Application of compound gel preparation in preparation of product for treating chloasma

Abstract

The invention discloses an application of a compound gel preparation in preparation of a product for treating chloasma. The compound gel disclosed by the invention is prepared from polypeptide gel capable of opening tight connection of skin through a self-assembly method. Finally, the hydrogel with certain flowability is formed. The polypeptide gel formed by the invention can penetrate through the surface layer of the skin, tranexamic acid, vitamin C and reduced glutathione are transferred to the basal layer of the skin through one-time operation, and then tranexamic acid is competitively combined with tyrosinase to inhibit the activity of the tyrosinase, so that the formation of melanin is reduced; the vitamin C inhibits the formation of melanin by reducing the formation of o-quinone and reducing oxidized melanin; the reduced glutathione is used as an antioxidant component, can inhibit the generation of free radicals, helps to stabilize the skin and restore the skin whiteness, can be used for treating chloasma, and provides a new solution for the field of skin health treatment.

Description

Technical Field

[0001] This invention relates to the field of gel drug delivery technology, and in particular to the application of a compound gel formulation in the preparation of products for treating melasma. Background Technology

[0002] Melasma is a common hyperpigmentation skin condition. It progresses slowly, is usually asymptomatic, and often presents symmetrically, primarily on the cheeks, forehead, nose, lips, and around the eyes. The spots are irregular in shape and range in color from dark brown to light brown. There are many treatment options for melasma, including oral and topical medications, phototherapy treatments, chemical peels, and skin whitening injections.

[0003] Tranexamic acid (TXA) is a protease inhibitor. On one hand, it inhibits melanin formation by interfering with the interaction between melanocytes and keratinocytes through the plasminogen-fibrinolytic system, thereby reducing tyrosinase activity. On the other hand, tranexamic acid has a similar chemical structure to tyrosine and can competitively bind to tyrosinase, inhibiting tyrosinase activity and thus reducing melanin formation, ultimately playing a role in treating melasma. Vitamin C (Vit C) is a polyhydroxy compound with strong reducing properties. It can effectively inhibit the oxidation of dopa, reducing existing melanin in the skin to colorless substances and converting melanin into water-soluble colloidal substances. Glutathione (GSH) is an antioxidant with antioxidant, free radical scavenging, and tyrosinase-inhibiting effects, thereby reducing melanin formation and deposition in the skin.

[0004] Transdermal hydrogels are an emerging transdermal technology widely used in the medical field, such as drug delivery, wound healing promotion, vaccination, interstitial fluid extraction and biomarker detection, and cosmetic applications. Peptides, a major component of the skin, possess excellent biocompatibility and in vivo biodegradability, making them a natural material for hydrogel preparation.

[0005] Currently, microneedling combined with topical tranexamic acid is commonly used in clinical practice to treat melasma, but the procedure is quite cumbersome. Therefore, a novel polypeptide gel combining tranexamic acid and vitamin C / reduced glutathione for the treatment of melasma has been designed and prepared. It can be applied directly, is easy to use, has significant effects, and has strong practical value. Summary of the Invention

[0006] To address the above technical problems, this invention provides an application of a compound gel formulation in the preparation of products for treating melasma.

[0007] The purpose of this invention is to provide an application of a compound gel formulation in the preparation of a drug for treating melasma, wherein the compound gel formulation is prepared by the following method: (1) Add polypeptide, tranexamic acid, vitamin C and reduced glutathione to water, shake and sonicate to dissolve to obtain a mixture; (2) Heat the mixture obtained in step (1) and let it stand and cool naturally to room temperature to obtain the compound gel preparation.

[0008] In some embodiments of the present invention, in step (1), the concentration of the polypeptide in the mixture is 15-40 mg / mL.

[0009] In some embodiments of the present invention, in step (1), the concentration of the polypeptide in the mixture is 20-30 mg / mL.

[0010] In some embodiments of the present invention, in step (1), the concentration of tranexamic acid in the mixture is 2-7 mg / mL.

