Scar-removing microneedle body and scar-removing microneedle composite patch

Abstract

The application discloses a scar-removing microneedle body and a scar-removing microneedle composite patch, and belongs to the technical field of microneedle patches. The scar-removing microneedle composite patch comprises a patch layer and a microneedle layer. The patch layer comprises a silica gel layer and a substrate layer, and the substrate layer is arranged between the microneedle layer and the silica gel layer. The microneedle layer comprises a plurality of microneedle bodies. The microneedle body comprises an epidermis section and a dermis section. The epidermis section is composed of a matrix and a first scar-removing component. The dermis section is composed of a matrix and a second scar-removing component. The scar-removing microneedle body in the application is designed in a two-section structure, two scar-removing components are combined, and different scar-removing components targeted to the epidermis layer and the dermis layer are accurately provided to the target skin layer. The individual scar-removing components can be concentrated in the target skin layer, and the side effects or interference of the scar-removing components in different skin layers can be avoided, so that the accurate and efficient composite scar-removing effect is achieved.

Description

Technical Field

[0001] This invention belongs to the field of microneedle patch technology, specifically relating to a scar removal microneedle body and a scar removal microneedle composite patch. Background Technology

[0002] Scars are non-functional fibrotic tissue masses that form on the skin due to delayed or excessive healing. Pathological scars are generally divided into hypertrophic scars and keloids, typically characterized by excessive deposition of extracellular matrix (ECM) and disordered collagen arrangement. Hypertrophic scars usually develop in a short period and then become quiescent, with growth not exceeding the boundaries of the original wound. Keloids, on the other hand, develop more slowly and can continue to develop for several years, generally exceeding the boundaries of the original wound. Pathological scars differ in appearance from the surrounding normal skin, are red or purple in color, and are usually contracted, flat, stretched, depressed, or raised. They exhibit a range of symptoms including inflammation, redness, swelling, itching, or pain, not only affecting appearance and physiological function but also causing significant psychological stress, leading to anxiety, lack of self-esteem, or depression, severely impacting the patient's quality of life. In pathological scars, the activity of some growth factors such as TGF-β, PDGF, FGF-β, and IGF-1 is abnormally increased, promoting the proliferation and differentiation of fibroblasts and increasing the production of collagen, fibronectin, elastin, and some proteoglycans. When fibroblasts undergo phenotypic differentiation, their structure and function change, and they begin to express actin filaments and stress fibers. This phenotype is myofibroblasts, which primarily provide mechanical support to tissues by increasing the production of collagen extracellular matrix. In scar tissue, fibroblasts and myofibroblasts persist, leading to collagen synthesis several times higher than in healthy skin. This imbalance between extracellular matrix synthesis and degradation results in scar formation. Therefore, controlling fibroblast proliferation in the later stages of healing and regulating the balance between collagen and extracellular matrix formation and degradation can effectively control keloid proliferation. Furthermore, keratinocytes have also been shown to induce pathological scars. Current research has confirmed that some growth factors produced by keratinocytes, such as HIF-1α and IL-1, can promote fibroblast proliferation and induce fibroblasts to produce KGF, GM-CSF, TGF-α, IL-6, IL-8, IL-1, COX-2, and PGE2. Conversely, these fibroblast-produced factors can also promote keratinocyte proliferation, thus forming a positive amplification loop. Studies have shown that cells in the wound healing stage exhibit epithelial-mesenchymal transition (EMT) characteristics. Columnar keratinocytes extend pseudopodia and transform into a spindle shape, increasing their migration and invasive abilities. Fibroblasts derived from EMT lead to scar formation by contracting and secreting extracellular matrix. Therefore, inhibiting EMT can reverse the morphological changes of keratinocytes, suppress their invasive abilities, and effectively inhibit the formation of pathological scars.

[0003] Currently, the traditional methods for treating scars are surgical and non-surgical treatments. Surgical excision itself is prone to scarring and has a high recurrence rate. Non-surgical treatments include drug treatments such as ointments, intralesional injections, and oral medications. Non-pharmacological treatments such as fixation therapy (adhesive tape or plaster cast), pressure therapy (bandages or supports), laser therapy, cryotherapy, and radiotherapy all have unsatisfactory treatment results due to significant side effects, high treatment costs, time consumption, intense patient pain, and poor patient compliance.

