Degradable microneedle temperature control type striae gravidarum repairing film patch and preparation method thereof

Abstract

The invention relates to the technical field of cosmetics, and particularly discloses a degradable microneedle temperature control type striae gravidarum repairing film patch and a preparation method thereof. Comprising four layers of structures which are sequentially compounded from outside to inside: a nanofiber substrate layer; a microneedle essence layer; a temperature control adjusting layer; and attaching a fixing layer. By constructing a four-layer collaborative system, the day and night temperature rhythm of the skin is converted into a trigger signal, and a temperature response-microneedle degradation-drug release linkage closed loop is achieved. The degradable microneedle can be utilized to break through a cutin barrier, repair components are accurately delivered to a corium layer, anti-inflammatory and collagen-promoting components can be released at night in an accelerated manner through a temperature control mechanism, and the mode is automatically switched to a slow-release stability maintaining mode in the daytime, so that accurate matching with a human physiological repair rhythm is achieved.

Description

Technical Field

[0001] This invention relates to the field of cosmetics technology, and specifically discloses a biodegradable microneedle temperature-controlled stretch mark repair film and its preparation method. Background Technology

[0002] Transdermal drug delivery is a highly attractive treatment method in areas such as stretch mark repair, as it avoids the first-pass effect of the liver and gastrointestinal side effects associated with oral administration, and provides a continuous and stable local drug concentration. However, the outermost layer of the skin, the stratum corneum, forms a strong barrier, severely limiting the penetration efficiency of active ingredients, especially large-molecule peptides and polysaccharides, thus limiting the repair effects of traditional ointments, creams, and patches.

[0003] To overcome this obstacle, existing technologies are mainly developing along two paths: one is to enhance the penetration and release of the epidermis through materials science methods; the other is to actively penetrate the stratum corneum through physical means.

[0004] Existing technology (CN114259425A) discloses a dry-state essence mask with temperature-sensitive absorption-promoting function. It achieves stable dry-state storage and rapid release upon contact with warm water (40-50℃) by loading essence ingredients into the fiber core layer and constructing a temperature-sensitive gel layer on the fiber surface. This technology effectively solves the problems of short shelf life in wet masks and difficulty in ingredient release in dry masks; however, its mechanism of action still essentially relies on the passive diffusion and penetration of ingredients on the skin surface. For stretch mark repair that requires action on the dermal reticular layer to promote collagen remodeling, the improvement in efficacy is limited.

[0005] Existing technology (CN114259479A) discloses a microneedle patch based on natural biodegradable materials (such as chitosan). The microneedle array can mechanically pierce the stratum corneum, forming micron-sized channels to directly deliver active ingredients to the superficial dermis, thus fundamentally overcoming the transdermal barrier. However, the drug release kinetics of such microneedle systems typically rely entirely on the self-swelling and degradation process of the matrix material (such as chitosan) in tissue fluid, a passive, fixed, and uncontrollable open-loop process. It cannot respond to dynamic changes in the skin microenvironment (such as temperature and inflammatory state), nor can it provide time-programmable control over the release sequence and rate of multiple components according to the needs of the repair process.

[0006] Therefore, it is necessary to propose a biodegradable microneedle temperature-controlled stretch mark repair patch and its preparation method that can respond to the skin's physiological state, dynamically coordinate transdermal depth and release sequence, and thus deliver repair ingredients to the skin depth in a timely and appropriate manner with optimal kinetics, achieving precise synchronization between treatment behavior and the body's internal biological cycle, so as to achieve optimal repair efficacy. Summary of the Invention

[0007] To address the aforementioned issues, this invention provides a biodegradable microneedle temperature-controlled stretch mark repair patch and its preparation method. By constructing a four-layer synergistic system, the skin's own diurnal temperature rhythm is transformed into a trigger signal, achieving a closed-loop linkage of temperature response, microneedle degradation, and drug release. Not only can the biodegradable microneedles penetrate the stratum corneum barrier to precisely deliver repair ingredients to the dermis, but the temperature-controlled mechanism also accelerates the release of anti-inflammatory and collagen-promoting components at night, automatically switching to a slow-release stabilization mode during the day, thus achieving precise matching with the body's physiological repair rhythm. It significantly surpasses existing single-function transdermal products in terms of deep transdermal efficiency, time-controlled release, long-lasting repair effect, and application stability, providing an efficient and user-friendly solution for skin repair such as stretch marks.

