Skin disease treatment agent

Abstract

To provide a skin disease treatment agent that has no side effects and is sufficiently effective in treating acne. [Solution] A skin disease treatment agent containing micro- and nanobubbles.

Description

[Technical Field]

[0001] The present invention relates to a skin disease treatment agent, and more particularly to a skin disease treatment agent that is effective in treating acne.

[0002] What is commonly known as "acne" is a type of skin disease called acne vulgaris, and clinically, it is defined as chronic inflammatory changes occurring in the hair follicles, primarily in the pilosebaceous gland system. Acne is characterized by seborrhea (redness of the skin with scaling), comedones (black and white comedones), papules (pinhead-sized bumps), pustules (pimples), nodules (larger papules), and, in some cases, areas of scarred skin. These areas include the face, upper chest, and back. Severe acne is inflammatory, but acne can also present in non-inflammatory forms.

[0003] Acne most commonly occurs during adolescence, affecting over 90% of middle and high school students, and often persisting into adulthood. In adolescence, acne is usually caused by an increase in male hormones, and both boys and girls are affected during puberty.

[0004] Acne scars are caused by inflammation in the dermis resulting from acne. Acne scars are formed when collagen is excessively produced in one area as the wound attempts to heal naturally. Physical acne scars are often referred to as "icepick scars" because they tend to cause depressions in the skin's surface.

[0005] Acne scars caused by hyperpigmentation are usually due to nodular or cystic acne (painful bumps under the skin). These types of acne scars often leave inflamed, red marks. In most cases, hyperpigmentation can be prevented simply by avoiding the worsening of nodules or cysts. If a patient tries to "pop" the nodules or cysts, the hyperpigmentation can worsen significantly and even cause bruising of the affected area. Hyperpigmentation almost always fades over time, but it can take anywhere from 3 months to 2 years to disappear.

[0006] Although the pathogenesis of acne is still largely unknown, it is generally a skin disease in which various factors are intricately intertwined, with excessive sebum secretion, keratinization of hair follicles, and bacteria within hair follicles playing important roles. Acne generally develops through the following process.

[0007] Hyperkeratinization and the formation of keratin plugs and sebum plugs (microcomedones) are the earliest changes. With increased androgen (DHEA-S) production during the manifestation of adrenal cortical signs, sebaceous gland enlargement and increased sebum production occur. Microcomedones may enlarge and form open comedones (blackheads) or closed comedones (milia). Comedones are a direct result of sebaceous gland blockage with sebum, naturally occurring oil, and dead skin cells. In these conditions, naturally occurring and commensal Propionibacterium acnes causes inflammation, leading to inflammatory lesions (papules, infectious pustules, or nodules) in the dermis surrounding the microcomedones or comedones, which may result in redness, scarring, or hyperpigmentation.

[0008] -Hormone- Hormonal activity, such as that associated with the menstrual cycle and puberty, can contribute to acne formation. During puberty, increased levels of androgens (male hormones) cause pitted glands to grow larger and sebum production to increase. The use of anabolic steroids can have a similar effect. Several hormones, including the androgens testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEAS), as well as insulin-like growth factor 1 (IGF-1), are associated with acne.

[0009] While the development of acne vulgaris after puberty is uncommon, this is the age range in which rosacea, which can have a similar appearance, is prevalent. True acne vulgaris in adult women can be a clinical feature of underlying conditions such as pregnancy and disorders (polyovarian syndrome or, rarely, Cushing's syndrome). Acne associated with menopause occurs because the production of estradiol, a natural anti-acne ovarian hormone, ceases after menopause. Estradiol deficiency can lead to hair loss, flushing, thinning skin, wrinkles, vaginal dryness, increased susceptibility to osteopenia and osteoporosis, and can also trigger acne.

[0010] -Genetic Causes- Acne is hereditary within families. For example, school-aged boys with acne often have other members of their family with acne. A family history of acne is associated with early onset of acne and an increased number of persistent acne lesions.

[0011] -Psychological causes- The relationship between acne and stress has been debated, but scientific studies have shown that "increased acne severity" is "significantly associated with increased stress levels." The National Institutes of Health (NIH) in the United States lists stress as a factor that can cause the redness of acne to worsen.

[0012] -Infectious causes- Propionibacterium acnes (Propionibacterium acnes) is an anaerobic bacterium that may be involved in the formation of acne.

[0013] -Dietary causes- High blood sugar loads from diets and milk consumption have been linked to worsening acne.

[0014] -Previous knowledge- For acne, various treatments exist, including benzoyl peroxide, antibiotics, retinoids, anti-seborrheic drugs, and nicotinamide. Apart from these treatments, keratolytic soaps containing salicylic acid and sulfur are used as adjuvants in acne treatment, helping to reduce skin oiliness. These treatments are thought to work in at least four ways: normalizing skin exfoliation into pores to prevent clogged pores, killing Propionibacterium acnes, anti-inflammatory effects, and hormonal treatment. However, these treatments often take a long time to treat acne.

[0015] For example, Patent Document 1 discloses a disinfectant containing gold ions as an active ingredient, which is used to kill acne bacteria. However, even if the disinfectant disclosed in Patent Document 1 can kill acne bacteria, it cannot effectively treat acne.

[0016] Furthermore, Patent Document 2 discloses "a composition comprising one or more probiotic bacterial strains and optionally a thickening topical formulation of a probiotic compound, a protective agent, a moisturizer, a emollient, an abrasive, a salt, and / or a surfactant, wherein the one or more probiotic bacterial strains comprise one or more bacterial strains selected from the group consisting of S. capitis, S. epidermidis, and any combination thereof, the composition is formulated for topical treatment of abnormal disorders of the skin, scalp, or mucous membranes, and the composition is a composition that inhibits the growth of Propionibacterium acnes, and a method for treating acne by applying an effective amount of the composition to the skin or mucous membrane of a target requiring it." However, even if the treatment method disclosed in Patent Document 2 can kill Propionibacterium acnes, it cannot effectively treat acne.

[0017] Furthermore, Patent Document 3 discloses "a skin disease treatment device including a handpiece having an accommodation space for accommodating the skin tissue of the treatment target, a suction module that provides a suction pressure to the accommodation space, a treatment light lamp provided in the handpiece that irradiates high-output pulsed light (IPI, Intense Pulsed Light) toward the skin tissue, and a sterilization light lamp provided in the handpiece that irradiates sterilization light toward the skin tissue." In the example of Patent Document 3, ultraviolet rays are described as the sterilization light. However, when the skin is irradiated with ultraviolet rays, "the immune system may overreact, causing symptoms such as itching, eczema, and redness on the skin," and ultraviolet allergy may develop.

Prior Art Documents

Patent Documents

[0018]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0019] As described above, acne is a skin disease that occurs due to various causes being intricately intertwined, but there is still no effective acne treatment agent provided. The present invention of the application has been made in view of such problems of the prior art, and its purpose is to provide a skin disease treatment agent that has no side effects and has a sufficient acne treatment effect.

Means for Solving the Problems

[0020] The first invention of the present application for solving the above problems is (1) a skin disease treatment agent containing micro-nanobubbles that can effectively treat acne.

[0021] The second invention of this application is a skin disease treatment agent as described in (1), which includes (2) pharmaceuticals, quasi-drugs, medicated cosmetics, or cosmetics.

[0022] The third invention of this application is a skin disease treatment agent as described in (2), wherein (3) the pharmaceutical, quasi-drug, medicated cosmetic, or cosmetic is an agent having anti-inflammatory, antioxidant, blood circulation promoting / blood flow improving effects.

[0023] The fourth invention of this application is a skin disease treatment agent according to (1), (2), or (3), wherein (4) the micro-nanobubbles are micro-nanobubbles produced from one or more gases selected from the group consisting of hydrogen, oxygen, carbon dioxide, and air.

[0024] The fifth invention of this application is a skin disease treatment agent according to (4), comprising (5) one or more liquids selected from water and ethanol.

