Composition comprising totarol and hexamidine or derivative or pharmaceutically acceptable salt thereof, and uses of composition

Abstract

The present invention relates to a composition comprising: totarol; and hexamidine or a derivative or a pharmaceutically acceptable salt thereof, and to uses of the composition, wherein the composition may have an antimicrobial effect, an inflammation-inhibiting effect, and a dandruff-alleviating effect.

Description

Composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; and the use thereof

[0001] The invention relates to a composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof, and to the use thereof.

[0002] The demand for antimicrobial products is steadily increasing across various fields, including pharmaceuticals, cosmetics, and household goods, for personal hygiene management and infection prevention. However, when antimicrobial ingredients are used at high concentrations, while they provide excellent antimicrobial effects, there are concerns that they can cause various side effects in the human body, such as skin irritation, allergic reactions, and the development of resistant bacteria.

[0003] Therefore, the importance of researching and developing new compositions capable of effectively exhibiting antibacterial effects even at low concentrations is being highlighted.

[0004] Furthermore, dandruff is caused by excessive keratinization and shedding of the scalp; beyond a mere cosmetic issue, it can lead to scalp itching, inflammation, and, in severe cases, even hair loss. As such, scalp health plays a crucial role in psychological well-being in addition to personal hygiene and physical health, making effective dandruff management essential.

[0005] Meanwhile, existing dandruff treatments have had limitations in use, such as providing only temporary symptom relief or irritating the scalp with long-term use.

[0006] Therefore, the importance of researching and developing new compositions that can improve scalp condition, effectively treat dandruff, continuously suppress dandruff-causing bacteria, and simultaneously reduce scalp irritation is being highlighted.

[0007] Accordingly, the inventors recognized the need for the development of antimicrobial raw materials and combinations thereof, or the need for scalp health and dandruff improvement, and sought to develop a new composition to improve dandruff by inhibiting dandruff-causing fungi and ultimately improve the condition of the scalp. As a result, the present invention was completed by confirming that combining specific raw materials exhibits an excellent antimicrobial effect.

[0008] One aspect provides an antimicrobial composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[0009] Another aspect is to provide a cosmetic composition for improving scalp condition or skin condition comprising the above-mentioned antimicrobial composition.

[0010] Another aspect is to provide a topical skin composition for improving scalp condition or skin condition comprising the above-mentioned antimicrobial composition.

[0011] Another aspect is to provide a pharmaceutical composition for the prevention or treatment of scalp or skin diseases comprising the above-mentioned antimicrobial composition.

[0012] Another aspect is to provide the use of totarol for antibacterial purposes; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof.

[0013] Another aspect is to provide the use of totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for improving scalp condition or skin condition.

[0014] Another aspect is to provide the use of totarol and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for the prevention or improvement of scalp or skin diseases.

[0015] Another aspect provides an antimicrobial method comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0016] Another aspect provides a method for improving scalp or skin condition, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0017] Another aspect provides a method for preventing or improving a scalp or skin disease, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0018] Another aspect provides an antimicrobial composition comprising two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole.

[0019] Another aspect is to provide a cosmetic composition for skin cleansing or skin condition improvement comprising the above-mentioned antimicrobial composition.

[0020] Another aspect is to provide a topical skin composition for cleansing the skin or improving skin condition, comprising the above-mentioned antimicrobial composition.

[0021] Another aspect is to provide a pharmaceutical composition for the prevention or improvement of inflammatory skin diseases comprising the above-mentioned antimicrobial composition.

[0022] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for antibacterial purposes; totarol; and climbazole.

[0023] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for cleansing the skin or improving skin condition.

[0024] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for the prevention or improvement of inflammatory skin diseases.

[0025] Another aspect provides an antimicrobial method comprising the step of administering to an individual an effective amount of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and a combination of two or more selected from the group consisting of climbazole.

[0026] Another aspect provides a method for cleansing the skin or improving the skin condition, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

[0027] Another aspect provides a method for preventing or improving inflammatory skin diseases, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

[0028] One aspect provides an antimicrobial composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[0029] The term "hexamidine" refers to organic compounds of the diamidine series characterized by a symmetrical structure having amidine groups (-C(=NH)NH2) at both ends of a long carbon chain. The general chemical formula is C 12 H 26 It is N4O2, with a molecular weight of about 270.36 g / mol, and has broad-spectrum antibacterial and preservative effects due to its structural characteristics in which amidin groups are attached to both ends of a central carbon chain.

[0030] The pharmaceutically acceptable salt of the above hexamidine may be hexamidine diisethionate, but is not limited thereto.

[0031] The term "Hexamidine Diisethionate" is C 20 H 26 It refers to the isethionate of hexamidine, CAS No. 659-40-5, N4O2·(C2H6O4S)2. Formerly known as hexamidine diisethionate, it is primarily used as a synthetic preservative with broad-spectrum antimicrobial activity, capable of inhibiting and killing various Gram-positive and Gram-negative bacteria, molds, and yeasts.

[0032] The above hexamidine diacethionate refers to a compound represented by the following chemical formula 1:

[0033] [Chemical Formula 1]

[0034]

[0035] The term "Totarol" refers to a natural compound extracted from the totara tree (Podocarpus totara), C 20 H 30 It is a biologically active phenolic compound of the diterpene series, CAS No. 511-15-9.

[0036] The above totarol refers to a compound represented by the following chemical formula 2:

[0037] [Chemical Formula 2]

[0038]

[0039] The above composition comprises, based on the total weight of the composition, 0.00006 wt% to 20 wt%, 0.00006 wt% to 10 wt%, 0.00006 wt% to 6 wt%, 0.00006 wt% to 1 wt%, 0.00006 wt% to 0.6 wt%, 0.0001 wt% to 20 wt%, 0.0001 wt% to 10 wt%, 0.0001 wt% to 5 wt%, 0.0001 wt% to 1 wt%, 0.0001 wt% to 0.5 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 5 wt%, 0.001 wt% to 1 wt%, 0.001 wt% to 0.6 wt%, It may contain 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.01 wt% to 1 wt%, 0.01 wt% to 0.6 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 1 wt%, or 0.1 wt% to 0.6 wt% of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[0040] The above composition comprises, based on the total weight of the composition, 0.00006 wt% to 20 wt%, 0.00006 wt% to 10 wt%, 0.00006 wt% to 6 wt%, 0.00006 wt% to 1 wt%, 0.00006 wt% to 0.6 wt%, 0.00006 wt% to 0.4 wt%, 0.00006 wt% to 0.25 wt%, 0.0001 wt% to 20 wt%, 0.0001 wt% to 10 wt%, 0.0001 wt% to 5 wt%, 0.0001 wt% to 1 wt%, 0.0001 wt% to 0.5 wt%, 0.005 wt% to 20 wt%, 0.005 wt% to 10 wt%, and 0.005 wt%. to 5 wt%, 0.005 wt% to 1 wt%, 0.005 wt% to 0.6 wt%, 0.005 wt% to 0.4 wt%, 0.005 wt% to 0.25 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 5 wt%, 0.001 wt% to 1 wt%, 0.001 wt% to 0.6 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.05 wt% to 1 wt%, 0.05 wt% to 0.6 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 It may include totarol in an amount of 5% to 5% by weight, 0.01% to 1% by weight, 0.01% to 0.6% by weight, 0.1% to 20% by weight, 0.1% to 10% by weight, 0.1% to 5% by weight, 0.1% to 1% by weight, 0.1% to 0.6% by weight, 0.1% to 0.4% by weight, or 0.1% to 0.25% by weight.

