Anti-scar compound, preparation thereof, microneedle containing anti-scar compound and microneedle patch containing anti-scar compound
By reacting catechol compounds with reactive oxygen species-sensitive protective compounds to generate anti-scarring compounds, and combining them with microneedle formulations, the problems of multiple administrations, long treatment cycles, and poor transdermal effects of existing scar treatment products are solved, achieving efficient and convenient scar elimination.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-13
- Publication Date
- 2026-04-14
AI Technical Summary
Existing scar treatment products require multiple administrations, have long treatment cycles, poor transdermal efficacy, and lack novel therapeutic materials based on endogenous pathogenic mechanisms.
Anti-scarring compounds are generated by reacting catechol compounds and reactive oxygen species-sensitive protective compounds. Combined with microneedle formulation, transdermal drug delivery efficiency is improved. The compounds release corresponding concentrations of compounds to eliminate scars by responding to the reactive oxygen species environment at the scar site through dynamic borate ester bonds.
It significantly shortens the administration cycle, reduces the frequency of administration, improves transdermal efficacy, reduces compound toxicity, and is easy to mass-produce.
Smart Images
Figure CN121851044A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of anti-scar product preparation technology, specifically relating to an anti-scar compound, its preparation, and microneedles and microneedle patches containing it. Background Technology
[0002] Scars result from an uncontrolled wound healing process, characterized by growth that extends beyond the original injury boundary and persistently invades the surrounding normal skin, without spontaneous regression. Scar formation is a complex pathological process influenced by multiple factors, closely related to various cellular components, systems, and environmental factors. While some progress has been made in scar treatment, research on developing novel therapeutic materials based on their endogenous pathogenic mechanisms remains insufficient.
[0003] At the lesion site, various cells communicate with each other through the secretion of small extracellular vesicles, regulating key cellular biological processes. This mechanism plays a crucial role in maintaining physiological homeostasis and pathological progression. Small extracellular vesicles, acting as intercellular messengers, have a significant impact on scar formation and development. Simultaneously, abnormally elevated levels of reactive oxygen species in scars lead to excessive extracellular matrix deposition, affecting processes such as fibroblast migration and adhesion.
[0004] Currently available scar treatments primarily use silicone-based compounds, and are mostly administered via topical application or patches. However, existing products suffer from drawbacks such as frequent application, long treatment cycles, and poor transdermal absorption, highlighting the urgent need for more effective scar treatments. Summary of the Invention
[0005] To address the problems existing in the prior art, the primary objective of this invention is to provide an anti-scarring compound.
[0006] A second objective of this invention is to provide a method for preparing the anti-scarring compound as described above.
[0007] The third objective of this invention is to provide a microneedle for eliminating scars.
[0008] A fourth objective of this invention is to provide a method for preparing microneedles for scar removal as described above. The entire preparation process is simple, has low production costs, and is easy to mass-produce.
[0009] The fifth objective of this invention is to provide a microneedle patch.
[0010] To achieve the first objective mentioned above, the present invention adopts the following technical solution: This invention discloses an anti-scarring compound, wherein the raw materials for preparing the anti-scarring compound include a compound containing catechol and a compound containing a reactive oxygen species-sensitive protecting group; The compound containing catechol is selected from one or more of chlorogenic acid, epigallocatechin gallate, and quercetin; The compound containing a reactive oxygen species-sensitive protecting group is selected from one or more of 3-aminophenylboronic acid, 4-aminophenylboronic acid, 3-formylphenylboronic acid, and 4-formylphenylboronic acid.
[0011] Starting with the endogenous pathogenic mechanism of scars and the regulation of the lesion microenvironment, the applicant, through extensive experimental exploration, developed an anti-scarring compound. This anti-scarring compound is obtained by reacting a compound containing catechol (e.g., chlorogenic acid) with a compound containing a reactive oxygen species-sensitive protecting group (e.g., 3-aminophenylboronic acid). It possesses dynamic borate ester bonds, exhibiting excellent responsiveness to the reactive oxygen species microenvironment at the scar site. This not only effectively improves the stability of the anti-scarring compound in use and reduces its toxicity, but also allows it to respond to different concentrations of reactive oxygen species at the lesion site, releasing corresponding concentrations of catechol-containing compounds, thereby effectively eliminating scars. Furthermore, applying the anti-scarring compound to microneedle formulations can improve transdermal drug delivery efficiency, solving problems such as multiple dosing sessions, long dosing cycles, and poor transdermal efficacy.
