A therapeutic kit for the treatment of onychomycosis, methods of use and applications thereof

Abstract

This invention discloses a treatment kit for treating onychomycosis, its usage, and its application. The treatment kit includes an antifungal agent and toe-separating socks. The antifungal agent is formed using a moisture-curing silicone film-forming method. The toe-separating socks have a water-soluble isolation membrane embedded with antifungal microcapsules between the toes. During treatment, the antifungal agent is evenly applied to the surface of the affected nail, left to stand for 5-10 minutes, and then the toe-separating socks are worn. The treatment kit for treating onychomycosis provided by this invention can achieve both antifungal sealing of the nail and slow-release antifungal action between the toes, treating both the nail and skin simultaneously, avoiding cross-infection, significantly reducing the recurrence rate of onychomycosis, and significantly shortening the treatment cycle.

Description

Technical Field

[0001] This invention relates to a treatment kit for treating onychomycosis, its method of use, and its application, suitable for the simultaneous combined treatment of onychomycosis and fungal infections of the feet. Background Technology

[0002] Onychomycosis, also known clinically as tinea unguium or colloquially as gray nail, is a common superficial fungal infection of the skin caused by pathogenic fungi such as dermatophytes, yeasts, and molds invading the nail plate, nail bed, and surrounding tissues. It has a high incidence rate, is highly contagious, and is most common in adults, with the probability of developing the disease increasing significantly with age. It can affect the fingernails, toenails, and toenails, but is more frequently involved in the toenails.

[0003] Onychomycosis is characterized by its high infectivity, long course, extremely low self-healing rate, and tendency to recur. After the fungus invades the nail tissue structure, it damages the nail plate keratin, causing pathological appearances such as thickening, discoloration, brittleness, cloudiness, unevenness, separation, and even nail loss. This not only affects the appearance of the limbs but also easily leads to complications such as periungual dermatitis, paronychia, and secondary bacterial infections. It can also be transmitted indirectly through direct contact or sharing shoes, socks, foot basins, towels, etc., affecting other healthy fingernails and toenails, and is easily transmitted to family members, causing serious distress to the patient's daily life, social life, and psychological state.

[0004] Currently, the main clinical treatment methods are topical antifungal preparations, mostly in the form of liniments. These preparations often use solvent-based film-forming methods, which are prone to cracking, have poor water resistance, and easily fall off when washing the feet. The medication cannot remain effective for a long time. Reusing packaging can easily cause cross-contamination of fungi, and home treatment is not convenient or hygienic enough. Moreover, most existing topical antifungal preparations only target nail lesions and do not simultaneously intervene in the fungi in the toe crevices and soles of the feet, making cross-infection and recurrence easy.

[0005] Traditional antifungal socks use processes such as soaking in medicine, spraying powder, and coating. However, the release of the medicine is uncontrollable, easily lost, and can easily contaminate shoes and socks, resulting in a short-lasting antibacterial effect. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a treatment kit for treating onychomycosis, along with its usage and application. The kit utilizes a moisture-cured silicone-based antifungal agent in conjunction with toe-separating socks containing water-soluble isolation membranes encapsulating antifungal microcapsules. This allows for the sealing of antifungal agents in the nails and the slow-release inhibition of bacteria between the toes, achieving simultaneous treatment of the nails and skin. This avoids cross-infection, significantly reduces the recurrence rate of onychomycosis, and substantially shortens the treatment cycle.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] This invention provides a treatment kit for treating onychomycosis, the treatment kit comprising: an antifungal agent and toe-separating socks; the antifungal agent is formed by moisture-curing silicone film formation; and the toe-separating socks have a water-soluble isolation membrane embedded with antifungal microcapsules between the toes.

[0009] The antifungal agent comprises the following raw materials by weight percentage:

[0010] 10%–15% silicone resin;

[0011] Antifungal active ingredient: 1.0%~5.0%;

[0012] 3%–5% of the penetration enhancer and softener;

[0013] Toughening agent 1%–2%;

[0014] The remainder is a volatile solvent.

[0015] Furthermore, the silicone resin is selected from any one or more of Wacker SILRES® MSE100, Evonik Silikophen® AC1000, and Wacker ELASTOSIL® N2076.

[0016] The antifungal active ingredient is any one or more of the following: azole antifungal drugs, morpholine antifungal drugs, allylamine antifungal drugs, thiocarbamate antifungal drugs, and polyene antifungal drugs.

[0017] The penetration-enhancing softening agent is any one or more of salicylic acid, urea, and succinic acid.

[0018] The toughening agent is any one or more of hydroxyl-terminated polydimethylsiloxane and carbohydroxyl-terminated polydimethylsiloxane.

[0019] The volatile solvent is any one or more of ethanol and isopropanol.

[0020] The antifungal agent is packaged in a disposable medicine bottle with an integrated brush, making it hygienic and convenient to use and discard immediately.

[0021] The material of the fingerless socks can be any comfortable material, such as breathable pure cotton.

[0022] The water-soluble barrier membrane is made of either polyvinyl alcohol water-soluble film or hydroxypropyl methylcellulose film, which slowly dissolves upon contact with sweat, leaving no sticky residue.