[0025] The sixth invention of this application is a skin disease treatment agent described in (5), comprising (6) a hydrophilic thickening agent. [Effects of the Invention]

[0026] The present invention cleverly utilizes the effects of micro- and nanobubbles. Microbubbles are bubbles with a diameter of 0.1 mm to 0.001 mm, nanobubbles are bubbles with a diameter of 0.001 mm to 0.000001 mm (1 nm), and micro- and nanobubbles include both. Microbubbles have three properties: rising, contracting, and collapsing, and exhibit different behavior from ordinary bubbles. Microbubbles have high internal pressure and remain in water for a long time, slowly rising and contracting, and because microbubbles are negatively charged, they adsorb dirt during the rising and contracting process, and as they continue to rise and contract, they finally collapse and become nano-sized. As described above, the first to fifth inventions of this application utilize the characteristics of microbubbles, which are much smaller than ordinary bubbles, so that micro- and nanobubbles can easily penetrate the skin, have a blood circulation promoting and blood flow improving effect, and can effectively treat acne without side effects. Furthermore, by selecting one or more liquids from water and ethanol containing micro-nanobubbles to create micro-nanobubble water, and adding a hydrophilic thickener to this micro-nanobubble water, it can be made viscous and gelled, making it less likely to drip and easier to apply compared to watery skin disease treatments. Since hydrophilic thickeners have the function of holding water, applying a skin disease treatment containing a hydrophilic thickener to the skin can be expected to enhance the moisturizing effect and prevent moisture evaporation. Thus, according to the sixth invention of this application, obtained by adding a hydrophilic thickener to micro-nanobubble water, improvements in ease of use and moisturizing effect can be expected. Examples of hydrophilic thickeners include PEG-240, PEG-400, PEG-14M, polyvinylpyrrolidone, sodium acrylate, alginic acid, sodium alginate, carrageenan, xanthan gum, and guar gum. [Brief explanation of the drawing]

[0027] [Figure 1] Figure 1 is a front view of the micro-nanobubble generation system. [Figure 2] Figure 2 is a perspective view of a micro-nanobubble generation system. [Figure 3] Figure 3 is an enlarged cross-sectional view of a micro- and nanobubble generating nozzle. [Figure 4] Figure 4 is an enlarged plan view of the micro- and nanobubble generation nozzle. [Figure 5] Figure 5 is an enlarged side view of a micro- and nanobubble generating nozzle. [Figure 6] Figure 6(a) is a cross-sectional view taken along the BB arrow in Figure 6(b), and Figure 6(b) is a plan view of the high-speed jet liquid injection nozzle. [Figure 7] Figure 7 is an enlarged cross-sectional view of a high-speed jet liquid injection nozzle. [Figure 8] Figure 8 is a cross-sectional view of the gas-liquid mixing tank. [Figure 9] Figure 9 is an enlarged view of the region E enclosed by a circle in Figure 8. [Figure 10]Figure 10 is a cross-sectional view of a gas-liquid mixing tank, including a cross-section of the float. [Figure 11] Figure 11(a) is a photograph of the face of a monitor before treatment with the skin disease treatment agent of the present invention, and Figure 11(b) is a photograph of the face of the same monitor after 65 days of treatment with the skin disease treatment agent of the present invention. [Figure 12] Figure 12(a) is a photograph of the face of another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 12(b) is a photograph of the face of the same monitor after one year of treatment with the skin disease treatment agent of the present invention. [Figure 13] Figure 13(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 13(b) is a photograph of the face of the same monitor after 71 days of treatment with the skin disease treatment agent of the present invention. [Figure 14] Figure 14(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 14(b) is a photograph of the face of the same monitor after 84 days of treatment with the skin disease treatment agent of the present invention. [Figure 15] Figure 15(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 15(b) is a photograph of the face of the same monitor after one year of treatment with the skin disease treatment agent of the present invention. [Figure 16] Figure 16(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 16(b) is a photograph of the face of the same monitor after 76 days of treatment with the skin disease treatment agent of the present invention. [Figure 17] Figure 17(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 17(b) is a photograph of the face of the same monitor after 115 days of treatment with the skin disease treatment agent of the present invention. [Figure 18] Figure 18(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 18(b) is a photograph of the face of the same monitor after 125 days of treatment with the skin disease treatment agent of the present invention. [Figure 19]Figure 19(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 19(b) is a photograph of the face of the same monitor after 142 days of treatment with the skin disease treatment agent of the present invention. [Figure 20] Figure 20(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 20(b) is a photograph of the face of the same monitor after 84 days of treatment with the skin disease treatment agent of the present invention. [Figure 21] Figure 21(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 21(b) is a photograph of the face of the same monitor after 82 days of treatment with the skin disease treatment agent of the present invention. [Figure 22] Figure 22(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 22(b) is a photograph of the face of the same monitor after 180 days of treatment with the skin disease treatment agent of the present invention. [Figure 23] Figure 23(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 23(b) is a photograph of the face of the same monitor after 135 days of treatment with the skin disease treatment agent of the present invention. [Figure 24] Figure 24 shows the particle size distribution of micro- and nanobubbles in the skin disease treatment agent of the present invention used in the examples. [Figure 25] Figure 25 shows the particle size distribution of micro- and nanobubbles in the skin disease treatment agent of the present invention used in different embodiments. [Figure 26] Figure 26 shows the results of a comparative experiment on the bactericidal effect against acne bacteria based on the particle size of nanobubbles. [Figure 27] Figure 27(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 27(b) is a photograph of the face of the same monitor after 103 days of treatment with the skin disease treatment agent of the present invention. [Figure 28]Figure 28(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 28(b) is a photograph of the face of the same monitor after 58 days of treatment with the skin disease treatment agent of the present invention. [Figure 29] Figure 29(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 29(b) is a photograph of the face of the same monitor after 80 days of treatment with the skin disease treatment agent of the present invention. [Figure 30] Figure 30(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 30(b) is a photograph of the face of the same monitor after 90 days of treatment with the skin disease treatment agent of the present invention. [Figure 31] Figure 31(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 31(b) is a photograph of the face of the same monitor after 78 days of treatment with the skin disease treatment agent of the present invention. [Figure 32] Figure 32(a) is a photograph of the face of yet another monitor before treatment with the skin disease treatment agent of the present invention, and Figure 32(b) is a photograph of the face of the same monitor after 59 days of treatment with the skin disease treatment agent of the present invention. [Figure 33] Figure 33(a) is a photograph of the face of yet another monitor before treatment with a skin disease treatment agent containing purified water, and Figure 32(b) is a photograph of the face of the same monitor after 64 days of treatment with a skin disease treatment agent containing purified water. [Figure 34] Figure 34(a) is a photograph of the face of yet another monitor before treatment with a skin disease treatment agent containing purified water, and Figure 34(b) is a photograph of the face of the same monitor after 92 days of treatment with a skin disease treatment agent containing purified water. [Figure 35] Figure 35(a) is a photograph of the face of yet another monitor before treatment with a skin disease treatment agent containing purified water, and Figure 35(b) is a photograph of the face of the same monitor after 64 days of treatment with a skin disease treatment agent containing purified water. [Figure 36]Figure 36(a) is a photograph of the face of yet another monitor before treatment with a skin disease treatment agent containing purified water, and Figure 36(b) is a photograph of the face of the same monitor after 99 days of treatment with a skin disease treatment agent containing purified water. [Modes for carrying out the invention]

[0028] Micro- and nanobubbles have various characteristics, including (a) small bubble diameter, (b) slow rising speed, (c) reduced frictional resistance, (d) high internal bubble pressure, (e) large gas-liquid interface, (f) large gas dissolution capacity, (g) dissolution and contraction, (h) negatively charged bubble surface, (i) the buoyancy becomes much smaller compared to the viscous force as the particle diameter decreases, allowing them to remain in the liquid as ultrafine bubbles for a long period without floating to the surface, and (j) the spherical diameter of the bubbles becomes very small, making the liquid containing nanobubbles invisible to the naked eye and colorless and transparent. Therefore, applications in a wide range of fields such as food, cosmetics, pharmaceuticals, semiconductor cleaning, and plant cultivation are expected by utilizing these characteristics.