[0012] Furthermore, the mass ratio of the compound containing catechol to the compound containing the reactive oxygen species-sensitive protecting group is 0.5-2:0.5-2; exemplaryly, the mass ratio of the compound containing catechol to the compound containing the reactive oxygen species-sensitive protecting group can be 0.5:0.5, 0.5:1, 0.5:1.5, 0.5:2, 1:0.5, 1:1.5, 1.5:0.5, 1.5:1, 1.5:2, 2:0.5, 2:1.5, etc.
[0013] To achieve the second objective mentioned above, the present invention adopts the following technical solution: This invention discloses a method for preparing the anti-scarring compound as described above, comprising the following steps: A compound containing catechol is mixed with a compound containing a reactive oxygen species-sensitive protecting group to obtain a reaction solution. The reaction is stirred while maintaining the pH of the system at 7-9 during the reaction.
[0014] Furthermore, the concentration of the catechol compound in the reaction solution is 1.7-5.3 mg / ml.
[0015] Furthermore, the concentration of the compound containing the reactive oxygen species-sensitive protecting group in the reaction solution is 0.68-2 mg / ml.
[0016] Furthermore, the reaction temperature is from room temperature to 40°C, and the reaction time is 4-48 hours.
[0017] To achieve the third objective mentioned above, the present invention adopts the following technical solution: This invention discloses a microneedle for eliminating scars, wherein the microneedle comprises the following raw material components: Microneedle matrix material; anti-scarring compound as described above; water.
[0018] Furthermore, the mass ratio of the microneedle matrix material to the anti-scarring compound is (100-400):(0.1-10); for example, the mass ratio of the microneedle matrix material to the anti-scarring compound can be (100-400):0.1, (100-400):1, (100-400):2, (100-400):3, (100-400):4, (100-400):5, (100-400):6, (100-400):7, (100-400):8, (100-400):9, (100-400):10, etc.
[0019] Furthermore, the microneedle matrix material is selected from one or more of polyvinyl alcohol, polyvinylpyrrolidone, and sodium hyaluronate.
[0020] To achieve the fourth objective mentioned above, the present invention adopts the following technical solution: This invention discloses a method for preparing the scar-eliminating microneedles as described above, comprising the following steps: The microneedle matrix material is mixed with water to obtain a microneedle matrix material solution; The anti-scarring compound was dissolved in a microneedle matrix material solution to obtain a mixture; The mixture is poured into a mold, dried, and shaped to obtain the microneedles.
[0021] Furthermore, the concentration of the microneedle matrix material in the mixture is 0.1-0.4 g / ml.
[0022] Furthermore, the concentration of the anti-scarring compound in the mixture is 0.1-10 mg / mL; exemplaryly, the concentration of the anti-scarring compound in the mixture can be 0.1 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, etc.
[0023] To achieve the fifth objective mentioned above, the present invention adopts the following technical solution: This invention discloses a microneedle patch comprising microneedles for scar removal as described above. This microneedle patch effectively improves transdermal drug delivery efficiency, solving problems such as frequent drug administration, long drug administration cycles, and poor transdermal efficacy.
[0024] The beneficial effects of this invention are as follows: This invention discloses a microneedle for eliminating scars. By introducing anti-scarring compounds into the microneedle formulation, it can provide significant anti-scarring capabilities. Furthermore, based on the advantages of the microneedle dosage form, it can significantly shorten the administration cycle, reduce the administration frequency, and solve the problem of poor transdermal efficacy.
[0025] The microneedle preparation method provided by this invention is simple, has low production cost, and is easy to mass-produce.
