Acne bacteria biofilm destructive composition
The composition of specific ingredients destroys the acne bacteria biofilm, which solves the problems of poor drug permeability and poor antibacterial effect caused by the acne bacteria biofilm, and achieves fundamental improvements to acne.
Patent Information
- Application Number
- JP2024195692
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-11-08
- Publication Date
- 2025-01-24
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The prior art has not yet effectively solved the problems of poor drug permeability and weakened antibacterial effect caused by the formation of acne biofilms deep in hair follicles, and lack of efficient biofilm destructors.
Compositions containing specific ingredients, such as isopropyltolyl, salicylic acid, glycyrrhizine, sulfadiazine, tartaric acid, resorcinol, their salts and benzoyl peroxide, etc., are used to form a biofilm destruction composition for destroying the biofilm of acne bacteria.
Significantly reduce biofilm residue, improve the permeability and bactericidal effect of drugs on acne bacteria, thereby improving acne symptoms.
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Figure 2025013605000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a bacteria-prone biofilm-disrupting composition, and more particularly to a bacteria-prone biofilm-disrupting composition that inhibits the proliferation of bacteria and fundamentally improves acne. [Background technology]
[0002] Acne is a skin disease that can cause comedones, papules, nodules, and pustules, and may be accompanied by inflammation of hair follicles, and it mainly occurs on the face, chest, and back. It is known that the main causative agent of acne is Propionibacterium acnes (P. acnes), a common indigenous bacterium of the skin.
[0003] The anaerobic bacteria Propionibacterium acnes lives deep inside hair follicles, and grows using the sebum accumulated in the hair follicles as nutrients, causing inflammation, which causes pus to accumulate in the hair follicles and results in a skin rash. To treat these symptoms, various topical and oral agents have been developed to suppress sebum production, prevent infection, suppress inflammation, and normalize keratinization.
[0004] Some bacteria form biofilms, which are accumulations of bacterial secretions (polysaccharides, etc.) and adhere to surfaces with a viscous surface. For example, it is known that the slime on a sink is a biofilm formed by bacteria. In addition, plaque that forms between teeth or at the junction between the teeth and gums is considered to be a type of biofilm.
[0005] It is known that acne bacteria also form biofilms. Since biofilms are filled with polysaccharides secreted by acne bacteria, it is difficult for drugs such as antibacterial agents to penetrate into the biofilms, and the bactericidal effect is reduced. Therefore, the presence or absence of biofilm formation affects the pathogenicity of various bacterial infections (Non-Patent Document 1), and therefore the development of antibacterial agents that are highly effective against biofilms is also underway, and antibacterial preparations that are effective against Staphylococcus aureus, Streptococcus mutans, Escherichia coli, etc. have already been disclosed (Patent Document 1). In addition, amino sugar derivatives exhibit an effect of removing or destroying Pseudomonas aeruginosa biofilms and are known as therapeutic agents for biofilm infections that present difficult-to-treat infections (Patent Document 2). [Prior art documents] [Patent documents]
[0006] [Patent Document 1] Patent No. 3717960 [Patent Document 2] Patent No. 3769040 [Non-patent literature]
[0007] [Non-Patent Document 1] Tom Coenye et al., Infectious Disorders-Drug Targets, 2008, 8, P.156-159 Summary of the Invention [Problem to be solved by the invention]
[0008] However, there has been little progress in the development of a preparation capable of destroying the biofilm formed by Propionibacterium acnes deep inside the hair follicle. Therefore, an object of the present invention is to provide a preparation having a high effect of destroying such a biofilm. [Means for solving the problem]
[0009] In order to achieve the above object, a first gist of the present invention is a biofilm-disrupting composition containing at least one Propionibacterium acnes biofilm-disrupting component (A) selected from the group consisting of isopropylmethylphenol, salicylic acid, glycyrrhizic acid, ibuprofen piconol, sulfadiazine and salts thereof, ethanol, resorcinol, sulfur, and benzoyl peroxide.
[0010] The second gist of the present invention is that the Propionibacterium acnes biofilm destroying component (A) is at least one selected from the group consisting of isopropylmethylphenol, sulfadiazine and its salts, ethanol, resorcinol, and benzoyl peroxide.The third gist of the present invention is that the composition contains, in addition to the component (A), at least one destruction assistant component (B) selected from the group consisting of chlorobutanol, propyl gallate, sodium lactate, and orange oil.
