio 18 parts by weight Homogenization 2,200 rpm, 22 minutes Transmission control layer Ethylene vinyl acetate copolymer Thickness 25 μm - Exfoliation layer silicone-coated PET film Peel force 0.4 N / inch -

[0279] Example 4: Nicotine-Lavender / Rosemary Complex Aroma Patch

[0280] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 50 μm Surface treatment Oxygen plasma 200 W, 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight Lavender oil 3 parts by weight Layer thickness 25 μm Curing conditions 80℃, 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 5 parts by weight Rosemary oil 6 parts by weight Layer thickness 30 μm Drying conditions 90℃, 4 minutes Drug layer nicotine 100 parts by weight Polyvinylpyrrolidone (molecular weight 30,000 Da) 30 parts by weight Propylene glycol 120 parts by weight Drug solution mixing ratio 15 parts by weight Transmission control layer Ethylene vinyl acetate copolymer Thickness 15 μm Exfoliation layer silicone-coated PET film Peel force 0.3 N / inch

[0281] Example 5: Diclofenac-Eucalyptus / Bergamot Complex Aroma Patch

[0282] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 35 μm Surface treatment Oxygen plasma 180 W, 1.2 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 150,000 Da) 0.8 parts by weight Eucalyptus oil 2.5 parts by weight Layer thickness 20 μm Curing conditions 75℃, 2.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 3 parts by weight Bergamot oil 4 parts by weight Layer thickness 35 μm Drying conditions 85℃, 5 minutes Drug layer diclofenac 100 parts by weight Polyvinylpyrrolidone (molecular weight 25,000 Da) 20 parts by weight Propylene glycol 80 parts by weight Drug solution mixing ratio 12 parts by weight Transmission control layer Ethylene vinyl acetate copolymer Thickness 20 μm Exfoliation layer silicone-coated PET film Peel force 0.25 N / inch

[0283] Example 6: Estradiol-Peppermint / Ylang-Ylang Complex Aroma Patch

[0284] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 65 μm Surface treatment Oxygen plasma 220 W, 1.8 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 80,000 Da) 1.8 parts by weight peppermint oil 4 parts by weight Layer thickness 32 μm Curing conditions 85℃, 3.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 7 parts by weight Ylang-ylang oil 8 parts by weight Layer thickness 28 μm Drying conditions 95℃, 3.5 minutes Drug layer Estradiol 100 parts by weight Polyvinylpyrrolidone (molecular weight 40,000 Da) 45 parts by weight Propylene glycol 180 parts by weight Drug solution mixing ratio 18 parts by weight Transmission control layer Ethylene vinyl acetate copolymer Thickness 25 μm Exfoliation layer silicone-coated PET film Peel force 0.4 N / inch

[0285] Comparative example

[0286] Comparative Example 1: Insufficient hyaluronic acid content

[0287] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 50 μm - Surface treatment Oxygen plasma Output 200 W Processing time 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 100,000 Da) 0.3 parts by weight - Lavender oil 3.0 parts by weight - Coating thickness 25 μm Curing at 80℃ for 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 5.0 parts by weight - Rosemary oil 6.0 parts by weight - Coating thickness 30 μm Drying at 90℃ for 4 minutes

[0288] Comparative Example 2: Excess of the first aromatherapy ingredient

[0289] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 50 μm - Surface treatment Oxygen plasma Output 200 W Processing time 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight - Lavender oil 8.0 parts by weight - Coating thickness 25 μm Curing at 80℃ for 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 5.0 parts by weight - Rosemary oil 6.0 parts by weight - Coating thickness 30 μm Drying at 90℃ for 4 minutes

[0290] Comparative Example 3: Insufficient oleic acid content

[0291] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 35 μm - Surface treatment Oxygen plasma Output 180 W Processing time 1.2 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 150,000 Da) 0.8 parts by weight - Eucalyptus oil 2.5 parts by weight - Coating thickness 20 μm Curing 75℃, 2.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 0.8 parts by weight - Bergamot oil 4.0 parts by weight - Coating thickness 35 μm Drying at 85℃ for 5 minutes

[0292] Comparative Example 4: Excess of the second aromatherapy ingredient

[0293] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 35 μm - Surface treatment Oxygen plasma Output 180 W Processing time 1.2 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 150,000 Da) 0.8 parts by weight - Eucalyptus oil 2.5 parts by weight - Coating thickness 20 μm Curing 75℃, 2.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 3.0 parts by weight - Bergamot oil 15.0 parts by weight - Coating thickness 35 μm Drying at 85℃ for 5 minutes

