A dissolvable microneedle patch for acne grading treatment and a preparation method thereof

Abstract

The application discloses a soluble microneedle patch for acne grading treatment and a preparation method thereof. The microneedle patch comprises a backing layer and a microneedle array attached to the backing layer, and the microneedle array comprises three microneedle regions with different heights: a first needle length region with a needle height of 150±30 microns matches comedonal acne, a second needle length region with a needle height of 280±30 microns matches inflammatory papular acne, and a third needle length region with a needle height of 400±30 microns matches pustular / cystic acne; the microneedle is composed of a polymer matrix and liposomes dispersed in the polymer matrix, the liposomes internally load acne-removing active ingredients, the loading capacity of the liposomes in the three needle length regions is gradiently increased, and the types and concentrations of the active ingredients match the acne grading. Through four matching of lesion depth-needle length-liposome loading capacity-active ingredient, the application realizes precise layered treatment and differential drug release of acne, and the release is controllable and the irritation is low.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical and cosmetic technology, specifically to a soluble microneedle patch for graded treatment of acne and its preparation method. Background Technology

[0002] Acne is a common chronic inflammatory disease of the hair follicles and sebaceous glands, frequently occurring on the face, chest, back, and other areas with high sebum secretion. Globally, approximately 80%-90% of adolescents are affected, and symptoms can persist into adulthood for some patients. According to the "Chinese Guidelines for the Treatment of Acne" (2019 revised edition), acne is clinically classified into 3 degrees and 4 grades based on the nature of the skin lesions: mild (Grade I, comedones), moderate (Grade II, inflammatory papules; Grade III, pustules), and severe (Grade IV, nodules / cysts). The depth of lesions varies significantly among different types of acne: comedones are located in the superficial epidermis, with inflammatory contents accumulating approximately 10-50 μm below the stratum corneum; inflammatory papules are located in the superficial dermis, with the inflammatory center located approximately 50-300 μm at the root of the hair follicle; pustules / cysts can penetrate deep into the dermis to approximately 300-600 μm. Therefore, the core of acne treatment lies in precisely delivering medication to the dermal layer that matches the depth of the lesion.

[0003] Soluble microneedles, an emerging transdermal drug delivery technology, consist of a micron-sized array of needles made from biodegradable polymer materials. When used, they are applied to the skin with vertical pressure, allowing the needles to penetrate the stratum corneum barrier and dissolve within the epidermis and dermis, delivering the loaded drug directly to the lesion site. Compared to oral administration, microneedle delivery avoids the first-pass effect in the liver and improves local bioavailability. Compared to injection, microneedling offers advantages such as being painless, minimally invasive, and suitable for home administration, significantly improving patient compliance.

[0004] Liposomes are spherical vesicle carriers composed of a phospholipid bilayer and have been widely used in cosmetics and drug delivery. Existing research shows that liposomes can encapsulate acne-fighting active ingredients such as salicylic acid, retinoids, and azelaic acid, utilizing their phospholipid bilayer structure to achieve sustained release, reduce drug irritation to skin tissues, improve drug chemical stability, and enhance the dispersibility of poorly soluble components.

[0005] However, most existing soluble microneedle products use a uniform needle length design, such as 250μm or 300μm for some commercially available products. These products have the following drawbacks: First, when the needle is too short (e.g., 150μm), it cannot reach the deep inflammatory sites in the dermis where deep papules and cysts are located, resulting in drug deposition at a misaligned location with the lesion and limited efficacy. Second, when the needle is too long (e.g., 400μm), if used for superficial comedones, the needle tip may exceed the depth of the lesion, overstimulating healthy dermal tissue and causing pain, erythema, or even post-inflammatory hyperpigmentation. Third, traditional microneedles passively dissolve after insertion into the skin, and drug release is determined solely by the needle material, making it impossible to differentiate drug release based on the severity of acne. Fourth, existing microneedle products are not designed according to the three-degree, four-level grading system of the "Chinese Acne Treatment Guidelines," resulting in a lack of tiered and targeted clinical drug delivery.