[0008] To achieve the above objectives, the technical solution of the present invention is as follows: a biodegradable microneedle temperature-controlled stretch mark repair film patch, comprising a four-layer structure sequentially laminated from the outside to the inside: The nanofiber substrate layer, composed of polymer nanofibers carrying essential ingredients, serves as the support substrate for the microneedle array and forms a sustained-release reservoir. The microneedle essence layer is composed of a microneedle array made of biodegradable polymer material, with nanospheres containing active ingredients loaded at the tips of the microneedles. The temperature control layer is composed of temperature-responsive polymer materials and thermally conductive particles, with a critical response temperature of 34-36℃. The bonding and fixing layer, composed of flexible fabric material and medical pressure-sensitive adhesive, is used to adhere the essence film to the skin.

[0009] The core principle of this invention lies in the deep integration of three technologies at the mechanistic level: temperature-responsive controlled release, biodegradable microneedles for active transdermal delivery, and nanofiber reservoir for sustained release. This results in the construction of a synergistic repair system that uses the skin's own diurnal physiological rhythm (especially the nighttime micro-warming at 34-36°C) as a trigger signal, which involves perception, response, and execution.

[0010] Specifically, the system operates through a cross-layer linkage mechanism between the temperature-regulating layer and the microneedle essence layer. When the skin temperature rises to the repair window of 34-36℃ at night, the temperature-regulating layer undergoes reversible pore expansion. This change directly accelerates the exudation of the essence components in the nanofiber basal layer and actively regulates the degradation rate of the biodegradable polymer matrix in the microneedle essence layer through thermal conduction, prompting the core-shell nanospheres loaded at the microneedle tips to be exposed and released more rapidly. Specifically, the hydroxyascorbic acid in the outer shell of the nanospheres is preferentially and rapidly released to reduce inflammation, creating conditions for subsequent repair; while the palmitoyl tripeptide-5 in the core is subsequently released slowly, continuously promoting collagen regeneration. During the day, when the skin temperature drops, the system switches to a "stabilization mode" of pore contraction and slower degradation, achieving rhythmic and precise drug delivery by maintaining the concentration during the day and performing pulsed repair at night. Simultaneously, the unique nanofiber basal layer not only provides stable anchoring for the microneedle array, but its three-dimensional network structure also serves as a secondary reservoir, forming a gradient supplement with the microneedle release. This invention solves the systemic problems of insufficient transdermal depth, uncontrollable release, and disconnection from physiological repair rhythm in the prior art through the above-mentioned closed-loop synergistic mechanism.

[0011] Furthermore, the temperature-responsive polymer material in the temperature control layer is poly(N-isopropylacrylamide), and the thermally conductive particles are boron nitride nanoparticles, with the mass ratio of boron nitride nanoparticles in the temperature control layer being 5%-8%.

[0012] Furthermore, the biodegradable polymer material in the microneedle essence layer is polylactic acid-glycolic acid copolymer, which has a degradation cycle of 72-96 hours; the length of the microneedles in the microneedle array is 150-200μm.

[0013] Furthermore, the nanospheres have a core-shell structure, with the core consisting of palmitoyl tripeptide-5 and sodium hyaluronate, and the shell consisting of polycaprolactone modified with asiaticoside; the particle size of the nanospheres is 50-100 nm.

[0014] Furthermore, the nanofiber substrate is a composite nanofiber membrane of polylactic acid and Centella asiatica extract prepared by electrospinning technology.

[0015] Furthermore, the bonding and fixing layer is a composite fabric of modified bamboo fiber and polyurethane elastic fiber, with an arc-shaped structure that adapts to the abdominal curve.

[0016] A method for preparing a biodegradable microneedle temperature-controlled stretch mark repair film includes the following steps: S1: Fabrication of the temperature control layer; S2: Preparation of nanospheres loaded with active ingredients; S3: Inject the microneedle casting liquid containing the nanospheres into the mold, and directly prepare the nanofiber substrate layer on the surface of the mold by electrospinning technology. After drying and demolding, a composite layer of microneedle essence layer and nanofiber substrate layer is obtained. S4: Perform plasma activation treatment on the surface of the microneedles of the composite layer; S5: The activated composite layer and the temperature control layer are pressed together in a temperature and vacuum environment below 34°C to obtain the repair film.

[0017] Furthermore, in step S4, the working gas for the plasma activation treatment is argon, the processing power is 80-120W, and the processing time is 20-40 seconds.

