Antifungal compound ointment as well as preparation method and application thereof

Abstract

The invention discloses an antifungal compound ointment as well as a preparation method and application thereof. The ointment comprises the following effective components in percentage by mass: 0.1-3% of amorolfen and mangnolia officinalis extract, and the balance of an ointment substrate, the mangnolia officinalis extract is magnolol, and the mass ratio of amorolfen to magnolol is (1: 0.5)-(1: 2). The ointment substrate is an oily substrate containing vaseline, wool fat, liquid paraffin, stearic acid, glycerol monostearate, an antioxidant and laurocapram. According to the compound ointment disclosed by the invention, through the synergistic effect of amorolfen and magnolol, the antifungal effect is remarkably enhanced, and the drug resistance risk is reduced; through cooperation of the optimized matrix and the penetration enhancer laurocapram, the permeability and bioavailability of the medicine to the deck are improved. The ointment can be used for preparing medicines for treating fungal infection such as leuconychia and the like, and has the advantages of good curative effect, high safety and convenience in use.

Description

Technical Field

[0001] This application relates to the field of antifungal drugs, and in particular to an antifungal compound ointment, its preparation method, and its application. Background Technology

[0002] Onychomycosis, commonly known as tinea unguium or nail fungus, is a common nail disease caused by fungal infections such as dermatophytes, yeasts, and non-dermatophyte molds. It mainly manifests as nail discoloration, thickening, breakage, and separation, severely impacting patients' quality of life and mental health. Onychomycosis is highly contagious and has a high recurrence rate, making its treatment a challenging area in dermatology. Currently, clinical treatment primarily relies on oral antifungal drugs (such as terbinafine and itraconazole) and topical medications (such as amorolfine and ciclopirox olamine). While oral medications are highly effective, they have systemic side effects such as hepatotoxicity and drug interactions, and require long treatment courses, leading to poor patient compliance. Topical medications can act directly on the infected site and are relatively safe; however, due to the dense structure of the nail plate and the stratum corneum barrier, drug penetration is poor, often failing to reach effective therapeutic concentrations, resulting in limited efficacy and a high recurrence rate.

[0003] Amorolfine is a novel morpholine antifungal drug that exerts a broad-spectrum antifungal effect by inhibiting the synthesis of ergosterol in fungal cell membranes and disrupting the membrane structure. It exhibits strong in vitro antifungal activity, showing good inhibitory effects against dermatophytes, yeasts, and molds, and has been widely used in the topical treatment of onychomycosis (nail fungus). However, clinical practice shows that while amorolfine ointment or lotion alone can relieve symptoms, the complete cure rate is not high, and long-term use may induce fungal resistance, affecting treatment efficacy.

[0004] In recent years, natural plant extracts have received widespread attention in the field of antifungal treatment. Extracts from traditional Chinese medicines such as Ganoderma lucidum, Phellodendron chinense, Sophora flavescens, and Dictamnus dasycarpus are rich in active ingredients such as flavonoids, alkaloids, terpenes, and polysaccharides, exhibiting multiple effects including inhibiting fungal growth, reducing inflammation, antioxidation, and tissue repair. For example, triterpenoids in Ganoderma lucidum extract show significant antifungal activity, acting by disrupting fungal cell membranes and inhibiting enzyme activity; berberine in Phellodendron chinense inhibits various dermatophytes. These traditional Chinese medicine extracts are widely available, highly safe, and unlikely to induce drug resistance, providing new options for the treatment of onychomycosis (nail fungus). However, the practical application of traditional Chinese medicine extracts still faces many challenges: immature extraction processes may lead to loss of active ingredients or poor stability; the antifungal strength of single traditional Chinese medicine components is insufficient; poor permeability and low bioavailability when administered topically; and existing research mainly focuses on single components, with the development and application of compound preparations not yet fully explored.

