A topical administration dressing system for the prevention of infectious diseases after trauma exposure

Abstract

The present application relates to a kind of topical administration dressing system for preventing infectious disease after wound exposure, including patch carrier and the drug depot module arranged on the patch carrier, the patch carrier can be applied to the skin area of wound area or around wound, the drug depot module is loaded with immunologically active component, and in the application state, the immunologically active component is delivered to the body by local release or puncture delivery mode, to induce immunoprotection.The drug depot module is replaceable or non-replaceable delivery module structure, can be selectively configured as drug sustained-release dressing structure, microneedle array structure, lyophilized soluble microneedle structure and split microneedle structure including peripheral support needle and internal drug-loaded needle.The topical administration dressing system can realize the preventive treatment after wound exposure without injection, with the advantages of convenient to use, strong scene adaptability and flexible delivery mode.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and medical device technology, and in particular to a local drug delivery dressing system for preventing infectious diseases after trauma exposure. Specifically, it relates to a non-injectable infectious disease prevention system that delivers immune-active ingredients by being applied to a wound or the skin area surrounding the wound. Background Technology

[0002] Infectious diseases such as tetanus and rabies are usually caused by traumatic exposure. For example, animal bites, cuts from nails or metal objects, or puncture wounds from contaminated objects can all allow pathogenic microorganisms to enter the body through broken skin, leading to infection. To reduce the risk of infection, medical professionals generally recommend prophylactic treatment as soon as possible after trauma, such as vaccination or immunoglobulin administration. Tetanus and rabies vaccines, in particular, usually need to be administered within a specified timeframe after trauma to induce immune protection.

[0003] Currently, the most commonly used preventative method in clinical practice is injectable immunization. In this method, vaccines or immunoglobulins are injected directly into human tissues via a syringe, thereby delivering antigens and stimulating the immune system. However, this method still has certain limitations in practical application. For example, the injection procedure usually needs to be performed by professional medical personnel in a medical institution. In scenarios such as fieldwork, outdoor activities, or sudden trauma, it is often difficult to obtain timely medical care. Furthermore, the injection process may cause pain, discomfort, or psychological resistance, leading to lower compliance among children and certain special populations. In addition, in some grassroots or remote areas, medical resources are relatively insufficient, which may also result in the inability to complete preventative immunization promptly after an injury.

[0004] On the other hand, in routine wound care, people often use adhesive bandages or dressings to cover and protect wounds. Traditional adhesive bandages are mainly used for hemostasis, absorbing exudate, and isolating external contaminants; their structure typically includes a backing layer, an absorbent pad, and an adhesive layer. However, these dressings usually only provide physical protection and simple care and do not have the function of delivering immune-active ingredients to the body to induce immune protection. Furthermore, because the stratum corneum of the skin has a strong barrier function, ordinary dressings are difficult to achieve effective trans-skin delivery; therefore, even with the addition of drug components to the dressing, it is often difficult to achieve the delivery effect required for vaccines or immune-active ingredients.

[0005] In recent years, with the development of transdermal drug delivery technology, some studies have proposed using structures such as microneedle arrays to penetrate the stratum corneum of the skin, thereby achieving transdermal delivery of drugs or vaccines. However, most existing microneedle drug delivery devices are designed for normal skin and are mainly used in medical scenarios such as vaccination or drug administration. They lack specialized structural designs for situations requiring emergency infection prevention after traumatic exposure. Furthermore, existing technologies typically employ a single type of delivery structure, such as a simple microneedle array or a single drug-releasing layer, which lacks flexibility under different trauma conditions or usage scenarios.

[0006] Therefore, current technology still lacks a local drug delivery dressing system that can deliver immunologically active ingredients without injection in trauma exposure scenarios. In particular, when applied to wounds or surrounding skin areas, it is necessary to balance wound care, immunological ingredient delivery, and compatibility between different delivery methods to improve the effectiveness of post-traumatic exposure prevention. Therefore, how to provide a structurally sound local drug delivery dressing system suitable for trauma exposure scenarios and capable of effectively delivering immunologically active ingredients remains a technical problem that needs to be solved in this field. Summary of the Invention

[0007] The purpose of this invention is to provide a local drug delivery dressing system for preventing infectious diseases after trauma exposure, in order to solve the problem that the existing technology mainly relies on injection for immune prophylaxis, which is difficult to implement in a timely manner in the case of sudden trauma and non-medical scenarios. By setting a replaceable drug reservoir module loaded with immune active ingredients on the patch carrier, the dressing system can be applied to the wound area or the skin area around the wound, and deliver the immune active ingredients to the body through local release or puncture delivery, thereby achieving non-injectable prevention of infectious diseases.