[0004] Silicone patches are soft, self-adhesive, and semi-occlusive sheets, primarily composed of medical-grade silicone. Numerous clinical observations have confirmed that silicone patches can improve the appearance, texture, and patient pain associated with scars. Applying silicone patches softens scar tissue, improves the uneven appearance of scars, and promotes their transformation from a hyperplastic state to a mature scar. Currently, it is believed that silicone can mimic the function of the stratum corneum, reducing skin moisture loss, inhibiting collagen deposition and capillary proliferation, thereby preventing excessive scar growth. However, silicone can only stabilize the scar's condition and reduce scar hyperplasia; it cannot completely eliminate existing scars, and its effects are slow, requiring long-term use. Microneedling therapy is a novel transdermal drug delivery technology. When an array of micron-sized sharp needles penetrates the skin, it creates micropores that facilitate the delivery of therapeutic substances to the local skin, thereby enhancing the permeability of drug molecules on the skin. It has advantages such as minimal invasiveness, ease of use, and high patient acceptance, minimizing the risk of systemic side effects and maximizing drug utilization. However, microneedles are generally designed with tiered structures, which results in low precision in drug delivery and fails to meet the treatment needs of different skin layers. Summary of the Invention

[0005] The purpose of this invention is to provide a scar removal microneedle body and a scar removal microneedle composite patch, which combines the composite patch with the microneedle body to actively deliver multiple scar removal ingredients transdermally through the microneedles, effectively improving the scar removal efficacy.

[0006] This invention is achieved through the following technical solution:

[0007] A scar removal microneedle, comprising an epidermal segment and a dermal segment, wherein the epidermal segment is located below the dermal segment, and the epidermal segment is composed of a matrix and a first scar removal component; the dermal segment is composed of a matrix and a second scar removal component;

[0008] The first scar-removing ingredient is a mixture of TGF-β inhibitor, fat-soluble vitamin, epidermal growth factor, allantoin, chitosan quaternary ammonium salt, first chemotherapy drug, first traditional Chinese medicine extract and water;

[0009] The second scar-removing ingredient is a mixture of sodium hyaluronate, steroids, panthenol, fibroblast growth factor, peripheral vasodilators, a second chemotherapy drug, a second traditional Chinese medicine extract, and water.

[0010] Preferably, the first chemotherapy drug is one or more of bleomycin, mitomycin C, and tamoxifen.

[0011] Preferably, the first herbal extract is one or more of the following: Centella asiatica, aloe vera, quercetin, resveratrol, emodin, licorice, kaempferol, and tripterygium alkaloid.

[0012] Preferably, the second chemotherapy drug is one or more of paclitaxel, 5-fluorouracil, and hydroxycamptothecin.

[0013] Preferably, the second herbal extract is one or more of the following: emodin, gallic acid, ginsenosides, tanshinone, protocatechuic aldehyde, total saponins of Panax notoginseng, and resveratrol.

[0014] Preferably, the matrix of the epidermal segment and the dermal segment is at least one selected from gelatin, trehalose, sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol, polylactic acid, polyvinyl alcohol, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, chondroitin sulfate, or heparan sulfate.

[0015] A scar removal microneedle composite patch includes a patch layer and a microneedle layer, wherein the microneedle layer includes a plurality of microneedles as described above; the patch layer includes a silicone layer and a base layer, wherein the base layer is disposed between the microneedle layer and the silicone layer; the size of the silicone layer is larger than the size of the base layer; the silicone layer is used to apply to the skin and fix the microneedle layer; the base layer is used to bond the microneedle layer, and the base layer is formed by drying an aqueous solution of sodium hyaluronate.

[0016] Preferably, the silicone layer is composed of a combination of polydimethylsiloxane, vinyl polydimethylsiloxane, dimethyl silicone oil, pentyl ethylene glycol, horse fat, snake oil, stearyl alcohol, PEG-7 hydrogenated ricinoleic acid, water, glycerin, sodium polyacrylate, carrageenan, sodium carboxymethyl cellulose, tartaric acid, aluminum hydroxyl, disodium EDTA, ectoine, and sodium hyaluronate.

[0017] Preferably, the thickness of the silicone layer is 1-5 mm.

[0018] Preferably, the thickness of the substrate layer is 1-2 mm.