[0005] Current treatments for onychomycosis (nail fungus) have shortcomings in terms of efficacy, safety, and patient compliance. Oral medications have significant side effects, while topical monotherapy has limited penetration and cure rates. Although traditional Chinese medicine extracts show potential, they lack efficient and stable application methods. Therefore, there is an urgent need in this field to develop a novel topical formulation that combines the advantages of chemical drugs and natural extracts, improving drug penetration and antibacterial effects while reducing side effects and the risk of drug resistance, thus providing a safer and more effective solution for the treatment of onychomycosis. Summary of the Invention

[0006] To address the problems of significant side effects from oral medications, poor penetration of topical single-drug treatments, limited efficacy, and easy development of drug resistance in existing onychomycosis treatments, this application provides an antifungal compound ointment, its preparation method, and its application. This compound ointment effectively combines the chemical drug amorolfine with natural magnolia bark extract, and optimizes the formulation matrix and process to achieve synergistic effects, improved penetration, and enhanced safety.

[0007] On the one hand, this application provides an antifungal compound ointment, characterized in that it contains the active ingredients amorolfine and magnolia bark extract; the total mass percentage of the active ingredients in the ointment is 0.1% to 3%, with the remainder being the ointment base.

[0008] Preferably, the magnolia bark extract is magnolol; and the mass ratio of amorolfen to magnolol is 1:0.5 to 1:2.

[0009] Preferably, the magnolol is extracted and purified by ethanol reflux, with a purity of not less than 90% and a moisture content of not more than 5%. The ethanol reflux method includes the following steps: after crushing the magnolia bark raw material, it is refluxed with 70% to 95% ethanol solution at a material-to-liquid ratio of 1:3 to 1:10, the reflux temperature is 70°C to 85°C, and the time is 1 to 3 hours; after the extract is concentrated under reduced pressure, it is purified by filtration, low-temperature crystallization, and silica gel column chromatography to obtain high-purity magnolol powder.

[0010] Preferably, the ointment base is an oily base comprising the following components in weight percentage: petrolatum 40%-60%, lanolin 10%-20%, liquid paraffin 15%-30%, stearic acid 5%-10%, glyceryl monostearate 3%-8%, antioxidant 0.1%-1%, and transdermal absorption enhancer laurocapram 0.1%-0.5%.

[0011] On the other hand, this application provides a method for preparing the aforementioned antifungal compound ointment, characterized by comprising the following steps: (a) Preparation of active ingredients: Amorolfen and Magnolia officinalis extract were obtained separately, wherein the Magnolia officinalis extract was extracted and purified by ethanol reflux method and prepared into powder form; (b) Prepare the ointment base: Mix the oily base components under heating conditions of 50°C to 70°C and stir at 100 to 300 rpm for 10 to 30 minutes to form a uniform base; (c) Mixing the active ingredients with the base: Add the active ingredients prepared in step (a) to the ointment base prepared in step (b), and stir at 200 to 500 rpm for 15 to 45 minutes at 50°C to 70°C to completely disperse the active ingredients and form a homogeneous ointment. (d) Cooling and packaging: Cool the mixed ointment to room temperature and aseptically package it.

[0012] Preferably, the active ingredient in step (c) is dissolved in an appropriate amount of ethanol, propylene glycol or a mixture thereof before mixing, with the mass ratio of solvent to active ingredient being 1:1 to 5:1, the dissolution temperature being 30°C to 50°C, and the dissolution time being 5 to 15 minutes, in order to promote the uniform dispersion and stability of the active ingredient in the matrix.

[0013] Furthermore, this application provides the use of the aforementioned antifungal compound ointment in the preparation of antifungal drugs, particularly for the treatment of onychomycosis (fungal nail infection).

[0014] Beneficial effects Compared with the prior art, the antifungal compound ointment and its preparation method provided by the present invention exhibit the following significant beneficial effects: 1. Synergistic effect, comprehensively enhances antifungal efficacy and reduces the risk of drug resistance. The core advantage of this invention lies in the discovery that the effect of amorolfen and magnolia bark extract (especially its main active ingredient, magnolol) is not simply additive, but rather produces a significant synergistic antibacterial effect. Amorolfen, as a morpholine-based antifungal agent, primarily works by inhibiting two key enzymes in the ergosterol biosynthesis pathway of fungal cell membranes—Δ14-reductase and Δ7-Δ8-isomerase—leading to abnormal sterol accumulation and normal ergosterol deficiency in the fungal cell membrane. This disrupts the structural integrity and function of the cell membrane, ultimately causing fungal cell growth inhibition or death. Magnolol, on the other hand, is a polyphenolic compound derived from natural plants, with a more diverse antibacterial mechanism, including but not limited to: disrupting the synthesis of β-glucan and chitin in the fungal cell wall, interfering with the stability of the cell membrane phospholipid bilayer, inhibiting enzyme activity related to energy metabolism, and inducing oxidative stress within fungal cells.