[0008] To achieve the above-mentioned technical objectives, the present invention adopts the following technical solution: A local drug delivery dressing system for the prevention of infectious diseases after trauma exposure, comprising: a patch carrier and a drug reservoir module disposed on the patch carrier; The patch carrier is configured to be applied to the wound area or the skin area around the wound. The drug reservoir module is loaded with immune-active ingredients for the prevention of infectious diseases, and the immune-active ingredients are introduced into the body to induce immune protection when the patch is applied. The drug storage module can be a replaceable or non-replaceable delivery module structure. The replaceable delivery module structure can be selectively configured as at least one of the following delivery structures according to the wound condition: Drug-releasing dressing structure for achieving localized sustained release; Microneedle array structure for delivery by piercing the skin around the wound; Microneedle array structure formed from freeze-dried soluble materials; A split microneedle structure including a peripheral support needle and an internal drug-loaded needle. This enables the local delivery of immune-active ingredients to be achieved in trauma exposure scenarios.

[0009] Optionally, the drug reservoir module includes a microneedle array structure disposed on the skin contact side of the patch carrier. The microneedle array structure is configured to penetrate the stratum corneum and / or superficial epidermis when the patch carrier is applied to the skin area around the wound, so that the immunologically active ingredients can be delivered across the skin barrier to local tissues, thereby improving the absorption efficiency of macromolecular immunologically active ingredients in trauma exposure scenarios.

[0010] Optionally, the microneedle array structure includes multiple split microneedle units, each of which includes a peripheral support needle and a drug-loaded needle located inside the peripheral support needle. The peripheral support needle is used to provide the mechanical support strength required for puncture into the skin around the wound, and the drug-loaded needle is used to load and release the immune-active ingredient, so as to improve the effective drug loading and drug delivery accuracy per unit microneedle while ensuring puncture capability.

[0011] Optionally, the peripheral support needle is made of a high-strength biodegradable material, and the drug-carrying needle is made of a soluble biocompatible material. The high-strength biodegradable material includes polylactic acid-glycolic acid copolymer, and the soluble biocompatible material includes one or more of polyvinylpyrrolidone and sodium hyaluronate, so that the split microneedle unit has both structural support function and drug dissolution and release function.

[0012] Optionally, the microneedle array structure is a soluble microneedle array structure, which is formed of soluble polymer material. The immune active ingredient is dispersed inside the microneedle body, and the soluble microneedle array dissolves at least partially within 3-30 minutes after being inserted into the skin around the wound, so that the immune active ingredient is rapidly released in the early stage after trauma exposure.

[0013] Optionally, the soluble microneedle array structure is a soluble microneedle array formed by freeze-drying, and the drug storage module further includes a freeze-drying protection system, which includes one or more of trehalose, mannitol and histidine, to improve the structural stability and bioactivity retention of the immunomodulatory component during the preparation and storage process.

[0014] Optionally, the soluble microneedle array formed by freeze-drying is prepared by a three-stage freeze-drying process, which includes a pre-freezing stage, a primary sublimation stage, and a secondary desorption stage, wherein the temperature of the pre-freezing stage is -40°C to -60°C to obtain a microneedle array structure with room temperature storage stability.

[0015] Optionally, the drug storage module includes a drug sustained-release dressing structure, which is a three-layer composite structure, including an inner wound contact layer, a middle drug sustained-release layer, and a surface fixation layer. The drug sustained-release layer is formed of a polymer sustained-release material and continuously releases the immune active ingredient through diffusion release within 24-72 hours after the patch carrier is applied to the wound area.

[0016] Optionally, the patch carrier includes, from the outside in, a sterile release protective layer, a flexible backing layer, and a skin contact layer. The flexible backing layer provides overall flexible support and adapts to the surface morphology of the wound area. The skin contact layer is used to attach and fix the local drug delivery dressing system to the wound area or the skin area around the wound. The local drug delivery dressing system may also include an optional functional layer disposed in the area adjacent to the drug storage module. The optional functional layer includes one or more of a disinfection and hemostasis layer and an absorbent layer.

[0017] Optionally, the immunologically active ingredient includes one or more of tetanus toxoid, recombinant tetanus protein vaccine, tetanus mRNA vaccine, tetanus human immunoglobulin, and recombinant anti-tetanus neutralizing antibody; and the local drug delivery dressing system is suitable for immediate prophylaxis after trauma exposure, to replace or supplement traditional injectable prophylaxis in home first aid, outdoor work, primary healthcare, or on-site self-rescue conditions.

[0018] The main advantages of this invention compared to existing technologies are as follows: The local drug delivery dressing system provided by this invention sets a drug reservoir module loaded with immune-active ingredients on a patch carrier, and enables the patch carrier to be applied to the wound area or the skin area around the wound. In the applied state, the immune-active ingredients are delivered to the body through local release or transdermal delivery, thereby achieving the prevention of infectious diseases without injection. This effectively solves the problem that the existing technology mainly relies on injection for immune prophylaxis and is difficult to implement in a timely manner in the event of sudden trauma or in non-medical environments, thus improving the timeliness and convenience of post-traumatic exposure prophylaxis.