[0029] The skin disease treatment agent of the present invention contains micro-nanobubbles having the characteristics described above. As a medium for liquefying this skin disease treatment agent containing micro-nanobubbles, water or ethanol can be used to create micro-nanobubble water, but the medium is not limited to water or ethanol, and any medium that is obvious to those skilled in the art can be used. The water can be tap water, purified water, natural water, carbonated water, deionized water, alkaline ionized water, deep sea water, distilled water, RO water, purified water, etc., and any of these can be used, but purified water is preferred because it is a solvent used in medicine, has significantly better skin penetration than ordinary water, and does not contain impurities, so it can be used safely even by people with sensitive skin without worrying about skin irritation.

[0030] The skin disease treatment agent containing micro- and nanobubbles of the present invention is characterized in that the micro- and nanobubbles are dispersed in a liquid. Micro- and nanobubbles refer to a mixture containing both microbubbles with a diameter of 0.1 mm to 0.001 mm and nanobubbles with a diameter of 0.001 mm to 0.000001 mm (1 nm), but the diameter of the micro- and nanobubbles preferably includes 0.1 nm to 120.0 nm, and more preferably includes 0.1 nm to 55.0 nm. Hydrogen, oxygen, carbon dioxide, and air can be used as the gas for the micro- and nanobubbles.

[0031] As a pharmaceutical, quasi-drug, medicated cosmetic, or cosmetic that can be included in the skin disease treatment agent of the present invention, for example, Nizoral Lotion 2% (trade name) containing ketoconazole as an active ingredient can be used. Ketoconazole is one of the imidazole-based synthetic antifungal drugs used medically for the treatment of fungal infections, and is used for the treatment of tinea, candidiasis, tinea versicolor, and seborrheic dermatitis. Ketoconazole is a substance whose IUPAC name is "1-[4-(4-{[(2R,4S)-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one".

[0032] As an imidazole antifungal agent, miconazole can be used, similar to other imidazole antifungals, by inhibiting the biosynthesis of ergosterol contained in the cell membrane of fungi. Miconazole is mainly applied to skin and mucous membranes in the form of nitrates, and is also used as an oral medication on its own. It is sometimes included in shampoos, conditioners, and liquid soaps to prevent fungal scalp rashes and eczema. Miconazole is a substance whose IUPAC name is "(RS)-1-(2-(2,4-Dichlorophenyl)-2-(2,4-dichlorophenyl)ethyl)-1H-imidazol".

[0033] Other pharmaceuticals, quasi-drugs, medicated cosmetics, or cosmetics that can be included in the skin disease treatment agent of the present invention may be those described in paragraphs 0034 to 0057 below.

[0034] -Improves clogged pores- Acne occurs when pores become clogged with sebum and other substances, leading to inflammation caused by the proliferation of acne bacteria. Therefore, improving clogged pores is crucial for treating acne. For this reason, it is common to use topical medications to improve clogged pores when acne is present. For example, adapalene gel / Differin gel (brand names) can be used as such a topical medication. Adapalene gel / Differin gel is a topical medication with adapalene as its active ingredient. Adapalene suppresses the differentiation of keratinocytes in the epidermis, thinning the stratum corneum and preventing pore narrowing. In other words, by keeping the pore opening wide, it prevents and improves sebum buildup, thus preventing the progression to severe acne inflammation. According to adapalene gel / Differin gel, it can prevent pore clogging and suppress comedone formation. Using it at the whitehead stage can prevent it from progressing to red or yellow acne.

[0035] Additionally, Bepio Gel (trade name), which contains benzoyl peroxide as its active ingredient, can be used as a topical medication to improve clogged pores. Bepio Gel has a peeling effect that exfoliates dead skin cells. This is expected to improve the thickening of keratin at the entrance of pores. Furthermore, Bepio Gel also has antibacterial properties against acne bacteria and staphylococcus, so it can improve clogged pores by making it easier to remove old dead skin cells, while simultaneously suppressing the activity of acne-causing bacteria. According to Bepio Gel, it can also be expected to have an acne-preventive effect by improving inflammatory red acne and making pores less prone to clogging.

[0036] Furthermore, Epiduo Gel (brand name), which contains adapalene and benzoyl peroxide as active ingredients, can be used as a topical medication to improve clogged pores. Epiduo Gel is a topical medication that combines "adapalene," which thins the stratum corneum, and "benzoyl peroxide," which has peeling and antibacterial effects against acne bacteria. According to Epiduo Gel, improvement in symptoms ranging from whiteheads to severely inflamed red acne can be expected.

[0037] Alternatively, Duac Combination Gel (trade name), which contains clindamycin phosphate hydrate and benzoyl peroxide as active ingredients, can be used. Clindamycin phosphate hydrate is expected to have antibacterial effects against acne bacteria and anti-inflammatory effects by suppressing the accumulation of white blood cells, which cause inflammation, in the affected area. Furthermore, benzoyl peroxide exfoliates excess keratin and improves clogged pores, thus suppressing the formation of comedones. Thus, Duac Combination Gel can improve red and yellow acne.

[0038] -Antibiotics- When acne bacteria and other microorganisms proliferate in clogged pores, inflammation occurs, resulting in painful red pimples or yellow, suppurating pimples. Therefore, it is necessary to treat the inflammation occurring in the pores quickly, and thus it is necessary to use a topical medication containing antibiotics with bactericidal and antibacterial properties. As such an antibiotic, Dalacin T Gel (trade name), whose active ingredient is clindamycin, can be used. Dalacin T Gel prevents protein synthesis by acne bacteria and staphylococci, which worsen acne, and has the effect of suppressing inflammation in red pimples.

[0039] Additionally, a new quinolone antibiotic called Aquatim Cream (brand name), containing nadifloxacin as its active ingredient, can be used. Aquatim Cream suppresses acne-causing bacteria such as Propionibacterium acnes and Staphylococcus aureus, improving redness and swelling and reducing red acne.

[0040] Furthermore, Zeviax (trade name), which contains ozenoxacin as its active ingredient, can also be used as an antibiotic. Zeviax suppresses acne bacteria and staphylococcus bacteria that worsen acne, improving redness and swelling and reducing red acne.

[0041] In cases of inflamed, red acne, oral antibiotics may be used in addition to topical medications. Typical medications include the following:

[0042] Vibramycin (brand name), which contains doxycycline hydrochloride hydrate as its active ingredient, can be used. Vibramycin kills bacteria by inhibiting protein synthesis. Vibramycin is particularly effective in treating inflamed red acne.

[0043] Minomycin (brand name), which contains minocycline hydrochloride as its active ingredient, can be used. Minomycin is a drug that kills bacteria by inhibiting protein synthesis, and it is expected to have anti-inflammatory effects by suppressing the accumulation of white blood cells that cause inflammation at the affected area, as well as suppressing reactive oxygen species, making it effective in treating inflamed red acne.

[0044] Rulid (brand name), which contains roxithromycin as its active ingredient, can be used. Rulid also kills bacteria by inhibiting protein synthesis. Rulid is effective in treating inflamed red acne.

[0045] Faropenem sodium (brand name) can be used as the active ingredient. Faropenem kills bacteria by inhibiting cell wall synthesis. Faropenem is effective in treating inflamed red acne.

[0046] - Oral medication - Additionally, an oral medication called isotretinoin (brand name), which contains a vitamin A derivative, can be used. Isotretinoin is expected to have effects such as suppressing sebum secretion, improving clogged pores, reducing inflammation, and having an antibacterial effect against acne-causing bacteria. Furthermore, isotretinoin is expected to not only eliminate acne but also to suppress acne recurrence for a long period even after discontinuing treatment.

