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CN-122005428-A - Preparation method of composite microneedle loaded with tranexamic acid and resveratrol for synergistic treatment of chloasma

CN122005428ACN 122005428 ACN122005428 ACN 122005428ACN-122005428-A

Abstract

Based on the concept of physical penetration drug delivery-biochemical cooperative treatment, the hydrophilic tranexamic acid limit domain is encapsulated in a hydrophobic resveratrol-magnesium ion network through metal-polyphenol coordination self-assembly to form amorphous nanospheres (TXA@Res-Mg), and then chitosan and polyvinylpyrrolidone are used as a composite matrix to prepare the microneedle patch. The obtained microneedle array has high mechanical strength, can effectively penetrate through the stratum corneum, and can realize quick release of the medicament within 10 minutes. After entering the skin, the system efficiently eliminates active oxygen by virtue of enzyme-like catalytic activity, relieves oxidative stress and inflammation, and simultaneously has the inhibition rate of tyrosinase activity and melanin generation of more than 98%. The nanometer assembly and microneedle transdermal strategy overcomes the indissolvable and transdermal barriers of a single drug, realizes multidimensional synergy of antioxidation, antibiosis and targeted blackout inhibition, and provides an innovative platform for safe and efficient treatment of chloasma.

Inventors

  • Ye Haitong
  • WU SHUILIN
  • LIU XIANGMEI

Assignees

  • 湖北大学
  • 叶海彤

Dates

Publication Date
20260512
Application Date
20260320

Claims (5)

  1. 1. A preparation method of a soluble microneedle loaded with tranexamic acid and resveratrol-magnesium for treating chloasma and concurrent inflammation thereof is characterized by comprising the following steps: 1) Synthesis of resveratrol-magnesium (Res-Mg) nanoparticle 0.6 mmol Mg (CH 3 COO) 2 ·2H 2 O) and resveratrol (Res) 0.3 mmol were mixed and dissolved in ethanol 30 mL and stirred well, then 0.1 mM KOH solution was slowly added dropwise to the mixture, pH was adjusted to 8, and incubated at room temperature for 24h. Centrifuging the obtained product at 8000 rpm and 5: 5min, washing with ethanol twice, and vacuum freeze-drying; 2) Synthesis of nanoparticle nanoparticles of tranexamic acid @ resveratrol-magnesium (TXA@Res-Mg) 0.6 mmol of Mg (CH 3 COO) 2 ·2H 2 O and 0.3 mmol of resveratrol (Res) are mixed and dissolved in 30 mL of ethanol and stirred uniformly, 0.02 mmol of tranexamic acid (TXA) is added and stirred until complete dissolution, then 0.1 mM KOH of solution is slowly added dropwise to the mixed solution, pH is adjusted to 8, and incubation is carried out for 24 hours at room temperature. Centrifuging the obtained product at 8000 rpm and 5: 5min, washing with ethanol twice, and vacuum freeze-drying; 3) The preparation of chitosan and polyvinylpyrrolidone composite hydrogel microneedle (CS-PVP) comprises dissolving 1 g chitosan powder in 10 mL 10% (v/v) acetic acid aqueous solution to obtain solution a, dissolving 0.2 g PVP in 10 mL deionized water to obtain solution b, uniformly mixing ab solution, regulating pH of the solution to 5.5 to obtain uniform stable microneedle solution, pouring the solution into a mould made of Polydimethylsiloxane (PDMS), placing the mould into a flat bottom 50 mL centrifuge tube, centrifuging 3 min by a horizontal centrifuge 4000 rpm, drying in a 60 ℃ oven, and demolding for use; 4) The preparation of the TXA@Res-Mg loaded composite hydrogel comprises the steps of dissolving 1 g-shell polysaccharide powder in 10mL of 10% (v/v) acetic acid aqueous solution to obtain a solution a, dissolving 0.2 g PVP in 10mL deionized water to obtain a solution b, uniformly mixing a solution ab, adding 0.2 gTXA @Res-Mg to obtain a uniform and stable microneedle solution, pouring the microneedle solution into a mold made of Polydimethylsiloxane (PDMS), placing the mold into a flat bottom 50mL centrifuge tube, centrifuging 3 min by a horizontal centrifuge 4000 rpm, drying in an oven after sucking bubbles out, and demolding for standby.
  2. 2. The composite loaded hydrogel microneedle for treating chloasma and its complications according to claim 1, wherein the centrifuge of steps 1) and 2) is a refrigerated centrifuge.
  3. 3. The composite loaded hydrogel microneedle for treating chloasma and its complicated inflammation according to claim 1, wherein the microneedle solution prepared in the steps 3) and 4) is required to be refrigerated and defoamed in a refrigerator at 4 ℃.
  4. 4. The composite liquid-carrying hydrogel microneedle for treating chloasma and its complicated inflammation according to claim 1, wherein the centrifuges in steps 3) and 4) are horizontal centrifuges with parameters of 37 ℃ and 4000 rpm for 5 min.
  5. 5. The composite hydrogel microneedle according to claim 1, wherein the oven temperature in steps 3) and 4) is 60 ℃ and the oven drying time is about 12 h.