[0019] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0020] 1) The scar removal microneedle in this invention has a two-segment structure design, which combines two scar removal ingredients to accurately deliver different scar removal ingredients to the target skin layer, targeting the epidermis and the dermis. This not only concentrates individual scar removal ingredients in the target skin layer, but also avoids the side effects or interference that scar removal ingredients may produce in different skin layers, thus exerting a precise and efficient compound scar removal effect.

[0021] 2) The scar removal microneedle composite patch of the present invention can combine silicone and microneedles to achieve skin barrier function replacement, inhibition of epithelial-mesenchymal transition, inhibition of fibroblast proliferation and collagen synthesis, etc., effectively combining the advantages of silicone and microneedles to exert the most efficient scar removal effect.

[0022] 3) The scar removal microneedle composite patch in this invention differs from the passive skin barrier function of existing traditional silicone gel scar patches. The scar removal microneedle composite patch actively delivers multiple scar removal ingredients transdermally through microneedles, effectively improving scar removal efficacy. Attached Figure Description

[0023] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is a schematic diagram of the structure of the scar removal microneedle composite patch pair in this invention.

[0025] Figure 2 This is a top-view schematic diagram of the scar removal microneedle composite patch structure in this invention.

[0026] Figure 3 This is a schematic diagram showing the changes in Vancouver Scar Scale values ​​before and after local scar intervention in rabbit ears.

[0027] Figure 4 This is a schematic diagram showing the changes in transdermal water loss in the skin before and after local scar intervention in rabbit ears.

[0028] Figure 5 This is a schematic diagram showing the changes in the scar elevation index before and after local scar intervention in rabbit ears.

[0029] Wherein: 1-silicone layer, 2-base layer, 3-microneedles, 31-epidermal segment, 32-dermal segment. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments.

[0031] Example 1:

[0032] The scar-removing microneedle 3 includes an epidermal segment 31 and a dermal segment 32. The epidermal segment 31 is located below the dermal segment 32. The matrix of the epidermal segment 31 and the dermal segment 32 of the microneedle 3 is trehalose. The epidermal segment 31 is composed of trehalose and the first scar-removing component, and the dermal segment 32 is composed of trehalose and the second scar-removing component. The first scar-removing component of the epidermal segment 31 of the microneedle 3 is as follows by weight: 1 part TGF-β inhibitor, 3 parts vitamin A, 3 parts vitamin E, 3 parts epidermal growth factor, 1 part allantoin, 1 part chitosan quaternary ammonium salt, 1 part tamoxifen, 10 parts centella asiatica, and 77 parts water.

[0033] The second scar-removing component of the dermal segment 32 of the microneedle 3 is as follows by weight: 14 parts sodium hyaluronate, 8 parts steroids, 2 parts panthenol, 1 part fibroblast growth factor, 3 parts pentoxifylline, 1 part 5-fluorouracil, 8 parts resveratrol, and 63 parts water.

[0034] In the epidermis, keratinocytes undergo epithelial-mesenchymal transition (EMT), resulting in a change in cell shape from cubic to flat and elongated. This leads to reduced intercellular adhesion and cytoskeleton remodeling, ultimately producing cells with fibroblast-like morphology and invasive capabilities, promoting the formation and fibrosis of abnormal scar tissue. The first scar-reducing component in epidermal segment 31, along with its first chemotherapy drug and first traditional Chinese medicine extract, forms a drug layer that inhibits EMT. Its main function is to inhibit the activation of the mesenchymal-like phenotype of keratinocytes, reverse the morphological changes of keratinocytes, inhibit their invasiveness, reduce extracellular matrix secretion, and reduce the remodeling of scars by mesenchymal-like keratinocytes.

[0035] In the dermis, some pro-fibrotic growth factors such as TGF-β1 and PDGF can promote the proliferation of fibroblasts, induce their differentiation into myofibroblasts, and promote excessive accumulation of collagen. Furthermore, fibroblasts have the ability to autonomously induce TGF-β1 production, leading to tissue fibrosis and scar formation. The second scar-reducing component of dermal segment 32, along with its second chemotherapy drug and second traditional Chinese medicine extract, forms a drug layer that inhibits dermal fibrosis. Its main functions are anti-inflammatory and anti-fibrotic, targeting and reducing the proliferation of scar fibroblasts, inhibiting their differentiation into myofibroblasts, reducing collagen production and TGF-β1 expression, thereby softening scars and exerting a therapeutic effect.