[0006] Chinese patent CN114272510B discloses a soluble microneedle with layered and segmented drug loading, which achieves layered drug loading through a segmented design of the needle tip and base. However, this patent only involves the distribution of drugs in different segments within the same needle, and its inventive concept lies in controlling the timing of drug release (immediate release + sustained release). It does not involve the design of setting different needle lengths on the same base to correspond to different acne lesion depths, nor does it solve the technical problem of matching lesion depth with needle length.

[0007] Furthermore, existing liposome microneedles all use a single needle length and are not designed to differentiate for acne grading. Current technologies also do not disclose technical solutions that correlate liposome loading with needle length gradients or match active ingredient types with acne grading. Therefore, how to provide a soluble microneedle patch with needle length matching the depth of acne lesions according to grading, a gradient distribution of liposome loading, and active ingredient types adapted to grading has become a pressing technical problem to be solved in this field. Summary of the Invention

[0008] To address the technical shortcomings of existing soluble microneedle products, such as the inability to adapt the uniform needle length to acne lesions of different depths, uncontrollable drug release behavior, and lack of differentiated design according to acne grading, this invention provides a soluble microneedle patch that integrates three microneedles of different heights on the same substrate. Through a four-fold matching of lesion depth, needle length, liposome loading, and active ingredient, precise stratified drug delivery and differentiated drug release are achieved.

[0009] According to one objective of the present invention, a soluble microneedle patch for graded treatment of acne is provided, comprising a backing layer and a microneedle array attached to the backing layer. The microneedle array comprises three microneedle regions of different heights: The first needle in the long area has a height of 150±30μm, which is used to match the depth of comedo acne lesions. The second needle in the long area has a height of 280±30μm, which is used to match the depth of inflammatory papular acne lesions; The third needle in the long area has a height of 400±30μm and is used to match the depth of pustular / cystic acne lesions.

[0010] The microneedles are composed of a polymer matrix and liposomes dispersed in the polymer matrix, and the liposomes are loaded with acne-removing active ingredients. The liposome loading rate increases progressively in the first, second, and third long-range injections: The types and concentrations of acne-fighting active ingredients in the first, second, and third long-area injections are matched with the acne grading.

[0011] Furthermore, the liposome loading in the first injection of the long region is 0.5%-2% (w / w), in the second injection it is 2%-5% (w / w), and in the third injection it is 5%-10% (w / w).

[0012] Furthermore, the active ingredients for acne treatment in the first injection area include salicylic acid and niacinamide, with salicylic acid comprising 0.5%-1.5% of the injection solution and niacinamide comprising 1%-3% of the injection solution, used to quickly unclog pores and dissolve keratin. The active ingredients for acne treatment in the second injection area include salicylic acid and azelaic acid, with salicylic acid comprising 1%-3% of the injection solution and azelaic acid comprising 1%-4% of the injection solution, used for anti-inflammatory and antibacterial purposes. The active ingredients for acne treatment in the third injection area include niacinamide and asiaticoside, with niacinamide comprising 2%-5% of the injection solution and asiaticoside comprising 0.2%-1% of the injection solution, used for long-lasting repair and promoting wound healing. The total concentration of active ingredients in the three injection areas increases progressively with the injection length, matching the severity of acne grading.

[0013] Furthermore, the liposomes are composed of phospholipids and cholesterol, with a molar ratio of phospholipids to cholesterol of (5-10):1, an average particle size of 50-200 nm, and an encapsulation efficiency of 85%-98%.

[0014] Furthermore, the polymer matrix is ​​selected from at least one of hyaluronic acid, polyvinyl alcohol, and polyvinylpyrrolidone.

[0015] Furthermore, it is preferably composed of hyaluronic acid, polyvinyl alcohol, and polyvinylpyrrolidone in a mass ratio of (5-8):(1-3):(0.5-2). This composite matrix has both good mechanical strength and rapid dissolution performance: hyaluronic acid gives the needle excellent biocompatibility and moisturizing properties, polyvinyl alcohol provides the mechanical support required for needle insertion, and polyvinylpyrrolidone regulates the dissolution rate and flexibility of the needle.

