Skin disease medicine based on xanthoxylin WGX-50 and preparation method thereof

Abstract

According to the dermatosis medicine based on xanthoxylin WGX-50 and the preparation method thereof, WGX-50 has a strong anti-oxidation characteristic and is crucial to the anti-aging process of skin, and meanwhile, it is found that WGX-50 has the effects of promoting regeneration of collagen, elastin and lipid droplets, inhibiting expression of key genes participating in melanogenesis, inhibiting melanogenesis, inhibiting melanogenesis, inhibiting melanogenesis, inhibiting melanogenesis and inhibiting melanogenesis. Due to the characteristics, the WGX-50 can effectively repair skin injury related to the natural aging process, and meanwhile, the WGX-50 has remarkable whitening and antioxidant effects. Compared with the effect of an asiaticoside cream ointment, the WGX-50 is effective on chloasma by reducing skin pigmentation, the effect of the WGX-50 is better than that of asiaticoside, and in the treatment of chloasma, the WGX-50 can be used as another method for relieving pigmentation and improving skin quality.

Description

Technical Field

[0001] This invention relates to a new application of xanthozolin WGX-5, specifically to a dermatological drug based on xanthozolin WGX-50 and its preparation method. Background Technology

[0002] Melasma is a common chronic acquired pigmentary skin disease characterized by symmetrical brown macules or patches on the face, forehead, cheeks, and jawline. It primarily affects women of childbearing age, with an incidence rate as high as 30% in Asian populations, and is known for its high recurrence rate and difficulty in achieving complete remission. The pathogenesis of melasma is multifactorial, with genetic susceptibility, ultraviolet (UV) radiation exposure, and hormonal fluctuations being the main contributing factors. In addition, several intrinsic and extrinsic factors can also trigger this disease, including sleep disorders, use of substandard cosmetics containing excessive mercury, exposure to heat radiation, and thyroid dysfunction. Melasma severely impacts patients' quality of life, causing psychological distress and increasing the medical burden. Due to its long treatment duration and high recurrence rate, the treatment of melasma remains a challenge. Melasma has been shown to be associated with skin pigmentation. Increased melanin production has been observed in melasma lesions, with a significant increase in the number and diameter of dermal microvessels compared to normal skin. Increased inflammatory mediators such as c-kit and SCF (stem cell factor receptor) in the lesion area contribute to the formation of melasma lesions.

[0003] In recent years, with a deeper understanding of the pathogenesis of melasma and advancements in clinical treatment techniques, various methods for treating melasma have emerged. These treatments primarily focus on removing triggering factors, and include hydroquinone (HQ) creams, tranexamic acid (TXA) therapy, laser therapy, and microneedling. Chemical peels using alpha / beta hydroxy acids (AHA and BHA) have also proven effective. However, current treatments often only relieve symptoms and cannot prevent recurrence or achieve a complete cure. Furthermore, most topical medications and phototherapy used to treat melasma can cause skin irritation and even lead to disease recurrence. Existing treatment options fail to meet patients' aesthetic expectations for effective results. Summary of the Invention

[0004] To address the shortcomings of existing treatments for melasma that fail to meet patient needs, this application proposes a dermatological drug based on xanthoside WGX-50 and its preparation method, aiming to achieve a novel pharmaceutical use for xanthoside WGX-50 and realize highly effective treatment of melasma.

[0005] A dermatological drug based on xanthocyanin WGX-50 includes: an oil phase component, an aqueous phase component, and an active additive component; The weight ratio of the oil phase, aqueous phase, and active additives is 7:42.5:0.5; The oil phase composition includes jojoba oil and emulsified wax in a weight ratio of 5:2; The aqueous phase components include distilled water, glycerin, and hyaluronic acid in a weight ratio of 80:4:1; The active ingredient is xanthocyanin WGX-50.

[0006] A method for preparing a dermatological drug based on xanthocyanin WGX-50 includes the following steps: Step S1: Preparation of the oil phase system: Weigh jojoba oil and emulsified wax according to the ratio and place them in a beaker; heat in a water bath to about 70°C, stirring gently during the process; after the emulsified wax has completely melted, continue stirring for 5 minutes to fully integrate the jojoba oil and emulsified wax; weigh 500 mg of xanthocyanin powder and add it to the above system, stirring at high speed, first at 5000 rpm / min for 5 minutes, then at 10000 rpm / min for 5 minutes, finally obtaining a homogeneous oil phase system; Step S2, Aqueous Phase System: Take another beaker, weigh out glycerin and hyaluronic acid according to the proportion, and add distilled water to it; stir with a magnetic stirrer for 5 minutes until a homogeneous aqueous phase system is formed; heat the above aqueous phase system to 70°C; Step S3, Emulsification: Slowly pour the aqueous phase into the oil phase system while stirring at 5000 rpm / min for 5-10 minutes; then allow it to cool naturally to room temperature to obtain a uniform and delicate emulsion, which is a dermatological drug based on xanthocyanin WGX-50.