[0018] Furthermore, the pressing process in step S5 adopts a gradient pressure process: first, pre-pressing at a pressure of 0.1-0.2MPa for 3-5 minutes, and then increasing the pressure to 0.4-0.6MPa for 10-20 minutes.

[0019] Furthermore, the nanospheres are prepared in step S2 using a dual emulsification-solvent evaporation method.

[0020] A series of targeted processes address the challenges of compatibility and performance preservation when combining multiple materials and heterogeneous functional structures, such as temperature-sensitive layers, microneedle layers, and nanofiber layers. Among these, the co-forming process anchors the microneedle roots to the nanofiber substrate in situ, ensuring mechanical stability; plasma activation introduces active groups onto the surface of hydrophobic microneedles, significantly enhancing interlayer bonding; and most importantly, the low-temperature (<34℃) and gradient pressure composite process achieves tight and uniform bonding between layers while preventing premature phase change in the temperature-sensitive layer. This ensures that the final product accurately achieves the designed intelligent temperature control response, microneedle structural integrity, and interlayer synergy during storage and use.

[0021] The beneficial effects of the present invention are: (1) It achieves precise synergy between deep transdermal penetration and rhythmic repair. By physically penetrating the stratum corneum through a biodegradable microneedle array, core repair ingredients (such as palmitoyl tripeptide-5) are directly delivered to their target layer—the dermis—fundamentally solving the core bottleneck of low transdermal efficiency in traditional membrane patches. Innovatively, the temperature control response threshold is set at 34-36℃, synchronizing with the golden window for skin repair during the natural nighttime warming period. The system automatically activates at night, prioritizing the release of anti-inflammatory ingredients, followed by a slow-release of collagen-promoting components; during the day, it switches to a stabilization mode. This sensor-response mechanism enables programmed drug delivery matched to physiological rhythms, significantly improving the accuracy and timeliness of repair.

[0022] (2) A three-in-one guarantee system of intelligent controlled release, long-term stability maintenance, and solid fit has been constructed. By employing a dual regulation of dynamic gating through a temperature-controlled layer and sequential release from core-shell nanospheres, the drawbacks of traditional microneedles—such as burst release and short duration of action—are overcome. This achieves the sequential release of anti-inflammatory and repairing components, maintaining effective drug concentrations in the dermis even during the day, thus extending the effective duration of a single application. The active ingredients are loaded in a dry state onto the microneedle or nanofiber substrate, and the temperature-controlled layer isolates them from external factors during storage, improving product stability and potentially extending shelf life.

[0023] (3) The curved adhesive layer and medical pressure-sensitive adhesive, specially designed for the abdominal curve, ensure the stability of the patch during long-term application (especially when turning over in sleep at night). A stable fit is a prerequisite for ensuring effective microneedle puncture and accurate temperature sensing of the skin by the temperature control layer, thereby ensuring the reliable operation of the entire intelligent system.

[0024] (4) It solved the compatibility problem of multi-technology integration, ensuring the feasibility and reliability of the product. A cross-layer linkage closed loop for temperature-triggered microneedle degradation rate was created, achieving a highly efficient synergistic effect. Plasma activation and low-temperature vacuum composite processes effectively solved the technical challenge of weak bonding between the hydrophobic microneedle layer and the temperature-sensitive hydrogel layer. Gradient pressure bonding ensured tight interlayer bonding while protecting the integrity of the delicate microneedle structure. These process innovations guarantee the mass production feasibility and performance consistency of complex multilayer structure products.

[0025] (5) The microneedle size design enables effective transdermal delivery while avoiding nerve endings, achieving painless or minimally painful drug administration and providing a better user experience. The product design is suitable for home use, allowing users to receive highly effective repair treatment without professional operation, thus improving treatment compliance. Core materials such as PLGA, PNIPAM, and chitosan derivatives are all biocompatible medical polymers, reducing the risk of irritation or allergies. Attached Figure Description

[0026] Figure 1 This is an isometric view of the biodegradable microneedle temperature-controlled stretch mark repair film patch in Embodiment 1 of the present invention.

[0027] Figure 2 This is a side cross-sectional view of the biodegradable microneedle temperature-controlled stretch mark repair film patch in Embodiment 1 of the present invention.

[0028] Figure 3 for Figure 2 Enlarged view of section A.

[0029] Figure 4 This is a schematic diagram of the preparation method of the biodegradable microneedle temperature-controlled stretch mark repair film in Example 1 of the present invention.