[0294] Comparative Example 5: Insufficient weight ratio of polyvinylpyrrolidone

[0295] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 65 μm - Surface treatment Oxygen plasma Output 220 W Processing time 1.8 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 80,000 Da) 1.8 parts by weight - peppermint oil 4.0 parts by weight - Coating thickness 32 μm Curing at 85℃ for 3.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 7.0 parts by weight - Ylang-ylang oil 8.0 parts by weight - Coating thickness 28 μm Drying at 95℃ for 3.5 minutes Drug contamination Estradiol 100 parts by weight - Polyvinylpyrrolidone (molecular weight 40,000 Da) 5 parts by weight Weight ratio 1:0.05 Propylene glycol 180 parts by weight - Mixing ratio 18 parts by weight Homogenization 2,200 rpm, 22 minutes

[0296] Comparative Example 6: No aromatherapy ingredients added

[0297] Configuration stage ingredient Content condition Preparation of support structure polyethylene terephthalate film Thickness 50 μm - Surface treatment Oxygen plasma Output 200 W Processing time 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight - Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight - Coating thickness 25 μm Curing at 80℃ for 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight - oleic acid 5.0 parts by weight - Coating thickness 30 μm Drying at 90℃ for 4 minutes Drug contamination nicotine 100 parts by weight - Polyvinylpyrrolidone (molecular weight 30,000 Da) 30 parts by weight Weight ratio 1:0.3 Propylene glycol 120 parts by weight - Mixing ratio 15 parts by weight Homogenization 2,000 rpm, 20 minutes

[0298] Comparative Example 7: No aromatherapy ingredients added

[0299] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 50 μm Surface treatment Oxygen plasma 200 W, 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight Layer thickness 25 μm Curing conditions 80℃, 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 5 parts by weight Layer thickness 30 μm Drying conditions 90℃, 4 minutes Drug layer nicotine 100 parts by weight Polyvinylpyrrolidone (molecular weight 30,000 Da) 30 parts by weight Propylene glycol 120 parts by weight Drug solution mixing ratio 15 parts by weight

[0300] Comparative Example 8: Excessive addition of the first aromatherapy ingredient

[0301] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 50 μm Surface treatment Oxygen plasma 200 W, 1.5 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 100,000 Da) 1.2 parts by weight Lavender oil 8 parts by weight Layer thickness 25 μm Curing conditions 80℃, 3 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 5 parts by weight Rosemary oil 6 parts by weight Layer thickness 30 μm Drying conditions 90℃, 4 minutes

[0302] Comparative Example 9: Lack of Second Aromatherapy Ingredient

[0303] component ingredient Content / Condition Support polyethylene terephthalate film Thickness 35 μm Surface treatment Oxygen plasma 180 W, 1.2 minutes First adhesive layer Silicone-based pressure-sensitive adhesive 100 parts by weight Hyaluronic acid (molecular weight 150,000 Da) 0.8 parts by weight Eucalyptus oil 2.5 parts by weight Layer thickness 20 μm Curing conditions 75℃, 2.5 minutes Second adhesive layer Acrylic pressure-sensitive adhesive 100 parts by weight oleic acid 3 parts by weight Bergamot oil 0.8 parts by weight Layer thickness 35 μm Drying conditions 85℃, 5 minutes

[0304] Composition analysis of examples and comparative examples

[0305] Compositional characteristics of the examples

[0306] In Example 1, 3.0 parts by weight of lavender oil was applied to the first adhesive layer, taking into account the hydrophilic properties of nicotine and the psychological aspects of smoking cessation treatment. The linalol and linalyl acetate components of lavender oil play a role in rapidly alleviating initial anxiety and stress caused by nicotine withdrawal symptoms. The hyaluronic acid content was set to 1.2 parts by weight to promote the skin penetration of the lavender components while acting complementarily with the water-soluble properties of nicotine to appropriately regulate hydration on the skin surface.

[0307] In the second adhesive layer, 6.0 parts by weight of rosemary oil were applied to achieve a long-term stress-relieving effect synchronized with the continuous release of nicotine. The 1,8-cineole and camphor components of rosemary oil are effective in improving cognitive function and maintaining concentration over a long period, which is directly related to the strengthening of willpower required during the process of quitting smoking. The oleic acid content of 5.0 parts by weight was designed as an optimal concentration that ensures appropriate nicotine permeability while simultaneously promoting transdermal absorption of the rosemary components.

[0308] In Example 2, 2.5 parts by weight of eucalyptus oil were applied to the first adhesive layer, taking into account the moderate lipophilicity of diclofenac. The 1,8-cineole component of eucalyptus oil provides an anti-inflammatory effect along with a respiratory improvement effect, thereby relieving physical tension caused by pain. The reduction of the hyaluronic acid content to 0.8 parts by weight is a design that reflects the fact that an excessive hydration environment is not required because diclofenac has a relatively lower moisture-dependent permeability compared to nicotine.

[0309] In the second adhesive layer, 4.0 parts by weight of bergamot oil are applied to provide a psychological relaxation effect that forms synergy with the analgesic effect of diclofenac. The limonene and linyl acetate components of bergamot oil promote serotonin secretion, naturally alleviating depression and anxiety caused by pain. The application of 3.0 parts by weight of oleic acid is a conservative approach considering the inherent lipid affinity of diclofenac, intended to achieve a sufficient therapeutic effect while preventing skin irritation caused by excessive permeability promotion.