[0016] Furthermore, the tips of the microneedles in the microneedle array are conical, the bottom diameter of the microneedles is 150-250μm, and the spacing between the microneedles is 300-500μm.

[0017] Furthermore, the backing layer is a flexible polymer film, preferably selected from at least one of polyvinyl alcohol film, polyurethane film, and polyethylene film, with a thickness of 50-200 μm, and has good flexibility and adhesion.

[0018] This invention also provides a method for preparing the above-mentioned soluble microneedle patch, comprising the following steps: Step 1: Prepare liposomes loaded with acne-fighting active ingredients using a thin-film dispersion method; Step 2: Dissolve the polymer matrix in deionized water to prepare a polymer solution with a mass fraction of 10%-30%; Step 3: Add the liposomes obtained in Step 1 to the polymer solution to prepare three perfusion solutions with different liposome concentrations, corresponding to the first long injection region, the second long injection region, and the third long injection region, respectively. Step 4: Use 3D printing to prepare a male mold with three different heights of needle protrusions, and use casting to prepare a PDMS female mold with three different depths of pits; Step 5: Inject the three types of injection liquids into the corresponding pit areas of the PDMS female mold, degas under vacuum, and then solidify to form microneedles; Step 6: Pour the backing layer solution onto the surface of the cured microneedle body and let it cure to form the backing layer; Step 7: Demold to obtain soluble microneedle patches.

[0019] The preparation of liposomes in step 1 includes: dissolving phospholipids and cholesterol in an organic solvent at a molar ratio of (5-10):1, and rotary evaporating to form a lipid film; dissolving the acne-removing active ingredient in phosphate buffer, adding it to the lipid film for hydration for 30-60 minutes; after ultrasonic or high-pressure homogenization, extruding it sequentially through 200nm and 100nm polycarbonate membranes to obtain liposomes with an average particle size of 50-200nm.

[0020] The vacuum degree of vacuum degassing in step 5 is -0.06 to -0.10 MPa, and the degassing time is 10-20 minutes; the curing is carried out at 30-40℃ for 4-12 hours.

[0021] The backing solution in step 6 is a 5%-15% (w / w) polyvinyl alcohol aqueous solution; the curing is performed at 30-40°C for 2-6 hours.

[0022] The demolding described in step 7 involves cutting into the mold at an angle of 10-20° from the edge and peeling it off at a uniform speed of 1-3 mm / s.

[0023] This invention utilizes a microneedle array with three needle length regions that precisely match the skin layers of comedo-type, inflammatory papular type, and pustular / cystic acne, ensuring the insertion depth matches the anatomical location of the lesion. This overcomes the limitation of traditional single-needle lengths, which cannot address acne grading. Simultaneously, the liposome loading in the three needle length regions increases in a gradient, and the types and concentrations of active ingredients match the acne grading, achieving differentiated drug release from low doses in the superficial layer to high doses in the deep layer. This ensures adequate treatment of deep, severe cases while avoiding excessive administration to the superficial layer. The active ingredients are encapsulated in liposomes and released in a controlled manner along with the polymer matrix, significantly reducing the risk of local irritation and systemic exposure. Furthermore, a single patch can simultaneously cover lesions of multiple grades, making it convenient to use. Attached Figure Description

[0024] Figure 1 This is a top view of the soluble microneedle patch of the present invention. Figure 2 This is a schematic diagram of the cross-sectional structure of the soluble microneedle patch of the present invention, showing the correspondence between the three needle lengths and the skin layers; Figure 3 This is a schematic diagram of the liposome structure loaded with acne-reducing active ingredients in this invention; Figure 4 A schematic diagram showing the gradient distribution of liposome loading in three needle length regions; Figure 5 This is a schematic diagram illustrating the mechanism of liposome-mediated drug release after the microneedle patch of the present invention is inserted into the skin.