[0015] When combined in a specific mass ratio (1:0.5 to 1:2), the two drugs can simultaneously attack fungal cells from multiple targets. This multi-pathway, multi-target combined action mode makes it difficult for fungi to circumvent the effects of both drugs simultaneously through single gene mutations or metabolic pathway alterations, thereby greatly improving antibacterial efficiency and significantly delaying or reducing the development of fungal resistance. In vitro inhibition zone tests and minimum inhibitory concentration (MIC) determinations both confirmed that the inhibitory effects of this compound preparation on common dermatophytes (such as Trichophyton rubrum and Trichophyton mentagrophytes), yeasts (such as Candida albicans), and molds are significantly superior to those of amorolfine or magnolol alone at equivalent doses. Its fractional inhibitory concentration index (FICI) is mostly less than 0.5, clearly demonstrating the existence of a synergistic effect. This provides an effective solution to the thorny problem of easy relapse and drug resistance with long-term use of monotherapy in clinical practice.

[0016] 2. Deeply optimizes the penetration-enhancing system, significantly improving local drug permeability and bioavailability. One of the biggest challenges in treating onychomycosis (nail fungus) is the difficulty for medications to penetrate the dense nail plate and keratin layer to reach the infection foci deep in the nail bed. This invention successfully overcomes this barrier through a carefully designed and deeply optimized "penetration-enhancing system" for the ointment. This system comprises two layers: Firstly, there is enhanced physical penetration: the oily matrix selected in this invention, composed of petrolatum, lanolin, liquid paraffin, etc., possesses excellent sealing and lubricating properties. When applied to the nail plate surface, it effectively softens the keratin, increases the plasticity of the nail plate, and creates favorable conditions for drug molecule diffusion. Simultaneously, components such as stearic acid and glyceryl monostearate in the matrix contribute to the formation of a stable emulsion structure, promoting uniform drug distribution within the matrix and sustained release into the skin / nail plate.

[0017] Secondly, there is the enhanced chemical penetration: the key lies in the addition of a highly effective transdermal absorption enhancer—lauryl azedarach (Azone). Lauryl azedarach can reversibly and non-destructively disrupt the orderly arrangement of the lipid bilayer in the stratum corneum, increasing the fluidity of intercellular lipids, thus significantly reducing the resistance to drug penetration of the stratum corneum, much like "opening a channel." Especially for drug molecules with certain hydrophobicity, such as amorolfine and magnolol, lauryl azedarach can greatly promote their transmembrane transport. In vitro Franz diffusion cell assays and in vitro nail plate penetration models both show that, compared with the control group without lauryl azedarach, the cumulative penetration of the two active ingredients in the ointment of this invention increased by 2-3 times within 24 hours, ensuring sufficient active ingredients penetrate the nail plate and reach and maintain an effective therapeutic level above the minimum inhibitory concentration at the nail bed, thereby achieving thorough eradication of deep fungi.

[0018] 3. Balancing efficiency and safety, constructing a green medication solution that complements "chemical-natural" approaches. This invention introduces magnolol, a naturally derived compound, to construct a complementary treatment strategy combining chemical drugs and natural extracts. This approach significantly improves medication safety while ensuring excellent efficacy. Firstly, as mentioned earlier, the compound formulation allows for a reduction in the concentration of the chemical drug amorolfen while achieving the same or better therapeutic effect. This directly reduces the risks of local skin irritation and allergic reactions that may result from high concentrations of chemical drugs. Secondly, magnolol not only possesses antifungal activity but has also been widely reported to have adjuvant pharmacological effects such as anti-inflammatory, antioxidant, and wound-healing properties. In treating fungal infections (especially onychomycosis accompanied by periungual inflammation), these adjuvant effects of magnolol can effectively reduce inflammation at the infection site, eliminate free radical damage to tissues, and accelerate the repair of damaged periungual tissue, creating a favorable microenvironment for the healthy regeneration of the nail plate.

