Uses of hypochlorous acid in the preparation of compositions for the treatment or prevention of onychomycosis

Abstract

This invention relates to the use of hypochlorous acid in the preparation of a composition for treating or preventing onychomycosis, comprising: about 1 to 50,000 ppm of hypochlorous acid; a pH adjuster to adjust the pH of the composition to 2 to 9; and water. Preferably, the composition comprises 100 to 200 ppm of hypochlorous acid. Preferably, the composition comprises a pH adjuster of less than 240 ppm. Preferably, the pH adjuster adjusts the pH of the composition to 5 to 6.5. Preferably, the pH adjuster comprises one of sodium carbonate, sodium bicarbonate, and calcium hydroxide. This hypochlorous acid can inhibit or kill Trichophyton rubrum, Candida albicans, Fusarium, Aspergillus, Cladosporium, Columnar Aureobasidium, and Cladosporium brevestigma, as well as other fungal strains and spores that have the potential to cause onychomycosis, thus effectively treating the fungi and spores within the nail and other pathogens causing onychomycosis, preventing recurrence of onychomycosis, and providing patients with a complete solution.

Description

Technical Field

[0001] This invention relates to a synthetic compound for treating onychomycosis, and more particularly to a synthetic compound containing hypochlorous acid for treating onychomycosis. Prior Technology

[0002] Onychomycosis (also known as nail fungus) is caused by fungal infection (such as yeast, mold, and dermatophytes). It commonly occurs on the nails, such as fingernails or toenails. When the fungus enters the nail bed, it feeds on keratin. If not treated in time, the nail will first show white patches, then gradually turn yellow and thicken, eventually leading to breakage and nail loss. For patients, in addition to being unsightly and affecting their personal image, it can also be contagious to others. In severe cases, it can cause complications such as inflammation, pain, and bacterial infection, and even cellulitis, making treatment more difficult.

[0003] However, current treatments for onychomycosis mainly include topical antifungal medications (such as ointments, solutions, and oils), oral antifungal medications (such as terbinafine and itraconazole), and laser therapy. However, because the nail structure is quite strong, patients must file their nails before using topical antifungal medications; otherwise, the medication cannot penetrate the affected area to improve the infection. While oral antifungal medications can effectively inhibit fungi, they also produce many side effects (such as nausea, diarrhea, headaches, etc.) and can affect liver and kidney function. Laser surgery uses photothermal principles to kill fungi within the nail. Although it does not damage the nail bed, nail groove, or the nail itself, compared to the other two methods, laser treatment is not only expensive but also cannot completely cure onychomycosis, only temporarily improving its appearance, and it tends to recur after a period of time.

[0004] However, the recurrence and reinfection rate of onychomycosis is high, mainly because the fungus can divide into arthroconidia, which remain in the keratin layer and nail. Arthroconidia are resistant to adverse environments and can survive for a long time in the nail, evading the host's immune surveillance. When the environment becomes favorable for growth, the arthroconidia transform back into active, reproductive hyphae and invade the host epidermis. Arthroconidia formation is known to be induced by various factors, such as changes in the host tissue environment (e.g., subungual hyperkeratosis due to hyphal growth), or the use of antifungal drugs, which can also stimulate arthroconidia formation. Therefore, when using antifungal drugs, the dosage needs to be increased to a sufficient concentration to eliminate fungal spores and prevent recurrence. However, high doses of drugs can harm the host and may also lead to drug resistance in the fungal strain.

[0005] Therefore, in summary, this invention designs a synthetic compound containing hypochlorous acid for treating onychomycosis, which can effectively kill the fungi and spores that cause onychomycosis, thereby improving the symptoms of onychomycosis and preventing recurrence. It aims to improve upon the shortcomings of conventional technology and enhance its industrial implementation and utilization, bringing a complete solution to patients. Summary of the Invention

[0006] The main objective of this invention is to provide a synthetic compound containing hypochlorous acid for treating onychomycosis, which avoids patients from taking large amounts of oral medication and is safe for human contact. Through its hypochlorous acid component, it kills the fungi and spores that cause onychomycosis, allowing the patient's nails to gradually return to normal growth. The nails not only become stronger and the newly grown parts become light-colored and shiny, but also reduce pain and odor, and improve problems such as itching, cracking and redness of the skin around the nails.