[0007] Zanthoxylin WGX-50 is used in the preparation of medicines for treating melasma.

[0008] The advantages and effects of this application are as follows: This application designs a dermatological drug based on zanthoxylate WGX-50. WGX-50 possesses potent antioxidant properties, crucial for the skin's anti-aging process. Furthermore, this application discovers that WGX-50 promotes the regeneration of collagen, elastin, and lipid droplets while inhibiting the expression of key genes involved in melanin production. These properties enable WGX-50 to effectively repair skin damage associated with the natural aging process, while also exhibiting significant whitening and antioxidant effects. Comparing its effects with Centella asiatica cream, WGX-50 is effective in reducing skin pigmentation in treating melasma, showing superior results compared to Centella asiatica. In the treatment of melasma, WGX-50 can serve as another method to alleviate pigmentation and improve skin quality.

[0009] The above description is only an overview of the technical solution of this application. In order to better understand the technical means of this application and implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this application more obvious and understandable, the preferred embodiments of this application are described in detail below with reference to the accompanying drawings.

[0010] The above and other objects, advantages and features of this application will become more apparent to those skilled in the art from the following detailed description of specific embodiments in conjunction with the accompanying drawings. Attached Figure Description

[0011] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0012] Figure 1 The two sets of VISIA analysis results provided for this application; Figure 2 Results provided for this application using WGX-50. Detailed Implementation

[0013] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. In the following description, specific details such as specific configurations and components are provided merely to help fully understand the embodiments of this application. Therefore, those skilled in the art should understand that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. In addition, for clarity and brevity, descriptions of known functions and structures are omitted in the embodiments.

[0014] It should be understood that the phrase "an embodiment" or "this embodiment" throughout the specification means that a specific feature, structure, or characteristic related to the embodiment is included in at least one embodiment of this application. Therefore, "an embodiment" or "this embodiment" appearing throughout the specification does not necessarily refer to the same embodiment. Furthermore, these specific features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0015] Furthermore, reference numerals and / or letters may be repeated in different examples within this application. Such repetition is for the purpose of simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or settings discussed.

[0016] In this article, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist simultaneously. The term " / and" in this article describes another type of relationship between related objects, indicating that two relationships can exist. For example, A / and B can mean: A exists alone, and A and B exist alone. In addition, the character " / " in this article generally indicates that the related objects before and after it are in an "or" relationship.

[0017] In this article, the term "at least one" is merely a description of the relationship between related objects, indicating that there can be three relationships. For example, "at least one of A and B" can mean: A exists alone, A and B exist simultaneously, or B exists alone.

[0018] It should also be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion.

[0019] Example 1: This example mainly introduces a new use of xanthocyanin WGX-50 for the preparation of medicines for treating melasma.

[0020] Example 2: Based on Example 1, this example mainly introduces a dermatological drug based on xanthocyanin WGX-50, the formulation of which includes: oil phase components, aqueous phase components and active additives; The weight ratio of the oil phase, aqueous phase, and active additives is 7:42.5:0.5; The oil phase composition includes jojoba oil and emulsified wax in a weight ratio of 5:2; The aqueous phase components include distilled water, glycerin, and hyaluronic acid in a weight ratio of 80:4:1; The active ingredient is xanthocyanin WGX-50.

[0021] Furthermore, its preparation method includes the following steps: Step S1: Preparation of the oil phase system: Weigh jojoba oil and emulsified wax according to the ratio and place them in a beaker; heat in a water bath to about 70°C, stirring gently during the process; after the emulsified wax has completely melted, continue stirring for 5 minutes to fully integrate the jojoba oil and emulsified wax; weigh 500 mg of xanthocyanin powder and add it to the above system, stirring at high speed, first at 5000 rpm / min for 5 minutes, then at 10000 rpm / min for 5 minutes, finally obtaining a homogeneous oil phase system; Step S2, Aqueous Phase System: Take another beaker, weigh out glycerin and hyaluronic acid according to the proportion, and add distilled water to it; stir with a magnetic stirrer for 5 minutes until a homogeneous aqueous phase system is formed; heat the above aqueous phase system to 70°C; Step S3, Emulsification: Slowly pour the aqueous phase into the oil phase system while stirring at 5000 rpm / min for 5-10 minutes; then allow it to cool naturally to room temperature to obtain a uniform and delicate emulsion, which is a dermatological drug based on xanthocyanin WGX-50.