[0047] -Moisturizer- Moisturizing is also important for improving acne. When the skin dries out, it can lead to excessive sebum secretion to compensate for the dryness, a weakened skin barrier function, and disrupted cell turnover. Therefore, moisturizers can be used in conjunction with medications that improve clogged pores or antibiotics. A typical moisturizer that can be used is Hirudoid (brand name), which contains heparinoid as its active ingredient. In addition to moisturizing, Hirudoid is expected to promote blood circulation and have anti-inflammatory effects. Furthermore, continuous use of Hirudoid can help maintain the skin's barrier function and is expected to improve acne.

[0048] -Traditional Chinese Medicine- Traditional Chinese medicine (Kampo) can be used to improve one's constitution and make acne less likely to occur. Kampo is a good option when conventional acne treatments are ineffective, when medications do not suit one's constitution, or when one does not want to take antibiotics for a long period of time. Kampo can be used to select a Kampo that is appropriate for the condition and location of the acne. Kampo that can be used to treat inflamed red acne are listed below: Jumi Haidokuto, Keigai Rengyoto, and Seijo Bofuto.

[0049] Jumi Haidoku-to is a traditional Chinese medicine used to treat eczema with pus and moisture, and is sometimes used to treat dermatitis and hives in addition to acne. It is expected to improve swelling, redness, itching, and suppuration of the skin, and the licorice and schizonepeta contained in Jumi Haidoku-to are also expected to have antibacterial properties. Jumi Haidoku-to can be used as a treatment for red acne with inflammation.

[0050] Jingjie Lianqiao Tang is a traditional Chinese medicine primarily used for nasal symptoms, but it has been shown to suppress the production of reactive oxygen species and has anti-allergic effects, making it usable as a treatment for inflamed red acne.

[0051] Seijo Bofu-to is a traditional Chinese medicine used to treat acne, as well as eczema and dermatitis on the face and scalp. It can be used to treat both whiteheads and inflamed red acne.

[0052] Acne is also thought to be related to poor blood circulation, and herbal medicines that improve blood flow can be used. Furthermore, if acne does not heal easily, herbal medicines such as Ninjinto, Rikkunshito, and Hochuekito can be used to improve internal organ function.

[0053] -Vitamins- While the effectiveness of vitamin supplements against acne is not clear, they can be used as an aid in improving overall health and as a supplement to acne treatment.

[0054] You can use Cinal (product name), which contains ascorbic acid (vitamin C) and pantothenic acid (oxygenated vitamin B5) as active ingredients. Cinal is expected to promote collagen production, suppress reactive oxygen species that cause skin damage, inhibit melanin production, and prevent and improve hyperpigmentation from acne scars.

[0055] You can use Hithiol (trade name), which contains the amino acid L-cysteine ​​as its active ingredient. Like vitamin C, it acts as an antioxidant and is said to prevent oxidative stress, and is expected to suppress melanin production and prevent hyperpigmentation.

[0056] You can use Neurobitan (brand name), which contains octotiamine (vitamin B1 derivative), riboflavin (vitamin B2), pyridoxine hydrochloride (vitamin B6), and cyanocobalacin (vitamin B12) as active ingredients. These vitamins help maintain healthy skin and mucous membranes, and vitamins B2 and B6 play important roles in cell turnover.

[0057] You can use Yuvera (trade name), which contains tocopherol acetate (a vitamin E derivative) as its active ingredient. Yuvera is expected to improve blood flow, normalize cell turnover, improve pigmentation, blemishes, and freckles, and protect skin cells from oxidative damage.

[0058] Examples of cosmetic ingredients that can be included in the skin disease treatment agent of the present invention include anti-inflammatory ingredients, antioxidant ingredients, blood circulation promoting / blood flow improving ingredients, antioxidants, preservatives, thickeners, moisturizing ingredients, chelating agents, pH adjusters, plant extracts, fragrances, and pigments.

[0059] Next, a method for generating micro- and nanobubbles contained in the skin disease treatment agent of the present invention will be described. Figure 1 is a front view of the system for generating micro- and nanobubbles, and Figure 2 is a perspective view of the system for generating micro- and nanobubbles. In Figures 1 and 2, 1 is a bellows cylinder pump, 2 is a pump controller, 3 is a gas-liquid mixing tank, 4 is a pressure sensor, 5 is a micro- and nanobubble generation nozzle mounting section, 6 is a liquid suction pipe, 7 is a gas suction port, and 8 is a gas suction adjustment valve.

[0060] In the bellows cylinder pump 1, whose wetted parts are made of fluororesin, the amount of gas is adjusted using a liquid suction pipe 6 and a gas suction adjustment valve 8 to draw in a mixture of liquid and gas into the pump, agitate it inside the bellows, compress it, and dissolve the gas in the liquid. In the present invention, the bellows cylinder pump 1 only needs to be metal-free, and at least one of the following types of plastics may be used: general-purpose plastics such as polyethylene, polypropylene, and polyethylene terephthalate; engineering plastics such as polyacetal, polyamide, polycarbonate, and modified polyphenylene ether; and super-engineering plastics such as polyethersulfone, polyphenylene sulfide, polyetheretherketone, and liquid crystal polymer. In that case, by using fluororesin and the above-mentioned various plastics not only for the pump but also for the wetted parts, a highly reliable and clean micro-nanobubble generator can be made. Furthermore, in the present invention, if strict metal-free cleaning and sterilization are not required, metals or ceramics may be used in addition to the above-mentioned plastics.

[0061] Next, the gas and liquid are agitated by a bellows cylinder pump 1 and pumped into a gas-liquid mixing tank 3. While a compressed air-started bellows cylinder pump 1 is primarily used, an electric pump may also be used. The gas and liquid in the gas-liquid mixing tank 3 are under pressure from the bellows cylinder pump 1, making it easier for the gas to dissolve. In other words, the pressure at which the gas and liquid are pumped from the bellows cylinder pump 1 is monitored by a pressure sensor 4. This method increases the amount of dissolved gas, preparing the system to increase the amount of micro- and nanobubbles generated.

[0062] The liquid, which is pumped under pressure into the gas-liquid mixing tank 3, is mixed with the gas, dissolving the gas within the liquid before being sent to the micro-nanobubble generation nozzle attachment section 5. The micro-nanobubble generation nozzle attachment section 5 is the part that connects the dissolved gas to a nozzle that produces a large number of micro-nanobubbles with a diameter of 60 μm or less, preferably 15 μm or less.

[0063] At this time, the pressure sensor 4 monitors the liquid pressure fluctuations between the micro- and nanobubble generation nozzle mounting section 5 and the gas-liquid mixing tank 3 to monitor the dissolved state of the gas and liquid. This makes it possible to achieve a constant pressure state necessary for a stable micro- and nanobubble generation nozzle.

[0064] A method for generating micro-nanobubbles using the micro-nanobubble generation system shown in Figures 1 and 2 will be described. Gas and liquid are drawn in using a gas suction port 7, a liquid suction tube 6, and a gas suction adjustment valve 8. Next, the liquid containing the gas is pressurized using a bellows cylinder pump 1. Subsequently, the dissolved gas is enriched using a pump controller 2 and a gas-liquid mixing tank 3 to mix the pressurized liquid containing the gas with new gas. After that, the high-speed jet liquid injection nozzle, described later, is connected to the micro-nanobubble generation nozzle mounting section 5, and then micro-nanobubbles are generated. This process is a dissolved gas atomization process, but micro-nanobubbles can be generated by injecting a gas-dissolved liquid from the outside of a cylindrical body having two or more through-holes through the through-holes at a pressure greater than atmospheric pressure, and causing the gas-dissolved liquid to collide at a single point inside the cylindrical body.

[0065] Next, a method for generating a large quantity of micro- and nanobubbles from a gas-dissolved liquid containing dissolved gas will be described. Figure 3 is an enlarged cross-sectional view of a nozzle for generating micro- and nanobubbles, where 11 and 12 are the outer casings of the nozzle. The outer casings 11 and 12 are positioned opposite each other and fixed with bolts 13 and nuts 14. The gas-dissolved liquid, pressurized by the bellows cylinder pump 1, is supplied into the opposing outer casings 11 and 12 as indicated by the arrows. 15 and 16 are high-speed jet liquid injection nozzles, and the discharge flow rate and flow velocity of the gas-dissolved liquid can be determined by the size of the holes in these nozzles.