[0019] Furthermore, Magnolia officinalis extract is derived from traditional Chinese medicine, with a long history of human application and relatively complete safety data. This combination makes this compound ointment a more comprehensive, gentler, and more nature-in line with the health concept of "returning to nature," making it particularly suitable for patients with onychomycosis who require long-term medication or are sensitive to purely chemical drugs, and is expected to significantly improve patient treatment adherence.

[0020] 4. Standardized processes throughout the entire supply chain ensure stable and controllable product quality and batch consistency. The beneficial effects of this invention are evident throughout the entire preparation chain, from raw materials to finished product. For the key raw material, magnolol, we have overcome the problems of low extraction rate, unstable purity, and high risk of organic solvent residue found in traditional extraction processes, and developed a standardized and quantifiable extraction and purification process. This process clearly specifies the operating parameters and quality control points for each step, from raw material crushing, ethanol concentration, material-to-liquid ratio, reflux temperature and time, to subsequent vacuum concentration, precision filtration, low-temperature crystallization, and silica gel column chromatography (e.g., final product purity ≥90%, moisture ≤5%). This meticulous control ensures a high degree of consistency in the chemical composition and biological activity of each batch of magnolol, laying a solid foundation for the therapeutic stability of the final ointment product.

[0021] In the ointment preparation process, by precisely controlling key process parameters such as mixing temperature, stirring rate, and time, and by innovatively introducing a "pre-dissolving of active ingredients" step (using ethanol / propylene glycol as a solvent), the technical challenges of hydrophobic drugs easily agglomerating and unevenly dispersing in an oily matrix are effectively solved. This step ensures that amorolfen and magnolol are highly uniformly dispersed throughout the matrix in a molecular or microcrystalline state, avoiding localized excessively high or low concentrations due to uneven drug distribution. This ensures that each unit dose of ointment releases a stable and expected efficacy. The entire process is stable and reproducible, making it very suitable for large-scale industrial production and ensuring a high degree of uniformity in quality across different batches.

[0022] 5. With a clear application objective, it provides a highly effective, safe, and well-compliant new local treatment option for onychomycosis. This invention was designed from the outset with a strong focus on specific applications, aiming to provide an ideal local treatment solution for onychomycosis, a condition that plagues many patients. Compared to systemic oral medications (such as terbinafine and itraconazole), this compound ointment, as a topical medication, primarily acts on the target site with minimal systemic absorption. This fundamentally avoids the systemic side effects such as hepatotoxicity and drug interactions that may occur with oral antifungal drugs, making its safety advantages particularly prominent.

[0023] Compared to existing single-agent topical preparations (such as amorolfine lotion and ciclopirox olamine cream), this invention achieves a qualitative leap in efficacy due to its unique compound synergistic effect and advanced penetration-enhancing technology. It not only kills fungi more effectively but also improves periungual conditions through the adjuvant anti-inflammatory effect of magnolol, and ensures long-term treatment effectiveness by reducing the risk of drug resistance. Furthermore, the ointment formulation itself has good spreadability and adhesion, allowing for prolonged coverage and action on the nail plate, making it convenient to use and resulting in high patient compliance.

[0024] This invention successfully integrates the advantages of chemical drugs and natural products, and combines advanced formulation technology and rigorous preparation process to create an antifungal compound ointment with comprehensive advantages such as strong antibacterial effect, deep penetration, high safety, stable quality and convenient use. It is expected to become a breakthrough product in the field of topical treatment of onychomycosis, with great clinical value and social and economic benefits. Detailed Implementation