[0036] like Figure 1 and Figure 2 As shown, the scar removal microneedle composite patch includes a patch layer and a microneedle layer. The microneedle layer includes several microneedles 3. The patch layer includes a silicone layer 1 and a base layer 2. The base layer 2 is disposed between the microneedle layer and the silicone layer 1. The epidermal segment 31 of the microneedle 3 is located between the base layer 2 and the dermal segment 32. The size of the silicone layer 1 is larger than that of the base layer 2. The thickness of the silicone layer 1 is 2 mm, and the thickness of the base layer 2 is 1 mm. The silicone layer 1 is used to apply to the skin and fix the microneedle layer. The base layer 2 is used to bond the microneedle layer. The base layer 2 is formed by drying a sodium hyaluronate aqueous solution with a mass fraction of 1 wt%. The composition of the silicone layer 1 by weight is: 45 parts polydimethylsiloxane, 37 parts dimethyl silicone oil, 4 parts pentyl ethylene glycol, 3 parts horse fat, 3 parts snake oil, 5 parts stearyl alcohol, 2.5 parts glycerin, and 0.5 parts ectoine. The microneedle body 3 in the microneedle layer has a bottom radius of 400 µm, the epidermal segment 31 has a length of 500 µm, and the dermal segment 32 has a length of 1000 µm.

[0037] Applying a silicone layer can reduce the evaporation of local skin moisture, achieve an ideal humidity balance, inhibit capillary regeneration, and inhibit collagen deposition. At the same time, the silicone layer 1 covering the scar surface can compress the scar tissue, significantly reduce the tension on the scar surface, thereby inhibiting scar hyperplasia and fading the scar.

[0038] When preparing the scar-removing microneedle composite patch: the second scar-removing component of the dermal segment 32 in the microneedle body 3 is mixed with trehalose, with trehalose as the matrix, and homogenized for 15 minutes to obtain drug mixture A. The first scar-removing component of the epidermal segment 31 in the microneedle body 3 is mixed with trehalose and homogenized for 15 minutes to obtain drug mixture B. Sodium hyaluronate with a molecular weight of 1ω is dissolved in water to obtain solution C. The components of silicone layer 1 are homogenized for 15 minutes to obtain silicone layer 1 mixture D.

[0039] The prepared drug solution A is added to the needle groove of the microneedle mold. After eliminating air bubbles, excess solution A in the microneedle mold is aspirated and dried. Then, drug solution B is added to the needle shaft hole of the microneedle mold. After eliminating air bubbles, excess solution B in the microneedle mold is aspirated and dried again. Then, 200 μL of solution C is added to the baffle of the microneedle mold. After eliminating air bubbles between the solution and the drug-loaded layer, it is dried and cured. After forming, it is demolded to obtain the scar-reducing microneedle. The repeated drying of solution A during the drying of solution B has no effect on the activity of its scar-reducing components. Finally, solution D is evenly coated in the mold for making silicone layer 1. The length and width of the mold are larger than the length and width of the base layer 2. After removing air bubbles, it is dried and cured to obtain the silicone layer 1 patch. The base layer 2 and the silicone layer 1 patch are tightly attached together to obtain the scar-reducing microneedle composite patch.

[0040] The first set of scar removal microneedle composite patches was prepared according to the above method.

[0041] Example 2:

[0042] The composition of silicone layer 1 by weight is as follows: 45 parts polydimethylsiloxane, 38 parts dimethyl silicone oil, 4 parts pentyl ethylene glycol, 4 parts horse fat, 4 parts snake oil, 4 parts stearyl alcohol, and 1 part PEG-7 hydrogenated ricinoleic acid.

[0043] The base layer 2 is formed by drying an aqueous solution of sodium hyaluronate with a mass fraction of 2ω.

[0044] The first scar-removing component of the epidermal segment 31 of the microneedle 3 is as follows by weight: 2 parts TGF-β inhibitor, 4 parts vitamin A, 4 parts vitamin E, 4 parts epidermal growth factor, 2 parts allantoin, 2 parts chitosan quaternary ammonium salt, 1 part tamoxifen, 15 parts centella asiatica, and 66 parts water.