[0066] Figure 4 is an enlarged plan view of the micro-nanobubble generating nozzle, where the liquid containing micro-nanobubbles is discharged in the direction indicated by the arrow.

[0067] This section describes a method for producing micro- and nanobubbles using the water flow discharged from this high-speed jet liquid injection nozzle. The gas-dissolved liquid discharged from the bellows cylinder pump 1 at a pressure of 0.2 MPa to 0.6 MPa from the high-speed jet liquid injection nozzles 15 and 16 collide with each other, and the resulting water hammer force breaks up the gas-dissolved liquid, generating a large quantity of micro- and nanobubbles.

[0068] Figure 6(a) is a cross-sectional view taken along the BB arrow in Figure 6(b), and Figure 6(b) is a plan view of the high-speed jet liquid injection nozzle. The high-speed jet liquid injection nozzles 15 and 16 are centered using a center pin 17 to determine the center, and then positioned and fixed using positioning pins 18 and 19.

[0069] Figure 7 is an enlarged cross-sectional view of a high-speed jet liquid injection nozzle. As shown in Figure 6, the high-speed jet liquid injection nozzles 15 and 16 are arranged opposite each other. The gas-dissolved liquid discharged from one high-speed jet liquid injection nozzle 15 or 16 collides with the gas-dissolved liquid discharged from the other high-speed jet liquid injection nozzle 15 or 16, and the resulting water hammer force breaks up the gas-dissolved liquid, generating a large amount of micro- and nanobubbles. In order to deliver the gas-dissolved liquid as a high-speed jet, the gas-dissolved liquid is rapidly narrowed from the small flow path holes 15a and 16a to the nozzle sections 15b and 16b and ejected from the nozzle sections 15b and 16b. The jet streams ejected from the nozzle sections 15b and 16b collide, breaking up the gas-dissolved liquid and generating a large amount of micro- and nanobubbles.

[0070] The reason for sending liquid under high pressure is to increase the velocity of the liquid as it exits through small holes. In other words, by causing the liquid to collide at high speed, the impact energy increases, making it possible to generate a larger quantity of smaller micro- and nanobubbles.

[0071] Let F be the force generated when a gas-dissolved liquid collides. Let ρ (g / cm³) be the density of the liquid. 3 Let S be the cross-sectional area of ​​the nozzle (cm²). 2Let the fluid velocity be V (cm / sec), then F = ρSV 2 The following relationship holds true. In order to optimize F, it is necessary to consider the relationship between the liquid density, the cross-sectional area of ​​the nozzle, and the liquid velocity.

[0072] Furthermore, it is believed that a larger number of micro- and nanobubbles can be generated using pumps that generate higher pressures. For example, there are high-pressure pumps with discharge pressures of 0.5 MPa to 250 MPa, and when using such pumps, the liquid velocity increases in proportion to the pressure, and the water hammer force F increases with the square of V, so it is believed that the amount of micro- and nanobubbles generated will increase. However, applying such high-pressure pumps to a micro- and nanobubble generator would make it difficult to meet various requirements such as lightweight, compact size, metal-free design, and low maintenance costs.

[0073] However, in the micro-nanobubble generation system shown in Figures 1 and 2, by using the micro-nanobubble generation nozzles shown in Figures 3 to 5 and the high-speed jet liquid injection nozzles shown in Figures 6 and 7, if the pressure when injecting the gas-dissolved liquid in a gas-liquid mixture state is equal to or greater than atmospheric pressure (approximately 0.1 MPa), the amount of micro-nanobubbles generated can be equal to or greater than conventional methods. Furthermore, by setting this pressure to 0.2 MPa or higher, a sufficient amount of micro-nanobubbles for thorough cleaning and sterilization can be generated. Thus, since the lower limit of the injection pressure of the gas-dissolved liquid can be lowered to 0.2 MPa compared to conventional methods, it becomes possible to use a pump suitable for eliminating the effects of metal contamination, namely, a compressed air-driven or electric bellows cylinder pump 1 made of fluororesin, as shown in Figures 1 and 2. Also, when using a compressed air-driven or electric bellows cylinder pump, the amount of micro-nanobubbles generated tends to saturate when the injection pressure of the dissolved liquid exceeds 0.6 MPa. Therefore, in the present invention, the pressure when injecting the gaseous dissolved liquid is preferably 0.2 to 0.6 MPa.

[0074] The micro-nanobubble generating nozzle of the present invention is designed to inject a jet stream of gas-dissolved liquid at a pressure higher than atmospheric pressure, preferably 0.2 to 0.6 MPa, which is lower than conventional pressures. Therefore, the diameter of the nozzle section shown in Figure 7, 15b and 16b, is preferably 0.1 to 6.0 mm. In Figure 7, the small flow channel holes 15a and 16a only need to have a throttling function for sending the gas-dissolved liquid as a high-speed jet, and may be formed in a continuously tapered shape toward the nozzle sections 15b and 16b. The amount of micro-nanobubbles generated is mainly determined by the diameters of the nozzle sections 15b and 16b, and the portions of the small flow channel holes 15a and 16a can be omitted.

[0075] Figure 8 is a cross-sectional view of the gas-liquid mixing tank 3. Figure 9 shows an enlarged view of the area E enclosed by a circle in Figure 8. Conventional gas-liquid mixing tanks mix gas and liquid under high pressure, but when the gas and liquid are mixed and sent by the pump, the mixing inside the gas-liquid mixing tank is done by spraying it upwards like a fountain. However, this method is inefficient in terms of mixing, so it is not possible to increase the amount of micro- and nanobubbles generated.

[0076] Therefore, as shown in Figure 8, the gas and liquid are sent from the pump from arrow A to arrow B, and then to the gas-liquid insertion pipes 22 and 23. As shown in Figure 9, in order to increase the efficiency of gas-liquid mixing, the gas and liquid are discharged from the hole 22a of the gas-liquid insertion pipe 22 and the hole 23a of the gas-liquid insertion pipe 23. By utilizing the water hammer caused by colliding the liquid from the direction of arrow X and arrow Y, the gas and liquid are mixed efficiently, a gas-liquid mixture that will become the raw material for micro- and nanobubbles can be quickly produced, and the mixing ratio of gas and liquid can also be increased. In Figure 8, 24 is the Teflon® side wall.

[0077] The float 21 shown in Figure 8 is positioned to discharge excess gas when too much gas enters during gas-liquid mixing. It safely discharges excess gas and adjusts the gas-liquid ratio to the appropriate level. In other words, it eliminates the problem of excess gas remaining in the nozzle and hindering the generation of micro- and nanobubbles, thereby ensuring that the amount of micro- and nanobubbles generated is appropriate and stable.

[0078] Figure 10 is a cross-sectional view of a gas-liquid mixing tank, including a cross-section of the float. The float 21 has a float tip 21a (which is pointed), reinforcing ribs 21b to prevent the float 21 from collapsing under liquid pressure, and a stopper 21c.

[0079] To mix gases and liquids, it is important to increase the contact area between the gas and liquid, thereby improving the efficiency of gas dissolution within the liquid. If this gas dissolution efficiency decreases, it leads to a critical shortage of gas for micro- and nanobubble generation, resulting in a deficiency in the amount of micro- and nanobubbles produced.