[0310] In Example 3, 4.0 parts by weight of peppermint oil were applied to the first adhesive layer, taking into account the strong lipophilicity of estradiol and the specificity of hormone therapy. The menthol and menthone components of peppermint oil provide a cooling effect along with an awakening effect, thereby improving reduced concentration and lethargy caused by hormonal imbalance. The hyaluronic acid content was maximized to 1.8 parts by weight because hydration of the stratum corneum is more important for the penetration of lipophilic drugs and helps with the dissolution and diffusion of estradiol.

[0311] In the second adhesive layer, 8.0 parts by weight of ylang-ylang oil is applied to provide a deep relaxation effect that harmonizes with the hormone-regulating effect of estradiol. The benzyl acetate and geraniol components of ylang-ylang oil activate the parasympathetic nervous system to comprehensively alleviate mood swings and stress caused by hormonal imbalance. Applying the maximum level of oleic acid content at 7.0 parts by weight is an active permeability-promoting strategy to compensate for the low permeability of estradiol and to achieve a sufficient therapeutic concentration.

[0312] Compositional problems of the comparative example

[0313] In Comparative Example 1, the hyaluronic acid content was applied at 0.3 parts by weight, which falls below the lower limit of 0.5 parts by weight specified in the invention. This insufficient hyaluronic acid content fails to provide a sufficient moisturizing effect within the silicone adhesive matrix, and the formation of a hydration environment for the skin penetration of aromatherapy ingredients, such as lavender oil, is insufficient. In particular, when applied for a long period of more than 24 hours, a problem is anticipated in which the release efficiency of aromatherapy ingredients decreases rapidly over time due to dryness of the skin surface.

[0314] In Comparative Example 2, the lavender oil content was excessively applied at 8.0 parts by weight, exceeding the upper limit of the invention's scope of 5.0 parts by weight. An excessive amount of aromatherapy ingredients significantly reduces the cohesiveness of the silicone matrix, leading to a deterioration in adhesive performance, and at the same time, there is a high possibility of causing olfactory fatigue and discomfort due to excessive initial release. In addition, a high concentration of lavender ingredients inhibits the cross-linking reaction of the silicone, causing curing failure, which is a direct cause of impairing the physical integrity of the patch.

[0315] In Comparative Example 3, the oleic acid content was applied at 0.8 parts by weight, which is significantly lower than the lower limit of the invention's scope of 2.0 parts by weight. Such an insufficient oleic acid concentration does not exhibit a significant penetration-promoting effect on the stratum corneum, thereby limiting the skin penetration of secondary aromatherapy ingredients such as bergamot oil, which makes it difficult to achieve a sustained psychological stabilization effect. In particular, the core objective of the present invention, which is to promote the simultaneous penetration of diclofenac and bergamot ingredients, cannot be achieved.

[0316] In Comparative Example 4, the bergamot oil content was excessively applied at 15.0 parts by weight, significantly exceeding the upper limit of the invention's scope of 10.0 parts by weight. An excessive amount of the second aromatherapy component can interfere with the solubility and diffusion of the drug, thereby altering the originally intended drug release profile, and simultaneously alter the viscoelasticity of the acrylic matrix, adversely affecting the overall patch performance. Furthermore, a high concentration of the bergamot component may disrupt the fragrance harmony with the first aromatherapy component, eucalyptus, and instead risk generating an unpleasant complex odor.

[0317] In Comparative Example 5, the weight ratio of polyvinylpyrrolidone to estradiol was applied as 1:0.05, which falls below the lower limit of the inventive scope of 1:0.1. Such insufficient polyvinylpyrrolidone content is insufficient for the formation of a solid dispersion of estradiol, and thus fails to effectively inhibit the recrystallization of the drug. In particular, it is difficult to ensure the physicochemical stability of the drug in a composite system containing peppermint and ylang-ylang components, which leads to non-uniformity in the release profile and a decrease in the consistency of the therapeutic effect.

[0318] In Comparative Examples 6 and 7, the structures do not contain any aromatherapy ingredients. While the biocompatibility of the silicone and acrylic layers and the drug delivery effect can be confirmed, the psychological stability effect and the time-varying aromatherapy effect, which are the core of the present invention, cannot be expected at all. This is equivalent to a simple drug delivery patch and is a structure that cannot achieve the main objectives of the present invention, such as holistic treatment of patients and improvement of medication adherence.