[0019] This invention designs the drug storage module as a replaceable delivery module structure, enabling the same local drug delivery dressing system to select different delivery structures according to the type of trauma or usage requirements, such as drug sustained-release dressing structure, microneedle array structure, lyophilized soluble microneedle structure or split microneedle structure, thereby improving the system's adaptability and flexibility in different application scenarios.

[0020] When using a microneedle array structure, microneedles are inserted into the skin area around the wound, allowing immune-active ingredients to cross the skin's stratum corneum barrier and directly enter the skin tissue, improving the delivery efficiency of immune-active ingredients. This is beneficial for achieving more effective immune prophylaxis in the early stages after trauma exposure.

[0021] When using a split microneedle structure, by setting up a combination of an outer support needle and an inner drug-carrying needle, the effective drug loading of a unit microneedle can be increased while maintaining sufficient penetration strength, thereby improving the utilization rate of immune active ingredients while ensuring delivery stability.

[0022] When using a lyophilized soluble microneedle structure, a lyophilization protection system is set in the drug storage module to enable the immune-active ingredients to maintain good stability under normal temperature conditions, which is beneficial for the storage and use of this local drug delivery dressing system in scenarios such as home first aid, outdoor activities and primary healthcare. Attached Figure Description

[0023] Figure 1 This is a system structure diagram of the local drug delivery dressing system of the present invention; Figure 2 This is a schematic diagram showing the local drug delivery dressing system of the present invention in contact with the skin and wound; Figure 3 This is a schematic diagram of the structure of the drug storage module of the present invention and a schematic diagram of its contact with skin and wound; Figure 4 This is a schematic diagram of the microneedles in the drug storage module of the present invention. Detailed Implementation

[0024] To make the objectives, technical solutions, and beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the following specific embodiments are only for explaining the invention and are not intended to limit the scope of protection of the invention. Equivalent substitutions or conventional modifications made by those skilled in the art based on the content of this specification without departing from the concept of the invention should all fall within the scope of protection of the invention.

[0025] This invention provides a local drug delivery dressing system for post-exposure prophylaxis of infectious diseases. The local drug delivery dressing system is preferably a band-aid, dressing patch, hydrocolloid patch, foam dressing, or hydrogel patch type local application structure, capable of being directly attached to the wound area or surrounding skin area, and delivering immune-active ingredients to the body through a provided drug reservoir module, thereby achieving prevention of infectious diseases without injection. In this embodiment, tetanus is preferred, and in extended embodiments, it can also be rabies or other infectious diseases suitable for post-exposure prophylaxis via local application. Document 4 defines this inventive concept as a dressing system that "achieves non-injectable immune protection by delivering tetanus prophylactic active ingredients through local application."

[0026] like Figure 1 and Figure 2 As shown, the local drug delivery dressing system in this embodiment, such as a band-aid, mainly includes a patch carrier 1 and a drug reservoir module 2 disposed on the patch carrier 1. The patch carrier 1 is used to attach to the wound area or the skin area around the wound, playing a role in bearing, fixing, sealing and physical protection; the drug reservoir module 2 is used to load immune-active ingredients, and in the patch state, the immune-active ingredients are introduced into the body through diffusion release, microneedle puncture release, soluble dissolution release or other local delivery methods to induce immune protection.

[0027] Preferably, the local drug delivery dressing system may include, from the outside in, a release protective layer, a flexible backing layer, a drug reservoir module, an optional functional layer, and a skin contact layer. The release protective layer is preferably made of medical PET release film, silicone release paper, laminated release sheet, or other peelable protective materials. Its function is to maintain the sterility of the drug reservoir module and skin contact layer before product storage, transportation, and use, prevent adhesion contamination, and allow for removal by the operator during use. The release protective layer can be a single sheet or composed of two split release sheets along the center line, allowing the user to peel it off sequentially from the center outwards, improving ease of operation.

[0028] The flexible backing layer is preferably a polyurethane film, medical non-woven fabric film, composite breathable film, or other flexible medical film materials. Its main function is to provide overall support for the entire dressing system, maintain the stability of the patch's shape, and adapt to the curvature changes of different body parts such as the hands, feet, and elbows. Furthermore, the flexible backing layer can also have waterproof, breathable, and antibacterial properties to maintain local environmental stability after the wound is exposed, preventing external moisture, dust, and contaminants from entering the wound area.