[0025] In the diagram: 1. First needle long area; 2. Second needle long area; 3. Third needle long area; 4. Phospholipid bilayer; 5. Acne-fighting active ingredients; 6. Backing layer; 7. Needle body; 8. Stratum corneum; 9. Epidermis; 10. Dermis. Detailed Implementation

[0026] The present invention will be further described below with reference to the accompanying drawings and embodiments. The following embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the invention. Experimental methods not specifically described in the embodiments were performed under conventional conditions or conditions recommended by the manufacturer.

[0027] The raw materials used in the examples are all commercially available products: soybean lecithin (phosphatidylcholine content of about 90%), cholesterol, hyaluronic acid (molecular weight 10-50kDa), polyvinyl alcohol (degree of alcoholysis 88%, molecular weight 20-30kDa), polyvinylpyrrolidone (K30), salicylic acid, nicotinamide, azelaic acid, and asiaticoside, all of which are cosmetic or pharmaceutical grade.

[0028] Example 1 This embodiment provides a soluble microneedle patch for graded treatment of acne and its preparation method, including the following steps: Step 1: Preparation of liposomes loaded with acne-fighting active ingredients Thin-film dispersion was employed: soybean lecithin and cholesterol were dissolved in chloroform at a molar ratio of 8:1, and the organic solvent was removed by rotary evaporation at 40°C, forming a uniform lipid film on the inner wall of a round-bottom flask. The acne-fighting active ingredient was dissolved in phosphate buffer (pH 7.4), and the resulting hydrated solution was added to the lipid film. The mixture was then hydrated by shaking at room temperature for 45 minutes to obtain a multilayer liposome suspension. The suspension was ultrasonically treated with a probe (300W power, 3 seconds on, 3 seconds off, total duration 10 minutes), and then extruded three times each through 200nm and 100nm polycarbonate membranes to obtain liposomes with an average particle size of approximately 120nm and an encapsulation efficiency of approximately 92%.

[0029] In this embodiment, three types of liposomes were prepared: liposome A loaded with salicylic acid and nicotinamide; liposome B loaded with salicylic acid and azelaic acid; and liposome C loaded with nicotinamide and asiaticoside.

[0030] Step 2: Preparation of polymer matrix solution Hyaluronic acid, polyvinyl alcohol, and polyvinylpyrrolidone were mixed in a mass ratio of 6:2:1, dissolved in deionized water, and stirred at 50°C until completely dissolved to prepare a polymer solution with a mass fraction of 20%.

[0031] Step 3: Preparation of the three perfusion solutions The polymer solution obtained in step 2 was divided into three equal parts: Liposome A was added to the first part to make the final concentration of liposomes 1.5% (w / w), salicylic acid 1.0% (w / w), and nicotinamide 2.0% (w / w), resulting in perfusion solution A, corresponding to the first injection length region (150 μm); Liposome B was added to the second part to make the final concentration of liposomes 3.5% (w / w), salicylic acid 2.0% (w / w), and azelaic acid 2.5% (w / w), resulting in perfusion solution B, corresponding to the second injection length region (280 μm); Liposome C was added to the third part to make the final concentration of liposomes 7% (w / w), nicotinamide 3.0% (w / w), and asiaticoside 0.5% (w / w), resulting in perfusion solution C, corresponding to the third injection length region (400 μm).

[0032] Step 4: Preparation of the hierarchical microneedle mold A photosensitive resin male mold was fabricated using 3D printing technology. It consisted of three arrays of conical needle protrusions of different heights (150μm, 280μm, and 400μm), with a needle base diameter of approximately 200μm and a needle spacing of approximately 400μm. Liquid PDMS (a mixture of prepolymer and curing agent at a mass ratio of 10:1) was cast onto the surface of the resin male mold. After vacuum degassing, the mold was cured at 65℃ for 4 hours. The PDMS was then peeled off to obtain a female mold with pits of three different depths.

[0033] Step 5: Pouring and Curing Injection solutions A, B, and C are slowly injected into the corresponding recessed areas of the PDMS female mold at a 45° angle against the mold wall. Excess solution on the mold surface is scraped off with a scraper. The mold is then placed in a vacuum drying oven and degassed at -0.08 MPa for 15 minutes. After removal, it is transferred to a constant temperature drying oven and cured at 35°C for 8 hours to form microneedles.