[0030] Figure labels: 1. Nanofiber base layer; 2. Microneedle essence layer; 3. Temperature control layer; 4. Adhesion and fixation layer; 5. Microneedle; 6. Nanospheres. Detailed Implementation

[0031] The specific implementation method is described below with reference to the accompanying drawings.

[0032] Example 1 Basic as Figure 1 , Figure 2 , Figure 3 and Figure 4 As shown: This embodiment provides a biodegradable microneedle temperature-controlled stretch mark repair film and its preparation method, the specific structure of which is as follows: It includes a four-layer structure that is sequentially combined from the outside to the inside: The nanofiber substrate 1 is composed of polymer nanofibers carrying the essence ingredients, serving as the support substrate for the microneedle 5 array and forming a slow-release reservoir. The microneedle essence layer 2 is composed of an array of microneedles 5 made of biodegradable polymer materials, and the tips of the microneedles 5 are loaded with nanospheres 6 containing active ingredients. The temperature control layer 3 is composed of temperature-responsive polymer materials and thermally conductive particles, and its critical response temperature is 34-36℃. The bonding and fixing layer 4, made of flexible fabric material and medical pressure-sensitive adhesive, is used to adhere the essence film to the skin.

[0033] Its preparation process is as follows: I. Core Raw Materials Temperature control layer: poly(N-isopropylacrylamide) (PNIPAM), boron nitride nanoparticles (50nm particle size), N,N-dimethylformamide (DMF), deionized water.

[0034] Microneedle essence layer: polylactic acid-glycolic acid copolymer (PLGA, LA / GA=75:25), palmitoyl tripeptide-5, sodium hyaluronate, asiaticoside, polycaprolactone (PCL), dichloromethane, ethyl acetate, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP, K30).

[0035] Nanofiber substrate: polylactic acid (PLA), centella asiatica extract (purity ≥98%), trifluoroacetic acid, dichloromethane.

[0036] Bonding and fixing layer: Modified bamboo fiber (90g / m²) 2 Polyurethane elastic fiber (10%), medical-grade water-based adhesive (30% solid content), and low-sensitivity pressure-sensitive adhesive (0.8μm thickness).

[0037] Auxiliary reagents: sodium hydroxide, sodium hypophosphite, citric acid, sodium dodecyl sulfate.

[0038] II. Preparation Equipment Casting machine (LY-800 type), plasma treatment system (PT-100 type), double emulsifier (JRJ300-S type), freeze dryer (FD-1A-50 type), electrospinning equipment (ET-2000 type), microneedle mold (PDMS material, needle tip array 35 / cm) 2 Vacuum laminating machine (ZK-300 type), CNC cutting machine (CNC-1325 type), high performance liquid chromatograph (HPLC, Agilent 1260 type), scanning electron microscope (SEM, SU8010 type).

[0039] III. Step-by-step preparation and implementation process (1) Preparation of temperature control layer (batch production: 100 pieces, each piece area 20cm×15cm) Weigh out 10 parts of PNIPAM and 5 parts of nano boron nitride by weight, add 85 parts of a mixed solvent of DMF and water (volume ratio 3:1), and stir continuously at 60℃ and 300rpm for 3 hours until completely dissolved to form a uniform casting solution.

[0040] The casting solution was poured into the casting machine trough, the casting speed was set to 0.5 m / min and the film thickness to 25 μm, and the film was dried in an oven at 60℃ for 2 h. After peeling, a temperature-controlled film with a thickness of 25 ± 2 μm was obtained and set aside.

[0041] The pore size of the temperature control membrane was measured using SEM to ensure that the pore size was 50-80nm at room temperature (25℃) and expanded to 200-250nm at 35℃, which met the temperature response requirements.

[0042] (2) Preparation of nanospheres Preparation of the internal aqueous phase: Weigh 52 parts of palmitoyl tripeptide-5 and 3 parts of sodium hyaluronate, dissolve them in 95 parts of deionized water, and ultrasonically disperse for 15 min (power 300W) to form a homogeneous aqueous solution.

[0043] Oil phase preparation: Weigh 2 parts of hydroxyascorbic acid and 10 parts of PCL, dissolve them in 88 parts of dichloromethane, and stir until completely dissolved.

[0044] Primary emulsification: The aqueous phase is slowly added to the oil phase and ultrasonically emulsified for 10 minutes (power 400W) to form a W / O emulsion.