[0011] A fourth aspect is that the acne bacteria biofilm destroying component (A) is at least one selected from the group consisting of isopropylmethylphenol, salicylic acid, glycyrrhizic acid, ibuprofen piconol, sulfadiazine and salts thereof, resorcin, sulfur, and benzoyl peroxide, and the content of the component (A) is 0.05 to 8 wt % of the entire acne bacteria biofilm destroying composition. A fifth aspect is that the acne bacteria biofilm destroying component (A) is ethanol, and the content of the ethanol is 2.5 to 50 wt % of the entire acne bacteria biofilm destroying composition. A sixth aspect is a composition for destroying a Propionibacterium acnes biofilm according to any one of the first to fifth aspects above, which is applied to the skin.
[0012] That is, as a result of extensive research into biofilms formed by P. acnes, the inventors have confirmed that some components have a bactericidal effect against P. acnes but do not have the effect of destroying P. acnes biofilms. However, they have discovered a biofilm-destroying composition that has the effect of destroying P. acnes biofilms, and have found that use of this biofilm-destroying composition can destroy P. acnes biofilms and fundamentally improve acne, thereby arriving at the present invention. Effect of the Invention
[0013] That is, the biofilm-disrupting composition of the present invention contains at least one biofilm-disrupting component (A) selected from the group consisting of isopropylmethylphenol, salicylic acid, glycyrrhizic acid, ibuprofen piconol, sulfadiazine and salts thereof, ethanol, resorcinol, sulfur, and benzoyl peroxide, and therefore has an excellent effect in destroying acne bacteria biofilms.
[0014] In addition, when the Propionibacterium acnes biofilm-disrupting component (A) in the biofilm-disrupting composition is at least one selected from the group consisting of isopropylmethylphenol, sulfadiazine and its salts, ethanol, resorcinol, and benzoyl peroxide, the composition has a so-called bactericidal effect while also having an Propionibacterium acnes biofilm-disrupting effect that is different from the bactericidal effect.
[0015] When the acne bacteria biofilm destroying composition contains, in addition to component (A), at least one destruction auxiliary component (B) selected from the group consisting of chlorobutanol, propyl gallate, sodium lactate, and orange oil, the acne bacteria biofilm destroying effect is further improved, or even if the content of the biofilm destroying component (A) is low, a sufficient biofilm destruction effect can be observed.
[0016] When the Propionibacterium acnes biofilm destroying component (A) is at least one selected from the group consisting of isopropylmethylphenol, salicylic acid, glycyrrhizinic acid, ibuprofen piconol, sulfadiazine and salts thereof, resorcin, sulfur, and benzoyl peroxide, the content thereof is preferably 0.05 to 8% by weight of the entire Propionibacterium acnes biofilm destroying composition, from the viewpoint of the biofilm destroying effect.
[0017] When the Propionibacterium acnes biofilm destroying component (A) is ethanol, the content of the ethanol is preferably 2.5 to 50% by weight of the entire Propionibacterium acnes biofilm destroying composition, from the viewpoint of the biofilm destroying effect.