[0034] Step 6: Formation of the backing layer A 10% (w / w) polyvinyl alcohol aqueous solution was poured onto the surface of the needle body after curing in step 5, smoothed, and cured at 35°C for 4 hours to form a backing layer with a thickness of about 100 μm. The backing layer was integrated with the needle body substrate.

[0035] Step 7: Demolding The cured mold is removed, and the PDMS mold is peeled off at a 15° angle from the edge of the mold at a uniform speed of 2 mm / s to obtain a complete hierarchical microneedle patch. The obtained microneedle patch is as follows: Figure 1 , Figure 2 As shown.

[0036] Example 2 The difference between this embodiment and Embodiment 1 is that in this embodiment, the final concentration of liposomes in the first injection long region is 1.0% (w / w), in the second injection long region it is 2.5% (w / w), and in the third injection long region it is 5.5% (w / w). The remaining steps are the same as in Embodiment 1.

[0037] Example 3 The difference between this embodiment and Embodiment 1 is that in this embodiment, the final concentration of liposomes in the first injection long region is 2.0% (w / w), in the second injection long region it is 5.0% (w / w), and in the third injection long region it is 10.0% (w / w). The remaining steps are the same as in Embodiment 1.

[0038] Example 4 The difference between this embodiment and Embodiment 1 is that in this embodiment, the polymer matrix is ​​composed of hyaluronic acid and polyvinylpyrrolidone in a mass ratio of 7:2; the backing layer is a polyurethane film (approximately 80 μm thick), which is that in step 6, the polyurethane prepolymer is coated and cured into a film, and the remaining steps are the same as in Embodiment 1.

[0039] Comparative Example 1 The difference between this comparative example and Example 1 is that in this comparative example, the microneedle array uses a uniform needle length of 280 μm, there are no three needle length regions, the three perfusion solutions are mixed and perfused uniformly, and the liposome loading is 3.5% (w / w). The remaining steps are the same as in Example 1.

[0040] Comparative Example 2 The difference between this comparative example and Example 1 is that the microneedle array in this comparative example contains three needle lengths, but the liposome loading in the regions of the three needle lengths is the same, which is 3.5% (w / w). The remaining steps are the same as in Example 1.

[0041] Performance testing like Figures 3-5 As shown, the microneedle patches obtained in Examples 1-4 and Comparative Examples 1-2 were subjected to the following tests: 1. Puncture force test: The single-needle puncture force was determined using a modified texture analyzer, with fresh detached pigskin as the test medium. The single-needle puncture forces of Examples 1-4 were 0.12-0.18 N, all greater than the quality standard of 0.1 N, indicating that the needles of all three lengths could effectively penetrate the skin; the single-needle puncture forces of Comparative Examples 1-2 were comparable to those of Example 1.

[0042] 2. Dissolution performance test: The microneedle patch was applied to the surface of an agarose-based simulated skin model and kept at a constant temperature of 37°C. In Example 1, the 150μm region completely dissolved within 2 hours, the 280μm region completely dissolved within 4 hours, and the 400μm region completely dissolved within 8 hours. The dissolution rate was positively correlated with the needle height. In Comparative Example 1, the 280μm region dissolved within 4 hours.

[0043] 3. Transdermal Release Test: Using a Franz diffusion cell and isolated rat abdominal skin as a barrier, salicylic acid was used as a model drug to determine the cumulative transdermal release over 24 hours. The cumulative transdermal release over 24 hours in Example 1 was 3.2 times that of the ordinary hydrogel patch, and the drug release time in the 400 μm region reached 12 hours, significantly longer than the 6 hours in the 150 μm region. The cumulative transdermal release over 24 hours in Comparative Example 1 was 1.8 times that of the ordinary hydrogel patch, lower than that in Example 1. In Comparative Example 2, there was no significant difference in drug release time between the 400 μm and 150 μm regions, indicating that a liposome loading gradient is a necessary condition for deep sustained release.