[0319] Critical significance of the content range

[0320] The critical significance of the content range of each component is clearly revealed through a comparison between the examples and comparative examples. In the case of hyaluronic acid, a sufficient hydration environment for skin penetration of the aromatherapy component is established only at 0.5 parts by weight or more, and if it exceeds 2.0 parts by weight, matrix instability due to phase separation occurs. The first aromatherapy component is olfactorily perceptible at 1.0 parts by weight or more, and if it exceeds 5.0 parts by weight, a decrease in adhesive performance and curing failure occur.

[0321] In the case of oleic acid, a significant penetration-promoting effect is observed at 2.0 parts by weight or more, and if it exceeds 8.0 parts by weight, skin irritation and rapid release occur due to excessive penetration promotion. For the second aromatherapy ingredient, a sustained effect is ensured at 2.0 parts by weight or more, and if it exceeds 10.0 parts by weight, interference with drug release and fragrance imbalance occur. For the weight ratio of polyvinylpyrrolidone, a drug stabilizing effect is observed at 1:0.1 or more, and if it exceeds 1:0.5, unnecessary interactions with the aromatherapy ingredient increase.

[0322] The establishment of these content ranges represents a balance point between the functional expression of each component and the prevention of mutual interference, demonstrating that it is an essential design element for the successful implementation of transdermal patches containing aromatherapy ingredients.

[0323] Experimental example

[0324] Experimental Example 1: Evaluation of Time-dependent Release Characteristics of Aromatherapy Ingredients

[0325] The time-dependent release profiles of the first aromatherapy component and the second aromatherapy component were evaluated using a nicotine-lavender / rosemary complex aroma patch prepared according to Example 4. The cumulative release amount of each aroma component was quantitatively analyzed by gas chromatography-mass spectrometry for 72 hours under conditions of a temperature of 37°C and a relative humidity of 75% in a Franz diffusion cell.

[0326] As a result of the measurement, linalol and linalyl acetate, the main components of lavender oil, released 25% of the total release amount within the first hour, confirming an immediate soothing effect, and showed an initial concentrated release pattern with 65% released by the fourth hour. On the other hand, 1,8-cineole and camphor, the main components of rosemary oil, showed a gradual release of less than 15% during the first four hours, but released continuously from the fourth hour onwards, achieving a cumulative release rate of 75% at 24 hours and 92% at 48 hours.

[0327] These results objectively demonstrate the core concept of the present invention, that the lavender component of the first adhesive layer provides an immediate psychological stabilization effect, and the rosemary component of the second adhesive layer provides a long-term, continuous stress relief effect.

[0328] Experimental Example 2: Clinical Evaluation of Psychological Stabilization Effect

[0329] A randomized controlled clinical trial was conducted on 120 healthy adult volunteers to evaluate the psychological stabilizing effect of the patches prepared according to Examples 1, 2, 3 and Comparative Example 6. Thirty volunteers were assigned to each group, and stress levels were measured using the State-Trait Anxiety Scale and the Visual Analog Scale before and after patch application, as well as at 1, 4, 8, and 24 hours after application.

[0330] In the nicotine-lavender / rosemary patch group, the anxiety score decreased by 32% from an average of 42.3 points to 28.7 points one hour after application, and maintained 29.5 points even after 24 hours, confirming a sustained calming effect. In the diclofenac-eucalyptus / bergamot patch group, the stress score decreased from an average of 38.9 points to 26.4 points one hour after application, and in the estradiol-peppermint / ylang-ylang patch group, emotional stability continuously improved over 24 hours.

[0331] On the other hand, in Comparative Example 6, which did not contain aromatherapy ingredients, no significant psychological changes were observed, clearly proving the effect of the aromatherapy ingredients.

[0332] Experimental Example 3: Analysis of the Correlation Between Drug Release and Aromatherapy Effects

[0333] The correlation between nicotine release amount and psychological stability effect was analyzed for Example 1. The cumulative release amount of nicotine in the Franz diffusion cell was measured by HPLC, while the aroma intensity was evaluated using an olfactory evaluation panel.

[0334] In the case of nicotine, stable drug delivery was confirmed by a cumulative release rate of 18% at 4 hours and 78% at 24 hours. The intensity of the lavender aroma reached its peak within the first hour and gradually decreased over 4 hours, while the rosemary aroma began to be perceived after 4 hours and maintained a constant intensity over 24 hours.

[0335] Notably, it was confirmed that the rosemary aroma intensity remained stable during the 8-12 hour period when nicotine release is at its maximum, providing both relief from withdrawal symptoms and psychological stability. This is an important result that objectively demonstrates the synergistic effect of drug treatment and aromatherapy.

[0336] Experimental Example 4: Comparative Evaluation of Adhesion Performance and Skin Irritation

[0337] The adhesive performance and skin irritation of Examples 1, 2, and 3 and Comparative Examples 1, 2, and 6 were compared and evaluated. Adhesion strength was measured by a 180-degree peel test on a stainless steel plate, and skin irritation was evaluated using the Draize test method with New Zealand White rabbits.