[0045] The second scar-removing component of the dermal segment 32 of the microneedle body 3 is as follows by weight: 21 parts sodium hyaluronate, 8 parts steroids, 1 part panthenol, 1 part pentoxifylline, 1 part fibroblast growth factor, 2 parts 5-fluorouracil, 3 parts tanshinone, and 63 parts water.

[0046] The second group of scar removal microneedle composite patches was prepared according to the formula components in Example 2. The preparation method is the same as that in the above examples, and will not be repeated here.

[0047] Example 3:

[0048] Skin barrier recovery period test: Two SD rats weighing 180-220g were randomly selected. The rats were anesthetized and their abdominal skin was dehaired. The microneedles 3 of the first group of scar removal microneedle composite patches and the microneedles 3 of the second group of scar removal microneedle composite patches were pressed into the skin of different rats at the dehaired sites. After 5 minutes of action, the microneedles were removed, and the skin recovery was observed every half hour.

[0049] At 0 hours, the skin surface of two rats showed obvious redness and regularly arranged micropores; after 0.5 hours, the redness of the skin of the two rats significantly subsided and the micropores gradually became blurred due to contraction; after 1 hour, only a slight redness was observed in some areas of the skin of the two rats, and the micropores were almost invisible; after 2 hours, there was no redness in the skin of the two rats and no micropores were visible. The above experimental results indicate that the segmented microneedles 3 have good biocompatibility, and the micro-trauma formed after application to the skin can heal in a short time.

[0050] Example 4:

[0051] Puncture test: (1) Aluminum foil puncture test: Lay the complete aluminum foil flat on the foam board, place the needle tip of the microneedle body 3 of the first group of scar removal microneedle composite patch and the second group of scar removal microneedle composite patch downward, press for 30 seconds under a certain pressure and then remove it, and observe the surface morphology of the aluminum foil.

[0052] The results showed that the microneedles 3 of both groups of microneedle silicone core patches could completely puncture the aluminum foil, forming neat and complete cavities on the surface.

[0053] (2) Ex vivo skin puncture test

[0054] After hair removal treatment, rat skin was removed from the body, the skin surface was dried, and the stratum corneum was fixed upward on a foam board. The microneedles of the first and second groups of scar removal microneedle composite patches were placed with the three needle tips facing downward. After pressing for 30 seconds under a certain pressure, the microneedles were removed. Immediately afterward, cyanide dye was applied to the skin. After standing for 10 minutes, the excess dye was removed, the skin surface morphology was observed, and the insertion rate was calculated according to the following formula.

[0055] P = N / T × 100%

[0056] In the formula: N refers to the number of micropores generated, and T refers to the total number of needles in the microneedle array.

[0057] The results showed that the skin surface was punctured and formed uniformly distributed blue dot-like holes. The insertion rates of microneedles 3 in the first group of scar removal microneedle composite patches and the second group of scar removal microneedle composite patches were 92.89% and 93.47%, respectively, indicating that the microneedles 3 in both silicone composite patches have good ability to be inserted into the ex vivo skin.

[0058] Compare with Example 1:

[0059] This control example uses only silicone patches to provide a comparative analysis of the experimental results with the first and second groups of scar-reducing microneedle composite patches. The silicone formulation, by weight, consists of: 45 parts polydimethylsiloxane, 37 parts dimethyl silicone oil, 4 parts pentyl ethylene glycol, 3 parts horse fat, 3 parts snake oil, 5 parts stearyl alcohol, 2.5 parts glycerin, and 0.5 parts ectoine, with a thickness of 2 mm.

[0060] The silicone components are homogenized for 15 minutes to ensure even mixing, then injected into a silicone mold. After removing air bubbles, the mixture is dried and cured to form a silicone patch.

[0061] Compare with Example 2:

[0062] This control example uses a non-segmented scar removal microneedle composite patch to provide a horizontal comparison of experimental results with the first and second groups of scar removal microneedle composite patches. The difference between this control example and the microneedles 3 of the first and second groups of scar removal microneedle composite patches is that the microneedles are not segmented, containing all the active ingredients from the epidermis and dermis, and the base radius of the microneedles is 400 µm, with a length of 1500 µm.