[0007] Therefore, in order to achieve the above objectives, the present invention provides a synthetic compound containing hypochlorous acid for treating onychomycosis, comprising: 1 to 50,000 ppm of hypochlorous acid; a pH adjuster to adjust the pH value of the compound to between 2 and 9; and water.

[0008] Preferably, the compound comprises 100 to 200 ppm of hypochlorous acid.

[0009] Preferably, the pH adjuster adjusts the pH of the synthesized compound to between 5 and 6.5.

[0010] Preferably, the hypochlorous acid is produced by methods including electrolysis, synthesis, or ion exchange.

[0011] Preferably, the pH adjuster includes one of sodium carbonate, sodium bicarbonate, calcium hydroxide, and other food-grade weakly alkaline additives with pH-adjusting capabilities.

[0012] Preferably, the compound includes a pH adjuster at a concentration below 240 ppm.

[0013] Preferably, the hypochlorous acid can inhibit or kill Trichophyton rubrum, Candida albicans, Fusarium, Aspergillus, Cladosporium, Columnar Aureomyces, and Cladosporium brevesii, as well as other fungal strains and spores that cause onychomycosis. Therefore, it effectively treats the fungi and spores within the nail and other pathogens causing onychomycosis, preventing recurrence and providing patients with a complete solution.

[0014] In summary, the present invention will be described in detail below with reference to specific embodiments. The following embodiments are merely illustrative and are not intended to limit the scope of protection of the present invention. Those skilled in the art will readily understand that various non-critical parameters can be changed or adjusted to produce substantially the same results. Simple Explanation of the Diagram

[0015] Figure 1 is an apparatus diagram and flowchart for preparing the hypochlorous acid-containing synthetic compound of the present invention for treating onychomycosis by electrolysis. Figure 2 shows the apparatus and flowchart for synthesizing the hypochlorous acid-containing synthetic compound of the present invention for treating onychomycosis by a synthetic method. Figures 3A and 3B show photographs of the affected area of ​​patient A before and after using the hypochlorous acid-containing synthetic compound of the present invention for treating onychomycosis. Figures 4A and 4B show photographs of the affected area of ​​patient B before and after using the hypochlorous acid-containing synthetic compound of the present invention for treating onychomycosis. Implementation

[0016] The embodiments of the present invention will now be described with reference to Figures 1 to 4B. This description is not intended to limit the embodiments of the present invention, but rather to illustrate one example of the invention.

[0017] First, the present invention provides a synthetic compound containing hypochlorous acid for treating onychomycosis, comprising: 1 to 50,000 ppm of hypochlorous acid; a pH adjuster to adjust the pH of the compound to between 2 and 9; and water.

[0018] In a preferred embodiment, the concentration of hypochlorous acid is between 100 and 200 ppm. The pH adjuster may be sodium carbonate (Na₂CO₃), sodium bicarbonate (NaHCO₃), or calcium hydroxide (Ca(OH)₂) at a concentration below 240 ppm. Other pharmaceutical-grade or food-grade weakly alkaline additives may also be used. Those skilled in the art will understand that the concentration of the pH adjuster can be adjusted according to the concentration of hypochlorous acid to achieve the desired hypochlorous acid concentration and pH value.