[0029] The skin contact layer is preferably a medical pressure-sensitive adhesive layer, a hypoallergenic adhesive layer, or a hydrogel adhesive layer disposed at the edge area of ​​the patch, used to reliably fix the entire local drug delivery dressing system to the wound area or the skin around the wound. Considering that the present invention is mainly aimed at on-site emergency scenarios after trauma exposure, the skin contact layer 15 is preferably arranged in the annular area around the wound, thereby avoiding the adhesive layer directly covering the center of the wound and reducing interference with wound healing.

[0030] Optional functional layers are located between the drug storage module and the wound contact area, or adjacent to the drug storage module, to further realize additional functions such as disinfection, hemostasis, exudate absorption, contamination isolation, or wound healing in addition to the delivery of immune active ingredients.

[0031] In a preferred embodiment, the optional functional layer may include a sterile absorbent matrix, such as a layer of absorbent cotton, a sponge absorbent layer, a chitosan fiber layer, an alginate absorbent layer, or a cellulose absorbent layer, to absorb wound exudate and provide coverage and protection for the wound. Furthermore, the optional functional layer may also incorporate disinfectant and antibacterial components such as povidone-iodine, povidone-iodine, chlorhexidine, silver ions, and metronidazole, or healing-promoting components such as recombinant human epidermal growth factor, collagen, and peptides, to constitute an integrated wound treatment dressing system.

[0032] It should be noted that the patch carrier is not limited to the traditional narrow strip bandage appearance. It can also be designed as a rectangular, round, oval, butterfly, or irregularly shaped piece depending on the actual application area. When used for large-area abrasions, lacerations, or irregular wounds, the patch carrier can adopt a larger dressing structure. When used for highly mobile areas such as fingers and heels, the patch carrier can also adopt a bandage structure with extended fixing wings to enhance the adhesion stability.

[0033] The drug storage module 2 is the core functional unit of this invention. It is disposed on the patch carrier 1 and loaded with immunologically active ingredients. The immunologically active ingredients preferably include one or more of tetanus toxoid, recombinant tetanus protein vaccine, tetanus mRNA vaccine, tetanus human immunoglobulin, and recombinant anti-tetanus neutralizing antibody; in extended embodiments, rabies prophylactic active ingredients may also be loaded to achieve combined prevention.

[0034] Unlike traditional adhesive bandages that only cover wounds, stop bleeding, or isolate contamination, the drug reservoir module in this invention is designed as a replaceable or non-replaceable delivery module structure. That is, within the same type of patch carrier and the same overall architecture of a local drug delivery dressing system, the drug reservoir module can be selectively configured with different delivery methods according to different application needs, wound conditions, and usage scenarios, thereby forming different immune component delivery mechanisms.

[0035] Example 1: Sustained-release layered drug reservoir module like Figure 2 As shown, in the first embodiment, the drug reservoir module 2 is configured as a drug sustained-release dressing structure (i.e., Figure 2 The drug reservoir module 2 shown is itself a regular dressing layer with a sustained-release drug on its surface. The structure is preferably a three-layer composite structure, including an inner wound contact layer, a sustained-release drug layer disposed thereon, and an outermost fixation layer.

[0036] The inner wound contact layer directly faces the wound area and is preferably made of soft, absorbent, and low-irritant medical contact materials, such as non-woven fiber pads, absorbent cotton matrix, alginate fiber mesh, or chitosan-based porous layers. This layer adheres to the wound surface, absorbs small amounts of exudate, and reduces wound friction. The middle drug-releasing layer is the core functional layer and can be formed from hydroxypropyl methylcellulose, sodium alginate, carboxymethyl cellulose, hydrogel matrix, or other polymeric sustained-release materials. It loads immunomodulatory components and allows for sustained release after application. The outermost fixation layer can be made of breathable medical tape, waterproof film, or composite backing material to ensure overall structural stability and encapsulate and protect the drug-releasing layer.

[0037] Preferably, the immunologically active ingredient loaded in the drug sustained-release layer is tetanus toxoid or tetanus immunoglobulin, and the concentration of tetanus toxoid can be set to 500-2000 Lf / mL.

[0038] When in use, after applying the sustained-release layered local drug delivery dressing system of this embodiment to the wound area, the immunologically active ingredients in the intermediate sustained-release drug layer can be continuously released into the wound and surrounding skin area for 24-72 hours by taking advantage of the local moist environment of the wound, the infiltration of tissue fluid and the diffusion path in the polymer matrix.

[0039] The advantages of this embodiment are: the overall structure is simple, the preparation process is relatively mature, and it is suitable as a basic local prevention solution; after the injury occurs, even without the use of a puncture structure, the immune active ingredients can maintain their effect on the wound periphery for a long time through local continuous release, thus making it suitable for relatively superficial wound scenarios such as small cuts, superficial abrasions, and minor puncture wounds.