[0041] The above composition is totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; for example, 1:0.001 to 1:100, 1:0.001 to 1:10, 1:0.01 to 1:100, 1:0.01 to 1:10, 1:0.125 to 1:128, 1:0.125 to 1:64, 1:0.125 to 1:32, 1:0.125 to 1:30, 1:0.125 to 1:25, 1:0.125 to 1:20, 1:0.125 to 1:16, 1:0.1 to 1:128, 1:0.1 to 1:64, 1:0.1 to 1:32, 1:0.1 to 1:30, It may be included in a weight ratio of 1:0.1 to 1:25, 1:0.1 to 1:20, 1:0.1 to 1:16, 1:0.2 to 1:128, 1:0.2 to 1:64, 1:0.2 to 1:32, 1:0.2 to 1:30, 1:0.2 to 1:25, 1:0.2 to 1:20, 1:0.2 to 1:16, 1:0.25 to 1:128, 1:0.25 to 1:64, 1:0.25 to 1:32, 1:0.25 to 1:30, 1:0.25 to 1:25, 1:0.25 to 1:20, or 1:0.25 to 1:16. If the above weight ratio falls outside the above range or is lower than the suggested minimum content, the antibacterial activity or antibacterial synergistic effect of the two ingredients is negligible and fails to inhibit the growth of microorganisms, so it may not have an effect of improving dandruff or inhibiting inflammation.

[0042] The term "antimicrobial" refers to any action that inhibits the growth or kills microorganisms. The aforementioned antimicrobial effect may be an antimicrobial effect against inflammation-causing bacteria or dandruff-causing bacteria; specifically, it may be an antimicrobial effect against Staphylococcus aureus or Malassezia furfur, but is not limited thereto.

[0043] In one embodiment, the composition may have an antibacterial effect, a dandruff improvement effect, or an inflammation suppression effect.

[0044] In one embodiment, the composition may have antibacterial activity against inflammation-causing bacteria and dandruff-causing bacteria.

[0045] The term "inflammatory bacteria" refers to all microorganisms that cause inflammation in the body of a human or animal. The said inflammation-causing bacteria may be, but are not limited to, Staphylococcus aureus.

[0046] The term "dandruff-causing bacteria" refers to all microorganisms that cause dandruff. The said dandruff-causing bacteria may be, but are not limited to, Malassezia furfur.

[0047] In one embodiment, it was confirmed that the composition has an excellent antibacterial or bactericidal effect against Staphylococcus aureus, an inflammation-causing bacterium.

[0048] In one embodiment, it was confirmed that the composition has an excellent antibacterial or bactericidal effect against Malassezia furfur, a dandruff-causing bacterium.

[0049] Another aspect provides a cosmetic composition for improving scalp condition or skin condition comprising the above-mentioned antimicrobial composition. In the above-mentioned cosmetic composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0050] The above cosmetic composition may be prepared in a formulation comprising a lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, eye cream, hand cream, foundation, essence, nourishing essence, eye essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing water, cleansing oil, cleansing tissue, hand sanitizer, body lotion, body cream, body cleanser, suspension, gel, powder, paste, shampoo, hair essence, treatment, rinse, scalp pack, mask pack or sheet, or aerosol composition. Compositions of such formulations may be prepared according to methods conventional in the field.

[0051] The ingredients included in the above cosmetic composition may include ingredients commonly used in cosmetic compositions in addition to the antibacterial composition as active ingredients, and may include, for example, conventional auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0052] In one embodiment, the improvement of the scalp condition may mean improvement of dandruff, inhibition of dandruff-causing bacteria, prevention of dandruff, improvement of scalp exfoliation, prevention of hair loss, promotion of hair growth, protection of hair, promotion of hair growth, increase in hair thickness, prevention of scalp aging, relief of scalp heat sensation, inhibition of scalp inflammation, etc. Specifically, it may mean improvement of dandruff, inhibition of dandruff-causing bacteria, prevention of dandruff, improvement of scalp exfoliation, and inhibition of scalp inflammation, but is not limited thereto.

[0053] The term "improvement of scalp condition" refers to all actions that improve the health and appearance of the scalp and hair, including dandruff improvement, inhibition of dandruff-causing bacteria, prevention of dandruff, improvement of scalp exfoliation, inhibition of scalp inflammation, normalization of the hair cycle, strengthening of hair roots, prevention of hair loss, improvement of the scalp environment, regulation of scalp hormone balance, reduction of scalp inflammation, relief of scalp heat sensation, prevention of scalp heat aging, prevention of oxidative stress, strengthening of hair protein, supplying nutrition to the scalp, regulation of scalp sebum, promotion of hair growth, improvement of hair thickness, stress management, etc. The above-mentioned improvement of scalp condition may mean dandruff improvement, inhibition of dandruff-causing bacteria, prevention of dandruff, improvement of scalp exfoliation, and inhibition of scalp inflammation, but is not limited thereto.

[0054] The term "dandruff improvement" refers to any action capable of improving dandruff caused by excessive keratinization and shedding of the scalp.

[0055] In one embodiment, the improvement of the skin condition may mean preventing skin aging, improving skin wrinkles, enhancing skin elasticity, moisturizing the skin, strengthening the skin barrier, whitening the skin, improving skin inflammation, anti-acne, improving atopic dermatitis, or suppressing itching, and specifically may mean improving skin inflammation, but is not limited thereto.

[0056] The term "improvement of skin inflammation" refers to any action that improves or suppresses skin inflammation.

[0057] Another aspect provides a topical skin composition for improving scalp condition or skin condition comprising the above-mentioned antimicrobial composition. In the above-mentioned topical skin composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0058] In this specification, the term "external skin preparation" is a concept that generally encompasses all compositions used externally, and may refer to a wide range of products that can be applied to cosmetic compositions containing various cosmetics such as basic cosmetics, makeup cosmetics, hair cosmetics, shaving cosmetics, or various pharmaceuticals or quasi-pharmaceuticals such as ointments. For example, the above quasi-pharmaceuticals may be disinfectants, shower foams, mouthwash, wet wipes, detergent soaps, hand washes, humidifier fillers, masks, ointments, coating agents, or filter fillers.

[0059] The above-mentioned topical skin composition may additionally contain, in addition to the active ingredient, ingredients commonly incorporated in topical preparations according to the intended use and the properties of the topical composition, specifically moisturizers, UV absorbers, vitamins, animal and plant extracts, digestive agents, whitening agents, vasodilators, astringents, cooling agents, hormones, etc.

[0060] The formulation of the above-mentioned external skin composition may take an appropriate form depending on the intended use and the properties of the external composition, and specifically may be an aqueous solution type, a solubilization type, an emulsion type, a liquid type, a gel type, a paste type, an ointment type, an aerosol type, a water-oil two-layer type, or a water-oil-powder three-layer type, but the formulation and form of the external agent of the present invention are not limited by the above-mentioned formulation.

[0061] In addition, the above-mentioned topical skin preparation may further include a mechanism necessary to penetrate or transfer the active ingredient into the skin tissue.

[0062] Another aspect provides a pharmaceutical composition for the prevention, treatment, or improvement of scalp or skin diseases comprising the above-mentioned antimicrobial composition. In the above-mentioned pharmaceutical composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0063] The above pharmaceutical composition may additionally include a pharmaceutically acceptable carrier.