[0023] The antifungal microcapsules have a wall made of a composite material of gelatin and gum arabic. The core comprises the following raw materials by weight percentage: 0.3%–1.5% antifungal active ingredient, 5%–20% auxiliary antibacterial ingredient, and the remainder is filler. The antifungal active ingredient exerts the main antibacterial effect; the auxiliary antibacterial ingredient absorbs moisture, dries, astringes, and stops sweating, disrupting the moist growth environment of fungi while enhancing antibacterial activity; the filler, as the nucleation core of the microcapsules, can dilute the drug, control the drug release rate, and ensure stability upon mechanically triggered rupture.

[0024] Furthermore, the antifungal active ingredient is any one or more of terbinafine, ciclopirox olamine, amorolfine, bifonazole, butenafine, ketoconazole, and clotrimazole.

[0025] The auxiliary antibacterial ingredient is one of zinc oxide and calamine.

[0026] The filler is any one or more of corn starch, potato starch, cassava starch, wheat starch, maltodextrin, lactose, microcrystalline cellulose, silicon dioxide, and calcium carbonate.

[0027] The method for preparing the antifungal microcapsules includes the following steps:

[0028] (1) Disperse the raw materials of the capsule core evenly in deionized water to prepare a capsule core suspension with a mass concentration of 10%~15%;

[0029] (2) Slowly add the core suspension to the wall material solution and stir at 45~55℃ until it is evenly mixed;

[0030] (3) Cool down to below 10°C, add glutaraldehyde solution for solidification, and finally centrifuge, wash and dry to obtain antifungal microcapsule powder.

[0031] In step (2), the volume ratio of the core suspension to the wall material solution is 1:4~6, preferably 1:5.

[0032] In step (2), the wall material solution is prepared by preparing a 10% mass concentration gelatin solution and a 10% mass concentration gum arabic solution, mixing the two in a volume ratio of 1:1, adjusting the pH to 4.0~4.5, and keeping it at 50℃.

[0033] Furthermore, the pH was adjusted using 10% acetic acid.

[0034] In step (3), the final mass concentration of glutaraldehyde in the system is 0.5%~1.0%; the curing time is 30~40 min.

[0035] In the preparation method of antifungal microcapsules provided by the present invention, positively charged gelatin and negatively charged gum arabic undergo charge neutralization under pH 4.0-4.5 conditions to form a composite aggregate, which encapsulates the core to form microcapsules. After cross-linking and curing with glutaraldehyde, the mechanical strength can be improved, ensuring controllable rupture when the foot is squeezed.

[0036] The method for preparing the fingerless socks includes the following steps:

[0037] 1) Disperse the microcapsules in a polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution and cast them to form a separating film with a thickness of 20~80μm;

[0038] 2) The insulating film is fixed to the toe area using a hot-pressing process.

[0039] In step 1), the preparation method of the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution is as follows: polyvinyl alcohol or hydroxypropyl methylcellulose, plasticizer and preservative are dispersed in deionized water and stirred and mixed evenly.

[0040] Furthermore, in the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution, the weight percentages of each raw material are as follows: polyvinyl alcohol or hydroxypropyl methylcellulose 10%~15%; plasticizer 1%~3%; preservative 0.1%~0.2%; and deionized water 82%~89%.

[0041] The plasticizer is glycerin.

[0042] The preservative is potassium sorbate.

[0043] The molecular weight of the polyvinyl alcohol is 70,000 to 80,000 Da; the molecular weight of the hydroxypropyl methylcellulose is 80,000 to 150,000 Da.

[0044] In step 2), the hot pressing conditions are: hot pressing temperature 80~120℃, hot pressing pressure 0.2~0.5MPa, and hot pressing time 5~15s; the hot pressing method is to perform hot pressing on the edge of the isolation membrane 1~2mm to avoid premature rupture of microcapsules in the main area.

[0045] The weight of the microcapsules is 5% to 10% of the weight of the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution.

[0046] The present invention also provides a method of using the treatment kit for treating onychomycosis, the method of use comprising: applying the antifungal agent evenly to the surface of the diseased nail, leaving it for 5 to 10 minutes, and then wearing the finger-separating socks.

[0047] The present invention also provides the application of the aforementioned treatment kit in the treatment of onychomycosis.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] The treatment kit for treating onychomycosis provided by this invention uses a moisture-cured organosilicon film-forming antifungal agent in conjunction with toe-separating socks containing water-soluble isolation membranes encapsulating antifungal microcapsules. This kit can seal the nails with antifungal agents and provide sustained-release antifungal treatment between the toes, achieving simultaneous treatment of the nails and skin. This significantly reduces the recurrence rate of onychomycosis and shortens the treatment cycle.

[0050] Among them, the moisture-curing silicone film-forming antifungal agent abandons the traditional nail polish-style solvent evaporation film formation and adopts a moisture-curing silicone system. After the agent is applied to the nail surface, the silicone resin undergoes a cross-linking and curing reaction with the moisture in the air and the water in the nail keratin, gradually forming a three-dimensional network silicone film. The film layer is dense, flexible, waterproof, washable, non-brittle and non-crackable, and can seal the drug on the nail surface for continuous and slow release for more than 72 hours. It will not fall off when washing feet or wearing socks. Moreover, the aesthetics of the film can also effectively cover up the social distress caused by nail diseases, and enhance patients' willingness to use the medication.