[0045] Secondary emulsification: The above emulsion was added to an aqueous solution containing 2 wt% polyvinyl alcohol (volume ratio 1:5), and stirred at 1500 rpm for 30 min to form a W / O / W dual emulsion.

[0046] Solvent evaporation and drying: The solvent was evaporated by stirring at room temperature for 4 h, the precipitate was collected by centrifugation at 8000 rpm for 15 min, and then freeze-dried (-50℃, 24 h) to obtain core-shell structured nanospheres with a particle size controlled at 50-100 nm.

[0047] (3) Co-formation of microneedle essence layer and nanofiber base layer Preparation of microneedle casting solution: Weigh 15 parts of PLGA, dissolve 80 parts of dichloromethane / ethyl acetate mixed solvent (volume ratio 2:1), add 5 parts of the prepared nanospheres, and ultrasonically disperse for 20 min (power 300W) to obtain a uniform casting solution.

[0048] Microneedle mold pretreatment: Wipe the PDMS microneedle mold clean with anhydrous ethanol, dry it at 60℃ for 30 minutes, and cool it to room temperature.

[0049] Microneedle casting: Inject the casting solution into the groove of the microneedle mold, place it in a centrifuge and centrifuge at 3000 rpm for 30 minutes to ensure that the casting solution completely fills the needle tip and remove excess liquid from the surface of the mold.

[0050] Nanofiber substrate spinning: An electrostatic spinning nozzle is installed on the surface of the mold. The spinning solution formula is 10 parts PLA, 5 parts Centella asiatica extract, and 85 parts trifluoroacetic acid / dichloromethane mixed solvent (volume ratio 1:4). The spinning voltage is set to 18kV, the receiving distance is 15cm, and the injection speed is 0.8mL / h. A nanofiber membrane with a thickness of 60±5μm is formed on the surface of the mold by spinning.

[0051] Composite drying: The mold is placed in a vacuum drying oven at 50℃ and dried for 4 hours. After demolding, a "microneedle-nanofiber substrate" composite layer is obtained. The microneedles are 150-200μm in length and 5-8μm in tip diameter.

[0052] (4) Pretreatment of bonding and fixing layer Modified bamboo fiber and polyurethane elastic fiber were mixed and woven in a 9:1 ratio, and then subjected to hydrophilic finishing (finishing solution containing 2wt% sodium dodecyl sulfate, bath ratio 1:20, treatment at 40℃ for 30 min), and dried at 80℃ to obtain the bonding substrate.

[0053] A low-sensitivity pressure-sensitive adhesive is uniformly coated on the surface of the bonding substrate to a thickness of 0.8 μm, and cured at 60°C for 1 hour for later use.

[0054] (5) Integral composite and molding Microneedle layer surface activation: The "microneedle-nanofiber substrate" composite layer was placed in a plasma treatment instrument with argon as the working gas, the pressure was set to 0.8 Pa and the power to 100 W, and the treatment lasted for 30 seconds. After removal, the composite was immediately performed.

[0055] Precise adhesive application to the temperature-sensitive layer: Medical-grade water-based adhesive is applied to the bonding surface of the temperature-controlled layer in a dot matrix pattern using a dispensing machine. The dot matrix diameter is 0.5 mm, the spacing is 2 mm, and the adhesive application amount is 0.02 g / cm³. 2 .

[0056] Low-temperature lamination: Align the temperature-controlled layer after coating with the activated microneedle layer, place it in a vacuum laminator, set the temperature to 25℃ and the pressure to 0.3MPa, and maintain for 10 minutes.

[0057] Gradient pressing and curing: First, pre-press at 0.1MPa for 5 minutes, then increase to 0.5MPa for 15 minutes, and then cure in an oven at 30℃ for 2 hours to ensure tight adhesion between layers.

[0058] Molding and initial inspection: The structure is cut into an arc shape to fit the abdomen using a CNC cutting machine (size 20cm×15cm, edge arc radius 2cm). The integrity of the microneedles and the interlayer adhesion are inspected by microscope. After passing the inspection, it is vacuum sealed.

[0059] Comparative Example 1 This comparative example provides a method for preparing a temperature-controlled stretch mark repair film patch. The preparation process is as follows: I. Core Raw Materials Temperature control layer: Same as in Example 1.

[0060] Essence layer: Palmitoyl tripeptide-5, sodium hyaluronate, asiaticoside, centella asiatica extract, medical-grade water-based adhesive.

[0061] Adhesive fixing layer: Same as in Example 1.