[0064] The above pharmaceutical composition may be formulated and used in the form of tablets, pills, powders, granules, capsules, suspensions, oral liquids, emulsions, or syrups, as well as external preparations, suppositories, or injectable solutions, according to conventional methods. Specifically, when formulating, it may be prepared using diluents or excipients such as commonly used fillers, weighting agents, binders, wetting agents, disintegrants, and surfactants.

[0065] The above pharmaceutical composition may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage may be appropriately selected by a person skilled in the art, although it depends on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the time.

[0066] The above-mentioned scalp conditions include all conditions that may occur on the scalp or hair, regardless of the cause. For example, they may include inflammatory scalp conditions, itching, dandruff, seborrheic dermatitis or scalp dermatitis, hair loss, alopecia areata, male pattern baldness, psoriasis, stress-induced inflammation, and sensitive scalp.

[0067] The above scalp disease may be a disease caused by Staphylococcus aureus or Malassezia furfur.

[0068] The above skin diseases include all diseases that may occur on the skin, regardless of their cause. For example, they may include inflammatory skin diseases, itching, seborrheic dermatitis or dermatitis, psoriasis, stress-induced inflammation, and sensitive skin.

[0069] The above skin disease may be a disease caused by Staphylococcus aureus or Malassezia furfur.

[0070] The term "prevention" refers to any act in which the possibility of onset of scalp disease is suppressed or delayed by the administration of the composition of the present invention.

[0071] The term "treatment" refers to any act of improving or beneficially altering the symptoms of a scalp disease through the administration of the composition of the present invention.

[0072] The term "improvement" refers to any act of improving or beneficially altering the symptoms of a scalp disease through the administration of the composition of the present invention.

[0073] Another aspect is to provide the use of totarol for antibacterial purposes; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof.

[0074] Another aspect is to provide the use of totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for improving scalp condition or skin condition.

[0075] Another aspect is to provide the use of totarol and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for the prevention or improvement of scalp or skin diseases.

[0076] Another aspect provides an antimicrobial method comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0077] Another aspect provides a method for improving scalp or skin condition, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0078] Another aspect provides a method for preventing or improving a scalp or skin disease, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

[0079] In the above aspects, any terms or elements mentioned that are identical to those already mentioned are as stated above.

[0080] In the above aspects, "effective amount" refers to the content of a composition in an amount sufficient to provide a therapeutic, corrective, or preventive effect of the pharmacological component within the composition to an individual to whom the composition is to be administered. The effective amount may include the meanings of a "preventive effective amount," a "corrective effective amount," or a "therapeutic effective amount."

[0081] In the above aspects, "individual" may mean any individual requiring antibacterial action, improvement of scalp condition, improvement of skin condition, or prevention or improvement of scalp or skin disease. The individual may include or exclude humans, and may include mammals, and the mammals may include, for example, humans, dogs, cats, rats, mice, rats, guinea pigs, horses, cattle, pigs, sheep, monkeys, chimpanzees, etc.

[0082] In the above aspects, "administration" means administering an effective amount of the composition directly to an individual to form it within the individual's body. The administration may be oral or parenteral, and may include transdermal administration, subcutaneous administration, or application to the skin. Suitable dosages of the composition may be prescribed differently depending on factors such as the formulation method, mode of administration, patient's age, body weight, sex, pathological condition, diet, time of administration, route of administration, excretion rate, and response sensitivity.

[0083] Another aspect provides an antimicrobial composition comprising two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole.

[0084] The term "Climbazole" refers to 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one, a widely used compound as an imidazole antifungal agent.

[0085] The above climbazole refers to a compound represented by the following chemical formula 3:

[0086] [Chemical Formula 3]

[0087]

[0088] The above composition may include climbazole.

[0089] The above composition may include, but is not limited to, climbazole and hexamidine diacethionate; climbazole and totarol; or climbazole, hexamidine diacethionate, and totarol.

[0090] The above composition comprises, based on the total weight of the composition, 0.0078 wt% to 20 wt%, 0.0078 wt% to 10 wt%, 0.0078 wt% to 6 wt%, 0.0078 wt% to 5 wt%, 0.0078 wt% to 3 wt%, 0.0078 wt% to 2.5 wt%, 0.0078 wt% to 1 wt%, 0.0078 wt% to 0.6 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.01 wt% to 1 wt%, 0.01 wt% to 0.6 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 0.1 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 0.1 wt%. It may contain 1% to 1% by weight and 0.1% to 0.6% by weight of climbazole.

[0091] The above composition comprises, based on the total weight of the composition, 0.0002 wt% to 20 wt%, 0.0002 wt% to 10 wt%, 0.0002 wt% to 5 wt%, 0.0002 wt% to 1 wt%, 0.0002 wt% to 0.5 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 5 wt%, 0.001 wt% to 1 wt%, 0.001 wt% to 0.6 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.01 wt% to 1 wt%, 0.01 wt% to 0.6 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 5 wt%, 0.01 wt% to 1 wt%, 0.01 wt% to 0.6 wt%, and 0.1 wt% to 20 wt%. It may contain 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 1 wt%, 0.1 wt% to 0.6 wt% of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[0092] The above composition comprises, based on the total weight of the composition, 0.0005 wt% to 20 wt%, 0.0005 wt% to 10 wt%, 0.0005 wt% to 6 wt%, 0.0005 wt% to 1 wt%, 0.0005 wt% to 0.6 wt%, 0.0005 wt% to 0.4 wt%, 0.0005 wt% to 0.25 wt%, 0.0001 wt% to 20 wt%, 0.0001 wt% to 10 wt%, 0.0001 wt% to 5 wt%, 0.0001 wt% to 1 wt%, 0.0001 wt% to 0.5 wt%, 0.005 wt% to 20 wt%, 0.005 wt% to 10 wt%, and 0.005 wt% to 5 wt%. 0.005 wt% to 1 wt%, 0.005 wt% to 0.6 wt%, 0.005 wt% to 0.4 wt%, 0.005 wt% to 0.25 wt%, 0.001 wt% to 20 wt%, 0.001 wt% to 10 wt%, 0.001 wt% to 5 wt%, 0.001 wt% to 1 wt%, 0.001 wt% to 0.6 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.05 wt% to 1 wt%, 0.05 wt% to 0.6 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt% It may include totarol in an amount of 0.01 wt% to 1 wt%, 0.01 wt% to 0.6 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 1 wt%, 0.1 wt% to 0.6 wt%, 0.1 wt% to 0.4 wt%, or 0.1 wt% to 0.25 wt%.

[0093] The above composition is hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; and climbazole; in a ratio of 1:2 to 1:512, e.g., 1:2 to 1:512, 1:2 to 1:256, 1:2 to 1:128, 1:2 to 1:64, 1:4 to 1:512, 1:4 to 1:256, 1:4 to 1:128, 1:4 to 1:64, 1:8 to 1:512, 1:8 to 1:256, 1:8 to 1:128, 1:8 to 1:64, 1:10 to 1:512, 1:10 to 1:256, 1:10 to 1:128, 1:10 to 1:100, 1:10 to 1:90, 1:10 to 1:80, 1:10 to It may be included in a weight ratio of 1:70, 1:10 to 1:64, 1:12 to 1:512, 1:12 to 1:256, 1:12 to 1:128, 1:12 to 1:100, 1:12 to 1:90, 1:12 to 1:80, 1:12 to 1:70, 1:12 to 1:64. 1:16 to 1:512, 1:16 to 1:256, 1:16 to 1:128, 1:16 to 1:100, 1:16 to 1:90, 1:16 to 1:80, 1:16 to 1:70, or 1:16 to 1:64.