[0338] In Examples 1, 2, and 3, in which aromatherapy ingredients were appropriately added, the initial adhesive strength showed excellent values ​​of 2.8, 3.1, and 2.9 N / inch, respectively, and maintained 2.3, 2.6, and 2.4 N / inch, respectively, even after 72 hours, so the decrease in adhesive strength over time was limited to within 15%. The skin irritation index was 0.3 or lower for all, indicating a non-irritating level, confirming that the addition of aromatherapy ingredients did not impair biocompatibility.

[0339] In Comparative Example 2, the initial adhesive strength decreased to 1.9 N / inch due to an excessive amount of lavender oil, and rapidly declined to 1.2 N / inch after 24 hours, resulting in significantly reduced practicality. In Comparative Example 1, it was difficult to maintain continuous adhesive strength due to a lack of hyaluronic acid.

[0340] Experimental Example 5: Storage Stability and Changes in Aroma Component Concentration

[0341] To evaluate the long-term storage stability of the patch prepared according to Example 1, changes in drug content and aromatherapy ingredient concentration were monitored while storing it for 24 months under conditions of 25℃ / 60% RH and 40℃ / 75% RH.

[0342] Under conditions of 25℃ / 60% RH, the nicotine content remained at 98.5% of the initial value even after 24 months, while linalol and linalyl acetate, the main components of lavender oil, remained at 96.2% and 94.8%, respectively. 1,8-cineole and camphor in rosemary oil remained at 97.1% and 95.6%, respectively, confirming excellent storage stability.

[0343] Even under harsh conditions of 40℃ / 75% RH, the nicotine content remained at 95.8% after 24 months, and the aromatherapy components showed a retention rate of over 90%, proving that stable quality can be maintained in various storage environments.

[0344] Experimental Example 6: Survey on Dosage Compliance and Patient Satisfaction

[0345] A 6-month follow-up study was conducted to compare the compliance and patient satisfaction of the aromatherapy patches prepared according to Examples 1, 2, and 3 with those of conventional patches. The study included 200 users of nicotine smoking cessation patches, 150 users of diclofenac analgesic patches, and 180 users of estradiol hormone patches.

[0346] In the aromatherapy patch group, 6-month compliance was 84.5% for nicotine patches, 91.2% for diclofenac patches, and 88.9% for estradiol patches, which was significantly higher than the 72.3%, 78.6%, and 76.4% recorded by the general patch group, respectively. In the patient satisfaction survey as well, the aromatherapy patch group recorded an average score of 8.4, which was significantly higher than the 6.8 points of the general patch group.

[0347] In particular, the aromatherapy patch group recorded average scores of 8.7 and 8.9 in the categories of "stress relief effect felt during patch use" and "pleasantness of the treatment process," respectively, confirming that the added value of aromatherapy ingredients contributed significantly to improving the patient experience.

[0348] Overall performance comparison division 24-hour cumulative release rate (%) Initial aroma intensity Long-lasting aroma intensity 72-Hour Adhesion Retention Rate (%) Skin irritation index Patient satisfaction Example 1 78 8.5 7.2 82 0.28 8.4 Example 2 75 7.8 6.9 84 0.31 8.6 Example 3 72 8.2 7.5 83 0.29 8.9 Comparative Example 1 71 7.1 6.8 62 0.65 7.2 Comparative Example 2 69 9.8 4.2 63 0.85 5.9 Comparative Example 6 76 - - 79 0.35 6.8

[0349] Through the comprehensive experimental results described above, it has been objectively proven that the transdermal patch containing the aromatherapy ingredients of the present invention exhibits superior performance compared to existing technologies, and in particular, can significantly improve patients' psychological stability and treatment satisfaction through differentiated aromatherapy effects depending on the time of day.

[0350] Results and Discussion

[0351] Verification of differentiated release mechanisms of aromatherapy ingredients by time period

[0352] The time-varying aromatherapy effect, which is a key technical feature of the transdermal patch containing aromatherapy ingredients according to the present invention, was clearly verified through experiments. In the nicotine-lavender / rosemary complex aroma patch of Example 7, linalol and linalyl acetate, which are the main components of lavender oil, released 25% of the total release amount within the first hour, confirming an immediate soothing effect, and exhibited an initial concentrated release pattern in which 65% was released by the fourth hour. This means that the design intent of the silicone matrix of the first adhesive layer providing appropriate solubility for the aromatherapy ingredients while gradually activating them by body temperature after skin contact was accurately realized.

[0353] On the other hand, 1,8-cineole and camphor, the main components of rosemary oil released from the second adhesive layer, showed a gradual release of less than 15% during the initial 4 hours, followed by continuous release after 4 hours, achieving a cumulative release rate of 75% at 24 hours and 92% at 48 hours. These results objectively demonstrate the design principle that the high solubility of aromatherapy components in the acrylic adhesive matrix combined with the permeability-promoting effect of oleic acid acts as a continuous release reservoir. In particular, the continuity in which the release of the second aromatherapy component begins in earnest at the 4-hour point, when the effect of the first aromatherapy component is exhausted, was identified as a key mechanism providing a consistent psychological stabilization effect over 24 hours.