[0019] The hypochlorous acid-containing compound used to treat onychomycosis can be prepared by various methods, including electrolysis, synthesis, ion exchange, or other feasible methods. The following are examples illustrating the preparation methods using electrolysis or synthesis. Different concentrations and pH values ​​can be adjusted accordingly. The preparation method using electrolysis is as follows:

[0020] Electrolysis

[0021] Electrolysis of dilute hydrochloric acid produces hydrogen and chlorine gas. When chlorine gas is passed into water, it forms hydrochloric acid and hypochlorous acid, as shown in the following reaction equation: 2HCl → H2 + Cl2 Cl₂ + H₂O → HCl + HClO

[0022] Therefore, referring to Figure 1, in the preparation of hypochlorous acid, one side of the electrolytic cell is connected to a dilute hydrochloric acid feed cylinder via a dilute hydrochloric acid pump, and the other side is connected to a filtered water tank via a water pump. The controller controls the dilute hydrochloric acid pump and the water pump to ensure that the dilute hydrochloric acid and water flow into the electrolytic cell at a predetermined rate. Simultaneously, the controller controls the voltage of the electrolytic cell to obtain hypochlorous acid with a specific pH value and effective chlorine concentration. At this point, the pH value of the hypochlorous acid is approximately below 3. Afterward, the hypochlorous acid is drained into a storage tank through a drain valve, and a pH adjuster is added, stirring until the ideal pH range of 5.0-6.5 is reached. Preferably, the effective chlorine concentration is 120-140 ppm.

[0023] Synthesis

[0024] Sodium hypochlorite reacts with dilute hydrochloric acid to release chlorine gas. When the chlorine gas is passed into water, it forms a salt and hypochlorous acid, as shown in the following reaction equation: NaClO + HCl → HClO + NaCl

[0025] Referring to Figure 2, in the preparation of hypochlorous acid, the mixer is connected to the hypochlorous acid cylinder, the hydrochloric acid cylinder, and the filtered water tank via a sodium hypochlorite pump, a hydrochloric acid pump, and a water pump, respectively. A controller directs the sodium hypochlorite pump, hydrochloric acid pump, and water pump to ensure that sodium hypochlorite, hydrochloric acid, and water flow into the mixer at predetermined rates, thus producing hypochlorous acid. The flow rates of each material can be determined based on the desired pH value and ppm. The resulting hypochlorous acid flows into a storage tank through a drain valve, without the need for additional pH adjuster. Preferably, the pH value is between 5.0 and 6.5, and the available chlorine concentration is 135-145 ppm. This method may produce sodium chloride as a byproduct; sodium chloride is neutral and does not affect the pH value.

[0026] Therefore, the hypochlorous acid in the synthetic compound containing hypochlorous acid used to treat onychomycosis can be produced through electrolysis and synthesis, and each method has its advantages, as shown below:

[0027] Electrolysis

[0028] 1. The hypochlorous acid water produced after electrolysis has a high ability to eliminate microorganisms.

[0029] 2. Only dilute hydrochloric acid is required as raw material, resulting in low operating costs.

[0030] 3. The machine is less affected by other parameters (such as changes in water quality and raw materials).

[0031] 4. The machine can be quickly adjusted to achieve the preset pH value and concentration.

[0032] 5. Low power consumption, energy-saving and environmentally friendly.

[0033] Synthesis

[0034] 1. High available chlorine concentration: When the pH value is maintained between 5 and 6.5, it is prepared using dilute hydrochloric acid and sodium hypochlorite, and the available chlorine concentration is 30-500 ppm.

[0035] 2. The hypochlorous acid water produced after synthesis has high pH stability.

[0036] 3. No additives are needed to adjust the pH value.

[0037] 4. Low operating costs and few consumables.

[0038] 5. The machine is highly automated and easy to adjust.

[0039] Under normal circumstances, the synthetic compound containing hypochlorous acid used in the treatment of onychomycosis of the present invention will kill bacteria, viruses and fungi (containing spores) by inhibiting protein action or destroying protein structure through its strong oxidizing properties.

[0040] Furthermore, hypochlorous acid rapidly transforms into other compounds upon exposure to air or ultraviolet light. Therefore, it is necessary to block ultraviolet light, including UV light, when storing hypochlorous acid to extend its shelf life. In one embodiment, the invention further includes a storage bottle made of plastic for storing the hypochlorous acid-containing compound used to treat onychomycosis. In one embodiment, the plastic contains titanium dioxide, making the storage bottle opaque and blocking the effects of ultraviolet light on the stability of the hypochlorous acid concentration. This eliminates the need for additional stabilizers, preventing harm to animals, plants, and the environment. Furthermore, storage in a cool, dark environment at room temperature prevents a decrease in the effective chlorine concentration in the hypochlorous acid, allowing the compound to maintain at least 85% of its original concentration for at least one year.