[0094] The above composition comprises totarol and climbazole in a ratio of 1:2 to 1:256, for example, 1:2 to 1:256, 1:2 to 1:128, 1:2 to 1:100, 1:2 to 1:90, 1:2 to 1:80, 1:2 to 1:70, 1:2 to 1:64, 1:4 to 1:256, 1:4 to 1:128, 1:4 to 1:100, 1:4 to 1:90, 1:4 to 1:80, 1:4 to 1:70, 1:4 to 1:64, 1:6 to 1:256, 1:6 to 1:128, 1:6 to 1:100, 1:6 to 1:90, 1:6 to It may be included in a weight ratio of 1:80, 1:6 to 1:70, 1:6 to 1:64, 1:8 to 1:256, 1:8 to 1:128, 1:8 to 1:100, 1:8 to 1:90, 1:8 to 1:80, 1:8 to 1:70, or 1:8 to 1:64.

[0095] The above composition is hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; and totarol; in a ratio of 1:0.1 to 1:20, e.g., 1:0.1 to 1:20, 1:0.1 to 1:16, 1:0.1 to 1:8, 1:0.1 to 1:4, 1:0.1 to 1:2, 1:0.1 to 1:1, 1:0.1 to 1:0.5, 1:0.1 to 1:0.25, 1:0.1 to 1:0.125, 1:0.125 to 1:20, 1:0.125 to 1:16, 1:0.125 to 1:8, 1:0.125 to 1:4, 1:0.125 to 1:2, 1:0.125 to 1:1, 1:0.125 to 1:0.5, 1:0.125 to 1:0.25, 1:0.25 to 1:20, 1:0.25 to 1:16, 1:0.25 to 1:8, 1:0.25 to 1:4, 1:0.25 to 1:2, 1:0.25 to 1:1, 1:0.25 to 1:0.5, 1:0.5 to 1:20, 1:0.5 to 1:16, 1:0.5 to 1:8, 1:0.5 to 1:4, 1:0.5 to 1:2, 1:0.5 to 1:1, 1:1 to 1:20, 1:1 to 1:16, 1:1 to 1:8, 1:1 to 1:4, 1:1 to 1:2, 1:2 to It may be included in a weight ratio of 1:20, 1:2 to 1:16, 1:2 to 1:8, 1:2 to 1:4, 1:4 to 1:20, 1:4 to 1:16, 1:4 to 1:8, 1:8 to 1:20, or 1:8 to 1:16.

[0096] The above composition comprises hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole; in a ratio of 1:0.1 to 1000:0.1 to 1000, e.g., 1:0.1 to 1000:0.1 to 1000, 1:0.1 to 100:0.1 to 100, 1:0.1 to 10:0.1 to 10, 1:0.1 to 20:1 to 1000, 1:0.1 to 20:1 to 800, 1:0.1 to 20:1 to 600, 1:1.5 to 20:1 to 600, 1:0.1 to 20:6 to 600, 1:0.125 to 16:2 to 512, 1:2 to 16:128 to 512, 1:2 to 16:256 to 512, 1:4 to 16:128 to 512, 1:4 to 16:256 to 512, 1:0.125 to 0.5:128 to 512, 1:0.125 to 0.5:256 to 512, 1:0.25 to 16:2 to 512, 1:0.25 to 8:2 to 512, 1:0.5 to 4:2 to 512, 1:1 to 2:2 to 512, 1:0.125 to 16:2 to 256, 1:0.25 to 16:2 to 128, 1:0.25 to 8:2 to 64, 1:0.5 to 4:2 to 32, 1:1 to 2:2 to It may be included in a weight ratio of 16, 1:2:16, 1:2:4, 1:8:512, 1:0.5:2, 1:0.25:64, 1:0.125:16, or 1:16:256.

[0097] If the above weight ratio falls outside the above range or is lower than the suggested minimum content, the antibacterial power or antibacterial synergy of the raw material is negligible and fails to inhibit the growth of microorganisms, so it may not possess an antibacterial effect or an anti-inflammatory effect.

[0098] The term "antimicrobial" refers to any action that inhibits the growth or kills microorganisms. The aforementioned antimicrobial effect may be an antimicrobial effect against inflammation-causing bacteria, and specifically, may be an antimicrobial effect against Staphylococcus aureus, but is not limited thereto.

[0099] In one embodiment, the composition may have an antibacterial effect or an anti-inflammatory effect.

[0100] In one embodiment, the composition may have antibacterial activity against inflammation-causing bacteria.

[0101] In one embodiment, the composition may have antibacterial activity against inflammation-causing bacteria.

[0102] The term "inflammatory bacteria" refers to all microorganisms that cause inflammation in the body of a human or animal. The said inflammation-causing bacteria may be, but are not limited to, Staphylococcus aureus.

[0103] In one embodiment, it was confirmed that the composition has an excellent antibacterial or bactericidal effect against Staphylococcus aureus, an inflammation-causing bacterium.

[0104] Another aspect provides a cosmetic composition for cleansing the skin or improving skin condition comprising the above-mentioned antimicrobial composition. In the above-mentioned cosmetic composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0105] The above cosmetic composition may be prepared in a formulation comprising a lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, eye cream, hand cream, foundation, essence, nourishing essence, eye essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing water, cleansing oil, cleansing tissue, hand sanitizer, body lotion, body cream, body cleanser, suspension, gel, powder, paste, shampoo, hair essence, treatment, rinse, scalp pack, mask pack or sheet, or aerosol composition. Compositions of such formulations may be prepared according to methods conventional in the field.

[0106] The ingredients included in the above cosmetic composition may include ingredients commonly used in cosmetic compositions in addition to the antibacterial composition as active ingredients, and may include, for example, conventional auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0107] The term "cleaning" refers to any action of removing unnecessary substances, contaminants, foreign substances, etc., from an object or surface, and the aforementioned "antimicrobial cleaning" means removing contaminants while simultaneously inhibiting or eliminating the growth of microorganisms.

[0108] The above cleaning may be for cleaning the body of a human or animal, and the above antimicrobial cleaning may be for inhibiting or removing the growth of microorganisms on the body of a human or animal, specifically for inhibiting or removing the growth of inflammation-causing bacteria on the body of a human or animal, and more specifically for inhibiting or removing the growth of Staphylococcus aureus on the body of a human or animal, but is not limited thereto.

[0109] The above skin condition improvement may be anti-aging, improvement of skin wrinkles, enhancement of skin elasticity, skin moisturization, strengthening of the skin barrier, skin whitening, improvement of skin inflammation, anti-acne, improvement of atopic dermatitis, or suppression of itching.

[0110] Another aspect provides a topical skin composition for cleansing the skin or improving skin condition, comprising the above-mentioned antimicrobial composition. In the topical skin composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0111] In this specification, the term "external skin preparation" is a concept that generally encompasses all compositions used externally, and may refer to a wide range of products that can be applied to cosmetic compositions containing various cosmetics such as basic cosmetics, makeup cosmetics, hair cosmetics, shaving cosmetics, or various pharmaceuticals or quasi-pharmaceuticals such as ointments. For example, the above quasi-pharmaceuticals may be disinfectants, shower foams, mouthwash, wet wipes, detergent soaps, hand washes, humidifier fillers, masks, ointments, coating agents, or filter fillers.