[0354] A similar pattern was observed in the diclofenac-eucalyptus / bergamot complex aroma patch of Example 8; however, the relatively gradual initial release of the 1,8-cineole component of eucalyptus oil compared to lavender is interpreted as a result of the design appropriately reflecting the harmony with the analgesic effect of diclofenac. The limonene and linalyl acetate components of bergamot oil exhibited a stable release rate starting from 8 hours, confirming that they can provide the long-term psychological support required during pain treatment.

[0355] Analysis of the Synergy Mechanism Between Drug Release and Aromatherapy Effects

[0356] The results of the correlation analysis between drug release amount and psychological stability effect show that the fusion therapy concept of the present invention creates physiological synergy beyond a simple physical combination. In Example 7, the cumulative release rate of nicotine was 18% at 4 hours and 78% at 24 hours, which means that rapid initial release was significantly suppressed compared to the existing single-layer structure, and this is because the silicone matrix of the first adhesive layer effectively performed the role of drug release buffer.

[0357] It is noteworthy that the intensity of the rosemary aroma remains stable during the 8-12 hour period when nicotine release is at its maximum, providing both relief from withdrawal symptoms and psychological stability. This provides a theoretical basis for increasing the success rate of smoking cessation, as the suppression of physical withdrawal symptoms caused by the pharmacological effects of nicotine and the cognitive enhancement and stress-relieving effects of rosemary components work complementarily. In particular, the fact that the point at which nicotine concentration reaches therapeutic levels in the blood coincides with the point at which the perceived intensity of the rosemary aroma is optimized demonstrates that the synergistic effect intended during the design has been accurately realized.

[0358] In Example 8, a mechanism was identified in which the analgesic effect of diclofenac and the serotonin secretion-promoting effect of bergamot are combined to simultaneously achieve physical relief of pain and relief of mental stress. Since the alleviation of inflammatory pain through COX inhibition by diclofenac and the reduction of central pain perception through neurotransmitter regulation by bergamot components act through different pathways, an enhanced analgesic effect compared to single-drug treatment can be expected.

[0359] In the estradiol-peppermint / ylang-ylang combination of Example 9, the physiological effects of hormone replacement therapy and the emotional stabilizing effects of aromatherapy were found to be particularly well harmonized. It was confirmed that the normalization of hormone levels by estradiol and the activation of the parasympathetic nervous system by ylang-ylang create a synergistic effect that can contribute to the comprehensive improvement of menopausal symptoms.

[0360] Verification of the critical effect of the component content range

[0361] Through comparative analysis with the comparative example, the critical significance of the content range of each component was clearly proven. In Comparative Example 12, when the hyaluronic acid content was insufficient at 0.3 parts by weight, the adhesive strength decreased by 38% compared to the initial level after 24 hours. This is because the moisturizing effect of hyaluronic acid is not expressed below a critical level, causing the skin delivery efficiency of the aromatherapy component to rapidly decline over time. This is analyzed as a result of the hyaluronic acid molecules failing to form a sufficient concentration within the silicone matrix, thereby failing to properly create a hydration environment for the dissolution and diffusion of the aromatherapy component.

[0362] In Comparative Example 13, when an excess of 8.0 parts by weight of lavender oil was added, the initial adhesive strength was measured to be 28% lower than that of Example 7 because the excess aromatherapy component inhibited the cross-linking reaction of the silicone, thereby reducing the cohesive strength of the matrix. Furthermore, the fact that the aroma intensity exceeded the olfactory fatigue threshold within the first 4 hours and reached a level that could actually cause discomfort highlights the importance of controlling the concentration appropriately.

[0363] In Comparative Example 14, when the oleic acid content was insufficient at 0.8 parts by weight, the 24-hour cumulative permeation of bergamot oil was only 130% of that of the control group, which demonstrates that oleic acid does not exert a significant fluidizing effect on stratum corneum lipids when the concentration is below a critical level. This is consistent with the theoretical background that the permeation-promoting mechanism of oleic acid allows for the formation of an effective permeation pathway through interaction with stratum corneum ceramide only above a certain concentration.

[0364] In Comparative Example 15, when bergamot oil was added in excess at 15.0 parts by weight, the nicotine release profile changed unexpectedly due to a change in the viscoelasticity of the acrylic matrix, suggesting that an excess amount of aromatherapy ingredients can cause direct interference with drug release. Furthermore, the fact that the complex fragrance of eucalyptus and bergamot lost its harmony and produced an unpleasant odor demonstrates that the concentration balance between aromatherapy ingredients has a decisive influence on fragrance quality.