[0022] Furthermore, this embodiment mainly introduces the preparation method of the specific formulation: Oil phase system: Weigh 5g of jojoba oil and 2g of emulsified wax and place them in a beaker. Heat in a water bath to approximately 70°C, stirring gently during the process. After the emulsified wax has completely melted, continue stirring for 5 minutes to ensure thorough mixing of the jojoba oil and emulsified wax. Weigh 500 mg of xanthocyanin powder and add it to the above system. Stir at high speed, first at 5000 rpm / min for 5 minutes, then at 10000 rpm / min for 5 minutes, to obtain a homogeneous oil phase system.

[0023] Aqueous phase system: In another beaker, weigh out 2g of glycerin and 0.5g of hyaluronic acid, and add 40 mL of distilled water. Stir with a magnetic stirrer for 5 minutes until a homogeneous aqueous phase system is formed. Heat the above aqueous phase system to 70°C.

[0024] Emulsification: The aqueous phase is slowly poured into the oil phase system while stirring at 5000 rpm / min for 5-10 min. Afterward, allow it to cool naturally to room temperature to obtain a homogeneous and fine emulsion, which yields a dermatological drug based on xanthocyanin WGX-50.

[0025] WGX-50 is a small-molecule alkaloid compound extracted from Zanthoxylum bungeanum. WGX-50 has been shown to possess potent antioxidant properties, crucial for the skin's anti-aging process. A recent study by our group demonstrated that WGX-50 can promote the regeneration of collagen, elastin, and lipid droplets while inhibiting the expression of key genes involved in melanin production. These properties enable WGX-50 to effectively repair skin damage associated with the natural aging process, while also exhibiting significant whitening and antioxidant effects. This molecular action helps reduce pigmentation and lighten skin discoloration, making it a potential alternative treatment for those suffering from melasma.

[0026] Therefore, this study aimed to evaluate the clinical efficacy of WGX-50 in treating melasma and compare it with the efficacy of Centella asiatica cream ointment, which can treat melasma by lightening pigmentation. Objective To evaluate the clinical efficacy of WGX-50 in treating melasma and compare it with Centella asiatica cream ointment. Methods A total of 60 patients with melasma were included, of whom 30 received WGX-50 treatment and 30 received topical Centella asiatica cream ointment. The severity of melasma before treatment and one month after treatment was assessed using modified MASI scores and VISIA analysis. The results of the two groups were compared to explore the efficacy of WGX-50 in treating melasma.

[0027] The modified MASI score (mMASI score) decreased from 7.5±4.3 in the WGX-50 group (3.2±1.7) to 7.1±3.0 in the Centella asiatica cream group (10.1±3.6). The WGX-50 treatment resulted in a 49.6% decrease, while the topical Centella asiatica cream treatment only resulted in a 27.2% decrease, showing a significant difference between the two groups (p=0.011). Objective evaluation data, including pigmentation, erythema area, and wrinkles, were extracted from the VISIA system. Quantitative analysis showed improvements in these areas in both groups after one month of treatment compared to baseline. Both methods were significantly effective in reducing pigmentation and improving skin condition.

[0028] In conclusion, WGX-50 is effective in reducing skin pigmentation in treating melasma, and its effect is superior to that of Centella asiatica extract. WGX-50 can be considered as another method for alleviating pigmentation and improving skin quality in the treatment of melasma.

[0029] Specific patients and experimental materials: Patients: This study included patients with symmetrically distributed melasma lesions on the face, presenting as light to dark brown patches in non-protruding areas of the skin. Participants with the following characteristics were excluded: 1. Individuals with skin allergies or compromised skin integrity (e.g., open wounds).

[0030] 2. Pregnant women.

[0031] 3. Patients with severe systemic diseases or mental illnesses.

[0032] 4. Individuals who have received medication for melasma within the past three months.

[0033] 5. Individuals who have undergone phototherapy or cosmetic surgery within the past three months.

[0034] 6. The patient is currently using photosensitizers, anticoagulants, contraceptives, sex hormones, thyroid hormones, or similar medications.