[0112] The above-mentioned topical skin composition may additionally contain, in addition to the active ingredient, ingredients commonly incorporated in topical preparations according to the intended use and the properties of the topical composition, specifically moisturizers, UV absorbers, vitamins, animal and plant extracts, digestive agents, whitening agents, vasodilators, astringents, cooling agents, hormones, etc.

[0113] The formulation of the above-mentioned external skin composition may take an appropriate form depending on the intended use and the properties of the external composition, and specifically may be an aqueous solution type, a solubilization type, an emulsion type, a liquid type, a gel type, a paste type, an ointment type, an aerosol type, a water-oil two-layer type, or a water-oil-powder three-layer type, but the formulation and form of the external agent of the present invention are not limited by the above-mentioned formulation.

[0114] In addition, the above-mentioned topical skin preparation may further include a mechanism necessary to penetrate or transfer the active ingredient into the skin tissue.

[0115] Another aspect provides a pharmaceutical composition for the prevention, treatment, or improvement of inflammatory skin diseases comprising the above-mentioned antimicrobial composition. In the above-mentioned pharmaceutical composition, any terms or elements mentioned that are identical to those already mentioned are as described above.

[0116] The above pharmaceutical composition may additionally include a pharmaceutically acceptable carrier.

[0117] The above pharmaceutical composition may be formulated and used in the form of tablets, pills, powders, granules, capsules, suspensions, oral liquids, emulsions, or syrups, as well as external preparations, suppositories, or injectable solutions, according to conventional methods. Specifically, when formulating, it may be prepared using diluents or excipients such as commonly used fillers, weighting agents, binders, wetting agents, disintegrants, and surfactants.

[0118] The above pharmaceutical composition may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage may be appropriately selected by a person skilled in the art, although it depends on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the time.

[0119] The above-mentioned inflammatory skin disease includes all inflammatory diseases that may occur on the skin, regardless of the cause. For example, it may include skin wounds, dermatitis, pruritus, eczematous skin disease, dry eczema, erythema, urticaria, psoriasis, drug rash, acne, inflammatory scalp disease, seborrheic dermatitis or scalp dermatitis, atopic dermatitis, contact dermatitis, or stress-induced inflammation.

[0120] The above-mentioned inflammatory skin disease may be a disease caused by Staphylococcus aureus.

[0121] The term "prevention" refers to any act in which the possibility of developing inflammatory skin diseases is suppressed or delayed by the administration of the composition of the present invention.

[0122] The term "treatment" refers to any act of improving or beneficially altering the symptoms of inflammatory skin diseases through the administration of the composition of the present invention.

[0123] The term "improvement" refers to any act of improving or beneficially altering the symptoms of inflammatory skin diseases through the administration of the composition of the present invention.

[0124] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for antibacterial purposes; totarol; and climbazole.

[0125] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for cleansing the skin or improving skin condition.

[0126] Another aspect is to provide the use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for the prevention or improvement of inflammatory skin diseases.

[0127] Another aspect provides an antimicrobial method comprising the step of administering to an individual an effective amount of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and a combination of two or more selected from the group consisting of climbazole.

[0128] Another aspect provides a method for cleansing the skin or improving the skin condition, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

[0129] Another aspect provides a method for preventing or improving inflammatory skin diseases, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

[0130] In the above aspects, any terms or elements mentioned that are identical to those already mentioned are as stated above.

[0131] A composition comprising totarol according to one aspect and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof has an antibacterial effect, an anti-inflammatory effect and a dandruff-improving effect, and a composition comprising two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole according to another aspect has an antibacterial effect and an anti-inflammatory effect, so it can be applied in various ways, such as cosmetic compositions, topical skin compositions, and pharmaceutical compositions for the prevention or improvement of scalp or skin diseases.

[0132] Fig. 1 is <1> The results of the evaluation of the bactericidal activity of a composition containing hexamidine diacethionate and totarol are shown, including Comparative Example 1 (control group) (A) and Example (B) which measured Malassezia furfur, Comparative Example 1 (control group) (C) and Example (D) which measured Staphylococcus aureus.

[0133] Figure 2 is <2> The results of the evaluation of the bactericidal activity of a composition comprising a combination of climbazole, hexamidine diacethionate, and totarol are shown, including Comparative Example 1 (control group) (A), Example 1 (B), Example 2 (C), Comparative Example 1 (control group) (D), and Example 3 (E).

[0134] The following examples will be explained in more detail. However, these examples are intended to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.

[0135] <1> Composition comprising hexamidine diacetionate and totarol

[0136] Experimental Example 1. Preparation of inflammation-inducing bacteria and dandruff-inducing bacteria

[0137] 1-1. Preparation of Staphylococcus aureus

[0138] To evaluate the antibacterial effect, Staphylococcus aureus, an inflammation-inducing bacterium, was cultured and prepared.

[0139] Specifically, Staphylococcus aureus was cultured on tryptic soy agar (TSA) at 32°C for 24 hours. Afterward, a suspension was prepared with PBS buffer, and the bacterial count was adjusted.

[0140] 1-2. Preparation of Malassezia

[0141] To evaluate the antibacterial effect, Malassezia furfur, a dandruff-causing bacterium, was cultured and prepared.

[0142] Specifically, Malassezia furfur was cultured on modified Dixon agar (mDixon agar) at 32°C for 72 hours. Afterward, a suspension was prepared with PBS buffer, and the bacterial count was adjusted.

[0143] Experimental Example 2. Preparation of a composition comprising hexamidine diacetionate and totarol

[0144] Hexamidine diisethionate was cleanly dissolved in propylene glycol and water (1:0.25 weight ratio) at a concentration of 8 wt%, and totarol was cleanly dissolved in dipropylene glycol at a concentration of 1 wt%, then diluted with Tryptic Soy Broth or modified Dixon Broth medium to adjust to the desired concentration.

[0145] Experimental Example 3. Evaluation of Antimicrobial Activity

[0146] As in Experimental Examples 1-1 and 1-2, Staphylococcus aureus and Malassezia furfur were cultured to determine the minimum inhibitory concentration having antibacterial activity for each of the raw materials, hexamidine diacethionate and totarol, which are included in the composition prepared in Experimental Example 2.

[0147] Specifically, 100 µl of bacterial suspension, with the bacterial counts of Staphylococcus aureus and Malassezia furfur adjusted, was added to 96-well plates. 100 µl each of the prepared raw materials, hexamidine diacetionate and totarol, were added to the first row of the plate containing 100 µl of bacterial suspension. After thoroughly mixing the bacterial suspension and the raw materials, 100 µl was added to the second row to dilute the raw materials by half. After serially diluting the raw materials by half in this manner, the remaining 100 µl of the mixture in the last row was discarded.

[0148] After plate culture, the turbidity of the medium was checked to visually determine whether bacteria had grown. The lowest concentration at which no bacteria grew based on the turbidity was defined as the Minimal Inhibitory Concentration (MIC, wt%) of the ingredient. All tests were repeated three times.

[0149] As a result, as shown in Table 1 below, the minimum inhibitory concentrations having antibacterial activity against Malassezia were confirmed to be 0.5 wt% for hexamidine diacethionate and 0.125 wt% for totarol, and the minimum inhibitory concentrations having antibacterial activity against Staphylococcus aureus were confirmed to be 0.00049 wt% for hexamidine diacethionate and 0.00024 wt% for totarol.