[0041] In addition, to test the effectiveness of the hypochlorous acid-containing synthetic compound used to treat onychomycosis in killing bacteria and fungi, the applicant conducted tests on various bacterial species according to testing standards such as EN1040, EN1650, and EN13704:2002. The test results are shown in Table 1 below: Table 1: Bactericidal effects of the synthetic compounds of this invention against different bacterial species Test bacteria Original inoculum quantity (CFU / mL) Final count (CFU / mL) effect time Sterilization rate test in accordance with E. coli (Escherichia coli) ATCC 10536 1.8x108 <140 30 seconds >99.999% EN 1040 Staphylococcus aureus (Staphylococcus aureus) ATCC 6538 2.4x108 <140 30 seconds >99.999% EN 1040 salmonella (Salmonellaspp.) ATCC 14028 2.6x108 <140 30 seconds >99.999% EN 1040 Listeria monocytogenes (Listeria monocytogenes) ATCC 14028 4.2x108 <140 30 seconds >99.999% EN 1040 Candida albicans (Candida albicans) ATCC 10231 1.6x107 <140 1 minute >99.99% EN 1650 Candida albicans (Candida albicans) ATCC 10231 1.6x107 <140 5 minutes >99.99% EN 1650 Bacillus cereus (Bacillus cereus) DSM 12001 2.45x106 <140 60 minutes ± 10 seconds >99.9% EN 13704:2002 Trichophyton mentagrophytes (Trichophyton mentagrophytes) CBS 570.80 3.05x107 <140 2 minutes ± 10 seconds >99.99% EN 1650

[0042] The following explains each of the above testing standards:

[0043] Test standard EN1040: Add 8 parts of the test product to 1 part of the test microorganism and 1 part of water. Allow the mixture to interact within the contact time. Add 1 part of the mixture to 8 parts of neutralizer and 1 part of water for 5 minutes to stop the bactericidal activity. Obtain the final mixture and incubate for 2 days to allow surviving bacteria (if any) to multiply. Count the bacterial colonies and compare them with the original culture. The test conditions include: test temperature 20℃±1℃; maximum contact time: 5min±10sec; bactericidal effect requirement (log): ≥5.

[0044] Test standard EN1650: Add 8 parts of the test product to 1 part of the test microorganism and 1 part of the interfering substance. Allow the mixture to interact within the contact time. Add 1 part of the mixture to 8 parts of neutralizer and 1 part of water for 5 minutes to terminate the fungicidal or yeasticidal activity. Then obtain the final mixture and incubate for 3 days to allow surviving microorganisms (if any) to multiply. Count the colonies and compare them with the original culture. The test conditions include: test temperature 20℃±1℃; maximum contact time: 15 min; interfering substance (clean conditions): 0.3 g / L bovine serum albumin solution; interfering substance (non-clean conditions): 3 g / L bovine serum albumin solution; bactericidal effect requirement (log): ≥4.

[0045] Test standard EN13704:2002: Add 8 parts of the test product to 1 part of the test microorganism and 1 part of the interfering substance. Allow the mixture to interact within the contact time. Add 1 part of the mixture to 8 parts of neutralizer and 1 part of water for 5 minutes to terminate antimicrobial activity. Then obtain the final mixture and incubate for 3 days to allow surviving spores (if any) to multiply. Count the colonies and compare the size with the original culture. The test conditions include: test temperature 4℃-75℃; contact time: 1min-60min; interfering substance (clean conditions): 0.3g / L bovine serum albumin solution; interfering substance (non-clean conditions): 3g / L bovine serum albumin solution; additional interfering substance for dairy products: 10g / L reconstituted milk; sterilization effect requirement (log): ≥3.