[0044] 4. Human Efficacy Testing: A third-party testing agency was commissioned to conduct a human efficacy evaluation trial. The subjects were patients with mild to moderate acne. After using the product of Example 1 for 3 days, the redness and swelling of the acne significantly subsided, and after 7 days, the number of skin lesions significantly decreased. The incidence of adverse events during the trial was 0. The decrease in the number of skin lesions after 7 days for Comparative Example 1 was significantly less than that for Example 1.

[0045] Test results show that the present invention achieves precise stratified drug delivery and differentiated drug release through a four-fold matching of lesion depth, needle length, liposome loading, and active ingredient, with significantly better results than comparative methods with uniform needle length or uniform loading.

[0046] In the above embodiments, the phospholipid may be one or more of egg yolk lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, and distearate phosphatidylcholine to replace soybean lecithin; the organic solvent may be one or more of methanol, ethanol, and diethyl ether to replace chloroform.

[0047] In the above embodiments, the shape of the microneedle can also be a triangular pyramid, a square pyramid, or other conical structure; the diameter of the bottom of the needle can be adjusted within the range of 150-250μm, and the needle spacing can be adjusted within the range of 300-500μm.

[0048] In the above embodiments, the backing material may also be a flexible polymer film such as polyethylene film, polyvinyl alcohol-polyurethane composite film, or hydrocolloid film; the thickness of the backing layer can be adjusted within the range of 50-200μm.

[0049] In the above embodiments, the acne-removing active ingredients can also be replaced according to the acne grade: salicylic acid in the first injection long area can be partially or completely replaced with one of mandelic acid or fruit acid; azelaic acid in the second injection long area can be partially or completely replaced with one of benzoyl peroxide or tea tree oil; and asiaticoside in the third injection long area can be partially or completely replaced with one of panthenol or epidermal growth factor analogues.

[0050] In the above embodiments, the hyaluronic acid in the polymer matrix can be selected with a molecular weight of 10-100 kDa; the degree of alcoholysis of polyvinyl alcohol can be adjusted within the range of 85%-90%; the mass fraction of the polymer solution in step 2 can be adjusted within the range of 10%-30%, and the curing time can be adjusted accordingly.

[0051] In the above embodiments, the vacuum degree of vacuum degassing in step 5 can be adjusted within the range of -0.06 to -0.10 MPa, and the degassing time can be adjusted within the range of 10-20 minutes; the curing temperature can be adjusted within the range of 30-40℃, and the curing time can be adjusted within the range of 4-12 hours; the demolding cut angle in step 7 can be adjusted within the range of 10-20°, and the peeling speed can be adjusted within the range of 1-3 mm / s.

[0052] In the above embodiments, the three needle length regions are arranged on the patch substrate in the following ways: Figure 1 In addition to the sector-shaped partition shown, it can also be a concentric ring partition, a horizontal strip partition, or an interlaced array partition. As long as the three needle lengths are integrated on the same substrate, the technical effect of the present invention can be achieved.

[0053] The present invention has the following beneficial effects: First, precise physical matching. The three needle lengths (150μm, 280μm, and 400μm) correspond to the lesion depths of three types of acne: comedones, inflammatory papules, and pustules / cysts, respectively, achieving a precise match between lesion depth and needle length. This avoids the problem of inappropriate medication caused by a one-size-fits-all design: when used for superficial comedones, it will not excessively penetrate the healthy dermis, and when used for deep cysts, the medication can directly reach the inflamed area.

[0054] Second, the release is sustained and controllable. The phospholipid bilayer structure of liposomes allows for continuous drug release after dissolution by microneedles, prolonging the drug's duration of action at the lesion site while avoiding direct contact between the drug and skin tissue, thus reducing irritation.

[0055] Third, graded drug delivery. The liposome loading in the three needle length regions increases in a gradient, and the types and concentrations of active ingredients are matched with the acne grade, achieving a precise match between lesion depth, drug dosage, and drug release rate.