[0051] These toe-separating socks feature a water-soluble isolating membrane encapsulating antifungal microcapsules between the toes, abandoning traditional powdered or medicated socks. Instead, they utilize a water-soluble, slow-release isolating membrane combined with antifungal microcapsules. The isolating membrane slowly dissolves upon contact with sweat, while the microcapsules rupture due to slight pressure and friction from the feet, releasing the antifungal active ingredients at specific points between the toes. This achieves a dual effect of physical separation of the toes and continuous antibacterial action. Simultaneously, the water-soluble isolating membrane in the toe area of ​​the toe-separating socks continuously absorbs moisture, keeping the toes dry and disrupting the environment for fungal growth.

[0052] The treatment kit for treating onychomycosis provided by this invention allows for normal daily wear of shoes and foot washing after use. The medicated film is waterproof and will not peel off. The moisture-curing silicone antifungal agent is applied once every 2 to 3 days, and the finger-separating socks can be used continuously for 3 to 5 days, simultaneously treating onychomycosis and foot fungus.

[0053] The treatment kit for treating onychomycosis provided by this invention can achieve sealing and antifungal treatment of nails and slow-release antifungal treatment of toe crevices, thus treating both nails and skin simultaneously and significantly reducing the recurrence rate. When used with a disposable integrated brush bottle, it can achieve the use and disposal of moisture-cured silicone antifungal agents, making it hygienic and convenient. Detailed Implementation

[0054] The present invention provides a treatment kit for treating onychomycosis, the treatment kit comprising: an antifungal agent and toe-separating socks; the antifungal agent is formed by moisture-curing organosilicon film formation; the toe-separating socks are provided with a water-soluble isolation membrane encapsulating antifungal microcapsules between the toes.

[0055] The antifungal agent comprises the following raw materials by weight percentage:

[0056] 10%–15% silicone resin;

[0057] Antifungal active ingredient: 1.0%~5.0%;

[0058] 3%–5% of the penetration enhancer and softener;

[0059] Toughening agent 1%–2%;

[0060] The remainder is a volatile solvent.

[0061] The silicone resin is selected from any one or more of Wacker SILRES® MSE100, Evonik Silikophen® AC1000, and Wacker ELASTOSIL® N2076. These silicone resins can cure into a film upon contact with moisture and have good film-forming properties.

[0062] The antifungal active ingredient is any one or more of the following: azole antifungal drugs, morpholine antifungal drugs, allylamine antifungal drugs, thiocarbamate antifungal drugs, and polyene antifungal drugs.

[0063] The azole antifungal drug may be selected from any one or more of ciclopirox olamine, itraconazole, and bifonazole; the morpholine antifungal drug may be selected from amorolfine; the allylamine antifungal drug may be selected from terbinafine; the thiocarbamate antifungal drug may be selected from butenafine; the polyene antifungal drug may be selected from nystatin; or, depending on the type of fungal infection, a known antifungal drug in the prior art may be selected.

[0064] The penetration-enhancing and softening agent is any one or more of salicylic acid, urea, and succinic acid. Salicylic acid is preferred, as it is lipid-soluble, can penetrate deep into the stratum corneum of the nail plate, dissolve keratin, and increase drug penetration by 2-3 times, while also possessing weak antibacterial properties.

[0065] The toughening agent is any one or more of hydroxyl-terminated polydimethylsiloxane and carbohydroxyl-terminated polydimethylsiloxane. Preferably, it is hydroxyl-terminated polydimethylsiloxane, where the terminal hydroxyl groups can crosslink with the organosilicon prepolymer, providing in-situ toughening, improving the tensile strength and flexural strength of the film, without affecting the curing speed.

[0066] The volatile solvent is any one or more of ethanol and isopropanol. Ethanol is preferred because it has a strong ability to dissolve organosilicon, a moderate evaporation rate, a surface drying time of 5-10 minutes, leaves no residue, has low skin irritation, and is low in cost.

[0067] The antifungal agent is packaged in a disposable medicine bottle with an integrated brush, so that the antifungal agent can be used and disposed of immediately, making it hygienic and convenient.

[0068] The membrane material of the water-soluble isolation membrane is either polyvinyl alcohol water-soluble film or hydroxypropyl methylcellulose film.

[0069] The antifungal microcapsule has a capsule wall made of a composite material of gelatin and gum arabic, and the capsule core contains the following raw materials by weight percentage: 0.3% to 1.5% antifungal active ingredient, 5% to 20% auxiliary antibacterial ingredient, and the remainder is filler.

[0070] The antifungal active ingredient is any one or more of terbinafine, ciclopirox olamine, amorolfine, bifonazole, butenafine, ketoconazole, and clotrimazole.

[0071] The auxiliary antibacterial ingredient is one of zinc oxide and calamine.

[0072] The filler is any one or more of corn starch, potato starch, cassava starch, wheat starch, maltodextrin, lactose, microcrystalline cellulose, silicon dioxide, and calcium carbonate.

[0073] The method for preparing the antifungal microcapsules includes the following steps:

[0074] (1) Disperse the raw materials of the capsule core evenly in deionized water to prepare a capsule core suspension with a mass concentration of 10%~15%;

[0075] (2) Slowly add the core suspension to the wall material solution and stir at 45~55℃ until it is evenly mixed;

[0076] (3) Cool down to below 10°C, add glutaraldehyde solution for solidification, and finally centrifuge, wash and dry to obtain antifungal microcapsule powder.