[0046] The experimental results show that the hypochlorous acid-containing synthetic compound used to treat onychomycosis can achieve a bactericidal rate of at least 99.9% against Escherichia coli, Staphylococcus aureus, Salmonella, Listeria, Candida albicans, Bacillus cereus, and Trichophyton mentagrophytes. The bacterial species listed in the table can represent different genera; Staphylococcus aureus can represent pyogenic cocci in vegetative bacteria; Escherichia coli can represent intestinal bacteria in vegetative bacteria; Candida albicans can represent pathogenic fungi; Bacillus cereus can represent bacterial spores; Trichophyton mentagrophytes can represent Trichophyton mentagrophytes, etc., and are not all listed here.

[0047] Tinea unguium includes Candida albicans, Fusarium, Aspergillus, Acremonium, Scytalidium, Scopuliopsis brevicaulis, etc., all of which are fungi in both their strains and spores. Therefore, according to the sensitivity ranking of microorganisms to disinfectants in the "Disinfection Technical Specifications" (2022, 1.4.4.3), when the synthetic compound of this invention can eliminate bacterial spores (Bacillus cereus), Candida albicans, and Trichophyton mentagrophytes, it sufficiently demonstrates that this synthetic compound has a certain degree of killing ability against fungal strains and is effective in inhibiting or killing all the aforementioned tinea unguium fungi and their spores, thus effectively reducing the chance of onychomycosis recurrence.

[0048] In particular, among the pathogens causing onychomycosis, *Trichophyton rubrum* accounts for 91.0% and *Trichophyton mentagrophytes* accounts for 7.7% (Uwe Wollina, Holger Haenssle, Dtsch Arztebl Int 2016;113(29-30):509-518), making them the two major pathogens. The hypochlorous acid-containing synthetic compound of this invention for treating onychomycosis is suitable for inhibiting or killing major pathogens, including *Trichophyton rubrum* and *Trichophyton mentagrophytes*.

[0049] Therefore, this invention targets the main pathogen *Trichophyton rubrum* and its spores, and conducts separate experiments to analyze the bactericidal effect of the synthesized product of this invention on the pathogen and spores. The experimental procedure is as follows: (1) 0.1 mL of bacterial suspension is spread on a 90 mm PDA (Potato Dextrose Agar) medium (bacterial count approximately 1 x 10⁶ CFU / mL), and left for 5-15 minutes; (2) The synthesized product of this invention is sprayed onto the medium, with a spraying distance of 15 cm from the medium and a spraying time of 2 seconds. After spraying, the contact time is maintained for 10, 15, 20, 30, and 60 seconds, respectively; (3) At each of the aforementioned time points, the medium is rinsed with 5 mL of neutralizing solution to stop the contact time, and serial dilution is performed. The medium is then incubated at 25°C for 5 days, and the bacterial count is counted. Each experiment is repeated 3 times. The percentage of bactericidal effect is calculated based on the bacterial count of the control group. The results are shown in Tables 2 and 3 below: Table 2: The bactericidal effect of the synthetic compound of the present invention on Trichophyton rubrum fungi. Experimental strains vaccination method Contact time Sterilization rate Trichophyton rubrum ATCC strain no. MYA-4438 strain suspension 10 seconds 99.8% 15 seconds 99.8% 20 seconds ≥99.9% 30 seconds ≥99.9% 60 seconds ≥99.9% Table 3: Antibacterial effect of the synthetic compound of the present invention against Trichophyton rubrum spores Experimental strains vaccination method Contact time Sterilization rate Trichophyton rubrum ATCC strain no. MYA-4438 spore suspension 10 seconds 99.7% 15 seconds ≥99.9% 20 seconds ≥99.9% 30 seconds ≥99.9% 60 seconds ≥99.9%

[0050] The experimental results show that the hypochlorous acid-containing synthetic compound of the present invention for treating onychomycosis can achieve a bactericidal effect of at least 99.9% on both the cell and spore forms of Trichophyton rubrum when the contact time is maintained for more than 20 seconds.