[0040] Example 2: Soluble Microneedle Drug Storage Module like Figure 3 and Figure 4As shown, in the second embodiment, the drug reservoir module 2 is constructed as a soluble microneedle array structure 21. Specifically, its structure consists of a backing layer plus a soluble microneedle array. The microneedle material can be soluble materials such as sodium hyaluronate or polyvinylpyrrolidone. The drug is loaded within the microneedle body and dissolves and is rapidly released within 3-30 minutes after insertion into the skin. Specifically, the microneedle array structure 21 is a hollow structure filled with a sustained-release drug 211. After applying a bandage, the microneedles pierce the skin and / or wound, and the sustained-release drug 211 flows into the skin and / or wound through the gaps at the microneedle heads.

[0041] Specifically, the microneedle array structure comprises multiple microneedle units distributed regularly along an array. These microneedle units are positioned vertically or substantially vertically on the substrate and are arranged as a whole on the skin-facing side of the patch carrier. The microneedle units are preferably conical, pyramidal, truncated pyramidal, needle-like, or other elongated protrusions capable of penetrating the stratum corneum and superficial epidermis. The height, base diameter, tip angle, and array density of the microneedle units can be conventionally optimized based on the target drug delivery depth, local irritation level, and drug loading requirements.

[0042] The microneedle unit is formed of a soluble biocompatible material, preferably including sodium hyaluronate, polyvinylpyrrolidone, polyvinyl alcohol, sodium carboxymethyl cellulose, or a combination of the above materials. The immunologically active ingredients are preferably dispersed within the microneedle body or concentrated in the microneedle tip region, so as to be preferentially released into the superficial tissue after the microneedle penetrates the skin around the wound.

[0043] In use, the operator removes the release liner and applies the microneedle array structure to the skin area surrounding the wound. Since the central area of ​​the wound often has breaks, bleeding, or tissue damage, the microneedle array structure is preferably arranged in a ring around the wound, allowing the microneedles to penetrate the intact skin around the wound, crossing the stratum corneum barrier and improving the tissue penetration efficiency of macromolecular immunomodulatory components. Unlike ordinary adhesive bandages that only release drugs on the skin surface, the soluble microneedle array in this embodiment can at least partially dissolve within 3-30 minutes, allowing the loaded vaccine or immunoglobulin to be rapidly released into the skin tissue.

[0044] This embodiment is particularly suitable for trauma exposure scenarios where higher absorption efficiency is required. Its advantages are: on the one hand, it retains the convenience of easy on-site application and syringe-free operation of adhesive bandages or dressing systems; on the other hand, it utilizes microneedle penetration to break through the stratum corneum barrier, allowing macromolecular immune-active ingredients to be delivered more effectively to local tissues, thus making it suitable for post-exposure prophylaxis scenarios requiring rapid onset of action.

[0045] Example 3: Drug-loaded and supported split-type microneedle drug reservoir module Continue as Figure 3As shown, in the third embodiment, the drug reservoir module is constructed as a drug-loaded and support-type split microneedle structure. It is specifically defined as a coaxial core-shell double-layer microneedle structure, with the outer shell serving as the support needle and the inner core as the drug-loaded needle. The outer shell does not carry drug, while the inner core does. The support needle material can be a high-strength biodegradable material such as PLGA, and the drug-loaded needle material can be a soluble material such as PVP / HA. Furthermore, the drug utilization rate can reach over 95%. Specifically, as shown... Figure 3 As shown, the surface of the patch carrier 2 has a microneedle array structure 21, with the outermost ring being support needles 10, and the innermost and innermost rings being drug-carrying needles 20 and 30. After the patch is applied to the skin, the outermost support needles 10 are used to fix and support the patch to adhere firmly to the skin, while the drug-carrying needles 20 and 30 penetrate the skin and / or wound to release sustained-release medication 211 (e.g., ...). Figure 4 (As shown).

[0046] Specifically, each modular microneedle unit includes a peripheral support needle and an internal drug-loaded needle. The support needle forms the outer framework of the overall microneedle and is preferably made of PLGA, polylactic acid, polycaprolactone, gelatin crosslinkers, or other materials with high mechanical strength and biodegradability. Its main function is to ensure that the microneedle has sufficient penetration force during compression, preventing bending, collapse, or unstable penetration depth due to insufficient strength of purely soluble materials. The internal drug-loaded needle is preferably made of polyvinylpyrrolidone, sodium hyaluronate, polyvinyl alcohol, or other soluble biocompatible materials. It is used to load immunomodulatory components and rapidly or in stages dissolve and release the drug after insertion into the local tissue.