[0025] Example 1: Preparation of magnolol The dried Magnolia officinalis raw material was pulverized and passed through a 40-mesh sieve. 100 g of Magnolia officinalis powder was mixed with 500 g of 80% (v / v) ethanol solution and placed in a round-bottom flask. A reflux condenser was installed, and the mixture was extracted by reflux at 75°C for 2 hours. After extraction, the extract was concentrated to 1 / 5 of its original volume under reduced pressure at 60°C and -0.09 MPa. The concentrate was first filtered through a 1 μm pore size filter membrane, and then allowed to crystallize at 5°C for 12 hours. The crude crystallized product was purified by silica gel column chromatography using petroleum ether-ethyl acetate (2:1, v / v) as the elution system. The fraction corresponding to the main spot of magnolol was collected based on the thin-layer chromatography results. The fractions were combined and vacuum dried at 50°C and -0.1 MPa for 4 hours, finally obtaining a pale yellow magnolol crystalline powder. The purity was 92% as determined by high-performance liquid chromatography, and the moisture content was 3% as determined by Karl Fischer chromatography.

[0026] Example 2: In vitro verification of the synergistic antifungal effect of amorolfine and magnolol compound. 1. Experimental Objective This embodiment aims to determine the minimum inhibitory concentration (MIC) and inter-drug inhibitory concentration index (FICI) of amorolfine and magnolol at different ratios through in vitro drug susceptibility testing, and to verify whether the two have synergistic antifungal effects.

[0027] 2. Experimental Materials Strains: Clinically isolated Trichophyton rubrum standard strain, and Candida parapsilosis ATCC 22019 quality control strain.

[0028] Drugs: Amorolfen (purity ≥99%, Shanghai Yuanye Biotechnology Co., Ltd.), magnolol (extracted and purified by the ethanol reflux method described in Example 1, purity ≥90%, moisture ≤5%).

[0029] Culture media: RPMI-1640 liquid medium (containing MOPS buffer, pH 7.0) and Sabouraud dextrose agar (SDA).

[0030] Instruments: 96-well cell culture plate, incubator, sterile grinder, hemocytometer, pipette, etc.

[0031] 3. Experimental Methods 3.1 Preparation of drug solution Amorolfen and magnolol were dissolved in dimethyl sulfoxide (DMSO) to prepare stock solutions (amorolfen concentration 128 μg / mL, magnolol concentration 128 μg / mL), which were then serially diluted using RPMI-1640 medium.

[0032] Set up the following drug groups: Amorolfen monotherapy group Magnolol monotherapy group Amorolfine and magnolol compound groups (mass ratios are 1:0.25, 1:0.5, 1:1, 1:2, 1:4 respectively) Positive control group (terbinafine, 1 μg / mL) Blank control group (only culture medium) and growth control group (strain + culture medium).

[0033] 3.2 Preparation of bacterial suspension Inoculate Trichophyton rubrum strain on SDA plate and culture at 35 °C for 7 days. Collect spores and hyphal fragments with normal saline. After grinding evenly, adjust the concentration of the bacterial suspension to 5×10 6 CFU / mL, and then dilute it with RPMI-1640 medium to 2× the final concentration (1×10 6 CFU / mL).

[0034] 3.3 Determination of MIC Refer to the CLSI M38-A protocol: In a 96-well plate, add 100 μL of serially diluted drug solution to each well (final concentration range of amorolfine: 0.008–4 μg / mL; final concentration range of magnolol: 0.008–4 μg / mL; the compound groups are adjusted according to the ratio). Add 100 μL of bacterial suspension to each well to make the final concentration of hyphae 5×10^5 CFU / mL. After culturing at 35 °C for 5 days, visually determine the MIC endpoint (the lowest drug concentration corresponding to 80% growth inhibition). The MIC value of ketoconazole for the quality control strain ATCC 22019 should be within the reference range (0.06–0.25 μg / mL), otherwise the experiment is invalid.

[0035] 3.4 Calculation of FICI and evaluation of synergistic effect Calculate the fractional inhibitory concentration index (FICI): FICI = MIC of amorolfine (compound) / MIC of amorolfine (monotherapy) + MIC of magnolol (compound) / MIC of magnolol (monotherapy).

[0036] Criteria for judging synergistic effect: FICI ≤ 0.5: Synergistic effect 0.5 < FICI ≤ 1: Additive effect 1 < FICI ≤ 2: Irrelevant effect FICI > 2: Antagonistic effect.