[0063] The preparation method of the microneedle patch includes the following steps: the epidermal and dermal components of the microneedle body 3 in the first group of scar removal microneedle composite patches are mixed with trehalose (as a matrix matrix), homogenized for 15 minutes to obtain a uniform mixed solution E, solution E is added to the needle groove of the microneedle mold, after eliminating air bubbles, excess solution in the microneedle mold is removed, after drying and curing, 1 wt% sodium hyaluronate base solution is added to the baffle of the microneedle mold, after eliminating air bubbles between the base and the drug-loaded layer, it is dried and cured, and then molded and demolded to obtain a non-segmented scar removal microneedle patch.

[0064] Example 5:

[0065] The treatment scope of scar removal microneedle composite patches includes, but is not limited to, the prevention and treatment of conventional scars, hypertrophic scars, keloids, and atrophic scars.

[0066] The application of scar-reducing microneedles was verified through a rabbit ear scar intervention experiment. The modeling method for the rabbit ear scar intervention experiment involved purchasing 20 white rabbits (sex and weight 1.5-2 kg), acclimatizing them for 7 days, and then establishing a scar model. The rabbits were anesthetized by intravenous injection of 3% pentobarbital solution (30 mg / kg) into the ear margin. A circular full-thickness skin incision (1 cm in diameter) was made on the ventral side of each rabbit's ear, and the perichondrium was dissected. Two wounds were made per ear, with each area spaced more than 1 cm apart. Pressure was applied to stop bleeding, and iodine was applied for disinfection. The rabbits had free access to water and food during the intervention period. The formation of a hard scar mass after 21 days indicated successful model establishment.

[0067] Grouping and drug administration: Rabbits with successfully established scar models were randomly divided into 3 groups (n=3): negative control group (scarred skin), first control group, second control group, first embodiment group, and second embodiment group. The negative control group received no treatment. The first control group, second control group, first embodiment group, and second embodiment group had their respective patches applied 24 hours after scar model establishment, with applications every three days. Relevant data were recorded at 30 and 60 days.

[0068] Treatment efficacy assessment:

[0069] (1) Assessment based on the Vancouver Scar Scale (VSS)

[0070] Before intervention, at 30 and 60 days, the color, blood vessel distribution, thickness and softness of the scar tissue were observed and scored according to the VSS. The higher the score, the more severe the scar hyperplasia.

[0071] Table 1. Vancouver Scar Scale Scoring Criteria

[0072]

[0073] The results are as follows Figure 3 As shown, statistical analysis revealed no significant differences in VSS scores before intervention among the negative control group, the first control group, the second control group, the first implementation group, and the second implementation group. At 30 and 60 days, the VSS scores, from highest to lowest, were: negative control group, first control group, second control group, first implementation group, and second implementation group. This indicates that silicone patches have a certain scar-inhibiting effect, microneedles are more effective than silicone patches alone, and segmented microneedles are more effective than non-segmented microneedles. This demonstrates that the segmented microneedle silicone composite patch has a better targeted effect on scar improvement.

[0074] (2) Transepidermal water loss (TWEL) assay

[0075] Before intervention, and at 30 and 60 days, the skin at the scar site was lightly touched with the probe of a multifunctional skin tester (CK-MPA10, Germany), and the values ​​were read and statistically analyzed.

[0076] The results are as follows Figure 4 As shown, there were no significant differences in TWEL values ​​before intervention among the negative control group, the first control group, the second control group, the first embodiment group, and the second embodiment group. There were also no significant differences in TWEL values ​​at different time points in the negative control group. At 30 days and 60 days, the TWEL values ​​of each group, from highest to lowest, were: negative control group, first control group, second control group, first embodiment group, and second embodiment group. This indicates that the use of silicone patches can promote skin hydration, and patches with microneedles are more effective than silicone patches alone. The use of segmented microneedles is more effective than the use of non-segmented microneedles, and the segmented scar-removing microneedle composite patch has a better water-retention effect.

[0077] (3) Scar Elevation Index (SEI)

[0078] Three scar tissue samples were randomly collected for histological examination before intervention, at 30 days, and at 60 days. The SEI value was calculated as the ratio of wound tissue height to adjacent unwound tissue height in each sample, quantifying the degree of scar improvement. A smaller SEI value indicates better improvement.