[0026] The anti-scarring compound provided by this invention is obtained by reacting a compound containing catechol (e.g., chlorogenic acid) with a reactive oxygen species-sensitive protecting group (e.g., 3-aminophenylboronic acid). The structure has dynamic borate ester bonds, which have good responsiveness to the microenvironment of reactive oxygen species at the scar site. That is, it can not only effectively improve the stability of the anti-scarring compound in use and reduce its toxicity, but also respond to different degrees according to different concentrations of reactive oxygen species at the lesion site, thereby releasing the corresponding concentration of catechol-containing compound, thus effectively eliminating scars. Attached Figure Description
[0027] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.
[0028] Figure 1 The physicochemical properties of the compound and microneedles prepared in Example 1 are shown; A is the Fourier transform infrared spectrum, B is the nuclear magnetic resonance spectrum, and C is the SEM image of the microneedles.
[0029] Figure 2 The biocompatibility of the compound prepared in Example 1 is shown.
[0030] Figure 3 The EdU experiment of the compound prepared in Example 1 is shown.
[0031] Figure 4 The in vivo therapeutic effect of the microneedles prepared in Example 1 is shown; Figure 4 A shows the recovery process of rabbit ear scars, B shows the staining of scar tissue sections with hematoxylin and eosin, and C shows the comparison of granulation tissue thickness in scar tissue sections. Detailed Implementation
[0032] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further clarifies the invention. Those skilled in the art should understand that the specific description below is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.
[0033] In this invention, the preparation methods are all conventional unless otherwise specified, and the raw materials used can be obtained from publicly available commercial sources or prepared according to existing technology unless otherwise specified.
[0034] Example 1 10 mM 3-aminophenylboronic acid was added to 10 mM chlorogenic acid at a volume ratio of 1:1.2, and the mixture was stirred at 37 °C for 8 h. During the reaction, the pH of the mixture was kept at 8. After freeze-drying, the anti-scarring compound powder was obtained, denoted as CB.
[0035] Polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) were used as microneedle matrix materials. They were mixed with water to obtain 20 wt% PVP solution and 20 wt% PVA solution. Then, the 20 wt% PVP solution and 20 wt% PVA solution were mixed at a volume ratio of 1:1 to obtain the matrix solution.
[0036] 5 mg of CB was dissolved in 1 mL of matrix solution and poured into a PDMS microneedle mold. The solution was then filled into the mold under vacuum conditions and dried overnight to obtain microneedles.
[0037] Fourier transform infrared spectrometer was used in the range of 4000-400 cm⁻¹ -1 The FT-IR spectra of chlorogenic acid (CGA), 3-aminophenylboronic acid (3-APBA), and CB were detected within the specified range. The FT-IR spectra of CGA, 3-APBA, and CB are shown below. Figure 1 As shown in Figure A, CGA is at 3357cm. -1 The corresponding carboxyl stretching vibration is located at 1684 cm⁻¹. -1 The corresponding carbonyl stretching vibration is nearby. 3-APBA is at 3262 cm⁻¹. -1 The vicinity exhibits the OH stretching vibration of the B(OH)2 group at 1358 cm⁻¹. -1 There is stretching vibration of the BO bond nearby. 3394 cm in CB. -1 The OH stretching vibration peak near the point narrows significantly because the phenolic hydroxyl group in CGA participates in the reaction and disappears, and the boron hydroxyl group in 3-APBA also disappears. (1362 cm⁻¹) -1 The peaks near the point represent the stretching vibrations of BO. FT-IR spectra of CGA, 3-APBA, and CB further confirm the successful synthesis of CB.
[0038] CGA, 3-APBA, and CB were dissolved in DMSO, transferred to NMR tubes, and analyzed using an NMR spectrometer. (CB...) 1 The H NMR results are as follows Figure 1 As shown in Figure B, the signal of the phenolic hydroxyl group (δ ~9.0-10.0 ppm) has completely disappeared, while the signal of the catechol aromatic hydrogen has shifted significantly and weakened from the δ ~6.8-7.2 ppm region before the reaction. The ¹¹B NMR spectrum of CB shows a characteristic peak at ~10 ppm, which is significantly shifted to a higher field compared to the characteristic peak of the reactant 3-APBA (approximately 30 ppm). 1 HNMR and11 B NMR results indicate that CB was successfully synthesized.