[0037] 4. Experimental results 4.1 MIC values of monotherapy and compound The MIC of amorolfine monotherapy against Trichophyton rubrum is 0.025 μg / mL, and the MIC of magnolol monotherapy is 0.045 μg / mL. The MIC and FICI of the compound groups at different ratios are shown in Table 1.

[0038] Table 1: MIC and FICI of amorolfine and magnolol compound against Trichophyton rubrum Compound ratio (amorolfen: magnolol) MIC Amorolfine (compound) MIC magnolol (compound) FICI value Function type 01:00.3 0.015 0.035 1.12 irrelevant 01:00.5 0.008 0.02 0.45 Collaboration 1:01 0.006 0.012 0.32 Collaboration 1:02 0.005 0.01 0.28 Collaboration 1:04 0.01 0.038 0.95 Add 4. Experimental Conclusions This embodiment demonstrates through in vitro drug sensitivity testing that when amorolfine and magnolol are used in combination at a mass ratio ranging from 1:0.5 to 1:2, the FICI values ​​are all ≤0.5, exhibiting a significant synergistic antifungal effect. This verifies the synergistic effect of this compound in antifungal efficacy and provides experimental evidence for addressing the problems of poor drug penetration and high drug resistance in the treatment of onychomycosis.

[0039] Example 3: Preparation of antifungal compound ointment The active ingredients, amorolfine and magnolol, are each accurately weighed at 0.15 grams, for a total ointment weight of 100 grams. First, the ointment base components are accurately weighed according to their mass percentages: 52 grams of petrolatum, 15 grams of lanolin, 20 grams of liquid paraffin, 7 grams of stearic acid, 5 grams of glyceryl monostearate, 0.5 grams of antioxidant, and 0.2 grams of lauryl diazoline. These base components are placed in a mixing container and mixed at 200 rpm for 20 minutes under heating at 60°C until a homogeneous and stable oily base is formed.

[0040] Next, add 0.15g of amorolfine raw material and 0.15g of magnolol powder directly to the ointment base, which has been preheated to 60°C. While maintaining the temperature at 60°C, increase the stirring speed to 350 rpm and continue stirring for 30 minutes to ensure that the two powdered active ingredients are fully dispersed and evenly distributed in the base. Special attention should be paid to the uniformity of stirring during this process to avoid any local aggregation or clumping, until a smooth and uniform ointment system is formed.

[0041] Finally, the mixed ointment was removed from the heat source and allowed to cool and solidify naturally at room temperature. After it had completely cooled, it was dispensed and sealed under aseptic conditions to obtain the final product. The prepared compound ointment had a total active ingredient content of 0.3%, a uniform and fine appearance, met the predetermined quality standards, and was suitable for subsequent antifungal applications.

[0042] Example 4: Human Clinical Trial This embodiment evaluates the efficacy and safety of the antifungal compound ointment of the present invention in treating onychomycosis (nail fungus) through a randomized, single-blind, parallel-controlled clinical study. A total of 120 confirmed patients were included in the trial and randomly divided into an experimental group (using the compound ointment prepared in Example 3, with a total effective ingredient content of 0.3%) and a control group (using 0.3% amorolfine ointment, with the same base as the experimental group). The treatment period was 24 weeks, with follow-up up to 36 weeks. Results showed that at the end of treatment, the experimental group was significantly superior to the control group in terms of clinical cure rate, mycological cure rate, and overall effective rate. Specifically, the clinical cure rate in the experimental group reached 78.3%, while it was 55.0% in the control group; the mycological cure rate was 81.7% in the experimental group and 58.3% in the control group. Furthermore, the time to improvement of nail plate in the experimental group was earlier, with an average of 4.2 weeks, significantly faster than the 6.5 weeks in the control group, indicating that the compound ointment has superior permeability and onset of action. During long-term follow-up, the recurrence rate in the experimental group was only 8.3%, far lower than the 20.0% in the control group, confirming the synergistic advantage of this compound in reducing drug resistance and recurrence risk. Regarding safety, the incidence of adverse events was low in both groups with no significant difference; all reported reactions were mild local erythema or itching, and no serious adverse reactions or abnormal laboratory indicators were observed. This clinical validation fully demonstrates that this antifungal compound ointment is not only significantly effective, rapidly acting, and has a low recurrence rate, but also has good safety, providing an ideal solution for the local treatment of onychomycosis that combines synergistic efficacy and clinical practical value.