[0011] In some embodiments of the present invention, in step (1), the concentration of vitamin C in the mixture is 3-5 mg / mL.

[0012] In some embodiments of the present invention, in step (1), the concentration of the reduced glutathione in the mixture is 1-4 mg / mL.

[0013] In some embodiments of the present invention, in step (1), the rotation speed of the oscillation is 800-1000 rpm and the time is 1-2 min; the power of the ultrasound is 80-100 W and the time is 20-30 min.

[0014] In some embodiments of the present invention, in step (2), the heating temperature is 50~70°C and the time is 10min~20min.

[0015] In some embodiments of the present invention, the drug further includes a pharmacologically acceptable carrier.

[0016] The technical solution of the present invention has the following advantages compared with the prior art: The compound gel formulation developed in this invention fully utilizes the biocompatibility of peptides and innovatively loads multiple effective ingredients such as tranexamic acid, vitamin C, and reduced glutathione. Furthermore, by optimizing the relative amounts of the effective components, the formulation's skin-lightening effect is enhanced. This formulation design aims to achieve efficient drug penetration and release through peptide gel transdermal technology, providing a new treatment strategy for skin health.

[0017] The compound gel formulation developed in this invention is simpler to operate than traditional local injection methods of tranexamic acid, requiring no professional personnel. Compared to the two-step method of traditional microneedling combined with topical application of tranexamic acid, the tranexamic acid in the compound formulation of this invention can directly reach the basal layer of the skin along with the polypeptide gel, simplifying the operation steps and enabling rapid diffusion and efficacy. Compared to single-component microneedle loading of tranexamic acid, the vitamin C and glutathione in this invention can synergistically work with tranexamic acid, resulting in better efficacy and faster achievement of freckle removal.

[0018] This invention optimizes the dosage of the polypeptide carrier, achieving good skin penetration while maintaining suitable viscosity, high dissolution efficiency, and easy absorption, ensuring rapid release of the active ingredients. Therefore, compared to treatments such as local injection of tranexamic acid, microneedling combined with topical tranexamic acid, or microneedles loaded with a single component of tranexamic acid, the compound gel developed in this invention significantly shortens the administration time of topical medication, significantly increases drug concentration, and greatly simplifies the operation steps, reducing operational difficulty and making the treatment process more convenient and efficient. Simultaneously, this compound preparation significantly enhances the therapeutic effect, making the efficacy more pronounced and rapid, thereby improving patient compliance. Therefore, the compound gel developed in this invention shows excellent application prospects in the treatment of melasma, providing a new solution for the field of skin health treatment. Attached Figure Description

[0019] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein... Figure 1 Transmission electron microscopy morphology characterization of polypeptide composite gels; Figure 2 Study on the transdermal properties of polypeptide composite gel; Figure 3 In vivo safety study of polypeptide composite gel; Figure 4 In vivo pharmacodynamic study of polypeptide complex gel. Detailed Implementation

[0020] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.

[0021] The polypeptide (molecular weight Mw=1310 Da) in the following examples was purchased from Qiangyao Biotechnology Co., Ltd., catalog number MB7392, and its specific sequence is: naproxen-FGGRGGHGGGG-phenylboronic acid.

[0022] Example 1 This embodiment provides a compound gel formulation, the preparation method of which is as follows: (1) 25 mg of polypeptide, 5 mg of tranexamic acid, 3 mg of vitamin C, and 2 mg of reduced glutathione were added to 1 mL of ultrapure water and vortexed at 900 rpm for 2 min to initially disperse the raw materials. Then, the mixture was sonicated at 90 W for 25 min to promote complete dissolution and homogeneous mixing of the active ingredients. The mixture was then heated at 60℃ for 10 min and allowed to cool naturally to room temperature to obtain the polypeptide composite gel, i.e., the compound gel preparation. In this preparation, the components work synergistically: tranexamic acid inhibits melanin formation, vitamin C and reduced glutathione have antioxidant properties and interfere with melanin synthesis, while the polypeptide promotes repair and penetration. The morphology observed by transmission electron microscopy is fibrous, as shown in the image. Figure 1 As shown.