[0039] The structure of the microneedles was observed from different angles using a scanning electron microscope. For example... Figure 1 As shown in Figure C, the microneedles are evenly arranged and have a complete structure. The needle body is 1000 μm long, 300 μm in diameter, and the needle tip spacing is 800 μm.
[0040] Example 2 10 mM 4-aminophenylboronic acid was added to 10 mM epigallocatechin gallate at a volume ratio of 1:1.2, and the mixture was stirred at 37 °C for 8 h. During the reaction, the pH of the mixture was maintained at 7.5. After freeze-drying, the anti-scarring compound powder was obtained, denoted as CB.
[0041] Polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) were used as microneedle matrix materials. They were mixed with water to obtain 15 wt% PVP solution and 15 wt% PVA solution, respectively. Then, the 15 wt% PVP solution and 15 wt% PVA solution were mixed at a volume ratio of 1:1 to obtain the matrix solution.
[0042] 5 mg of CB was dissolved in 1 mL of matrix solution and poured into a PDMS microneedle mold. The solution was then filled into the mold under vacuum conditions and dried overnight to obtain microneedles.
[0043] Example 3 5 mM 3-aminophenylboronic acid was added to 5 mM epigallocatechin gallate at a volume ratio of 1:1, and the mixture was stirred at 37 °C for 12 h. During the reaction, the pH of the mixture was maintained at 8.5. After freeze-drying, the anti-scarring compound powder was obtained, denoted as CB.
[0044] Sodium hyaluronate and polyvinyl alcohol were used as microneedle matrix materials. They were mixed with water to obtain a 15 wt% sodium hyaluronate solution and a 20 wt% polyvinyl alcohol solution. Then, the 15 wt% sodium hyaluronate solution and the 20 wt% polyvinyl alcohol solution were mixed at a volume ratio of 1:1 to obtain the matrix solution.
[0045] 5 mg of CB was dissolved in 1 mL of matrix solution and poured into a PDMS microneedle mold. The solution was then filled into the mold under vacuum conditions and dried overnight to obtain microneedles.
[0046] Experimental Example 1 A 0.1 mg / mL CB solution was prepared using the CB prepared in Example 1. The CB solution and a 0.1 mM DPPH ethanol solution were mixed in a 1:1 volume ratio. The mixture was reacted at room temperature in the dark for 30 min, and the absorbance of the mixture at 517 nm was measured using a microplate reader. The in vitro antioxidant capacity of CB was evaluated using a DPPH free radical scavenging assay; the DPPH scavenging rate of the 0.1 mg / mL CB solution was approximately 84%.
[0047] A 5 mg / mL CB solution was prepared using the CB prepared in Example 1. The scavenging ability of different concentrations of CB solutions for hydrogen peroxide was tested using Ti(SO4)2 solution. 1 mM hydrogen peroxide was added to the CB solution and kept in the dark for 10 min, with 1 mM hydrogen peroxide serving as a control. Then, it was mixed with twice the volume of Ti(SO4)2, shaken for 10 s, and the absorbance of the mixture was measured at 405 nm. The H2O2 scavenging rate of the 5 mg / mL CB solution was approximately 74%. The results indicate that the CB prepared in Example 1 has good in vitro antioxidant properties.
[0048] Experimental Example 2 Good biocompatibility is the primary requirement for CB as a scar treatment material. CB solutions with concentrations of 0.1 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, and 5 mg / mL were prepared using the CB prepared in Example 1. Human skin fibroblasts (HSF) and keloid fibroblasts (HKF) were cultured in 96-well plates, respectively. After 24 hours, the experimental groups were replaced with culture media containing different concentrations of CB and cultured for another 48 hours, while the CB-free culture medium served as the control group. Cell viability was assessed using CCK8 reagent. Figure 2 The results showed that CB solutions exhibited good biocompatibility at concentrations of 0.5 mg / mL and below.