Claims

1. An antifungal compound ointment, characterized in that, It contains the active ingredients amorolfine and magnolia bark extract; the total mass percentage of the active ingredients in the ointment is 0.1% to 3%, with the remainder being the ointment base.

2. The antifungal compound ointment according to claim 1, characterized in that, The magnolia bark extract is magnolol; and the mass ratio of amorolfen to magnolol is 1:0.5 to 1:

2.

3. The antifungal compound ointment according to claim 2, characterized in that, The magnolol is extracted by ethanol reflux extraction, which includes the following steps: pulverizing the magnolia bark raw material and extracting it by reflux with ethanol solution to obtain an extract; concentrating the extract under reduced pressure to obtain a concentrate; subjecting the concentrate to filtration, crystallization, and column chromatography for purification to separate magnolol; and vacuum drying the separated magnolol at 40°C to 60°C for 2 to 6 hours to prepare magnolol powder, wherein the purity of the dried magnolol is not less than 90% and the moisture content is not more than 5%.

4. The antifungal compound ointment according to claim 3, characterized in that, The specific process parameters of the ethanol reflux method include: an ethanol concentration of 70% to 95%, a mass ratio of magnolia bark to ethanol of 1:3 to 1:10; a reflux time of 1 to 3 hours; a reflux temperature of 70°C to 85°C; the concentration step is carried out under reduced pressure, with a concentration temperature of 50°C to 70°C and a pressure of -0.05 MPa to -0.1 MPa; the filtration uses a filter membrane with a pore size of 0.45 μm to 5 μm; the crystallization temperature is 0°C to 10°C; the column chromatography uses silica gel as the stationary phase, and the eluent is a mixture of petroleum ether and ethyl acetate with a volume ratio of 1:1 to 3:

1.

5. The antifungal compound ointment according to claim 1, characterized in that, The ointment has an oily base comprising the following components in weight percentages: petrolatum 40% to 60%, lanolin 10% to 20%, liquid paraffin 15% to 30%, stearic acid 5% to 10%, glyceryl monostearate 3% to 8%, antioxidant 0.1% to 1%, and laurocapram 0.1% to 0.5%.

6. A method for preparing an antifungal compound ointment as described in any one of claims 1 to 5, characterized in that, Includes the following steps: (a) Preparation of active ingredients: Amorolfen and Magnolia officinalis extract were obtained separately, wherein the Magnolia officinalis extract was extracted by ethanol reflux method and prepared into powder form; (b) Preparation of ointment base: Mix the oily base components under heating conditions at a temperature of 50°C to 70°C, a stirring speed of 100 to 300 rpm, and a mixing time of 10 to 30 minutes until a uniform base is formed; (c) Mixing the active ingredients with the base: Add the active ingredients prepared in step (a) to the ointment base prepared in step (b), and stir evenly at 50°C to 70°C at a stirring speed of 200 to 500 rpm for 15 to 45 minutes until the active ingredients are completely dispersed in the base to form a homogeneous ointment. (d) Cooling and packaging: Cool the mixed ointment to room temperature and aseptically package it.

7. The preparation method according to claim 6, characterized in that, The mixing temperature in step (b) is 55°C to 65°C, the stirring rate is 150 to 250 rpm, and the mixing time is 15 to 25 minutes; the stirring temperature in step (c) is 55°C to 65°C, the stirring rate is 300 to 400 rpm, and the stirring time is 20 to 30 minutes.

8. The preparation method according to claim 6 or 7, characterized in that, The active ingredient in step (c) is dissolved in an appropriate amount of solvent before mixing. The solvent is ethanol, propylene glycol or a mixture thereof. The mass ratio of the solvent to the active ingredient is 1:1 to 5:

1. The dissolution temperature is 30°C to 50°C and the dissolution time is 5 to 15 minutes.

9. The use of an antifungal compound ointment as described in any one of claims 1 to 5 in the preparation of an antifungal drug.

10. The application according to claim 9, characterized in that, The antifungal drug is used to treat onychomycosis (fungal nail infection).