[0062] Auxiliary reagents: Same as in Example 1.

[0063] II. Preparation Equipment Compared with Example 1, the microneedle mold and centrifuge equipment related to microneedles are removed, and the rest is the same as in Example 1.

[0064] III. Step-by-step preparation and implementation process (1) Preparation of temperature control layer Completely identical to Example 1, a temperature-controlled film with a thickness of 25±2μm was obtained, ensuring a pore size of 50-80nm at room temperature and a pore size of 200-250nm at 35℃.

[0065] (2) The essence layer is combined with the nanofiber base layer. Nanofiber substrate spinning: Same as in Example 1, prepare PLA nanofiber membranes (thickness 60±5μm) containing Centella asiatica extract.

[0066] Essence Coating: Palmitoyl tripeptide-5 (2wt%), sodium hyaluronate (3wt%), and asiaticoside (2wt%) were dissolved in deionized water to prepare a 7wt% essence, which was then evenly coated onto the surface of the nanofiber membrane at a coating amount of 0.1 g / cm³. 2 Dry at 40℃ for 1 hour.

[0067] (III) Overall Composite and Molding Thermosensitive layer and essence layer composite: Using the low-temperature composite process of Example 1 (25℃, 0.3MPa, 10min), the temperature control layer is composited with the nanofiber membrane coated with essence.

[0068] Adhesive fixing layer lamination: The composite layer is pressed together with the pretreated adhesive fixing layer (0.5MPa, 30℃, 2h), cut into an arc-shaped structure, and vacuum sealed.

[0069] Comparative Example 2 I. Core Raw Materials Microneedle essence layer: Same as in Example 1.

[0070] Nanofiber substrate: Same as in Example 1.

[0071] Adhesive fixing layer: Same as in Example 1.

[0072] Auxiliary reagents: Same as in Example 1.

[0073] II. Preparation Equipment Remove the temperature-controlled casting machine equipment; otherwise, it is the same as in Example 1.

[0074] II. Step-by-step preparation and implementation process (1) Preparation of nanospheres Completely identical to Example 1, core-shell structured nanospheres (particle size 50-100 nm) were obtained.

[0075] (2) Co-formation of microneedle essence layer and nanofiber base layer Completely identical to Example 1, a "microneedle-nanofiber substrate" composite layer (microneedle length 150-200μm) was obtained.

[0076] (3) Integral composite and molding Microneedle layer and bonding layer composite: The temperature control layer coating and low temperature composite steps are omitted. The "microneedle-nanofiber substrate" composite layer and bonding fixation layer are directly activated by plasma (same parameters as in Example 1) and then pressed together (0.5MPa, 30℃, 2h).

[0077] Cutting and packaging: Same as in Example 1, cut into an arc-shaped structure and vacuum packaged.

[0078] Experimental Example 1 This experimental example verifies the synergistic response of the biodegradable microneedle temperature-controlled stretch mark repair film prepared in Example 1 under simulated diurnal skin temperature changes.

[0079] (1) Take the finished products of Example 1, Comparative Example 1 and Comparative Example 2 and cut them into circular pieces with a diameter of 1.5 cm. Place the samples in constant temperature shaking water baths at 32±0.5℃ (simulating daytime skin temperature) and 35±0.5℃ (simulating nighttime skin temperature rise), respectively. The release medium is phosphate buffer (PBS, pH 7.4) containing 0.5% sodium dodecyl sulfate (SDS) to simulate the tissue fluid environment.

[0080] (2) Samples were taken at predetermined time points (1, 2, 4, 8, 12, 24 h) and replenished with isothermal and equal-volume fresh medium. The cumulative release of asiaticoside and palmitoyl tripeptide-5 in the medium was determined by high performance liquid chromatography.

[0081] (3) After being treated at 32°C and 35°C for 24 hours respectively, the samples of Example 1 and Comparative Example 2 were taken out, dried at the critical point, and the microneedle morphology was observed using a scanning electron microscope, and the microneedle height residual rate was measured.

[0082] The results are shown in Table 1 below. The membrane patch prepared in Example 1 simultaneously achieved temperature-sensitive release of both components, and the degradation rate of its PLGA microneedles was temperature-regulated. This directly verifies the core linkage mechanism by which the temperature control layer actively regulates microneedle degradation through heat conduction, thereby controlling drug release. The membrane patch prepared in Comparative Example 1 can only accelerate the release of surface drugs and cannot achieve deep delivery; the membrane patch prepared in Comparative Example 2 exhibits a passive release mode independent of temperature.