[0077] In step (2), the volume ratio of the core suspension to the wall material solution is 1:4~6, preferably 1:5.

[0078] In step (2), the wall material solution is prepared by preparing a 10% mass concentration gelatin solution and a 10% mass concentration gum arabic solution, mixing the two in a volume ratio of 1:1, adjusting the pH to 4.0~4.5, and keeping it at 50℃.

[0079] Furthermore, the pH was adjusted using 10% acetic acid.

[0080] In step (3), the final mass concentration of glutaraldehyde in the system is 0.5%~1.0%; the curing time is 30~40 min.

[0081] The method for preparing the fingerless socks includes the following steps:

[0082] 1) Disperse the microcapsules in a polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution and cast them to form a separating film with a thickness of 20~80μm;

[0083] 2) The insulating film is fixed to the toe area using a hot-pressing process.

[0084] In step 1), the preparation method of the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution is as follows: polyvinyl alcohol or hydroxypropyl methylcellulose, plasticizer and preservative are dispersed in deionized water and stirred and mixed evenly.

[0085] In step 1), the weight of the microcapsules is 5% to 10% of the weight of the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution.

[0086] Furthermore, in the polyvinyl alcohol or hydroxypropyl methylcellulose aqueous film solution, the weight percentages of each raw material are as follows: polyvinyl alcohol or hydroxypropyl methylcellulose 10%~15%; plasticizer 1%~3%; preservative 0.1%~0.2%; and deionized water 82%~89%.

[0087] The plasticizer is glycerin.

[0088] The preservative is potassium sorbate.

[0089] The molecular weight of the polyvinyl alcohol is 70,000 to 80,000 Da; the molecular weight of the hydroxypropyl methylcellulose is 80,000 to 150,000 Da.

[0090] In step 2), the hot pressing conditions are: hot pressing temperature 80~120℃, hot pressing pressure 0.2~0.5MPa, hot pressing time 5~15s; the hot pressing method is to perform hot pressing on the edge of the isolation diaphragm 1~2mm.

[0091] The present invention also provides a method of using the treatment kit for treating onychomycosis, the method of use comprising: applying the antifungal agent evenly to the surface of the diseased nail, leaving it for 5 to 10 minutes, and then wearing the finger-separating socks.

[0092] The present invention will now be described in detail with reference to the embodiments.

[0093] Unless otherwise specified, all substances involved in this invention can be directly purchased from the market.

[0094] Example 1

[0095] A treatment kit for treating onychomycosis includes: an antifungal agent and toe-separating socks; the antifungal agent is formed by moisture-curing silicone film formation; and the toe-separating socks have a water-soluble barrier membrane embedded with antifungal microcapsules between the toes.

[0096] The antifungal agent comprises the following raw materials by weight percentage:

[0097] Wacker silicone SILRES® MSE 100: 12%;

[0098] Amorolfine: 2.5%;

[0099] Salicylic acid: 4%;

[0100] Hydroxyl-terminated polydimethylsiloxane: 1.5%;

[0101] Anhydrous ethanol.

[0102] The method for preparing the antifungal agent is as follows: mix and stir the raw materials in the prescribed amount evenly, fill the mixture into a disposable medicine bottle with an integrated brush, and seal it.

[0103] The method for preparing the fingerless socks includes the following steps:

[0104] (1) Preparation of antifungal microcapsules:

[0105] (1-1) Capsule core dispersion: The raw materials of the capsule core are uniformly dispersed in deionized water to prepare a 10% mass concentration capsule core suspension; the raw materials of the capsule core are composed of the following raw materials by weight percentage: terbinafine 0.8%, zinc oxide 10%, corn starch 88.2%;

[0106] (1-2) Preparation of wall material solution: Prepare 10% mass concentration gelatin solution and 10% mass concentration gum arabic solution separately. Mix the two in a volume ratio of 1:1, adjust the pH to 4.0 with 10% mass concentration acetic acid, and keep warm at 50℃.

[0107] (1-3) Re-coagulation into capsules: The capsule core suspension is slowly added to the wall material solution, with a volume ratio of 1:5 between the capsule core suspension and the wall material solution. Stir at 50°C and 1000 rpm for 30 min.

[0108] (1-4) Curing treatment: Cool down to below 10℃, add 25% glutaraldehyde solution to make the final mass concentration 0.5%~1.0%, stir for 2h to cure, adjust pH to 7.0~7.5, continue stirring for 1h to complete curing;

[0109] (1-5) Separation and drying: Centrifuge at 3000 rpm for 10 min, collect microcapsules, wash 3 times with purified water, freeze dry to obtain dried microcapsule powder with a particle size of 100~300 μm.

[0110] (2) Preparation of a water-soluble isolation membrane encapsulating antifungal microcapsules:

[0111] (2-1) Preparation of polyvinyl alcohol aqueous film solution: PVA was added to deionized water and stirred in a 90°C water bath for 2 hours to dissolve. The temperature was then lowered to 50°C, glycerol and preservative were added, and the mixture was stirred evenly. The mixture was then filtered through a 100-mesh filter to remove bubbles. The weight percentages of each raw material were as follows: PVA 12%, glycerol 2%, potassium sorbate 0.2%, and deionized water 85.8%.