[0080] An investigation into whether the ratio of liquid to gas increases the amount of micro- and nanobubbles generated revealed that an ideal balance in the gas-liquid mixing tank is 60% liquid and 40% gas. To automatically control the ratio of the two, the buoyancy of the liquid in the float 21 is used to discharge excess gas from the excess gas outlet 26 of the float holder 25, thereby automatically adjusting the amount of gas. This optimizes the mixing of dissolved gas and liquid, stabilizing the amount of micro- and nanobubbles generated and increasing their quantity. To increase the amount of micro- and nanobubbles generated, it is preferable to control the volume ratio of liquid to gas in the gas-liquid mixing tank within the range of liquid:gas = 50:50 to 95:5, so that the liquid ratio is larger. The float 21 may be installed not only inside the gas-liquid mixing tank 3 but also outside of it. In that case, the volume ratio of liquid to gas present inside the gas-liquid mixing tank 3 can be controlled by connecting the inside and outside of the gas-liquid mixing tank 3 with a connecting pipe or the like. [Examples]

[0081] The following describes an embodiment of the present invention using a skin disease treatment agent containing a pharmaceutical, quasi-drug, medicated cosmetic, or cosmetic, such as Nizoral, in purified water containing micro- and nanobubbles with the particle size distribution shown in Figure 24, which are produced from oxygen. However, this description does not limit the present invention. Various changes and modifications are possible as long as they do not deviate from the technical scope of the present invention.

[0082] To confirm the effectiveness of the skin disease treatment agent of the present invention, a study described below was conducted with 13 participants aged 16 to 32 years (2 males, 11 females) as monitors. Figures 11 to 23 show photographs of the faces of the 13 monitors before and after treatment with the skin disease treatment agent of the present invention, and Table 1 below shows the ages of the 13 monitors and the treatment period with the skin disease treatment agent of the present invention for each monitor.

[0083] [Table 1]

[0084] For the 13 monitors shown in Table 1, a liquid containing 10g of "Nizoral Lotion 2%" (containing 2% ketoconazole) and purified water containing oxygen micro-nanobubbles obtained by a micro-nanobubble generation system (explained using Figures 1-10) in a ratio of 10g to 80cc of the latter was applied directly to each monitor's face using a spray. After the liquid applied to the face appeared to have dried (approximately 30 seconds later), each monitor applied an appropriate amount of "Dalacin T Gel 1%" (containing 1% clindamycin phosphate) or "Aquatim Cream 1%" (containing 1% nadifloxacin) directly to their face by hand. There are no restrictions on the method of applying the skin disease treatment agent of the present invention to the face; it can be applied in a shower-like manner. The pressure and flow rate of the shower-like skin disease treatment agent can be increased or decreased as appropriate, within a range that does not cause damage to the face and does not cause discomfort to the person showering. If there is no particular discomfort, a stronger pressure and a higher flow rate are preferable. The application time of the skin disease treatment agent of the present invention to the face can be appropriately adjusted considering the condition of the acne on the face, and can be 10-20 seconds, 30-60 seconds, 1-2 minutes, 3-5 minutes, or even longer. The number of times the skin disease treatment agent of the present invention is applied to the face can be once a day, twice a day, three times a day, four times a day, or more. It is preferable to continue application until the desired effect appears, and usually the effect appears after several weeks to several months, for example, around 3-4 months.

[0085] The micro- and nanobubbles in the skin disease treatment agent of the present invention are preferably small in size and abundant in quantity. This is because when small, abundant micro- and nanobubbles are applied to the face, they can penetrate deep into the pores and remove more waste products. Figure 24 shows the particle size distribution of micro- and nanobubbles in purified water containing micro- and nanobubbles, which was used to prepare the liquid that was directly applied to the faces of 13 monitors shown in Table 1. In Figure 24, the horizontal axis represents particle size (nm), and the vertical axis represents the number of particles (particles). Since these micro- and nanobubbles contain minute particles with a diameter of about 0.1 to 5.0 nm, their particle size was measured using the AFM (atomic force microscope) method.

[0086] Conventional methods for measuring the diameter of bubbles in a liquid generally include particle trajectory analysis, dynamic light scattering, laser diffraction / scattering, electrical detection band method, resonant mass spectrometry, and dynamic image analysis. Dynamic light scattering and laser diffraction / scattering are considered particularly suitable for measuring minute bubbles. However, because the micro- and nanobubbles of the present invention have extremely small diameters, it is difficult to accurately measure their particle size and quantity using the above two methods due to measurement errors. The above two methods calculate the particle diameter by measuring the volume of the bubble from the light reflection of particles in the liquid and using a calculation formula. Therefore, they are affected by reflection from contaminants such as dust, uneven distribution of particles (for example, bubbles of different diameters existing on the upper and lower sides of the liquid), and multiple scattering. Furthermore, while these methods are suitable for measuring solid particles such as metal particles, it is difficult to ensure the same measurement accuracy for gaseous bubbles, which have different optical properties than solids. In particular, when the bubble diameter becomes extremely small, such as 55 nm or less, the light reflectivity tends to decrease.

[0087] Therefore, the inventors used AFM (Artificial Force Microscopy) to measure the minute bubble diameters contained in oxygen nanobubble water. AFM is a method in which a pointed needle is attached to a leaf spring called a cantilever, and detection is performed through the deflection (displacement) of the cantilever. Laser light is shone obliquely onto the back of the cantilever, and the difference in light intensity changes due to the change in the position of the reflected light, and this change is detected. High-sensitivity detection of cantilever displacement is possible, and displacements of 1 nm or less (error accuracy of 0.01 nm to 0.1 nm) can be easily detected. However, AFM has the characteristic that the measurement range is limited by its measurement method, and accurate data cannot be obtained for bubbles with large particle sizes (100 nm or more).

[0088] In the measurement of micro- and nanobubbles according to the present invention, a liquid containing bubbles is dropped onto a substrate whose surface is positively charged. Since oxygen bubbles are negatively charged, an amount of oxygen bubbles corresponding to the bubble density in the liquid adheres to the substrate surface. The cantilever of an atomic force microscope is driven to scan the bubbles present on the substrate surface to which the liquid droplets have adhered, and the bubbles are imaged based on the acquired scanning data. Non-circular data (foreign objects) are removed from the imaged data, and data on the diameter and quantity of bubbles in the scanning data are obtained.

[0089] The AMF measurement conditions are as follows: Circuit board type: Mica circuit board Substrate treatment: Positively charged by APTES (3-aminopropyltriethoxysilane) treatment. Nanobubble adsorption: Nanobubbles are adsorbed onto a positively charged substrate. Cantilever: NANOWORLD USC-F1.2-k0.15-10 Scan range: 2000nm x 2000nm X / Y Pixel count: 400px x 400px Measurement time: Measurement within 30 minutes after dropping the sample solution onto the substrate. Measurement count: Three different locations on the circuit board within the scan range are measured, and the total number of measurements is counted.

[0090] The AMF analysis conditions are as follows: Measurement error: ±0.1nm Minimum circularity: 0.70 Threshold width: 1 (represents height; 1 = 256 levels) Median filter: None

[0091] As shown in Figure 24, the total number of micro- and nanobubbles contained in the skin disease treatment agent of the present invention, measured by the AMF method under the above conditions within a scan range of 2000 nm × 2000 nm, is 300 or more in the diameter range of 0.1 to 55.0 nm, 300 or more in the diameter range of 0.1 to 30.0 nm, and 300 or more in the diameter range of 0.1 to 10.0 nm. In the embodiments of the present invention, micro- and nanobubbles corresponding to this particle size distribution, which are produced from oxygen, are referred to as oxygen micro- and nanobubbles.

[0092] The temperature of the skin disease treatment agent of the present invention can be any temperature range that does not cause discomfort to the person taking a shower, for example, 25-30°C, 30-33°C, 33-36°C, 36-39°C, or 40-42°C.

[0093] For the 13 monitors shown in Table 1, a liquid containing 2% ketoconazole ("Nizoral Lotion 2%") and purified water containing oxygen micro-nanobubbles obtained by the micro-nanobubble generation system, in a ratio of 10g of the former to 80cc of the latter, was applied to each monitor's face using a spray, at a rate of approximately 0.2-0.5cc per application, for approximately 20 seconds, 1-2 times per day. After the liquid applied to the face appeared to have dried (approximately 30 seconds later), each monitor applied an appropriate amount of either 1% clindamycin phosphate ("Dalacin T Gel 1%") or 1% nadifloxacin ("Aquatim Cream 1%") directly to their face by hand. Monitors who applied the product twice by spray left an interval of approximately 6-10 hours between the first and second applications. As a result, the monitor with the shortest treatment period showed improvement in just 65 days (see 16-year-old female in Table 1, Figure 11). The oxygen micro- and nanobubbles were generated under conditions where the volume ratio in the gas-liquid mixing tank was 60% liquid and 40% gas.