[0047] Preferably, the support needle and the drug-carrying needle together form a coaxial core-shell structure, wherein the support needle is the outer layer and the drug-carrying needle is the central core. This structural design allows the microneedle to obtain sufficient mechanical support while concentrating the limited drug loading space on the core portion where drug delivery is truly needed, thereby increasing the effective drug loading per unit needle and reducing the encroachment of ineffective materials on drug storage capacity.

[0048] Furthermore, not all microneedles in a modular microneedle array need to be drug-loaded. Based on the target dosage design, some microneedle units can be configured as pure support needles, while others can be configured as a combination of support needles and drug-loaded needles. This allows for more precise control of the total drug delivery volume through array arrangement. This structure is particularly advantageous for active ingredients that are difficult to load at high levels, such as large molecule vaccines and immunoglobulins.

[0049] In use, this split-type microneedle structure is preferably positioned in the skin area around the wound. After pressure application, the support needle first overcomes the mechanical resistance of the skin surface and completes the insertion. Subsequently, the internal drug-loaded needle begins to dissolve under the action of local tissue fluid, delivering the immunologically active ingredient into the tissue. Because this approach balances insertion strength and high drug loading capacity, it is more suitable for post-exposure prophylaxis scenarios where a higher effective dose needs to be delivered in a shorter time.

[0050] Example 4: Lyophilized Soluble Microneedle Drug Storage Module See also Figure 3 As shown, in the fourth embodiment, the drug reservoir module is constructed as a lyophilized soluble microneedle array structure. Specifically, it consists of a backing layer plus a lyophilized soluble microneedle array, prepared using a three-stage lyophilization method. The drug loading is tetanus vaccine plus a lyophilized protective agent, and it can be stored at room temperature for more than 24 months with an activity retention rate of not less than 90%. That is, the microneedle array structure 21 set on the surface of the patch carrier 2 is entirely a lyophilized soluble microneedle drug reservoir module. The entire microneedle array structure 21 is inserted into the skin and / or wound. After the lyophilized soluble needles thaw, the sustained-release drug 211 enters the wound.

[0051] Specifically, the lyophilized soluble microneedle array can be constructed based on the basic structure of the soluble microneedles in Example 2, but a lyophilization protection system and a lyophilization molding process are introduced during the preparation process. The lyophilization protection system preferably includes one or more of trehalose, mannitol, and histidine, which are used to protect the conformational stability and biological activity of vaccine proteins, peptides, or other bioactive components during the freeze-drying process.

[0052] Preferably, the lyophilized soluble microneedle array is prepared using a three-stage lyophilization method, including a pre-freezing stage, a primary sublimation stage, and a secondary desorption stage. In the pre-freezing stage, the microneedle precursor solution containing immunoactive components and a lyophilization protectant is rapidly frozen at -40°C to -60°C, causing the water in the solution to form a stable ice crystal structure. Subsequently, a primary sublimation is performed under reduced pressure to remove the main ice crystals. A secondary desorption stage further reduces residual water content, resulting in a lyophilized microneedle array with stable microneedle morphology and good preservation properties.

[0053] Before use, this lyophilized soluble microneedle array can be stored at room temperature for a long time, eliminating the need for the 2-8°C cold chain transportation and storage conditions required for traditional liquid vaccines. During use, the operator removes the release liner and applies the lyophilized microneedle array to the skin area around the wound. After the microneedles are inserted, they gradually rehydrate and dissolve under the influence of tissue fluid, releasing the loaded immunomodulatory components into the local tissue.

[0054] The key advantage of this embodiment is that it combines efficient transdermal delivery of microneedles with freeze-drying and stable preservation at room temperature, making it particularly suitable for use scenarios where professional injection services and cold chain storage and transportation conditions are inconvenient to obtain, such as home first aid, outdoor work, field exploration, primary healthcare points or remote areas.

[0055] In addition to the four core forms of drug storage modules mentioned above, the local drug delivery dressing system of the present invention can also be equipped with additional extended functions as needed.

[0056] In one extended embodiment, the drug reservoir module can also be additionally loaded with rabies prevention active ingredients, thereby forming a combined tetanus and rabies prevention dressing. This combined loading method can be achieved through mixed loading, layered loading, separate drug loading in different microneedle regions, or separate drug loading on different needles within the same array.

[0057] In another extended implementation, anaerobic-responsive fluorescent probes, Clostridium tetani-specific recognition probes, or other visual detection components can be incorporated into the hydrogel matrix of the drug reservoir module or functional layer for visual early warning of local wound infection risk. Operators can assess the local environmental risk based on changes in dressing color, fluorescence intensity, or pattern display, thereby determining whether further medical intervention is necessary.

[0058] In another extended implementation, a humanized tetanus toxin binding domain mutant can be added to the drug storage module to block the retrograde transport of the toxin via peripheral nerves, forming an auxiliary mechanism for toxin blocking in addition to vaccine prevention.