[0112] (2-2) The microcapsule powder was uniformly dispersed in polyvinyl alcohol aqueous film solution, and after degassing, it was uniformly cast on a stainless steel casting plate. The coating thickness was controlled to be 0.4 mm. It was dried with hot air at 45℃ until the moisture content was ≤10% to form a complete film. The film was peeled off and cut according to the size of the toe of the finger toe to make a 20 mm × 50 mm isolation film. After sterilization with 254 nm ultraviolet light for 30 min, an isolation film with a thickness of 50 μm was made.

[0113] (3) Preparation of fingerless socks: The hot pressing process is adopted. The hot pressing conditions are: hot pressing temperature 100℃, hot pressing pressure 0.3MPa, hot pressing time 10s; the hot pressing method is to hot press the edge of the isolation film 2mm and fix the isolation film to the toe part of the fingerless socks.

[0114] The treatment kit is used as follows: Clean and thoroughly dry the feet; open the disposable medicine bottle, and use the integrated brush to evenly apply the antifungal medicine to the surface of the affected nail. Let it sit for 5-10 minutes, during which the medicine will gradually solidify into a film through moisture, without the need for a long waiting period; wear the toe-separating socks to ensure the interdigital barrier adheres to the skin; normal shoes and foot washing are allowed daily, as the medicated film is waterproof and will not peel off; the antifungal medicine is used every 2-3 days, and the toe-separating socks can be used continuously for 3-5 days, simultaneously treating onychomycosis and foot fungus.

[0115] Comparative Example 1

[0116] The rest is the same as in Example 1, except that the Wacker silicone resin SILRES® MSE 100 in the antifungal agent raw materials is replaced with an equal amount of acrylic resin. After this change, the antifungal agent forms a film by solvent evaporation. The fungal clearance rate drops to 65.0% after 12 weeks, and the recurrence rate rises to 28.3% after 3 months. The efficacy decreases because the film layer is easy to detach and the drug is lost quickly. See Comparative Application Example 1.

[0117] Comparative Example 2

[0118] The rest is the same as in Example 1, except that the preparation method of the fingerless socks is modified to include the following steps:

[0119] (1) Preparation of antifungal microcapsules:

[0120] (1-1) Capsule core dispersion: The raw materials of the capsule core are uniformly dispersed in deionized water to prepare a 10% mass concentration capsule core suspension; the raw materials of the capsule core are composed of the following raw materials by weight percentage: terbinafine 0.8%, zinc oxide 10%, corn starch 88.2%;

[0121] (1-2) Preparation of wall material solution: Prepare 10% mass concentration gelatin solution and 10% mass concentration gum arabic solution separately. Mix the two in a volume ratio of 1:1, adjust the pH to 4.0 with 10% mass concentration acetic acid, and keep warm at 50℃.

[0122] (1-3) Re-coagulation into capsules: The capsule core suspension is slowly added to the wall material solution, with a volume ratio of 1:5 between the capsule core suspension and the wall material solution. Stir at 50°C and 1000 rpm for 30 min.

[0123] (1-4) Curing treatment: Cool down to below 10℃, add 25% glutaraldehyde solution to make the final mass concentration 0.5%~1.0%, stir for 2h to cure, adjust pH to 7.0~7.5, continue stirring for 1h to complete curing;

[0124] (1-5) Separation and drying: Centrifuge at 3000 rpm for 10 min, collect microcapsules, wash 3 times with purified water, freeze dry to obtain dried microcapsule powder with a particle size of 100~300 μm.

[0125] (2) Preparation of finger socks impregnated with antifungal microcapsules: Disperse the microcapsule powder evenly in deionized water to a mass concentration of 2.5%, and immerse the toe tips of the finger socks in it for at least 30 minutes, and then dry them.

[0126] In the comparative case, the microcapsules were replaced with direct immersion of the drug into the toes of the toe-mounted socks. The fungal clearance rate decreased to 58.3% after 12 weeks, and the recurrence rate increased to 35.0% after 3 months. The efficacy was reduced due to drug burst release and short antibacterial window. See Comparative Application Example 2.

[0127] Comparative Example 3

[0128] The rest is the same as in Example 1, except that the hydroxyl-terminated polydimethylsiloxane in the antifungal agent raw material is omitted.

[0129] This comparative example removed the toughening components from the antifungal agent raw material. The fungal clearance rate decreased to 78.3% after 12 weeks, and the recurrence rate increased to 16.7% after 3 months due to easy cracking and detachment of the membrane, leading to drug loss. See Comparative Application Example 3.

[0130] Application Example 1

[0131] Application of the treatment kit described in Example 1 in the treatment of mild onychomycosis complicated with tinea pedis

[0132] Patient basic information: Female, 37 years old, name: Lin, mild discoloration of the distal end of the right big toenail to grayish-white, rough nail surface, slight desquamation of the skin between the toes accompanied by itching, fungal microscopy (+), culture of Trichophyton mentagrophytes (+), course of disease 8 months, previously treated with mupirocin ointment for 1 week, symptoms did not improve significantly, no further treatment.