[0094] Figures 11 to 23, (a) are photographs of the monitor's face before treatment with the skin disease treatment agent of the present invention, and Figures 11 to 23, (b) are photographs of the same monitor's face after a predetermined number of days of treatment with the skin disease treatment agent of the present invention. A comparison of the face before treatment (left photograph) and the face after treatment (right photograph) in each figure is as follows.

[0095] Figure 11 shows that the acne in the center of the forehead has disappeared after treatment. Although Figure 11 is in black and white and therefore difficult to see clearly, the acne in the center of the forehead before treatment was a red pimple.

[0096] Figure 12 shows that the acne that was present on almost the entire face before treatment has almost completely disappeared after treatment. Figure 12 is shown in black and white, so it is not very clear, but the acne that was present on almost the entire face before treatment was red acne.

[0097] Figure 13 shows that the shadowed area on the left cheek before treatment has faded overall after treatment. Although Figure 13 is in black and white and therefore difficult to see clearly, it can be observed that a faint redness was visible on the left cheek before treatment, and that this redness has faded after treatment.

[0098] Figure 14 shows that the number of pimples, which were present across almost the entire forehead before treatment, has decreased after treatment. Although Figure 14 is shown in black and white and therefore difficult to see clearly, the pimples that were present across almost the entire forehead before treatment are red pimples.

[0099] Figure 15 shows that before treatment, there were numerous pimples on the forehead and right cheek. After treatment, it can be seen that the number of pimples decreased significantly, and their size also became considerably smaller. Figure 15 is shown in black and white, so it is not very clear, but the pimples seen on the forehead and right cheek before treatment were red pimples.

[0100] Figure 16 shows that the numerous pimples seen on both cheeks and the chin area below the lower lip before treatment have been significantly reduced in number and size after treatment. Although Figure 16 is in black and white and therefore difficult to see clearly, the pimples seen on both cheeks and the chin area below the lower lip before treatment are red pimples.

[0101] Figure 17 shows that the acne that was present on the left cheek and the chin area below the lower lip before treatment has almost completely disappeared after treatment. Figure 17 is in black and white, so it is not very clear, but the acne that was present on the left cheek and the chin area below the lower lip before treatment was red acne.

[0102] Figure 18 shows that the acne seen on the left cheek before treatment has almost completely disappeared after treatment. Although Figure 18 is in black and white and therefore difficult to see clearly, the acne seen on the left cheek before treatment was red acne.

[0103] Figure 19 shows that the four pimples visible between the left and right eyebrows before treatment have been reduced to one after treatment. Although Figure 19 is in black and white and therefore difficult to see clearly, the pimples visible between the left and right eyebrows before treatment are blackheads.

[0104] Figure 20 shows that the acne located near the left nostril before treatment has disappeared after treatment. Although Figure 20 is in black and white and therefore difficult to see clearly, the acne located near the left nostril before treatment is a red acne lesion.

[0105] Figure 21 shows that the shadowed areas on both cheeks before treatment have faded overall after treatment. Although Figure 21 is in black and white and therefore difficult to see clearly, it can be observed that there were faintly red areas on both cheeks before treatment, but these red areas have faded after treatment.

[0106] Figure 22 shows that the large pimple seen on the right cheek before treatment almost completely disappeared after treatment, and the numerous pimples seen on the left cheek before treatment became smaller overall after treatment. Figure 22 is shown in black and white, so it is not very clear, but the pimples seen on both cheeks before treatment are red pimples.

[0107] Figure 23 shows that the acne seen between the eyebrows and on the forehead above the left eyebrow before treatment has become significantly smaller after treatment. It also shows that the shadowed areas on both cheeks before treatment have faded overall after treatment. Although Figure 23 is in black and white and therefore difficult to see clearly, all the acne seen before treatment was red acne.

[0108] To summarize the observations in Figures 11-23, although there are differences in the degree of improvement among monitors, it is clear that the skin disease treatment agent of the present invention improves acne symptoms.

[0109] As described above, it can be seen that acne symptoms are improved by using the skin disease treatment agent of the present invention, which is formulated with a pharmaceutical, quasi-drug, medicated cosmetic, or cosmetic product such as Nizoral lotion, in purified water containing extremely fine oxygen micro-nanobubbles with a diameter of 0.1 to 55.0 nm, produced from oxygen.

[0110] Regarding the ratio of Nizoral lotion to purified water containing oxygen micro- and nanobubbles in the skin disease treatment agent of the present invention shown in the above examples, a liquid was used containing 10g of a 2% solution of Nizoral lotion and 80cc of purified water containing oxygen micro- and nanobubbles. However, the above effects can be obtained if the ratio of the former to the latter is 5-20g of a 2% solution of Nizoral lotion to 50-200cc of purified water containing oxygen micro- and nanobubbles. Furthermore, in the above test, a liquid containing 10g of a 2% solution of Nizoral lotion and 80cc of purified water containing oxygen micro-nanobubbles was applied to the monitor's face. After the liquid applied to the face appeared to have dried, "Dalacin T Gel 1%" or "Aquatim Cream 1%" was applied to the face. However, instead of "Dalacin T Gel 1%" or "Aquatim Cream 1%", an appropriate product from among the pharmaceuticals, quasi-drugs, medicated cosmetics, or cosmetics described in paragraphs 0034 to 0057 may be used.

[0111] Instead of a 2% solution of Nizoral lotion, miconazole may be used, or an appropriate product from among the pharmaceuticals, quasi-drugs, medicated cosmetics, or cosmetics described in paragraphs 0034 to 0057 may be used.

[0112] Furthermore, in order to compare the bactericidal effect against acne bacteria based on differences in nanobubble particle size, the inventors conducted an experiment using the most probable number method (MPN method), which estimates the number of bacteria killed in a sample based on estimation, at Sigma Technology Co., Ltd. from September 24 to October 4, 2024.

[0113] In other words, the acne bacteria obtained by culture in a petri dish (1.0 × 10 9(number) was mixed with 10 mg of each of the following sample solutions A to F shown in Table 2 below, held for 20 minutes, and a stock solution was obtained. A 10-fold dilution of the stock solution with GAM culture medium, which is a semi-solid agar medium, was set at the left end of the culture plate. Next, a 100-fold dilution obtained by diluting the 10-fold dilution with GAM culture medium was set second from the left end of the culture plate. Such 10-fold dilution operations were repeated, and 10-fold dilutions, 100-fold dilutions, 1000-fold dilutions, 10 4 -fold dilutions, 10 5 -fold dilutions, 10 6 -fold dilutions, 10 7 -fold dilutions, 10 8 -fold dilutions, 10 9 -fold dilutions, 10 10 -fold dilutions were set and held for 96 hours. As a result, results as shown in FIG. 26 showing the acne bacteria growth state below were obtained.

[0114]

Table 2

[0115] In Table 2, 100-nanobubble water is 10 mL of purified water containing nanobubbles having a particle size distribution as shown in FIG. 25 (nanobubbles mainly having a particle size of 76 nm and 112 nm), and 55-nanobubble water is 10 mL of purified water containing nanobubbles having a particle size distribution as shown in FIG. 24 (nanobubbles mainly having a particle size of 55 nm or less). In Table 2, ethanol has a concentration of 9.8% by weight and a volume of 1.0 mL, and ketoconazole has a concentration of 0.2% by weight and a volume of 20.0 mg.