[0018] The Propionibacterium acnes biofilm disrupting composition is preferably applied to the skin. [Brief description of the drawings]
[0019] [Figure 1] FIG. 1(a) is a graph showing the results of the biofilm survival rate in the Propionibacterium acnes biofilm destruction test for the product of Example 1 and the product of Comparative Example 1, and FIG. 1(b) is a graph showing the results of the bacterial viability rate for the product of Example 1 and the product of Comparative Example 1. [Diagram 2] FIG. 2(a) shows an optical microscope photograph of Reference Example 1 (Propionibacterium acnes biofilm formation in a control), and FIG. 2(b) shows an optical microscope photograph of Example 1. [Diagram 3] FIG. 3 is a graph showing the results of a Propionibacterium acnes biofilm destruction test for the products of Examples 2 to 9 and Comparative Example 2. [Figure 4] FIG. 4 is a graph showing the results of a Propionibacterium acnes biofilm destruction test with respect to changes in isopropyl methylphenol concentration for the products of Examples 1-1 to 1-4. [Diagram 5] FIG. 5 is a graph showing the results of a Propionibacterium acnes biofilm destruction test at different ethanol concentrations for the products of Examples 2-1 to 2-5. [Figure 6] FIG. 6 is a graph showing the results of a Propionibacterium acnes biofilm destruction test with respect to changes in resorcin concentration for the products of Examples 3-1 to 3-5. [Figure 7] FIG. 7 is a graph showing the results of a bacteria-prone biofilm destruction test for the products of Examples 10 to 13, which contain the bacteria-prone biofilm destruction component (A) and the destruction auxiliary component (B). [Figure 8] FIG. 8 is a graph showing the results of a bacteria-prone biofilm destruction test for the products of Examples 14 to 16, which contain the bacteria-prone biofilm destruction component (A) and the destruction auxiliary component (B). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] Next, embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
[0021] The acne bacteria biofilm disrupting composition of the present invention contains at least one acne bacteria biofilm disrupting component (A) selected from the group consisting of isopropylmethylphenol, salicylic acid, glycyrrhizic acid, ibuprofen piconol, sulfadiazine and its salts, ethanol, resorcinol, sulfur, and benzoyl peroxide. Here, disrupting acne bacteria biofilms means reducing the biofilms formed by microorganisms (acne bacteria). The reduction of the above biofilms is detected by a known method. However, if it is the method described in the test examples below, it is desirable that the biofilm residual rate is reduced to 80% or less, more preferably 60% or less, particularly preferably 50% or less, and especially preferably 40% or less. Hereinafter, disrupting acne bacteria biofilms may be abbreviated as "BF disruption".
[0022] Hereinafter, the BF disrupting component (A), which is an essential component of the BF disrupting composition, will be described in detail.
[0023] <BF disrupting component (A)> The BF disrupting component (A) refers to isopropylmethylphenol, salicylic acid, glycyrrhizic acid, ibuprofen piconol, sulfadiazine and its salts, ethanol, resorcinol, sulfur, and benzoyl peroxide. Among them, from the viewpoint of the BF disrupting effect, isopropylmethylphenol and its salts, ethanol, and resorcinol are preferable, and isopropylmethylphenol and its salts are more preferable. These BF disrupting components (A) can be used alone or in combination of two or more.
[0024] (I) Also, among the component (A), isopropylmethylphenol, sulfadiazine and its salts, ethanol, resorcinol, and benzoyl peroxide have been conventionally known as bactericidal components, and since they have not only a bactericidal effect but also a biofilm disrupting effect different from bactericidal action, they are preferably used.
[0025] (II) Furthermore, among the components (A), salicylic acid and its salts, and sulfur have been known as keratin softening components and are preferably used because they have a keratin softening effect that is different from the biofilm destruction effect, in addition to the biofilm destruction effect.
[0026] (III) Among the components (A), glycyrrhizinic acid, ibuprofen piconol and salts thereof have been known as anti-inflammatory components and are preferably used since they have an anti-inflammatory effect as well as a biofilm-destroying effect.
[0027] In addition, various positional isomers of isopropylmethylphenol, which is the component (A), are known, and any of them may be used in the present invention.Specifically, positional isomers of isopropylmethylphenol include 3-methyl-4-isopropylphenol (also called biosol), 2-isopropyl-5-methylphenol (also called thymol), and 2-methyl-5-isopropylphenol (also called carvacrol), but are not limited thereto.From the viewpoint of the effect of the present invention, 3-methyl-4-isopropylphenol is preferred.
[0028] The salt of isopropylmethylphenol, component (A), may be any pharmacologically acceptable salt, and examples thereof include salts of mineral acids such as sulfuric acid, hydrochloric acid, or phosphoric acid, salts of organic acids such as maleic acid or methanesulfonic acid, and salts of alkali metals such as sodium or potassium, and alkaline earth metals.
[0029] Furthermore, the salt of salicylic acid, component (A), may be any pharma- ceutically acceptable salt, and examples thereof include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; zinc salt; iron salt; ammonium salt; salts with basic amino acids such as arginine, lysine, histidine, and ornithine; and salts with amines such as monoethanolamine, diethanolamine, and triethanolamine.
[0030] Furthermore, the salt of glycyrrhizinic acid of component (A) may be any pharmacologically acceptable salt, and examples thereof include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and salts with amines such as triethylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc. Among these, from the viewpoint of exerting the effects of the present invention, alkali metal salts of glycyrrhizinic acid, and furthermore dipotassium glycyrrhizinate, are preferred.