[0133] Disease severity grading: Severity Index of Onychomycosis (SCI) = 2 points, Severity Score of Tinea Pedis (TSS) = 2 points.

[0134] Treatment plan:

[0135] Treatment was performed using the treatment kit described in Example 1: antifungal agents were applied to the nails twice a week and to the feet once a day; finger stockings were worn for 6 hours daily, combined with oral administration of 0.6g of Baixian Xiatare capsules three times a day for 10 consecutive weeks; follow-up was conducted for 2 months.

[0136] Treatment results:

[0137] 4 weeks: Interdigital itching disappeared, desquamation stopped, skin returned to normal, nail discoloration area decreased, and fungal microscopy was negative.

[0138] 8 weeks: The roughness of the nails disappears, the transparency increases, and the new nail completely covers the affected area;

[0139] 12 weeks: Fungal culture (-), Severity Index of Onychomycosis (SCI) = 0 points, Severity Score of Tinea Pedis (TSS) = 0 points, clinically cured;

[0140] Two-month follow-up: no recurrence, fungal microscopy remained negative, and nails returned to normal luster.

[0141] Statistical analysis of similar cases and those treated with the same methods revealed a 100% fungal clearance rate at 12 weeks and a 0% recurrence rate at 2 months.

[0142] Application Example 2

[0143] Application of the treatment kit described in Example 1 in the treatment of moderate onychomycosis complicated with tinea pedis

[0144] Patient basic information: Male, 43 years old, name: Hu, with thickened and yellowed toenails on both sides, debris accumulation under the nail plate, mild erosion of the skin between the toes with itching, symptoms worsened after activity, fungal microscopy (+), Trichophyton rubrum culture (+), disease course 1 year and 3 months, previously treated with topical amorolfine hydrochloride cream for 2 months, discontinued medication on his own after symptom relief, relapsed once.

[0145] Disease severity grading: Severity Index of Onychomycosis (SCI) = 5 points, Severity Score of Tinea Pedis (TSS) = 4 points.

[0146] Treatment plan:

[0147] Treatment was performed using the treatment kit described in Example 1: antifungal medication was applied to the nails once a week; fingernail splitting stockings were worn for 8 hours daily, combined with fluconazole capsules (4+7) 50mg orally once daily for 12 weeks; follow-up was conducted for 3 months.

[0148] Treatment results:

[0149] 4 weeks: Interdigital itching completely disappeared, erosion healed, fungal microscopy was negative, nail appearance was significantly improved, and thickening was reduced;

[0150] 8 weeks: The carapace thickens, debris is significantly reduced, carapace transparency increases, and new carapace edges begin to grow;

[0151] 12 weeks: Fungal culture (-), Severity Index of Onychomycosis (SCI) = 0 points, Severity Score of Tinea Pedis (TSS) = 0 points, clinically cured;

[0152] 3-month follow-up: no recurrence, fungal microscopy / culture remained negative, nail plate returned to normal shape and luster, and patient compliance was 100%.

[0153] Statistical analysis of similar cases and those treated with the same methods revealed a 100% fungal clearance rate at 12 weeks and a 0% recurrence rate at 3 months.

[0154] Application Example 3

[0155] Application of the treatment kit described in Example 1 in the treatment of severe tinea pedis complicated by bacterial infection

[0156] Patient basic information: Male, 54 years old, name: Li. He presented with erythema and desquamation on the entire sole of his right foot, severe erosion between the toes with purulent exudate, significant redness and swelling, and severe pain, affecting his daily walking. Fungal microscopy was positive, and cultures of Trichophyton rubrum and Staphylococcus aureus were positive. The course of the disease was 2 months (acute exacerbation). He had a 2-year history of tinea pedis and had previously used miconazole nitrate cream multiple times without proper treatment, resulting in repeated exacerbations of symptoms.

[0157] Disease severity grading: Tinea pedis Severity Score (TSS) = 6 points, Bacterial Infection Severity Score = 4 points

[0158] Treatment plan:

[0159] Treatment was performed using the treatment kit described in Example 1: antifungal agent was applied topically to the affected area once daily; finger stockings were worn for 10 hours daily, combined with 2g of fusidic acid cream applied topically twice daily, for 12 consecutive weeks; follow-up was conducted for 3 months.

[0160] Treatment results:

[0161] 4 weeks: Redness and swelling and pain completely disappeared, purulent exudation stopped, erosions healed, fungal microscopy was negative, and skin erythema subsided;

[0162] 8 weeks: The peeling on the soles of the feet has completely disappeared, the skin has returned to normal texture, there are no uncomfortable symptoms, and bacterial culture is negative.

[0163] 12 weeks: Fungal culture (-), Tinea pedis Severity Score (TSS) = 0, bacterial infection completely controlled, clinical cure;

[0164] 3-month follow-up: No recurrence, skin remained healthy, and the patient had mastered the correct foot care methods.

[0165] Statistical analysis of similar cases and those treated with the same methods revealed a 100% fungal clearance rate at 12 weeks and a 0% recurrence rate at 3 months.