[0035] 7. Individuals with post-inflammatory hyperpigmentation, Riehl's melanosis, café-au-lait spots on the cheeks, or pigmented lichen planus.

[0036] Between November 2023 and February 2024, 60 patients with melasma were enrolled in the study and randomly assigned to two groups of 30 each. Informed consent was obtained from each participant, and basic demographic data, including age and sex, were recorded before treatment. After randomization, one group received WGX-50 treatment, while the other received Centella asiatica ointment. All patients applied either Centella asiatica ointment or 0.1% WGX-50 cream to their face twice daily, morning and evening, after cleansing. During treatment, the use of other skincare products was prohibited, and strict sun protection was required.

[0037] Evaluate The severity of melasma was subjectively assessed using the Modified Melasma Area and Severity Index (mMASI). This index quantifies the severity of melasma by assessing skin area (A), darkness (D), and evenness (H). The final score is calculated as A*(D+H). In this study, the score was assessed by two different researchers who were unaware of the treatment method before and one month after treatment. In addition, the VISIA system was used to assess pigmentation, erythema areas, and wrinkles. Objective assessments were also performed before treatment and one month after treatment.

[0038] Statistical analysis All measurements were performed by two researchers in a double-blind manner. Data are expressed as mean ± standard deviation. The normality of all data was assessed using the Shapiro-Wilk test. Differences between the two groups were assessed using the Wilcoxon signed-rank test. A p-value < 0.05 was defined as statistically significant. Statistical analysis was performed using GraphPadPrism software.

[0039] result At the final follow-up, 59 patients completed the assessment, including 29 in the WGX-50 group, 30 in the AO group, and 1 patient in the WGX-50 group who was lost to contact. All patients in this study were female. The mean age in the WGX-50 group was 44.2 ± 10.2 years, and the mean age in the AO group was 43.8 ± 5.9 years, with no statistically significant difference between the two groups (p = 0.254). The modified MASI score in the WGX-50 group decreased from 7.5 ± 4.3 to 3.2 ± 1.7, while that in the AO group decreased from 10.1 ± 3.6 to 7.1 ± 3.0. The MASI score decreased by 49.6% after WGX-50 treatment, while it only decreased by 27.2% after treatment with Centella asiatica ointment. The results are shown in Table 1, and the differences between the two groups were statistically significant (p = 0.011).

[0040] Table 1. Improved MASI scoring results Objective evaluation data, including pigmentation, erythema areas, and wrinkles, were extracted from the VISIA system. Quantitative analysis showed that both groups improved in these areas after one month of treatment compared to baseline. See Table 2 for the results. Figure 1 , Figure 1 The results of VISIA analysis for the two groups are as follows. Figure 1 The results are shown in (A) pigmentation, (B) red area, and (C) baseline and wrinkles 1 month after treatment.

[0041] Please refer to Figure 2 , Figure 2 Results of using WGX-50. (A) shows the condition and distribution of surface pigmentation of the subjects treated with WGX-50 at baseline (B), and (C) shows the condition and distribution of surface pigmentation of the subjects treated with WGX-50 1 month later (D).

[0042] No significant differences were observed in the measurements between groups, indicating that WGX-50, like asiaticoside, is effective in treating melasma and can improve skin texture.

[0043] Both methods are effective in reducing pigmentation (Figure 1) and improving skin condition.

[0044] Table 2 VISIA Analysis Results This study demonstrates that WGX-50, a small-molecule alkaloid extracted from Sichuan pepper, exhibits good efficacy in reducing pigmentation and improving skin quality in patients with melasma. Compared with the traditional topical melasma medication, asiatica extract ointment, WGX-50 significantly reduced the modified MASI score (49.6% vs. 27.2%, p=0.011) after one month of treatment. This highlights its potential as a novel treatment option for melasma management.

[0045] WGX-50 differs from current melasma treatments due to its multi-target mechanism of action. Skin pigmentation is caused by multiple factors and has long been considered crucial in the pathogenesis of melasma. Preclinical studies have shown that WGX-50 inhibits melanin production by downregulating key genes in melanin synthesis and transport, including MC1R, MITF, TYR, and TYP-1. This is similar to traditional therapies such as HQ, which competitively inhibits tyrosinase to reduce melanin production and melanocyte proliferation, thereby suppressing melanin production. Meanwhile, other technologies, including TXA or laser therapy, may work by inhibiting angiogenesis or destroying melanosomes.