[0031] The salt of ibuprofen piconol, component (A), may be any pharmacologically acceptable salt, and examples thereof include salts of mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid, salts of organic acids such as maleic acid and methanesulfonic acid, and salts of alkali metals such as sodium and potassium, and alkaline earth metals.
[0032] The salt of sulfadiazine (A) may be any pharmacologically acceptable salt, and examples thereof include salts of mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid, salts of organic acids such as maleic acid and methanesulfonic acid, and metal salts such as sodium, potassium, and silver.
[0033] [(A) Component content] (I) In terms of effectiveness, the content of the poorly water-soluble component and the water-soluble solid component in the BF destruction component (A) is preferably 0.05 to 8% by weight of the entire BF destruction composition. Among the BF destruction components (A), the poorly water-soluble components include isopropylmethylphenol, salicylic acid, ibuprofen piconol, sulfadiazine and their salts, resorcin, sulfur, and benzoyl peroxide, and the water-soluble solid components include glycyrrhizic acid and its salts. These can be used alone or in combination of two or more.
[0034] Among them, the content of at least one of isopropylmethylphenol and a salt thereof is preferably 0.05 to 1.5% by weight, and particularly preferably 0.3 to 1% by weight, of the entire BF destruction composition. Within these ranges, an excellent biofilm destruction effect is exhibited, but if it is less than 0.05% by weight, the biofilm destruction effect tends to be relatively low, and if it exceeds 1.5% by weight, the odor intensity of the preparation tends to be high and is not suitable for practical use.
[0035] The content of resorcin is particularly preferably 0.5 to 4% by weight of the entire BF destruction composition. Within this range, an excellent biofilm destruction effect is exhibited, while if it is less than 0.5% by weight, the biofilm destruction effect tends to be insufficient, and if it exceeds 4% by weight, the formulation tends to become colored and become unsuitable for practical use.
[0036] (II) In terms of effectiveness, the content of the water-soluble liquid component among the BF destruction components (A) is preferably 2.5 to 50% by weight of the entire BF destruction composition, and particularly preferably 2.5 to 30% by weight. Within these ranges, an excellent biofilm destruction effect is exhibited, while if it is less than 2.5% by weight, the biofilm destruction effect tends to be insufficient, and if it exceeds 30% by weight, the odor tends to be too strong and not suitable for practical use. Among the BF destruction components (A), an example of the water-soluble liquid component is ethanol.
[0037] <Destruction aid component (B)> Next, the biofilm-disrupting composition of the present invention preferably contains not only the above-mentioned component (A) but also a biofilm-disrupting auxiliary component (B). Here, the biofilm-disrupting auxiliary component refers to a component for assisting in the destruction of Propionibacterium acnes biofilms.
[0038] Examples of the destruction aid component (B) include chlorobutanol, propyl gallate, sodium lactate, orange oil, etc., and among these, chlorobutanol, propyl gallate, and sodium lactate are more preferable. These destruction aid components (B) can be used alone or in combination of two or more kinds.
[0039] The above-mentioned chlorobutanol has been used as a preservative, propyl gallate as a food antioxidant, sodium lactate as a moisturizing ingredient, and orange oil as an additive added to foods and beverages, as well as to perfumes, detergents, etc. Thus, the destruction aid component (B) is a completely different component from the BF destruction component (A), but when used in combination with component (A), it effectively reinforces the biofilm destruction effect. Furthermore, because of its high reinforcing effect, even when the content of component (A) is low and tends to be insufficient, the biofilm destruction effect can be sufficiently obtained.
[0040] The content of the above breaking auxiliary component (B) is preferably 0.001 to 10% by weight, and more preferably 0.01 to 5% by weight, of the entire BF breaking composition from the viewpoints of effectiveness and practicality.
[0041] <Other ingredients> In addition, depending on various purposes, other components such as moisturizing components, polyhydric alcohols, scrubbing agents, ultraviolet absorbing components, ultraviolet scattering components, anti-inflammatory agents other than component (A), astringent components, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cleansing components, bactericidal components other than component (A), keratin softening components, cell activating components, anti-aging components, blood circulation promoting components, and whitening components may be contained within a range that does not impair the effects of the present invention. Among these, it is preferable to contain polyhydric alcohols, vitamins, and anti-inflammatory agents other than component (A). These other components may be used alone or in combination of two or more.