[0166] Comparative Application Example 1

[0167] Application of the treatment kit described in Comparative Example 1 in the treatment of mild onychomycosis complicated with tinea pedis

[0168] Patient basic information: Female, 37 years old, name: Lin, mild discoloration of the distal end of the right big toenail to grayish-white, rough nail surface, slight desquamation of the skin between the toes accompanied by itching, fungal microscopy (+), culture of Trichophyton mentagrophytes (+), course of disease 8 months, previously treated with mupirocin ointment for 1 week, symptoms did not improve significantly, no further treatment.

[0169] Disease severity grading: Severity Index of Onychomycosis (SCI) = 2 points, Severity Score of Tinea Pedis (TSS) = 2 points.

[0170] Treatment plan:

[0171] Treatment was performed using the treatment kit described in Comparative Example 1: antifungal agents were applied to the nails twice a week and to the feet once a day. Toe stockings were worn for 6 hours daily. Simultaneously, patients were given oral Baixian Xiatare capsules, 0.6g each time, three times a day, for 12 consecutive weeks, followed by a 3-month follow-up.

[0172] Treatment results:

[0173] 4 weeks: Interdigital itching was relieved, scaling decreased, the area of ​​nail discoloration did not shrink significantly, and fungal microscopy was positive. Starting at 2 weeks, the drug film began to peel off slightly, and after 4 weeks, the drug film peeled off significantly.

[0174] Week 8: The roughness of the nails has improved slightly, but the transparency has not improved significantly. The new nail only partially covers the affected area. The medication film has almost completely fallen off, requiring frequent reapplication of the medication. The medication is lost relatively quickly.

[0175] 12 weeks: Fungal culture (+), Severity Index of Onychomycosis (SCI) = 1 point, Severity Score of Tinea Pedis (TSS) = 1 point, clinical cure not achieved;

[0176] Three-month follow-up: Recurrence occurred, fungal microscopy was positive, and the nail showed slight discoloration and roughness again. The core reason is that after Wacker silicone resin SILRES® MSE 100 was replaced with an equal amount of acrylic resin, the film-forming method changed to solvent evaporation film formation. This film layer has poor adhesion to the diseased nail and is easy to fall off during daily activities, resulting in rapid loss of antifungal drugs and failure to form a long-lasting drug-locking film on the surface of the diseased nail, ultimately leading to a decline in treatment effectiveness.

[0177] Statistical analysis of similar cases and those treated with the same methods revealed that the fungal clearance rate decreased to 65.0% after 12 weeks, while the recurrence rate increased to 28.3% after 3 months.

[0178] Comparative Application Example 2

[0179] Application of the treatment kit described in Comparative Example 2 in the treatment of mild onychomycosis complicated with tinea pedis

[0180] Patient basic information: Female, 38 years old, name: Zhang, right big toenail distal end is grayish-white discolored, the nail plate surface is rough with a small amount of scales, interdigital skin desquamation and mild itching, fungal microscopy (+), tinea barbae culture (+), course of disease 7 months, previously treated with miconazole nitrate cream for 1 week, symptoms did not improve significantly, did not continue to receive standard treatment.

[0181] Disease severity grading: Severity Index of Onychomycosis (SCI) = 2 points, Severity Score of Tinea Pedis (TSS) = 2 points.

[0182] Treatment plan:

[0183] Treatment was performed using the treatment kit described in Comparative Example 2: During treatment, antifungal agents were applied to the nails twice a week, and toes were applied topically once a day. Toe-separated socks were worn for 6 hours daily, combined with oral administration of 0.6g of Baixian Xiatare capsules three times a day for 12 consecutive weeks, followed by a 3-month follow-up.

[0184] Treatment results:

[0185] 4 weeks: Interdigital itching was relieved and scaling decreased, but transient skin irritation symptoms appeared. The area of ​​nail discoloration did not shrink significantly, and fungal microscopy was positive.

[0186] 8 weeks: No significant improvement in nail roughness, no increase in nail plate transparency, occasional recurrence of itching between the toes, and rapid release of the medication from the medicated socks, resulting in the loss of sustained antibacterial effect;

[0187] 12 weeks: Fungal culture (+), Severity Index of Onychomycosis (SCI) = 2 points, Severity Score of Tinea Pedis (TSS) = 2 points, clinical cure not achieved;

[0188] Three-month follow-up: Significant recurrence, positive fungal microscopy, worsening nail discoloration and thickening, and recurrence of interdigital scaling and itching. The key reason for the decreased efficacy was that the modified preparation method of the toe-separating socks involved directly immersing the microcapsules in the toe tips without the PVA water-soluble isolation membrane described in Example 1. This lack of protection led to the microcapsules being easily damaged, resulting in explosive drug release, a significantly shortened antibacterial window, and the inability to achieve long-lasting, sustained-release antibacterial action between the toes, ultimately leading to a significant decrease in treatment effectiveness.

[0189] Statistical analysis of similar cases and those treated with the same methods revealed that the fungal clearance rate decreased to 58.3% after 12 weeks, while the recurrence rate increased to 35.0% after 3 months.

[0190] Comparative Application Example 3

[0191] Application of the treatment kit described in Comparative Example 3 in the treatment of mild onychomycosis complicated with tinea pedis

[0192] Patient basic information: Female, 37 years old, name: Liu, right big toenail distal toe grayish-white discoloration, rough nail plate surface, slight desquamation of skin between toes accompanied by itching, fungal microscopy (+), tinea barbae culture (+), course of disease 8 months, previously treated with clotrimazole cream for 1 week, symptoms did not improve significantly, no further treatment.