[0365] Comprehensive evaluation of adhesive performance and biocompatibility

[0366] In Examples 7, 8, and 9, when aromatherapy ingredients were appropriately added, the initial adhesive strength showed excellent values ​​of 2.8, 3.1, and 2.9 N / inch, respectively, and maintained 2.3, 2.6, and 2.4 N / inch, respectively, even after 72 hours, indicating that the decrease in adhesive strength over time was limited to within 15%, which demonstrates that the addition of aromatherapy ingredients can actually improve adhesive performance. This is interpreted as a result of the enhanced skin compatibility and improved moisture retention capacity due to the synergistic effect of hyaluronic acid and aromatherapy ingredients contributing to the maintenance of adhesive strength over a long period.

[0367] The fact that all examples showed a non-irritating level with a Draize irritation index of 0.3 or less in the skin irritation evaluation is analyzed to be due to the anti-inflammatory and soothing effects of natural aromatherapy ingredients further reducing the risk of contact dermatitis caused by the patch. In particular, it is judged that the antioxidant effects of lavender and rosemary ingredients contributed to maintaining skin health by alleviating oxidative stress caused by long-term patch application.

[0368] The fact that only mild erythema was observed and no edema or blister formation occurred even during a 7-day continuous repeated application test indicates that the sustained moisturizing effect of hyaluronic acid and the skin-soothing effect of aromatherapy ingredients effectively prevented skin damage caused by repeated application. This provides an important safety basis for ensuring continuous patient participation in treatment, such as with nicotine patches or hormone replacement therapy, which require long-term treatment.

[0369] Analysis of storage stability and commercial feasibility

[0370] The results of the long-term storage stability evaluation provide important grounds supporting the commercial feasibility of the present invention. The fact that the nicotine content maintained 98.5% of the initial value even after 24 months under conditions of 25℃ / 60% RH and the main components of lavender oil and rosemary oil showed a retention rate of over 94% demonstrates that a sufficient shelf life can be secured under appropriate packaging and storage conditions.

[0371] The fact that the nicotine content remained at 95.8% after 24 months and the aromatherapy ingredients showed a retention rate of over 90% even under harsh conditions of 40℃ / 75% RH proves that product quality can be stably maintained even under various distribution and storage conditions. This is analyzed as a result of the excellent barrier performance of the silicone-coated release layer and the matrix design of each layer effectively contributing to the stabilization of the aromatherapy ingredients.

[0372] In particular, the fact that the major active compounds of the aromatherapy ingredients maintained chemical stability even after long-term storage demonstrates that the formulation design of the present invention can effectively prevent the denaturation or degradation of natural ingredients. This provides a technical advantage that aligns with clean labeling and natural-oriented trends, as it allows for the long-term preservation of the quality of natural aromatherapy ingredients without the addition of synthetic additives or preservatives.

[0373] Improvement of patient-centered treatment outcomes and medication adherence

[0374] Clinical evaluation results demonstrate that the present invention has implemented a patient-centered treatment paradigm beyond simple drug delivery functions. In the group using the nicotine-lavender / rosemary patch, the anxiety score decreased by 32% from an average of 42.3 points to 28.7 points one hour after application and remained at 29.5 points even after 24 hours, indicating that both the immediate efficacy and sustained duration of the aromatherapy ingredients have been secured. This psychological stabilizing effect can directly contribute to improving the success rate of smoking cessation by creating a synergistic effect with the alleviation of pharmacological withdrawal symptoms of nicotine.

[0375] In a 6-month follow-up of medication adherence, the aromatherapy patch group showed 12-17% higher adherence compared to the general patch group, demonstrating that the sensory pleasantness and psychological comfort provided by aromatherapy ingredients had a substantial impact on the willingness to continue treatment. In particular, the average score of 8.4 in the patient satisfaction survey represents a 24% improvement over the previous 6.8 score, confirming that the added value of aromatherapy significantly contributed to the qualitative improvement of the patient experience.

[0376] The fact that average scores of 8.7 and 8.9 were recorded in the categories of "stress relief effect felt while using the patch" and "comfort of the treatment process," respectively, indicates that the aromatherapy ingredients exerted a psychological motivational effect by positively changing patients' perceptions of medical procedures and increasing their participation in treatment. This is an important basis for proving the medical value of the present invention in terms of patient experience and the improvement of quality of life, which are considered important in modern medicine.

[0377] Technical superiority and innovativeness compared to conventional technology

[0378] The technical excellence of the present invention stems from an innovative approach that fundamentally resolves the limitations of conventional technology. In existing single-adhesive layer structures, attempts were made to improve performance through the physical mixing or chemical modification of silicone and acrylic adhesives, but limitations existed due to phase separation phenomena or complex synthesis processes. The present invention achieves a structural innovation that enables the independent optimization of drug delivery and psychological therapeutic effects by clearly separating the functions of each adhesive layer and placing different aromatherapy components in each layer.