[0116] In FIG. 26, the blackened parts indicate that acne bacteria are growing. As shown in FIG. 26, sample solution F (containing nanobubbles mainly having a particle size of 55 nm or less and ketoconazole), which is an embodiment of the present invention, has a superior bactericidal power against acne compared to sample solution C (containing nanobubbles having a particle size exceeding 55 nm (nanobubbles mainly having a particle size of 76 nm and 112 nm) and ketoconazole).

[0117] Therefore, in order to confirm the effectiveness of the skin disease treatment agent of the present invention, a test described below was conducted with 10 participants aged 11 to 34 years (2 males and 8 females) as monitors. Specifically, the effectiveness of the skin disease treatment agent of the present invention was confirmed by applying a drug solution containing micro-nanobubbles or a drug solution containing purified water to the 10 monitors. Photographs of their faces before and after treatment are shown in Figures 27 to 36, and the ages of the 10 monitors and the treatment period for each monitor are shown in Table 3 below.

[0118] [Table 3]

[0119] Six of the ten monitors shown in Table 3 were given a liquid containing 2% ketoconazole in "Nizoral Lotion 2%" and the aforementioned 100 nanobubble water in a ratio of 10g of the former to 80cc of the latter (the particle size distribution of micro- and nanobubbles in this liquid is shown in Figure 25). This liquid was applied to each monitor's face using a spray, at a rate of approximately 0.2-0.5cc per application, for approximately 20 seconds per application, 1-2 times per day. After the liquid applied to the face appeared to have dried (approximately 30 seconds later), each monitor applied an appropriate amount of either 1% clindamycin phosphate in "Dalacin T Gel 1%" or 1% nadifloxacin in "Aquatim Cream 1%" directly to their face by hand. Monitors who received two applications by spray allowed approximately 6-10 hours between the first and second applications. As a result, in the shortest treatment period, the effect appeared after only 58 days (see Table 3, 15-year-old female; see Figure 28).

[0120] Furthermore, for four of the ten monitors shown in Table 3, a liquid containing 2% ketoconazole ("Nizoral Lotion 2%") and purified water in a ratio of 10g of the former to 80cc of the latter was applied to each monitor's face using a spray, at a rate of approximately 0.2-0.5cc per application, for approximately 20 seconds, 1-2 times per day. After the liquid applied to the face appeared to have dried (approximately 30 seconds later), each monitor applied an appropriate amount of either 1% clindamycin phosphate ("Dalacin T Gel 1%") or 1% nadifloxacin ("Aquatim Cream 1%") directly to their face by hand. Monitors who received two applications by spray allowed approximately 6-10 hours between the first and second applications.

[0121] Figures 27 to 32, (a) are photographs of the monitor's face before treatment with the skin disease treatment agent containing nanobubbles of the present invention, and Figures 27 to 32, (b) are photographs of the same monitor's face after treatment at a predetermined date and time with the skin disease treatment agent containing nanobubbles of the present invention. A comparison of the face before treatment (left photograph) and the face after treatment (right photograph) in each figure is as follows.

[0122] Figure 27 shows that the acne that was present on almost the entire face before treatment has almost completely disappeared after treatment. Figure 27 is shown in black and white, so it is not very clear, but the acne that was present on almost the entire face before treatment was red acne.

[0123] Figure 28 shows that the acne seen on both cheeks before treatment has largely disappeared after treatment. In particular, the acne near the lips has disappeared after treatment. Figure 28 is shown in black and white, so it is not very clear, but the acne seen on both cheeks and near the lips before treatment is red acne.

[0124] Figure 29 shows that the acne, which was present on almost the entire face before treatment, has almost completely disappeared after treatment. Although Figure 29 is shown in black and white and is not very clear, the acne that was present on almost the entire face before treatment was red acne.

[0125] As can be seen in Figure 30, in this man's case, the treatment did not have any effect.

[0126] Figure 31 shows that the acne that was present across the entire left cheek before treatment has completely disappeared after treatment. Figure 31 is in black and white, so it is not very clear, but the acne that was present across the entire left cheek before treatment was red acne.

[0127] As can be seen in Figure 32, in this woman's case, the treatment did not have any effect.

[0128] Figures 33 to 36, (a) shows a photograph of the monitor's face before treatment with a skin disease treatment agent containing purified water, and Figures 33 to 36, (b) shows a photograph of the same monitor's face after treatment with the skin disease treatment agent containing purified water at a predetermined date and time. A comparison of the face before treatment (left photograph) and the face after treatment (right photograph) in each figure is as follows.

[0129] As can be seen in Figure 33, in this woman's case, the treatment did not have any effect.

[0130] As can be seen in Figure 34, in this woman's case, the treatment did not have any effect.

[0131] As can be seen in Figure 35, in this man's case, the treatment did not have any effect.

[0132] As can be seen in Figure 36, in this woman's case, the treatment did not have any effect.

[0133] Based on the above, the following effects can be obtained with the skin disease treatment agent of the present invention. (1) Based on the observations in Figures 11 to 23, it is clear that all acne symptoms can be improved by a drug solution containing nanobubbles, mainly with a particle size of 55 nm or less. (2) When comparing the bactericidal effect against acne bacteria of a drug solution containing nanobubbles mainly with a particle size of 55 nm or less with the bactericidal effect against acne bacteria of a drug solution containing nanobubbles mainly with a particle size of 76 nm and 112 nm, the drug solution containing nanobubbles mainly with a particle size of 55 nm or less is superior. (3) According to the observations in Figures 27 to 36, acne symptoms can be improved by a drug solution containing nanobubbles mainly with particle sizes of 76 nm and 112 nm, but improvement is not always possible. In other words, medications containing nanobubbles have the effect of improving acne symptoms. However, this effect varies depending on the nanobubble size. The smaller the nanobubble size, the greater the effect on improving acne symptoms. Medications containing nanobubbles primarily with a particle size of 55 nm or less are more effective at improving acne symptoms than medications containing nanobubbles primarily with particle sizes of 76 nm and 112 nm. [Industrial applicability]

[0134] The skin disease treatment agent of the present invention can be widely applied to the treatment of acne. [Explanation of Symbols]

[0135] 1. Bellows Cylinder Pump 2 Pump Controller 3 Gas-liquid mixing tank 4. Pressure Sensor 5. Micro / Nanobubble Generating Nozzle Mounting Section 6 Liquid suction tube 7. Gas intake port 8. Gas intake adjustment valve 11 Outer case 12 outer case 13 volts 14 nuts 15 High-speed jet liquid injection nozzle 15a Small hole for flow path 15b Nozzle section 16 High-speed jet liquid injection nozzle 16a Small hole for flow path 16b Nozzle section 17 Center pin 18 positioning pins 19 Positioning pins 21 Floats 21a Float tip 21b Reinforcement rib 21c stopper 22 Gas-liquid insertion pipe 23. Gas-liquid insertion pipe 24 Teflon® sidewall 25 Float receiver 26 Excess gas outlet

Claims

1. A skin disease treatment agent comprising micro-nanobubbles having a diameter in the range of 0.1 to 55.0 nm, wherein when three different locations are measured using atomic force microscopy with a scan range of 2000 nm × 2000 nm and the data obtained as height is considered as diameter, the agent comprises 300 or more micro-nanobubbles having a diameter in the range of 0.1 to 55.0 nm.

2. A skin disease treatment agent according to claim 1, comprising a pharmaceutical product, a quasi-drug, a medicated cosmetic, or a cosmetic.

3. The skin disease treatment agent according to claim 2, wherein the pharmaceutical product, quasi-drug, medicated cosmetic, or cosmetic is an agent having anti-inflammatory, antioxidant, blood circulation promoting, and blood flow improving effects.

4. The skin disease treatment agent according to claim 1, 2, or 3, wherein the micro- and nanobubbles are produced from one or more gases selected from the group consisting of hydrogen, oxygen, carbon dioxide, and air.

5. The skin disease treatment agent according to claim 4, comprising one or more liquids selected from water and ethanol.

6. A skin disease treatment agent according to claim 5, further comprising a hydrophilic thickening agent.

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