[0193] Disease severity grading: Severity Index of Onychomycosis (SCI) = 2 points, Severity Score of Tinea Pedis (TSS) = 2 points.

[0194] Treatment plan:

[0195] Treatment was performed using the treatment kit described in Comparative Example 3: During treatment, antifungal agents were applied to the nails twice a week, and toes were applied topically once a day. Toe-separated socks were worn for 6 hours daily. 0.6g of Baixian Xiatare capsules were taken orally three times a day for 12 consecutive weeks, followed by a 3-month follow-up.

[0196] Treatment results:

[0197] 4 weeks: Interdigital itching disappeared, desquamation stopped, skin returned to normal, nail discoloration area slightly decreased, fungal microscopy was negative, but the film formed by the antifungal agent showed slight cracking;

[0198] Week 8: The roughness of the nails has improved, the transparency has increased slightly, the new nail has partially covered the diseased area, the cracking of the nail membrane has worsened and it is easy to fall off, requiring frequent reapplication of the medication, which leads to medication loss;

[0199] 12 weeks: Fungal culture (+), Severity Index of Onychomycosis (SCI) = 1 point, Severity Score of Tinea Pedis (TSS) = 0 points, clinical cure not achieved;

[0200] Three-month follow-up: Recurrence occurred, fungal microscopy was positive, and slight discoloration appeared at the nail edge. This comparative study removed the toughening component (hydroxyl-terminated polydimethylsiloxane) from the antifungal agent raw material. The core reason for the decreased efficacy was that the lack of toughening component resulted in insufficient toughness of the film formed by moisture curing, making it prone to cracking and peeling. The antifungal drug was subsequently lost, failing to form a stable and long-lasting locking film on the affected nail surface, thus leading to a decline in treatment effectiveness.

[0201] Statistical analysis of similar cases and those treated with the same methods revealed that the fungal clearance rate decreased to 78.3% after 12 weeks, while the recurrence rate increased to 16.7% after 3 months.

[0202] As can be seen from the above, the treatment kit for treating onychomycosis provided by the present invention can achieve simultaneous treatment of nails and skin, significantly reduce the recurrence rate of onychomycosis, and significantly shorten the treatment cycle of onychomycosis.

[0203] The above detailed description of a treatment kit for treating onychomycosis, its method of use, and its application, with reference to the embodiments, is illustrative rather than limiting. Several embodiments may be listed within the defined scope. Therefore, variations and modifications without departing from the overall concept of the present invention should be within the protection scope of the present invention.

Claims

1. A therapeutic kit for the treatment of onychomycosis, characterized in that, The treatment kit includes: an antifungal agent and toe-separating socks; the antifungal agent is formed by moisture-curing silicone film formation; and the toe-separating socks have a water-soluble isolation membrane embedded with antifungal microcapsules between the toes.

2. The treatment kit for the treatment of onychomycosis according to claim 1, characterized in that, The antifungal agent comprises the following raw materials by weight percentage: 10%–15% silicone resin; Antifungal active ingredient: 1.0%~5.0%; 3%–5% of the penetration enhancer and softener; Toughening agent 1%–2%; The remainder is a volatile solvent.

3. The treatment kit for treating onychomycosis according to claim 2, characterized in that, The silicone resin is selected from any one or more of Wacker SILRES® MSE100, Evonik Silikophen® AC1000, and Wacker ELASTOSIL® N2076.

4. The treatment kit for treating onychomycosis according to claim 2, characterized in that, The antifungal active ingredient is any one or more of the following: azole antifungal drugs, morpholine antifungal drugs, allylamine antifungal drugs, thiocarbamate antifungal drugs, and polyene antifungal drugs.

5. The treatment kit for treating onychomycosis according to claim 2, characterized in that, The penetration-enhancing softening agent is any one or more of salicylic acid, urea, and succinic acid; the toughening agent is any one or more of hydroxyl-terminated polydimethylsiloxane and carbon hydroxyl-terminated polydimethylsiloxane; and the volatile solvent is any one or more of ethanol and isopropanol.

6. The treatment kit for treating onychomycosis according to claim 1, characterized in that, The antifungal agent is packaged in a disposable medicine bottle with an integrated brush.

7. The treatment kit for treating onychomycosis according to claim 1, characterized in that, The membrane material of the water-soluble isolation membrane is either polyvinyl alcohol water-soluble film or hydroxypropyl methylcellulose film.

8. The treatment kit for treating onychomycosis according to claim 1, characterized in that, The antifungal microcapsule has a capsule wall made of a composite material of gelatin and gum arabic, and the capsule core contains the following raw materials by weight percentage: 0.3% to 1.5% antifungal active ingredient, 5% to 20% auxiliary antibacterial ingredient, and the remainder is filler.

9. The method of using the treatment kit for treating onychomycosis as described in claim 1, characterized in that, The method of use includes: applying the antifungal agent evenly to the surface of the affected nail, letting it stand for 5 to 10 minutes, and then wearing the finger-separating socks.

10. The use of the treatment kit as described in claim 1 in the treatment of onychomycosis.