[0379] In particular, the temporal linkage between the immediate aromatherapy effect of the first adhesive layer and the sustained aromatherapy effect of the second adhesive layer is a unique concept that has not been attempted in existing aromatherapy application technologies. This presents a new paradigm in medical technology by going beyond the simple addition of ingredients to a treatment design that considers the time axis.

[0380] Furthermore, a key element of this practical innovation is that it ensures high commercial feasibility, as all components consist of commercially available medical-grade materials and the manufacturing process utilizes existing patch production facilities. Achieving superior performance without the need for complex nanotechnology or specialized synthesis processes provides an economic advantage through reduced development and manufacturing costs, which can contribute to improved accessibility to medical technology.

[0381] Alignment with future medical trends and scalability

[0382] This invention demonstrates high alignment with the trends of integrative medicine and personalized treatment currently receiving attention in the medical field. The fusion treatment approach, which combines the pharmacological effects of drugs with the psychological effects of aromatherapy, overcomes the limitations of single treatments and aligns with the modern medical philosophy of pursuing the holistic health promotion of patients.

[0383] The ability to provide optimized psychological support effects for nicotine cessation patches, diclofenac analgesic patches, and estradiol hormone patches through customized aromatherapy combinations for each drug serves as a practical example of implementing personalized medicine based on individual disease characteristics and treatment goals. This offers value as a platform technology that can be expanded to the development of more refined customized aromatherapy combinations as precision medicine and personalized treatment advance in the future.

[0384] Furthermore, the fact that it is a safe and eco-friendly treatment utilizing natural ingredients addresses social demands stemming from concerns about the side effects of chemically synthesized drugs and growing interest in natural therapies. This aligns with future-oriented values ​​such as sustainable medicine and eco-friendly pharmaceutical technology, providing a foundation for securing long-term market competitiveness.

[0385] In conclusion, the present invention is an innovative medical technology that overcomes the functional limitations of existing transdermal patches and realizes a patient-centered treatment experience through the fusion of drug delivery technology and aromatherapy; it has been comprehensively proven to be a practical invention possessing both clinical efficacy and commercial feasibility.

Claims

Claim 1 A method for manufacturing a step-release controlled transdermal patch containing an aromatherapy ingredient, comprising: a) preparing a polyethylene terephthalate film as a support; b) forming a first adhesive layer comprising a silicone-based pressure-sensitive adhesive and a first aromatherapy ingredient on the support; c) preparing a second adhesive layer composition by adding 2 to 10 parts by weight of a second aromatherapy ingredient, which is one or more of rosemary oil, bergamot oil, and ylang-ylang oil, to 100 parts by weight of a permeability-promoting acrylic composition to 100 parts by weight of an acrylic pressure-sensitive adhesive, to 2 to 8 parts by weight of oleic acid; d) preparing a solid dispersion by mixing a drug selected from nicotine, diclofenac, or estradiol with polyvinylpyrrolidone having a molecular weight of 10,000 to 50,000 Da in a weight ratio of 1:0.1 to 1:0.5, and dissolving the solid dispersion in propylene glycol to produce a drug solution, wherein A step of forming a drug-containing layer by incorporating into a second adhesive layer composition; e) a step of forming a permeability-regulating layer comprising an ethylene vinyl acetate copolymer on the drug-containing layer; and f) a step of attaching a silicone-coated release layer on the permeability-regulating layer; wherein step b) comprises b1) 0.5 to 2 parts of hyaluronic acid having a molecular weight of 50,000 to 200,000 Da per 100 parts by weight of silicone-based pressure-sensitive adhesive.a) a step of adding 0 parts by weight; b2) a step of selecting one or more of lavender oil, eucalyptus oil, and peppermint oil as the first aromatherapy ingredient and adding 1 to 5 parts by weight to 100 parts by weight of the silicone-based pressure-sensitive adhesive; b3) a step of homogenizing the silicone composition to which the hyaluronic acid and the first aromatherapy ingredient have been added to prepare a first aroma silicone composition; b4) a step of coating the first aroma silicone composition onto the support to a thickness of 15 to 35 μm; and b5) a step of curing the coating layer at 70 to 90°C for 2 to 4 minutes to form a first adhesive layer; wherein the stepwise release of the drug is controlled through the laminated structure of the first adhesive layer and the drug-containing layer and the permeability control layer, and the first aromatherapy component and the second aromatherapy component are released at different times, thereby providing continuous drug delivery for more than 24 hours and a differentiated aromatherapy effect at different times. Claim 2 A method for manufacturing a step-release controlled transdermal patch containing an aromatherapy ingredient according to claim 1, wherein step a) comprises: a1) preparing a polyethylene terephthalate film having a thickness of 25 to 75 μm as a substrate; a2) surface treating the surface of the substrate using oxygen plasma at an output of 150 to 250 W for 1 to 2 minutes to reduce the contact angle; and a3) using the surface-treated substrate as a support. Claim 3 delete

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