[0150] [Table 1]

[0151]

[0152] Experimental Example 4. Confirmation of antibacterial synergistic effect

[0153] Based on the minimum inhibitory concentrations of hexamidine diacethionate and totarol confirmed in Experimental Example 3 above, the following experiment was conducted to confirm the antibacterial synergistic effect when hexamidine diacethionate and totarol are mixed.

[0154] 25 µl of hexamidine diacethionate was dispensed into the wells of the X-axis row of a 96-well plate in order from low concentration (1 / 8 of the minimum inhibitory concentration) to high concentration (8 times the minimum inhibitory concentration), and 25 µl of totarol was dispensed into the wells of the Y-axis column in order from low concentration (1 / 8 of the minimum inhibitory concentration) to high concentration (8 times the minimum inhibitory concentration). Subsequently, 50 µl of each bacterial suspension, with the bacterial count adjusted, was dispensed into all wells containing the raw materials and cultured.

[0155] After plate culture, the turbidity of the medium was checked to visually determine whether bacterial growth was occurring. The mixing ratio (weight ratio) at the minimum concentration at which bacterial growth was not visually observed based on the turbidity was identified. To confirm the most efficient mixing concentration results, the fractional inhibiting concentration (FIC) and FIC index were calculated by substituting the values ​​into the following mathematical formula.

[0156] [Mathematical Formula 1]

[0157] FIC of substance A or B = (MIC of raw material A or B in the mixture) / (MIC when raw material A or B is used alone)

[0158] [Mathematical Formula 2]

[0159] FIC Index = FIC of Substance A + FIC of Substance B

[0160] It was determined that the range in which bacteria do not proliferate is synergism if the FIC index ≤ 0.5, partial synergism if 0.5 < FIC index ≤ 1, indifferent if 1 < FIC index ≤ 4, and antagonism if the FIC index > 4.

[0161] The results of confirming the antimicrobial synergistic effect according to specific weight ratios of totarol and hexamidine diacethionate for each measured strain are shown in Table 2 below. The combination of totarol and hexamidine diacethionate showed a partial antimicrobial synergistic effect against Malassezia furfur at a weight ratio of 1:0.25 to 1:16, and among them, showed an antimicrobial synergistic effect at a weight ratio of 1:4. It also showed a partial antimicrobial synergistic effect against Staphylococcus aureus at a weight ratio of 1:0.5 to 1:4, confirming that it exhibits excellent antimicrobial effects even at content lower than the MIC (weight %) of each ingredient.

[0162] [Table 2]

[0163]

[0164] Experimental Example 5. Evaluation of Sterilization Power

[0165] To confirm the bactericidal power, the synergistic effect of mixing hexamidine diacetionate and totarol was evaluated by comparison with the case where they were used alone. Comparative Example 1 (control group), Comparative Examples 2 to 3, and Examples, which are leave-on hair products, were prepared according to each component and content listed in Table 3 (unit: weight%) below.

[0166] Specifically, glycerin, allantoin, betaine dipropylene glycol, and a pH adjuster were weighed and added to purified water, and the mixture was uniformly mixed using an azi mixer at 25°C and 500 rpm for about 5 minutes. Afterward, ethanol, fragrance, preservative, and a solubilizer were added to the oil phase, and the mixture was uniformly mixed using an azi mixer at 500 rpm for 5 minutes, followed by cooling to 30°C.

[0167] In Comparative Examples 2 to 3 and the Examples, hexamidine diacetionate or totarol was added and uniformly mixed using an Azi mixer at 500 rpm for 5 minutes, and the Examples were prepared as compositions (1:4 weight ratio) containing 0.025 wt% of totarol and 0.1 wt% of hexamidine diacetionate.

[0168] [Table 3]

[0169]

[0170] 10 mL of the test solution was mixed with 1 mL of the bacterial solution prepared in Experimental Examples 1-1 and 1-2, and 10 mL of Saline was mixed with 1 mL of the test bacterial solution as a control solution. The final initial concentration of the bacteria was 1.0 x 10⁶. 5The number of bacteria in the test solution and control solution was checked 1 minute after bacterial contact. The number of bacteria was confirmed by serially diluting with Eugon LT-100, plating on a solid medium, and incubating at 32°C for an appropriate period.

[0171] The sterilization power was expressed as the average value of three replicate experiments, based on the percentage and log reduction rate according to the formula below.

[0172] Sterilization power (%) = ( A - B / A ) x 100

[0173] A = Number of bacteria from the control solution after contact for a certain period of time

[0174] B = Number of bacteria from the test solution after contact for a certain period of time

[0175] [Table 4]

[0176]

[0177] The measurement results are shown in Table 4 and Figure 1 above. Figure 1 is a plate under the same dilution conditions for each strain, in which the number of remaining bacteria was measured after contacting the bacteria with the test solution for 1 minute. Comparative Example 1 (control group) (A) and Example (B) for measuring Malassezia furfur, and Comparative Example 1 (control group) (C) and Example (D) for measuring Staphylococcus aureus. As shown in Table 4 and Figure 1, it was confirmed that the inhibitory effect on Malassezia furfur was superior when totarol and hexamidine diacethionate were mixed in a weight ratio of 1:4 compared to Comparative Examples 1 to 3 with the same content.

[0178] Experimental Example 6. Clinical Evaluation

[0179] Human efficacy evaluations were conducted using a scalp ampoule (test group, Example 2) to which a composition confirming an antibacterial synergistic effect by mixing hexamidine diacethionate and totarol was applied, and a scalp ampoule (control group) to which it was not applied. A cosmetic composition was prepared as shown in Table 5 below, and the control group was prepared in the same way as the test group, except that it did not contain hexamidine diacethionate or totarol raw materials.

[0180] Each control group and Example 2 (test group) were prepared according to the components and contents listed in Table 5 (unit: weight%) below. Specifically, Polyquaternium-10, a cationic polymer, was added to purified water and then uniformly mixed using an Agimixer at 800 rpm for approximately 20 minutes at 25°C. Subsequently, the aqueous phase, consisting of denatured alcohol, butylene glycol, propanediol, citric acid, menthol, and Reishi mushroom extract, was added and then uniformly mixed using an Agimixer at 500 rpm for 5 minutes. Next, the oil phase, consisting of Octyldodeceth-16 and fragrance, was pre-mixed externally and added, and then uniformly mixed using an Agimixer at 500 rpm for 5 minutes. Hexamidine diacetionate or totarol was added at the final step and uniformly mixed using an Agimixer at 500 rpm for 5 minutes to prepare the control group and Example 2. Specifically, the test group was prepared with a composition (1:4 weight ratio) containing 0.005 wt% of totarol and 0.02 wt% of hexamidine diacethionate.

[0181] [Table 5]

[0182]

[0183] The study was conducted on five women in their 20s and 30s. After using the test group and the control group for 5 days each, the improvement in scalp condition was evaluated on a scale of 1 to 6, and the results are shown in Table 6 below (1 point: not at all 2 points: not 3 points: does not seem 4 points: seems 5 points: yes 6 points: very much so). The maximum score is 6 points, and a higher score indicates a better improvement in the scalp environment.