[0042] Examples of the moisturizing components include diglycerol trehalose; polymeric compounds such as sodium hyaluronate, heparinoids, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and chitosan; amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as urea and sodium pyrrolidone carboxylate; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.
[0043] The polyhydric alcohol preferably has 2 to 10 carbon atoms, and examples thereof include glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, ethylene glycol, diethylene glycol, isoprene glycol, 1,3-butylene glycol, sorbitol, xylitol, erythritol, mannitol, pentanediol, hexanediol, octanediol, decanediol, and neopentyl glycol.
[0044] Among these, glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, ethylene glycol, diethylene glycol, isoprene glycol, sorbitol, xylitol, erythritol, mannitol, pentanediol, hexanediol, and octanediol are preferred, and glycerin, diglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, diethylene glycol, isoprene glycol, sorbitol, xylitol, erythritol, mannitol, pentanediol, and hexanediol are more preferred.
[0045] Examples of the scrubbing agent include apricot kernel powder, almond shell powder, apricot kernel powder, sodium chloride granules, olive kernel powder, seawater dried granules, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder, hazel shell powder, polyethylene powder, and anhydrous silicic acid.
[0046] Examples of the ultraviolet absorbing component include octyl triazone, dimethoxybenzylidene dioxoimidazolidine octyl propionate, 2-ethylhexyl paramethoxycinnamate, and phenylbenzimidazole sulfonic acid.
[0047] Examples of the ultraviolet ray scattering component include inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and anhydrous silicic acid; these inorganic compounds are coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica, and talc; or are composited with resin powders such as polyamide, polyethylene, polyester, polystyrene, and nylon; and further treated with silicone oil, aluminum salt of a fatty acid, or the like.
[0048] Examples of anti-inflammatory agents other than the above-mentioned (A) component include allantoin and its derivatives, glycyrrhetinic acid and its derivatives, azulene and its derivatives, components derived from plants (e.g., comfrey), zinc oxide, tocopherol acetate, aminocaproic acid, hydrocortisone, prednisolone, and salts thereof.Among them, allantoin and its derivatives, glycyrrhetinic acid and its derivatives, azulene and its derivatives, and aminocaproic acid are preferred, and allantoin, allantoin chlorhydroxyaluminum, allantoin dihydroxyaluminum, glycyrrhetinic acid, stearyl glycyrrhetinate, epsilon aminocaproic acid, azulene, guaiazulene, and salts thereof are more preferred, and allantoin is particularly preferred.Note that "derivative" refers to esters, ethers, alkylated products, glycosides, etc. of the compounds described.
[0049] Examples of the astringent ingredient include zinc sulfate, zinc oxide, aluminum chloride, zinc sulfocarbonate, and tannic acid.
[0050] Examples of the vitamins include vitamin E such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate; vitamin B2 such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, and riboflavin tetranicotinate; nicotinic acid, dl-α-tocopherol nicotinate, benzyl nicotinate, and nicotinic acid. Nicotinic acids such as methyl, β-butoxyethyl nicotinate, 1-(4-methylphenyl)ethyl nicotinate, and nicotinamide; vitamin Cs such as ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, and L-ascorbyl dipalmitate; vitamin Ds such as methylhesperidin, ergocalciferol, and cholecalciferol; vitamin Ks such as phylloquinone and farnoquinone; γ-oryzanol, dibenzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, Vitamin B1 compounds such as thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate; Vitamin B6 compounds such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5'-phosphate, pyridoxamine hydrochloride; Cyanocobalamin, Hydroxocobalamin, vitamin B12 such as folic acid, pteroylglutamic acid, and other folic acids; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesine, D-pantethine, coenzyme A, pantothenyl ethyl ether, and other pantothenic acids; biotin, biocytin, and other biotin derivatives; ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, and other vitamin C derivatives;Vitamin-like factors such as carnitine, ferulic acid, α-lipoic acid, and orotic acid;
[0051] Examples of the above peptides or derivatives thereof include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzed peptides, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptides, hydrolyzed wheat protein, casein hydrolyzed peptides, acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.), and the like.
[0052] Examples of the above amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine, and the like.