[0083] Table 1. Comparison of Release Behavior and Morphological Changes

[0084] Experimental Example 2 This experimental example verifies the in vitro transdermal penetration and sequential release of the biodegradable microneedle temperature-controlled stretch mark repair patch prepared in Example 1. (1) Model: The Franz vertical diffusion cell was used, with fresh detached pig skin (subcutaneous fat removed, thickness approximately 1.0 mm) as the permeability barrier.

[0085] (2) Grouping: The samples prepared in Example 1, Comparative Example 1 and Comparative Example 2 were applied to the keratin layer of pig skin.

[0086] (3) Detection: The receptor pool was kept at a constant temperature of 35±0.5℃. Full-thickness receptor fluid was collected at 2, 4, 8, 12 and 24 h, and the epidermal components at 2 h and 8 h were collected by tape peeling method.

[0087] (4) Analysis: The contents of hydroxyasiaticoside and palmitoyl tripeptide-5 in different samples were quantitatively analyzed using LC-MS / MS.

[0088] The results are shown in Table 2 below. The patch prepared in Example 1 successfully achieved time-sequential release, with asiaticoside accumulating in the epidermis early on, while palmitoyl tripeptide-5 continuously penetrated into the dermis. It also achieved deep and long-lasting delivery of repairing ingredients. The total transdermal amount of palmitoyl tripeptide-5 after 24 hours was significantly higher than that of the patch in Comparative Example 2, which only used microneedles. This indicates that temperature control not only did not hinder delivery but also synergistically optimized the delivery efficiency of microneedles, avoiding the problem of insufficient post-release effect of microneedles alone. Furthermore, it was demonstrated that microneedles are a necessary condition for deep delivery, as the repairing ingredients in Comparative Example 1 could hardly penetrate the skin.

[0089] Table 2. Comparison of transdermal penetration and distribution

[0090] Experimental Example 3 This experimental example verifies the repair biological function of the biodegradable microneedle temperature-controlled stretch mark repair film prepared in Example 1.

[0091] (1) Cells and treatment: Human skin fibroblasts (HSF) were used. The release solutions (sterilized and filtered) of the samples prepared in Example 1 and Comparative Example 2 were collected after 24 hours at 35°C, as well as the corresponding release solutions of the sample prepared in Comparative Example 1.

[0092] (2) Grouping: A blank control group (normal culture medium), Example 1 group, Comparative Example 1 group, and Comparative Example 2 group were set up. The cells were treated with culture medium containing 10% release solution.

[0093] (3) Detection: Cell proliferation (CCK-8 method): Detected after 24 and 48 hours of treatment.

[0094] Collagen secretion (ELISA method): After 48 hours of treatment, the content of type I collagen in the cell supernatant was detected.

[0095] The results are shown in Table 3 below. The release solution of the film patch prepared in Example 1 had the strongest effects on promoting fibroblast proliferation and inducing collagen synthesis. This indicates that the time-series and efficient delivery achieved through the temperature-controlled-microneedle synergistic mechanism resulted in a synergistic effect of anti-inflammatory and repair components at the cellular level, rather than a simple additive effect, thus potentially leading to better in vivo stretch mark repair.

[0096] Table 3. Comparison of cell viability and collagen secretion

[0097] In summary, the embodiments successfully prepared a biodegradable microneedle temperature-controlled stretch mark repair film with a four-layer composite structure. The structure is complete, the functional layers are firmly bonded, the microneedle array has a uniform morphology, and the temperature control layer exhibits precise pore size response performance at a threshold of 34-36℃. This indicates that the entire preparation process is stable and reliable and can achieve the design intent.

[0098] Experimental data show that, under simulated nighttime skin temperature conditions, the microneedle degradation rate and drug release rate of the product of this invention are significantly higher than those under normal temperature conditions. This temperature-sensitive characteristic is not present in the comparative samples, directly verifying the core linkage mechanism of the temperature-controlled layer triggering and synergistically accelerating microneedle degradation and drug release. Further transdermal experiments demonstrate that the product can efficiently achieve sequential delivery of anti-inflammatory and repair effects, with the cumulative penetration amount and duration of action of the repair components in the dermis significantly superior to ordinary microneedle patches without a temperature-controlled layer.