Description

Preparation method of composite microneedle loaded with tranexamic acid and resveratrol for synergistic treatment of chloasma Technical Field The invention relates to the field of biomedical materials and transdermal delivery systems, in particular to a preparation method of a composite microneedle loaded with tranexamic acid and resveratrol for collaborative treatment of chloasma. Background Chloasma is a complex acquired pigmentation disorder involving abnormal pigment metabolism, vascular proliferation and chronic inflammation. In recent years, with the continuous and intensive research on the pathological mechanism, the academic community generally considers that chloasma is not the problem of simple epidermal pigment, but is a skin network disorder state which is induced by multiple factors such as ultraviolet rays, hormone, inheritance and the like and is characterized by abnormal increase of melanocyte activity, basal membrane destruction at the junction of euepidermis, capillary hyperplasia and continuous subclinical inflammation. Traditional first-line therapies, such as topical hydroquinone, chemical stripping and laser therapy, can lighten the color spots for a short period of time, but often cause recurrent or even aggravated pigmentation due to damage to the skin barrier function or induction of local inflammatory response, and particularly the risk of post-inflammatory Pigmentation (PIH) is significant, which becomes a prominent problem in clinical treatment. In response to this dilemma, transdermal drug delivery systems, and in particular, soluble microneedle technology, have recently demonstrated unique advantages that physically form micro-scale channels that enable efficient delivery of drugs without significantly damaging the epidermal barrier. On the basis, the hydrogel microneedle constructed by combining the intelligent response material can realize the controllable release of the medicine according to the specific microenvironment (such as pH, enzyme activity or active oxygen level) of the lesion part, and provides possibility for realizing accurate and long-acting treatment. Based on understanding of the multi-channel pathogenesis of chloasma, the selection of multi-target active ingredients for cooperative treatment becomes a new research direction. Tranexamic acid reduces the expression of melanogenesis stimulating factors and vascular endothelial growth factors by inhibiting a plasminogen/plasmin system, resveratrol is used as a powerful antioxidant, can inhibit NF- κB and NLRP3 inflammatory small body pathways, reduces oxidative damage and inflammatory reaction, and magnesium ions are critical for maintaining the integrity of skin barrier and normal enzyme functions. The three are integrated in a single intelligent delivery platform, so that a plurality of key pathological links such as pigment synthesis, vascular abnormality and inflammatory reaction are expected to be synchronously interfered, the bottleneck that the curative effect and the safety of the traditional therapy are difficult to be achieved is broken through, and an innovative, efficient and safe solution is provided for the clinical management of chloasma. Disclosure of Invention Aiming at the situation, the invention provides a preparation method of the composite microneedle loaded with tranexamic acid and resveratrol for the cooperative treatment of chloasma. The invention is based on the design concept of physical penetration drug delivery-biochemical cooperative therapy, utilizes metal-polyphenol coordination self-assembly to encapsulate tranexamic acid (TXA) in resveratrol-magnesium ion (Res-Mg) coordination network, successfully prepares a co-carried nano-composite, and then takes Chitosan (CS) and polyvinylpyrrolidone (PVP) as composite matrixes to load nano-particles to prepare the microneedle patch (TXA@Res-Mg@CS-PVP). The system can effectively overcome the self-delivery bottleneck of TXA and Res, and remarkably enhance the antioxidation and whitening effects through a synergistic mechanism. Can effectively solve the problems existing in the prior art. The preparation method of the load tranexamic acid and resveratrol-magnesium soluble microneedle for treating chloasma and the concurrent inflammation thereof is characterized by comprising the following steps: 1) Synthesis of resveratrol-magnesium (Res-Mg) nanoparticle 0.6 mmol Mg (CH 3COO)2·2H2 O) and resveratrol (Res) 0.3 mmol were mixed and dissolved in ethanol 30 mL and stirred well, then 0.1 mM KOH solution was slowly added dropwise to the mixture, pH was adjusted to 8, and incubated at room temperature for 24h. Centrifuging the obtained product at 8000 rpm and 5: 5min, washing with ethanol twice, and vacuum freeze-drying; 2) Synthesis of nanoparticle nanoparticles of tranexamic acid @ resveratrol-magnesium (TXA@Res-Mg) 0.6 mmol of Mg (CH 3COO)2·2H2 O and 0.3 mmol of resveratrol (Res) are mixed and dissolved in 30 mL of ethanol and stirred uniformly,