[0053] Examples of the cleaning components include soaps selected from alkali metal salts, alkanolamide salts, and amino acid salts, such as potassium laurate, potassium myristate, potassium palmitate, and potassium stearate; amino acid surfactants, such as sodium cocoyl glutamate and sodium cocoyl methyl taurate; ether sulfate salts, such as sodium laureth sulfate; ether carboxylates, such as sodium lauryl ether acetate; sulfosuccinate salts, such as sodium alkyl sulfosuccinate; fatty acid alkanolamides, such as coconut oil fatty acid monoethanolamide and coconut oil fatty acid diethanolamide; monoalkyl phosphate salts, such as sodium lauryl phosphate and sodium polyoxyethylene lauryl ether phosphate; betaine-type amphoteric surfactants, such as coconut oil fatty acid amidopropyl dimethylaminoacetate betaine, lauryl dimethylaminoacetate betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl hydroxysulfobetaine, and sodium lauroyl amidoethyl hydroxyethyl carboxymethyl betaine hydroxypropyl phosphate; and amino acid amphoteric surfactants, such as sodium lauryl aminopropionate.
[0054] Examples of bactericidal components other than the above component (A) include chlorhexidine, benzalkonium chloride, acrinol, benzethonium chloride, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, piroctoolamine, and miconazole.
[0055] Examples of the keratin softening ingredient include lactic acid, gluconic acid, citric acid, malic acid, fruit acid, phytic acid, urea, and sulfur.
[0056] Examples of the above-mentioned cell-activating components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponins, and photosensitizer No. 301.
[0057] Examples of the above-mentioned anti-aging components include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like.
[0058] Examples of the above-mentioned blood circulation-promoting components include components derived from plants (such as carrot, ashitaba, arnica, ginkgo, periwinkle, polygonum multiflorum, dutchmanspipe, chamomile, roman chamomile, carrot, gentiana, burdock, rice, Japanese quince, shiitake mushroom, ginger, European medlar, European spindle tree, Chinese foxglove, ginseng, centella asiatica, thyme, clove, Chinese cinnamon, capsicum, angelica, Chinese honeylocust, grape, button, paulownia, lemon balm, yuzu, codonopsis pilosula, green tea, rosemary, rose hip, peach, apricot, walnut, corn, etc.); acetylcholine, iktamol, cantharidin, gamma oryzanol, cephalanthin, tolazoline, nicotinic acid tocopherol, glucosyl hesperidin, and the like.
[0059] Examples of the above-mentioned whitening components include tocopherol, tranexamic acid, and the like.
[0060] <Method for producing BF-destroying composition> The method for producing the BF-destroying composition of the present invention is not particularly limited. In addition to the component (A) which is an essential component and the component (B) as required, various components necessary for producing ordinary pharmaceutical compositions, etc. (the above-mentioned other components, bases or carriers, additives, etc. described later) can be appropriately selected and formulated, and it can be produced by a conventional method.
[0061] In addition, the BF-destroying composition of the present invention may be an emulsified composition or a solubilized composition. In that case, it may be either an oil-in-water type or a water-in-oil type, but from the viewpoint of the expression of the effects of the present invention and the usability (stickiness, stretchability, moist feeling, etc.) of the BF-destroying composition, an oil-in-water type composition is preferred.
[0062] <Use of BF-destroying composition> In the BF-destroying composition of the present invention, as described above, since it contains the BF-destroying component (A), it can be used as a pharmaceutical composition that destroys acne bacteria biofilm and is particularly effective for the radical treatment of acne, and can be preferably used as an external preparation applied to the skin. As the external preparation, it can be formulated by a known method in the form of a liquid, suspension, emulsion, cream, ointment, gel, liniment, lotion, aerosol, powder, sheet, etc. Preferably, it is in the form of a liquid, suspension, emulsion, or cream, and more preferably in the form of a liquid, emulsion, or cream.
[0063] In addition, the usage and dosage of the BF-destroying composition of the present invention are not particularly limited and vary depending on the age of the user and the degree of symptoms, etc., but usually, it is applied (for example, applied, sprayed, pasted) to the outer skin such as the skin (especially the affected area that causes concern, for example, the area where acne occurs) several times a day (for example, about twice a day in the morning and evening) in an appropriate amount (for example, about 0.01 to 1 g). Specifically, it can be used for local administration on the skin surface such as the face, around the lips, scalp, neck, chest, back, abdomen, arms, oral cavity, armpits, buttocks, genitals, etc. It can be locally administered for various acne conditions, for example, for microcomedones (formation of comedones, initial comedone blockage), so-called pustules (adult acne), whiteheads (white papules), blackheads (open comedones), red acne with inflammation (red papules) or yellow acne (purulent acne), it can be used as a preventive and / or therapeutic agent. It is effectively used when acne bacteria proliferate and form a biofilm inside or around the hair follicles.