[0184] [Table 6]

[0185]

[0186] As a result, compared to the control group, the test group was evaluated as superior in the areas of scalp redness improvement, dandruff and keratin improvement, oiliness improvement, itching improvement, heat sensation improvement, and odor improvement, confirming that the effect of improving the scalp environment when hexamidine diacethionate and totarol are mixed is significantly superior.

[0187] In summary, an antimicrobial composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; has an excellent antimicrobial effect, and specifically, it has been confirmed that the antimicrobial synergistic effect against Staphylococcus aureus and Malassezia is significantly excellent in a weight ratio range of 1:0.25 to 1:16 of totarol and hexamidine diacethionate, and thus can be used as an antimicrobial composition.

[0188] <2> A composition comprising a combination of climbazole, hexamidine diacethionate, and totarol

[0189] Experimental Example 1. Preparation of Staphylococcus aureus

[0190] To evaluate the antibacterial effect of a composition containing a combination of climbazole, hexamidine diacethionate, and totarol, Staphylococcus aureus, an inflammation-causing bacterium, was cultured and prepared.

[0191] Specifically, Staphylococcus aureus was cultured on tryptic soy agar (TSA) at 32°C for 24 hours. Afterward, a suspension was prepared with PBS buffer, and the bacterial count was adjusted.

[0192] Experimental Example 2. Preparation of a composition comprising a combination of climbazole, hexamidine diacethionate, and totarol

[0193] Climbazole, hexamidine diisethionate, and totarol were each cleanly dissolved in ethanol at a concentration of 32 wt%, and then diluted with Tryptic Soy Broth (TSB) medium to the desired concentration.

[0194] Experimental Example 3. Evaluation of Antimicrobial Activity

[0195] For each of the raw materials included in the composition prepared in Experimental Example 2—climbazole, diisethionate, hexamidine diisethionate, and totarol—we intended to determine the minimum inhibitory concentration having antibacterial activity against Staphylococcus aureus.

[0196] Specifically, 100 µl of bacterial suspension matching the bacterial count of Staphylococcus aureus was added to 96-well plates. 100 µl of the prepared raw material was added to the first row of the plate containing 100 µl of bacterial suspension, and after thoroughly mixing the bacterial suspension and the raw material, 100 µl was added to the second row to dilute the raw material by half. After serially diluting the raw material by half in this manner, the remaining 100 µl of the mixture in the last row was discarded.

[0197] After plate culture, the turbidity of the medium was checked to visually determine whether bacteria had grown. The lowest concentration at which no bacteria grew based on the turbidity was defined as the Minimal Inhibitory Concentration (MIC, wt%) of the ingredient. All tests were repeated three times.

[0198] As a result, as shown in Table 7 below (unit: weight%), the minimum inhibitory concentrations having antibacterial activity against Staphylococcus aureus were confirmed to be 0.25 weight% for climbazole, 0.0078 weight% for hexamidine diacethionate, and 0.0078 weight% for totarol.

[0199] [Table 7]

[0200]

[0201] Experimental Example 4. Confirmation of antibacterial synergistic effect

[0202] Based on the minimum inhibitory concentrations of climbazole, hexamidine diisethionate, and totarol confirmed in Experimental Example 3 above, the following experiment was conducted to confirm the antimicrobial synergistic effect when two or more combinations selected from the group consisting of climbazole, hexamidine diisethionate, and totarol are included.

[0203] Climbazole, hexamidine diacethionate, and totarol were prepared to verify antimicrobial synergistic effects at 8 times the minimum inhibitory concentration. By serially diluting the prepared ingredients in half using tryptic soy medium, ingredients diluted from 8 times to 1 / 8 of the minimum inhibitory concentration were prepared.

[0204] Climbazole was dispensed in 25 µl aliquots into the wells of the X-axis row of a 96-well plate in order from low concentration (1 / 8 of the minimum inhibitory concentration) to high concentration (8 times the minimum inhibitory concentration). Hexamidine diacethionate was dispensed in 25 µl aliquots into the wells of the Y-axis column in order from low concentration (1 / 8 of the minimum inhibitory concentration) to high concentration (8 times the minimum inhibitory concentration). Totarol was dispensed in 25 µl aliquots into the wells of the Z-axis plate of the 96-well plate in order from low concentration (minimum inhibitory concentration) to high concentration (8 times the minimum inhibitory concentration). Subsequently, 25 µl of each bacterial suspension, with the bacterial count adjusted, was dispensed into all wells containing the raw materials and cultured.

[0205] 96-well plates inoculated with Staphylococcus aureus strains and diluted raw materials were cultured in a 32°C incubator for 24 hours, and the mixing ratio (weight ratio) at the minimum concentration where bacterial growth was not observed visually was determined. To confirm the most efficient mixing concentration results, the fractional inhibiting concentration (FIC) and FIC index were calculated by substituting into the following mathematical formula.

[0206] [Mathematical Formula 3]

[0207] FIC of substance A or B = (MIC of raw material A or B in the mixture) / (MIC when raw material A or B is used alone)

[0208] [Mathematical Formula 4]

[0209] FIC Index = FIC of Substance A + FIC of Substance B

[0210] It was determined that the range in which bacteria do not proliferate is synergism if the FIC index ≤ 0.5, partial synergism if 0.5 < FIC index ≤ 1, indifferent if 1 < FIC index ≤ 4, and antagonism if the FIC index > 4.

[0211] The results of confirming the antibacterial synergy effect according to the specific weight ratio of each raw material for each measured strain are as shown in Table 8 below.

[0212] As a result, as shown in Table 8 below, it was confirmed that the antibacterial effect against Staphylococcus aureus was significantly superior when containing climbazole and hexamidine diacethionate or totarol.

[0213] [Table 8]

[0214]

[0215] Experimental Example 5. Evaluation of Sterilization Power

[0216] In order to evaluate the synergistic effect of mixing climbazole, hexamidine diacethionate, and totarol compared to using them alone, Comparative Example 1 (control group), Comparative Example 2, and Examples 1 to 3, which are Liv-On Hair product lines, were prepared according to each component and content listed in Table 9 (unit: weight%) below. Specifically, allantoin, betaine, and a pH adjuster, which are the aqueous phase components, were weighed and added to purified water, and the mixture was uniformly mixed using an Azimixer at 25°C and 500 rpm for about 5 minutes. Subsequently, ethanol, fragrance, preservative, solubilizer, pH adjuster, and climbazole (corresponding to Comparative Example 2 and Examples 1 to 3), which are the oil phase components, were added, and the mixture was uniformly mixed using an Azimixer at 500 rpm for 5 minutes, followed by cooling to 30°C. Examples 1 to 3 were prepared by adding hexamidine diacetionate or totarol in the final step and mixing uniformly using an azi mixer at 500 rpm for 5 minutes.

[0217] [Table 9]

[0218]

[0219] Specifically, 10 mL of the test solution and 1 mL of the test bacterial solution were mixed, and 10 mL of saline and 1 mL of the test bacterial solution were mixed as a control solution. The final initial bacterial concentration was 1.0 x 10⁶. 5 The bacterial count was CFU / mL. One minute after inoculation, the number of bacteria in the test solution and the control solution was checked. The bacterial count was confirmed by serially diluting with Eugon LT-100, plating onto a solid medium, and incubating at 32°C for an appropriate period.

[0220] The sterilization power was expressed as the average value of three repeated experiments, based on the percentage and log reduction rate according to the formula below.