[0059] In addition, to address wound healing needs, metronidazole, recombinant human epidermal growth factor, chitosan, collagen, and other healing-promoting or antibacterial components can be introduced into the non-immune component areas of the functional layer or drug storage module, thereby achieving post-exposure prophylaxis for infectious diseases while also addressing wound treatment and local repair.

[0060] The topical drug delivery dressing system of the present invention is preferably used in the following process: When a user experiences an animal bite, nail scratch, metal puncture wound, contaminated abrasion, or other traumatic exposure with a risk of infection, the wound should first be cleaned routinely. Then, the sterile packaging of this invention should be opened, the release liner removed, and the drug reservoir module applied to the wound area or surrounding skin. Depending on the specific form of the drug reservoir module, the immune-active components can be delivered to the body through mechanisms such as sustained release, microneedle insertion and dissolution, split-type precise drug delivery, or lyophilized microneedle rehydration and dissolution release. After the prescribed application time, the entire dressing system can be removed, and if necessary, a new dressing system can be replaced for continued application.

[0061] For sustained-release layered formulations, a 24-72 hour application time is preferred. For soluble microneedles, split-type microneedles, or lyophilized soluble microneedles, it is preferable to maintain the application for several minutes to tens of minutes after insertion to ensure full drug release, and then retain the backing and functional layers as subsequent wound coverage structures as needed. The specific application time can be adjusted according to the type of immunomodulatory ingredient, drug loading, and application scenario.

[0062] It should be noted that the patch carrier in the above embodiments is not limited to the form of a band-aid, but can also be any local drug delivery dosage form that can be attached to the skin or wound, such as a dressing patch, hydrocolloid dressing, foam dressing, hydrogel patch, or bandage-type local drug delivery device; the drug storage module is also not limited to the above four forms. Without departing from the overall concept of the present invention, alternative methods such as liposome storage, nanoparticle storage, microsphere storage, multilayer composite membrane, electrospun fiber membrane, and hydrogel storage can also be used.

[0063] Similarly, the immunomodulatory components are not limited to a single tetanus prophylactic ingredient, but can be selected from different vaccines, immunoglobulins, neutralizing antibodies, or bioactive agents depending on the specific disease type, prevention needs, and regulatory requirements. For microneedle materials, backing layer materials, functional layer materials, adhesion methods, array morphology, and preparation process parameters, those skilled in the art can make conventional adjustments based on the disclosure of this invention.

[0064] In summary, the local drug delivery dressing system provided by this invention sets up a drug reservoir module loaded with immune-active ingredients on the patch carrier, and enables the patch carrier to be applied to the wound area or the skin area around the wound. In the applied state, the immune-active ingredients are delivered to the body through local release or transdermal delivery, thereby achieving the prevention of infectious diseases without injection. This effectively solves the problem that the existing technology mainly relies on injection for immune prophylaxis and is difficult to implement in a timely manner in the event of sudden trauma or in non-medical environments, thus improving the timeliness and convenience of post-exposure prophylaxis.

[0065] This invention designs the drug storage module as a replaceable delivery module structure, enabling the same local drug delivery dressing system to select different delivery structures according to the type of trauma or usage requirements, such as drug sustained-release dressing structure, microneedle array structure, lyophilized soluble microneedle structure or split microneedle structure, thereby improving the system's adaptability and flexibility in different application scenarios.

[0066] When using a microneedle array structure, microneedles are inserted into the skin area around the wound, allowing immune-active ingredients to cross the skin's stratum corneum barrier and directly enter the skin tissue, improving the delivery efficiency of immune-active ingredients. This is beneficial for achieving more effective immune prophylaxis in the early stages after trauma exposure.

[0067] When using a split microneedle structure, by setting up a combination of an outer support needle and an inner drug-carrying needle, the effective drug loading of a unit microneedle can be increased while maintaining sufficient penetration strength, thereby improving the utilization rate of immune active ingredients while ensuring delivery stability.

[0068] When using a lyophilized soluble microneedle structure, a lyophilization protection system is set in the drug storage module to enable the immune-active ingredients to maintain good stability under normal temperature conditions, which is beneficial for the storage and use of this local drug delivery dressing system in scenarios such as home first aid, outdoor activities and primary healthcare.

[0069] This invention constructs a local drug delivery dressing system with a replaceable drug reservoir module, which is compatible with four delivery pathways on the same adhesive bandage or dressing carrier platform: sustained-release layer type, soluble microneedle type, drug-loaded-support split microneedle type, and lyophilized soluble microneedle type. This enables the system to provide more suitable non-injectable immunoprophylaxis solutions for different trauma exposure scenarios.