[0051] Furthermore, the present invention has also been tested on actual patients, as described below:

[0052] Patient A: A woman aged 46 to 55 years old, who had onychomycosis for more than 5 years, as shown in Figure 3A (2023 / 12 / 11). The symptoms of onychomycosis were obvious. After using the synthetic compound of this invention as a wet compress 1-3 times a day for five consecutive months (2024 / 05 / 06), the affected area was significantly improved and new healthy nails began to grow, as shown in Figure 3B.

[0053] Patient B: A 23-year-old female who had been suffering from onychomycosis for more than 3 years, as shown in Figure 4A (2024 / 04 / 14). The onychomycosis symptoms were obvious and severe. After using the synthetic compound of this invention as a wet compress 2-3 times a day for six consecutive months (2024 / 10 / 12), the affected nails recovered and healthy nails grew back, as shown in Figure 4B.

[0054] Furthermore, on June 18, 2024, six months after Patient A used the synthetic compound containing hypochlorous acid for treating onychomycosis according to this invention, the toenail from the original affected area was cut off. A portion of the toenail was mixed with 2 mL of sterilized water, and the resulting solution was then dropped into a culture dish for fungal culture. Another portion of the toenail was directly examined under a microscope for the presence of spores. The experiment confirmed that no fungal spores or hyphae remained on either the culture dish or under the microscope, proving that the solution mixed with the hypochlorous acid compound can eliminate fungi and spores in the affected nail, preventing recurrence of onychomycosis and providing a complete solution for the patient.

[0055] Typical symptoms of onychomycosis include thickening, whitening, and brittleness of the nails or toenails. In particular, when onychomycosis develops over a long period, it can lead to onycholysis, a gradual separation of the nail from the skin. When symptoms become severe, permanent damage and deformation of the nail can impair appearance and function, thus affecting quality of life. This invention provides a synthetic compound containing hypochlorous acid for treating onychomycosis. It avoids the need for patients to take large amounts of oral medication and, while being safe for human contact, kills the fungi and spores that cause onychomycosis through its hypochlorous acid component, allowing the patient's nails to grow normally. The nails become strong, regain their light color and shine, and pain and odor are reduced. It also improves problems such as itching, cracking, and redness of the skin around the nail. This demonstrates that the solution mixed with this hypochlorous acid compound can eliminate fungi and spores in the affected nail, preventing recurrence of onychomycosis and providing a complete solution for patients.

[0056] However, the above description is only a preferred embodiment of the present invention and should not be construed as limiting the scope of the present invention. Any simple equivalent changes and modifications made in accordance with the scope of the patent application and the description of the invention shall still fall within the scope of the patent of the present invention.

[0057] none

Claims

1. Use of hypochlorous acid in the preparation of a composition for the treatment or prevention of onychomycosis, wherein the composition comprises: Hypochlorous acid at concentrations of 1 to 50,000 ppm; pH adjuster to adjust the pH of the composition to between 2 and 9; And water; the components have a killing effect on the strains and spores of the pathogens causing onychomycosis, so as to avoid the recurrence of onychomycosis and bring about a complete solution.

2. The use as described in claim 1, wherein the composition comprises 100 to 200 ppm of hypochlorous acid.

3. The use as described in claim 2, wherein the composition includes a pH adjuster at a concentration below 240 ppm.

4. The use as described in claim 1, wherein the pH adjuster adjusts the pH of the composition to between 5 and 6.

5.

5. The use as described in claim 1, wherein the pH adjuster comprises one of sodium carbonate, sodium bicarbonate, and calcium hydroxide.

6. The use as described in claim 1, wherein the hypochlorous acid is produced by means including electrolysis, synthesis or ion exchange.

7. The use as described in claim 1, wherein the pathogen causing the onychomycosis includes Trichophyton rubrum.

8. The use as described in claim 7, wherein the pathogens causing onychomycosis further include Candida albicans, Fusarium, Aspergillus, Cladosporium, Columnar Aureomyces, or Broomia breviculata.

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