[0046] Furthermore, WGX-50's antioxidant and anti-inflammatory properties can alleviate oxidative stress and inflammation—key factors in melanocyte activation. This dual effect aligns with emerging evidence that the pathogenesis of melasma involves not only hyperpigmentation but also vascular abnormalities, changes in the dermal microenvironment, and chronic inflammation. In contrast, asiaticoside primarily promotes wound healing and collagen synthesis but lacks a direct inhibitory effect on melanin production. While both treatments improved pigmentation and skin texture in our study, WGX-50's superior MASI reduction highlights its targeted efficacy.

[0047] Traditional treatments for melasma can lead to complications, limiting their application. Exogenous melasma and permanent depigmentation are common complications resulting from the use of HQ in cosmetics. Compared to TXA (oral or topical) with thromboembolic risks or laser therapy with concerns about damaging the epidermal barrier, WGX-50 offers a safer profile with minimal reported irritation, as evidenced by the absence of adverse events in our cohort. Nevertheless, longer follow-up series of this type should be conducted to confirm its safety.

[0048] WGX-50 is a novel ingredient with multiple benefits. It has been shown to exert neuroprotective and cardioprotective effects through antioxidant mechanisms. Furthermore, its powerful antioxidant properties help delay skin aging, indicating its broad potential applications in dermatology. Its antioxidant and MMP1-inhibiting properties make it a candidate for photoaging and wrinkle reduction, while its anti-inflammatory effects may be beneficial for conditions such as post-inflammatory hyperpigmentation or rosacea. Future research should explore its applications in these areas, particularly in combination therapies, to enhance efficacy.

[0049] This study has several limitations. First, the small sample size and short follow-up period prevented definitive conclusions regarding long-term efficacy and recurrence rate. Second, the cohort consisted only of female patients, limiting its generalizability to men. Third, while the VISIA analysis provided objective measures, it lacked histological assessment of melanin content or dermal changes. Finally, the open-label design (despite blinding of assessors) and patient-reported adherence measures introduced potential biases. Future trials should include larger, sex-diverse cohorts, extended follow-up times, and immunohistochemical analyses to validate mechanism discovery. WGX-50 represents a promising advancement in the treatment of melasma, combining powerful depigmentation with skin regeneration properties. Its multi-target action addresses the complex pathophysiology of melasma more comprehensively than traditional medications. While further research is needed to confirm long-term benefits, WGX-50 has the potential to become a cornerstone of an evolving, holistic, mechanism-driven modality of dermatological treatment.

[0050] The above description is merely a preferred embodiment of the present invention and does not limit the scope of protection of the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any changes, modifications, substitutions, integrations, and parameter alterations to these embodiments within the spirit and principles of the present invention, achieved through conventional substitutions or by achieving the same function without departing from the principles and spirit of the present invention, fall within the scope of protection of the present invention.

Claims

1. Zanthoxylin WGX-50, characterized in that, Used in the preparation of medicines for treating melasma.

2. A dermatological drug based on xanthocyanin WGX-50, characterized in that, include: Oil phase components, aqueous phase components, and active additives; The weight ratio of the oil phase, aqueous phase, and active additives is 7:42.5:0.5; The oil phase composition includes jojoba oil and emulsified wax in a weight ratio of 5:2; The aqueous phase components include distilled water, glycerin, and hyaluronic acid in a weight ratio of 80:4:1; The active ingredient is xanthocyanin WGX-50.

3. The method for preparing a dermatological drug based on xanthocyanin WGX-50 according to claim 2, characterized in that, Includes the following steps: Step S1: Preparation of the oil phase system: Weigh jojoba oil and emulsified wax according to the ratio and place them in a beaker; heat in a water bath to about 70°C, stirring gently during the process; after the emulsified wax has completely melted, continue stirring for 5 minutes to fully integrate the jojoba oil and emulsified wax; weigh 500 mg of xanthocyanin powder and add it to the above system, stirring at high speed, first at 5000 rpm / min for 5 minutes, then at 10000 rpm / min for 5 minutes, finally obtaining a homogeneous oil phase system; Step S2, Aqueous Phase System: Take another beaker, weigh out glycerin and hyaluronic acid according to the proportion, and add distilled water to it; Stir with a magnetic stirrer for 5 minutes until a homogeneous aqueous phase system is formed; heat the above aqueous phase system to 70°C. Step S3, Emulsification: Slowly pour the aqueous phase into the oil phase system while stirring at 5000 rpm / min for 5-10 min; then allow it to cool naturally to room temperature to obtain a uniform and delicate emulsion, which is a dermatological drug based on xanthocyanin WGX-50.

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