[0070] The above are merely preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Therefore, any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A local drug delivery dressing system for the prevention of infectious diseases after trauma exposure, characterized in that, include: A patch carrier and a drug reservoir module disposed on the patch carrier; The patch carrier is configured to be applied to the wound area or the skin area around the wound. The drug reservoir module is loaded with immune-active ingredients for the prevention of infectious diseases, and the immune-active ingredients are introduced into the body to induce immune protection when the patch is applied. The drug storage module can be a replaceable or non-replaceable delivery module structure, and the delivery module structure can be selectively configured as at least one of the following delivery structures according to the wound condition: Drug-releasing dressing structure for achieving localized sustained release; A microneedle array structure for delivery by inserting into the skin around the wound; Microneedle array structure formed from freeze-dried soluble materials; A split microneedle structure including a peripheral support needle and an internal drug-loaded needle. This enables the local delivery of immune-active ingredients to the localized dressing system in trauma exposure scenarios.

2. The local drug delivery dressing system according to claim 1, characterized in that, The drug storage module includes a microneedle array structure disposed on the skin contact side of the patch carrier. The microneedle array structure is configured to penetrate the stratum corneum and / or superficial epidermis when the patch carrier is applied to the skin area around the wound, so that the immune active ingredients can be delivered across the skin barrier to local tissues, thereby improving the absorption efficiency of macromolecular immune active ingredients in trauma exposure scenarios.

3. The local drug delivery dressing system according to claim 2, characterized in that, The microneedle array structure includes multiple split microneedle units. Each split microneedle unit includes a peripheral support needle and a drug-loaded needle located inside the peripheral support needle. The peripheral support needle is used to provide the mechanical support strength required for puncture into the skin around the wound. The drug-loaded needle is used to load and release the immune active ingredient, so as to improve the effective drug loading and drug delivery accuracy per unit microneedle while ensuring puncture capability.

4. The local drug delivery dressing system according to claim 3, characterized in that, The peripheral support needle is made of a high-strength biodegradable material, and the drug-carrying needle is made of a soluble biocompatible material. The high-strength biodegradable material includes polylactic acid-glycolic acid copolymer, and the soluble biocompatible material includes one or more of polyvinylpyrrolidone and sodium hyaluronate, so that the split microneedle unit has both structural support function and drug dissolution and release function.

5. The local drug delivery dressing system according to claim 4, characterized in that, The microneedle array structure is a soluble microneedle array structure, which is formed by soluble polymer materials. The immune active ingredients are dispersed inside the microneedle body, and the soluble microneedle array dissolves at least partially within 3-30 minutes after being inserted into the skin around the wound, so as to rapidly release the immune active ingredients in the early stage after trauma exposure.

6. The topical drug delivery dressing system according to claim 5, characterized in that, The soluble microneedle array structure is a soluble microneedle array formed by freeze-drying. The drug storage module also includes a freeze-drying protection system, which includes one or more of trehalose, mannitol and histidine, to improve the structural stability and bioactivity retention of the immune active ingredient during the preparation and storage process.

7. The topical drug delivery dressing system according to claim 6, characterized in that, The soluble microneedle array formed by freeze-drying is prepared by a three-stage freeze-drying process, which includes a pre-freezing stage, a first sublimation stage, and a second desorption stage. The temperature of the pre-freezing stage is -40°C to -60°C to obtain a microneedle array structure with room temperature storage stability.

8. The topical drug delivery dressing system according to claim 7, characterized in that, The drug storage module includes a drug sustained-release dressing structure, which is a three-layer composite structure, including an inner wound contact layer, a middle drug sustained-release layer, and a surface fixation layer. The drug sustained-release layer is formed of a polymer sustained-release material and continuously releases the immune-active components through diffusion release within 24-72 hours after the patch carrier is applied to the wound area.

9. The topical drug delivery dressing system according to any one of claims 1-8, characterized in that, The patch carrier comprises, from the outside in, a sterile release protective layer, a flexible backing layer, and a skin contact layer. The flexible backing layer provides overall flexible support and adapts to the surface morphology of the wound area. The skin contact layer enables the local drug delivery dressing system to be attached and fixed to the wound area or the skin area around the wound. The local drug delivery dressing system may also include an optional functional layer disposed in the area adjacent to the drug storage module. The optional functional layer includes one or more of a disinfection and hemostasis layer and an absorption layer.

10. The topical drug delivery dressing system according to any one of claims 1-8, characterized in that, The immunologically active ingredients include one or more of tetanus toxoid, recombinant tetanus protein vaccine, tetanus mRNA vaccine, tetanus human immunoglobulin, and recombinant anti-tetanus neutralizing antibody; and the local drug delivery dressing system is suitable for immediate prophylaxis after trauma exposure, to replace or supplement traditional injectable prophylaxis in home first aid, outdoor work, primary healthcare, or on-site self-rescue conditions.

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