[0023] Bioperformance testing (1) Transdermal absorption performance test: To evaluate the skin penetration ability of the active ingredients in this compound formulation, a fluorescent labeling method was used: 20 μg / mL Cy5.5 was set as the control group, and the compound gel formulation obtained in Example 1 was used as the experimental group, loaded with 20 μg / mL Cy5.5 dye. The Cy5.5-loaded peptide compound gel formulation or the peptide itself was applied to the skin of C57 mice, and skin tissue sections were collected after 12 h. Confocal microscopy was used to observe the samples under 675 nm excitation light. First, the focal plane with the strongest fluorescence signal was determined, and then the focus was adjusted along the Z-axis to the critical position where the fluorescence intensity significantly decreased. Within this range, fluorescence images were acquired at 10 μm intervals. Image analysis allowed for a direct assessment of the distribution of the active ingredients at different depths in the skin. The results are shown in [Figure number missing]. Figure 2 Experiments have shown that this preparation can effectively penetrate into the epidermis and upper dermis of the skin.

[0024] (2) In vivo efficacy evaluation of compound gel preparation Female nude mice were selected to establish a melasma model through subcutaneous injection of progesterone combined with periodic ultraviolet light exposure. The animal experimental procedures of this invention comply with the requirements of animal welfare and the principles of animal ethics. The polypeptide was set as the control group, and the compound gel preparation obtained in Example 1 was used as the experimental group. The compound gel preparation of this invention was applied evenly to the patch area on the back of the model mice once daily for 4–5 weeks. Changes in the area of ​​the melasma and pigmentation were assessed by regular photography and skin colorimetry. The experimental results are shown in [Figure 1]. Figure 3 The results showed that, compared with the model control group, the experimental group using this compound preparation had significantly lighter skin pigmentation and significantly reduced melanin deposition.

[0025] (3) In vivo biosafety of compound gel formulation To further verify the safety of this compound preparation, histological examinations of major organs were performed on C57 mice using the compound gel formulation. After the experiment, vital organs such as the heart, liver, spleen, lungs, and kidneys were harvested, fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE). The tissue structure and cell morphology were then observed under a light microscope. The experimental results are shown in [Figure number missing]. Figure 4 The results showed no obvious pathological changes in any organs, indicating that the compound preparation had good biocompatibility under the experimental conditions.

[0026] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. The application of a compound gel formulation in the preparation of products for treating melasma, characterized in that, The compound gel preparation is prepared by the following method: (1) Add polypeptide, tranexamic acid, vitamin C and reduced glutathione to water, shake and sonicate to dissolve to obtain a mixture; (2) Heat the mixture obtained in step (1) and let it stand and cool naturally to room temperature to obtain the compound gel preparation.

2. The application according to claim 1, characterized in that, In step (1), the concentration of the polypeptide in the mixture is 15-40 mg / mL.

3. The application according to claim 1, characterized in that, In step (1), the concentration of the polypeptide in the mixture is 20-30 mg / mL.

4. The application according to claim 1, characterized in that, In step (1), the concentration of tranexamic acid in the mixture is 2-7 mg / mL.

5. The application according to claim 1, characterized in that, In step (1), the concentration of vitamin C in the mixture is 3-5 mg / mL.

6. The application according to claim 1, characterized in that, In step (1), the concentration of the reduced glutathione in the mixture is 1-4 mg / mL.

7. The application according to claim 1, characterized in that, In step (1), the rotation speed of the oscillation is 800-1000 rpm and the time is 1-2 min.

8. The application according to claim 1, characterized in that, In step (1), the power of the ultrasound is 80-100 W and the duration is 20-30 min.

9. The application according to claim 1, characterized in that, In step (2), the heating temperature is 50~70℃ and the time is 10min~20min.

10. The application according to claim 1, characterized in that, The product also includes a pharmacologically acceptable carrier.

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