[0079] The results are as follows Figure 5As shown, there were no significant differences in SEI values ​​before intervention among the negative control group, the first control group, the second control group, the first embodiment group, and the second embodiment group. There were also no significant differences in SEI values ​​at different time points in the negative control group. At 30 days and 60 days, the SEI values ​​of each group, from highest to lowest, were: negative control group, first control group, second control group, first embodiment group, and second embodiment group. This indicates that silicone patches have a certain scar-reducing effect. The effect of using non-segmented microneedle patches is better than using silicone patches alone, and the effect of using segmented microneedle patches is better than using non-segmented microneedle patches. This suggests that segmented scar-reducing microneedle composite patches have a better effect on improving scars. Statistical analysis was performed using SPSS 23.0 software.

[0080] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., used to indicate the orientation or positional relationship are based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship that the product of this invention is usually placed in during use. They are only for the convenience of describing this invention and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0081] Furthermore, the use of terms such as "horizontal" and "vertical" in the description of this invention does not imply that the components are required to be absolutely horizontal or suspended, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0082] In the description of this invention, it should also be noted that, unless otherwise explicitly specified and limited, the terms "set," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0083] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications or equivalent changes made to the above embodiments based on the technical essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A scar removal microneedle body, characterized in that, The microneedle comprises an epidermal segment and a dermal segment, wherein the epidermal segment is located below the dermal segment and the epidermal segment is composed of a matrix and a first scar-reducing ingredient; the dermal segment is composed of a matrix and a second scar-reducing ingredient. Option 1: The first scar-removing ingredient, by weight, consists of 1 part TGF-β inhibitor, 3 parts vitamin A, 3 parts vitamin E, 3 parts epidermal growth factor, 1 part allantoin, 1 part chitosan quaternary ammonium salt, 1 part taximofen, 10 parts centella asiatica, and 77 parts water. The second scar-removing ingredient, by weight, is: 14 parts sodium hyaluronate, 8 parts steroids, 2 parts panthenol, 1 part fibroblast growth factor, 3 parts pentoxifylline, 1 part fluorouracil, 8 parts resveratrol, and 63 parts water. Option 2: The first scar-removing ingredient, by weight, consists of 2 parts TGF-β inhibitor, 4 parts vitamin A, 4 parts vitamin E, 4 parts epidermal growth factor, 2 parts allantoin, 2 parts chitosan quaternary ammonium salt, 1 part taximofen, 15 parts centella asiatica, and 66 parts water. The second scar-removing ingredient, by weight, is: 21 parts sodium hyaluronate, 8 parts steroids, 1 part panthenol, 1 part pentoxifylline, 1 part fibroblast growth factor, 2 parts fluorouracil, 3 parts tanshinone, and 63 parts water.

2. The scar removal microneedle body of claim 1, wherein, The matrix of the epidermal and dermal segments is at least one of gelatin, trehalose, sodium hyaluronate, polyvinylpyrrolidone, polyethylene glycol, polylactic acid, polyvinyl alcohol, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, chondroitin sulfate, or heparan sulfate.

3. A scar removal microneedle composite patch, characterized in that, The device includes a patch layer and a microneedle layer, wherein the microneedle layer comprises a plurality of microneedles as described in any one of claims 1-2; the patch layer comprises a silicone layer and a base layer, wherein the base layer is disposed between the microneedle layer and the silicone layer; the size of the silicone layer is larger than the size of the base layer; the silicone layer is used to adhere to the skin and fix the microneedle layer; the base layer is used to bond the microneedle layer, wherein the base layer is formed by drying an aqueous solution of sodium hyaluronate.

4. The scar-treating microneedle composite patch of claim 3, wherein the microneedle array is formed of a plurality of microneedles, and the plurality of microneedles are arranged in a matrix shape. The silicone layer is composed of a combination of polydimethylsiloxane, vinyl polydimethylsiloxane, dimethyl silicone oil, pentyl ethylene glycol, horse fat, snake oil, stearyl alcohol, PEG-7 hydrogenated ricinoleic acid, water, glycerin, sodium polyacrylate, carrageenan, sodium carboxymethyl cellulose, tartaric acid, aluminum hydroxyl, disodium EDTA, ectoine, and sodium hyaluronate.

5. The scar-removing microneedle composite patch as described in claim 3, characterized in that, The thickness of the silicone layer is 1-5mm.

6. The scar-removing microneedle composite patch as described in claim 3, characterized in that, The thickness of the base layer is 1-2 mm.

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