[0049] Experimental Example 3 Human skin fibroblasts (1×10) 5 Keloid fibroblasts (1×10⁶ cells / mL) were cultured in 6-well plates. After 24 hours, the control group was replaced with culture medium containing exosome-free serum, while the experimental group was replaced with culture medium containing different concentrations of CB (0.25 mg / mL, 0.4 mg / mL, 0.5 mg / mL, and 0.6 mg / mL) in exosome-free serum. After 48 hours, the supernatant was collected for use as conditioned medium. 5 Cells / mL were cultured in 6-well plates. After 24 hours, the medium for the control group was replaced with regular medium. The experimental group was cultured in conditioned medium. After 48 hours, the cell viability of keloid fibroblasts was assessed using CCK8 assay. Figure 3 The experimental results showed that, compared with the control group, different concentrations of CB could inhibit the cell proliferation of keloid fibroblasts.
[0050] Test Example 4 A 10mm diameter full-thickness circular incision was made on the exposed skin of the ventral side of each ear of a New Zealand rabbit, and the full-thickness skin and perichondrium were completely removed from each side. One week later, the newly formed scabs were removed, exposing the wounds again. After three weeks of recovery and epithelialization, the model was successfully established. The wounds were divided into a control group (no treatment) and a microneedling group (treated with the microneedles of Example 1). Medication was administered every three days, and the rabbits were euthanized and their tissues collected after two weeks. Skin scar tissue was harvested and stained with hematoxylin and eosin for histological evaluation. Figure 4 As can be seen, the scar thickness in the microneedling group was significantly reduced compared to the control group. Staining results showed that the relative thickness of granulation tissue in the microneedling group was 43.2% compared to the control group.
[0051] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.
Claims
1. An anti-scarring compound, characterized in that, The raw materials for preparing the anti-scarring compound include compounds containing catechol and compounds containing reactive oxygen species-sensitive protective groups; The compound containing catechol is selected from one or more of chlorogenic acid, epigallocatechin gallate, and quercetin; The compound containing a reactive oxygen species-sensitive protecting group is selected from one or more of 3-aminophenylboronic acid, 4-aminophenylboronic acid, 3-formylphenylboronic acid, and 4-formylphenylboronic acid.
2. The anti-scarring compound according to claim 1, characterized in that, The mass ratio of the compound containing catechol to the compound containing a reactive oxygen species-sensitive protecting group is 0.5-2:0.5-2.
3. The method for preparing the anti-scarring compound as described in claim 1 or 2, characterized in that, Includes the following steps: A compound containing catechol is mixed with a compound containing a reactive oxygen species-sensitive protecting group to obtain a reaction solution. The reaction is stirred while maintaining the pH of the system at 7-9 during the reaction.
4. The preparation method according to claim 3, characterized in that, The reaction solution contains a compound with a concentration of 1.7-5.3 mg / ml containing catechol and a compound with a concentration of 0.68-2 mg / ml containing reactive oxygen species-sensitive protecting groups.
5. The preparation method according to claim 3, characterized in that, The reaction temperature is from room temperature to 40°C, and the reaction time is 4-48 hours.
6. A microneedle for eliminating scars, characterized in that, The microneedles are formed from the following raw material components: Microneedle matrix material; the anti-scarring compound as described in claim 1 or 2; water.
7. The microneedle according to claim 6, characterized in that, The mass ratio of microneedle matrix material to anti-scarring compound is (100-400): (0.1-10).
8. The microneedle according to claim 6, characterized in that, The microneedle matrix material is selected from one or more of polyvinyl alcohol, polyvinylpyrrolidone, and sodium hyaluronate.
9. The method for preparing scar-eliminating microneedles according to any one of claims 6-8, characterized in that, Includes the following steps: The microneedle matrix material is mixed with water to obtain a microneedle matrix material solution; The anti-scarring compound was dissolved in a microneedle matrix material solution to obtain a mixture; The mixture is poured into a mold, dried and shaped to obtain the microneedles; In the mixture, the concentration of the microneedle matrix material is 0.1-0.4 g / ml, and the concentration of the anti-scarring compound is 0.1-10 mg / mL.
10. A microneedle patch, characterized in that, Including the scar-eliminating microneedles as described in any one of claims 6-8.