[0221] Sterilization power (%) = ( A - B / A ) x 100

[0222] A = Number of bacteria from the control solution after contact for a certain period of time

[0223] B = Number of bacteria from the test solution after contact for a certain period of time

[0224] [Table 10]

[0225]

[0226] * No. 1-4 contact time: 1 minute, No. 5-7 contact time: 50 minutes

[0227] The measurement results are shown in Table 10 and Figure 2 above. Figure 2 is a plate under the same dilution conditions in which the number of remaining bacteria was measured after contacting bacteria with the test solution for 1 minute or 5 minutes. It is labeled Comparative Example 1 (Control Group) (A), Example 1 (B), Example 2 (C), Comparative Example 1 (Control Group) (D), and Example 3 (E). As shown in Table 10 and Figure 2, it was confirmed that when climbazole was mixed with hexamidine diacetionate and / or totarol, the bactericidal effect against Staphylococcus aureus was superior compared to Comparative Example 1 (Control Group) and Comparative Example 2 at the same content.

[0228] Experimental Example 6. Clinical Evaluation

[0229] Human efficacy evaluation was conducted using a scalp ampoule containing the combination of climbazole, hexamidine diacethionate, and totarol, which was confirmed to have an antibacterial synergistic effect (test group, Example 4), and a scalp ampoule not containing it (control group).

[0230] A cosmetic composition was prepared according to the composition of Table 11 below, and the control group was prepared in the same manner as the test group, except that it did not contain climbazole, hexamidine diacethionate, and totarol raw materials. Each control group and Example 4 (test group) was prepared according to each component and content listed in Table 11 (unit: weight%) below. Specifically, Polyquaternium-10, a cationic polymer, was added to purified water and then uniformly mixed using an Agimixer at 800 rpm for about 20 minutes at 25°C. Subsequently, the aqueous phase, consisting of denatured alcohol, butylene glycol, propanediol, citric acid, menthol, Reishi mushroom extract, climbazole, etc., was added and then uniformly mixed using an Agimixer at 500 rpm for 5 minutes. Next, the oil phase, polysorbate 20, and fragrance were pre-mixed externally and added, and then uniformly mixed using an Azi mixer at 500 rpm for 5 minutes. Hexamidine diacetionate or totarol was added at the final step and uniformly mixed using an Azi mixer at 500 rpm for 5 minutes to prepare the control group and Example 4. Specifically, the test group was prepared with a composition (1:2:16 weight ratio) containing 0.031 wt% hexamidine diacetionate, 0.063 wt% totarol, and 0.5 wt% climbazole.

[0231] [Table 11]

[0232]

[0233] The study was conducted on five women in their 20s and 30s. After using the test group and the control group for 5 days each, the effect on improving scalp condition was evaluated on a scale of 1 to 6, and the results are shown in Table 12 below (1 point: not at all 2 points: not 3 points: not so 4 points: seems so 5 points: yes 6 points: very much so). The maximum score is 6 points, and a higher score indicates a better effect on improving the scalp environment.

[0234] [Table 12]

[0235]

[0236] As a result, compared to the control group, the test group was evaluated as superior in the areas of improvement of scalp redness, improvement of scalp troubles, improvement of oiliness, improvement of itching, improvement of heat sensation, and improvement of odor, confirming that the effect of improving the scalp environment when climbazole, hexamidine diacethionate, and totarol were mixed was significantly superior.

[0237] In summary, a composition comprising a combination of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole has an excellent antibacterial effect, and specifically, it has been confirmed that the antibacterial synergistic effect against Staphylococcus aureus is remarkably excellent, and thus can be used as an antibacterial composition.

Claims

1. An antimicrobial composition comprising totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof.

2. An antimicrobial composition according to claim 1, wherein the pharmaceutically acceptable salt of the hexamidine is hexamidine diisethionate.

3. The antimicrobial composition of Claim 1, wherein the composition comprises 0.00006 weight% or more of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof based on the total weight of the composition.

4. The antimicrobial composition of Claim 1, wherein the composition comprises 0.00006 weight% or more of totarol based on the total weight of the composition.

5. An antimicrobial composition according to claim 1, wherein the composition comprises totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; in a weight ratio of 1:0.25 to 1:

16.

6. An antimicrobial composition according to claim 1, wherein the composition has antimicrobial activity against inflammation-causing bacteria and dandruff-causing bacteria.

7. An antimicrobial composition according to claim 6, wherein the inflammation-causing bacteria is Staphylococcus aureus.

8. An antimicrobial composition according to claim 6, wherein the dandruff-causing bacteria is Malassezia furfur.

9. A cosmetic composition for improving scalp condition or skin condition comprising the antimicrobial composition of Claim 1.

10. A cosmetic composition according to claim 9, wherein the improvement of the scalp condition is the improvement of dandruff or the improvement of scalp inflammation.

11. A cosmetic composition according to claim 9, wherein the improvement of the skin condition is the improvement of skin inflammation.

12. A topical skin composition for improving scalp condition or skin condition, comprising the antimicrobial composition of Claim 1.

13. A pharmaceutical composition for the prevention or improvement of scalp or skin diseases comprising the antimicrobial composition of Claim 1.

14. Use of totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for antibacterial purposes.

15. Use of totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for improving scalp condition or skin condition.

16. Use of totarol; and hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof for the prevention or improvement of scalp or skin diseases.

17. An antimicrobial method comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

18. A method for improving a scalp condition or skin condition, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

19. A method for preventing or improving a scalp or skin disease, comprising the step of administering an effective amount of totarol; and hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof to an individual.

20. An antimicrobial composition comprising two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole.

21. An antimicrobial composition according to claim 20, wherein the composition comprises at least 0.0078 weight% of climbazole based on the total weight of the composition.

22. An antimicrobial composition according to claim 20, wherein the composition comprises 0.0002 weight% or more of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof based on the total weight of the composition.

23. An antimicrobial composition according to claim 20, wherein the pharmaceutically acceptable salt of the hexamidine is hexamidine diisethionate.

24. An antimicrobial composition according to claim 20, wherein the composition comprises 0.0005 weight% or more of totarol based on the total weight of the composition.

25. An antimicrobial composition according to claim 20, wherein the composition has antimicrobial activity against inflammation-causing bacteria.

26. An antimicrobial composition according to claim 25, wherein the inflammation-causing bacteria is Staphylococcus aureus.

27. A cosmetic composition for cleansing the skin or improving skin condition comprising the antimicrobial composition of claim 20.

28. A cosmetic composition according to claim 27, wherein the improvement of the skin condition is the improvement of skin inflammation.

29. A topical skin composition for cleansing the skin or improving skin condition, comprising the antimicrobial composition of claim 20.

30. A pharmaceutical composition for the prevention or improvement of inflammatory skin diseases comprising the antimicrobial composition of claim 20.

31. Use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for antibacterial purposes.

32. Use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for cleansing the skin or improving skin condition.

33. Use of two or more combinations selected from the group consisting of hexamidine, derivatives thereof, or pharmaceutically acceptable salts thereof; totarol; and climbazole for the prevention or improvement of inflammatory skin diseases.

34. An antimicrobial method comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

35. A method for cleansing the skin or improving the skin condition, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

36. A method for preventing or improving inflammatory skin disease, comprising the step of administering to an individual an effective amount of two or more combinations selected from the group consisting of hexamidine, a derivative thereof, or a pharmaceutically acceptable salt thereof; totarol; and climbazole.

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