[0099] Cellular function experiments have biologically confirmed that the drug components released by the product of this invention can most effectively promote the proliferation of skin fibroblasts and collagen synthesis, and its effect is superior to that of comparative products with individual functions. This indicates that the components delivered through an intelligent synergistic mechanism have a synergistic effect.

[0100] In summary, the examples and experimental cases together demonstrate that the present invention not only successfully integrates temperature control response and microneedle transdermal technology, but also creates an intelligent repair system that can respond to physiological rhythms and dynamically optimize delivery behavior through unique structural design and material coupling, thereby achieving breakthrough improvements in transdermal efficiency, release controllability and final repair efficacy.

Claims

1. A biodegradable microneedle temperature-controlled stretch mark repair film, characterized in that, It includes a four-layer structure that is sequentially combined from the outside to the inside: The nanofiber substrate (1) is composed of polymer nanofibers carrying essence ingredients, serving as the carrier substrate of the microneedle (5) array and forming a slow-release reservoir; The microneedle essence layer (2) is composed of a microneedle (5) array made of biodegradable polymer material, and the tip of the microneedle (5) is loaded with nanospheres (6) containing active ingredients. The temperature control layer (3) is composed of temperature-responsive polymer materials and thermally conductive particles, and its critical response temperature is 34-36℃. The bonding and fixing layer (4) is composed of flexible fabric material and medical pressure-sensitive adhesive, and is used to adhere the essence film to the skin.

2. The biodegradable microneedle temperature-controlled stretch mark repair film according to claim 1, characterized in that, The temperature-responsive polymer material in the temperature control layer (3) is poly(N-isopropylacrylamide), and the thermally conductive particles are boron nitride nanoparticles. The mass percentage of boron nitride nanoparticles in the temperature control layer (3) is 5%-8%.

3. The biodegradable microneedle temperature-controlled stretch mark repair film according to claim 1, characterized in that, The biodegradable polymer material in the microneedle essence layer (2) is polylactic acid-hydroxyacetic acid copolymer, and its degradation cycle is 72-96 hours; the length of the microneedles (5) in the microneedle (5) array is 150-200 μm.

4. The biodegradable microneedle temperature-controlled stretch mark repair film according to claim 1 or 3, characterized in that, The nanospheres (6) have a core-shell structure, with the core consisting of palmitoyl tripeptide-5 and sodium hyaluronate, and the shell consisting of polycaprolactone modified with asiaticoside; the nanospheres (6) have a particle size of 50-100 nm.

5. The biodegradable microneedle temperature-controlled stretch mark repair film according to claim 1, characterized in that, The nanofiber substrate (1) is a composite nanofiber membrane of polylactic acid and Centella asiatica extract prepared by electrospinning technology.

6. The biodegradable microneedle temperature-controlled stretch mark repair film according to claim 1, characterized in that, The bonding and fixing layer (4) is a composite fabric of modified bamboo fiber and polyurethane elastic fiber, with an arc-shaped structure that adapts to the abdominal curve.

7. A method for preparing a biodegradable microneedle temperature-controlled stretch mark repair film patch as described in any one of claims 1-6, characterized in that, Includes the following steps: S1: Prepare the temperature control layer (3); S2: Preparation of nanospheres loaded with active ingredients (6); S3: The microneedle (5) casting liquid containing the nanospheres (6) is injected into the mold, and the nanofiber substrate layer (1) is directly prepared on the surface of the mold by electrospinning technology. After drying and demolding, a composite layer of microneedle (5) essence layer and nanofiber substrate layer (1) is obtained. S4: Perform plasma activation treatment on the surface of the microneedles (5) of the composite layer; S5: The activated composite layer and the temperature control layer (3) are pressed together in a temperature and vacuum environment below 34°C to obtain the repair film.

8. The preparation method of the biodegradable microneedle temperature-controlled stretch mark repair film according to claim 7, characterized in that, In step S4, the working gas for the plasma activation treatment is argon, the processing power is 80-120W, and the processing time is 20-40 seconds.

9. The preparation method of the biodegradable microneedle temperature-controlled stretch mark repair film according to claim 7, characterized in that, The pressing process in step S5 adopts a gradient pressure process: first, pre-press at 0.1-0.2MPa for 3-5 minutes, and then increase the pressure to 0.4-0.6MPa for 10-20 minutes.

10. The method for preparing the biodegradable microneedle temperature-controlled stretch mark repair film according to claim 7, characterized in that, In step S2, the nanospheres (6) are prepared using a dual emulsification-solvent evaporation method.

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