[0056] Fourth, synergistic effect. The physical breakthrough of microneedles is combined with the chemical carrier of liposomes. After the microneedles penetrate the stratum corneum, the liposomes release the substance in situ, achieving the dual effect of improved transdermal efficiency and reduced irritation.

[0057] Fifth, it is scalable. By using 3D printing to prepare the male mold and PDMS casting to prepare the female mold, combined with standardized processes such as precision injection, vacuum degassing, low-temperature curing, and flexible demolding, it is possible to achieve mass production of micron-sized microneedles with high product consistency.

[0058] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A soluble microneedle patch for graded treatment of acne, characterized in that, Includes a backing layer and a microneedle array attached to the backing layer; The microneedle array comprises three microneedle regions of different heights: The first needle is applied to a long area with a needle height of 150±30μm, which is used to match the depth of comedo acne lesions. The second needle is placed in a long area with a needle height of 280±30μm, which is used to match the depth of inflammatory papular acne lesions. The third needle is placed in a long area with a needle height of 400±30μm, which is used to match the depth of pustular / cystic acne lesions. The microneedles are composed of a polymer matrix and liposomes dispersed in the polymer matrix, and the liposomes are loaded with acne-removing active ingredients. The liposome loading in the first, second, and third long injection regions increases in a gradient. The types and concentrations of acne-fighting active ingredients in the first, second, and third long-area injections are matched with the acne grading.

2. The soluble microneedle patch according to claim 1, characterized in that, The liposome loading in the first needle long region is 0.5%-2% (w / w), the liposome loading in the second needle long region is 2%-5% (w / w), and the liposome loading in the third needle long region is 5%-10% (w / w).

3. The soluble microneedle patch according to claim 1, characterized in that, The acne-fighting active ingredients in the first injection area include salicylic acid and niacinamide; the acne-fighting active ingredients in the second injection area include salicylic acid and azelaic acid; and the acne-fighting active ingredients in the third injection area include niacinamide and asiaticoside.

4. The soluble microneedle patch according to claim 1, characterized in that, The liposomes are composed of phospholipids and cholesterol, with a molar ratio of phospholipids to cholesterol of (5-10):

1.

5. The soluble microneedle patch according to claim 1, characterized in that, The liposomes have an average particle size of 50-200 nm and an encapsulation efficiency of 85%-98%.

6. The soluble microneedle patch according to claim 1, characterized in that, The polymer matrix is ​​selected from at least one of hyaluronic acid, polyvinyl alcohol, and polyvinylpyrrolidone.

7. The soluble microneedle patch according to claim 6, characterized in that, The polymer matrix is ​​composed of hyaluronic acid, polyvinyl alcohol, and polyvinylpyrrolidone in a mass ratio of (5-8):(1-3):(0.5-2).

8. The soluble microneedle patch according to claim 1, characterized in that, The microneedles in the microneedle array have conical tips, a bottom diameter of 150-250 μm, and a spacing of 300-500 μm.

9. The soluble microneedle patch according to claim 1, characterized in that, The backing layer is a flexible polymer film, which is selected from at least one of polyvinyl alcohol film, polyurethane film, and polyethylene film.

10. A method for preparing the soluble microneedle patch according to any one of claims 1 to 9, characterized in that, Includes the following steps: Step 1: Prepare liposomes loaded with acne-fighting active ingredients using a thin-film dispersion method; Step 2: Dissolve the polymer matrix in deionized water to prepare a polymer solution with a mass fraction of 10%-30%; Step 3: Add the liposomes obtained in Step 1 to the polymer solution to prepare three perfusion solutions with different liposome concentrations. The three perfusion solutions correspond to the first long injection region, the second long injection region, and the third long injection region, respectively. Step 4: Use 3D printing to prepare a male mold with three different heights of needle protrusions, and use casting to prepare a PDMS female mold with three different depths of pits; Step 5: Inject the three types of injection liquids into the corresponding pit areas of the PDMS female mold, degas under vacuum, and then solidify to form microneedles; Step 6: Pour the backing layer solution onto the surface of the cured microneedle body and let it cure to form the backing layer; Step 7: Demold to obtain the soluble microneedle patch.

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