[0064] Dry skin, which is often seen in adult acne, is prone to excessive sebum secretion and clogged keratin plugs, and such changes in the surrounding environment and stress may increase biofilm formation by acne bacteria. In addition, there is a concern that if biofilm formation increases, acne bacteria protected by the biofilm will be more likely to repeatedly develop acne symptoms. It is known that an increase in biofilm formation leads to an increase in lipase activity, and lipase breaks down triglycerides in sebum to produce free fatty acids, which cause inflammation in hair follicles. Therefore, the biofilm formation inhibitor of the present invention, more specifically, the BF-destroying composition of the present invention, can be used for the treatment or prevention of acne, and more specifically, can be used for the treatment or prevention of acne on dry skin, for the treatment or prevention of acne that tends to recur, or for the treatment or prevention of acne accompanied by inflammation in hair follicles.
[0065] <Preparation> The BF breaking composition of the present invention can be prepared into a BF breaking composition in various formulation forms by mixing the essential components and other components described above with a base or carrier commonly used in pharmaceuticals, etc., and, if necessary, with the additives described below in a conventional manner, and emulsifying or solubilizing as necessary.
[0066] Examples of the base or carrier include hydrocarbons such as liquid paraffin, squalane, petrolatum, gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, and light liquid paraffin; silicone oils such as methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, silicone / alkyl chain co-modified polyether-modified silicone, silicone / alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin; oils and fats such as coconut oil, olive oil, rice bran oil, and shea butter; waxes such as jojoba oil, beeswax, candelilla wax, and lanolin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. Conductors; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; esters such as diisopropyl adipate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether;Examples of the BF breaking composition of the present invention include water. When the BF breaking composition of the present invention contains a polyhydric alcohol, the polyhydric alcohol may also function as a base or carrier. In particular, the BF breaking composition of the present invention preferably contains water and / or a lower alcohol, and more preferably contains water.
[0067] When the BF destruction composition of the present invention contains a base or carrier other than water and lower alcohol, the base or carrier is preferably, for example, higher alcohol, hydrocarbon, oil, ester, silicone oil, wax, vinyl polymer, and more preferably higher alcohol, ester oil, silicone oil, vinyl polymer. Among these components, cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, glyceryl tri-2-ethylhexanoate, dimethicone, cyclomethicone, polyether modified silicone, polyglycerin modified silicone, and carboxyvinyl polymer are more preferable.
[0068] The bases or carriers described above may be used alone or in combination of two or more. The amounts of the bases or carriers used are appropriately selected from the ranges known to those skilled in the art.
[0069] <Dosage Form> The formulation of the BF-destroying composition of the present invention is not particularly limited, and examples thereof include ointments, liquids, suspensions, emulsions (milky lotions and creams), gels, liniments, lotions, poultices, aerosols, solids, etc. Among these, liquid to semi-solid formulations are preferred, and are particularly useful when applied to liquids, lotions, ointments, gels, and emulsions. These formulations can be manufactured according to conventional methods, such as the methods described in the General Provisions for Preparations of the 16th Edition of the Japanese Pharmacopoeia.
[0070] <Additives> The BF breaking composition of the present invention may contain known additives added to pharmaceuticals, such as surfactants, stabilizers, antioxidants, colorants, pearlescent agents, dispersants, chelating agents, pH adjusters, refreshing agents, preservatives, thickeners, and irritation reducers, within the scope of not impairing the effects of the present invention. Among these, it is preferable to add refreshing agents and thickeners. These additives may be used alone or in combination of two or more.
[0071] The surfactant may be any of nonionic surfactants, cationic surfactants, anionic surfactants, amphoteric surfactants, and the like, and examples thereof include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexyl acid, and diglycerol sorbitan tetra-2-ethylhexyl acid; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene monolaurate, Examples of suitable surfactants include polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococoate glyceryl; glycerin alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Of these, nonionic surfactants are preferred, and hydrogenated castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, and polyoxyalkylene alkyl ethers are more preferred.
[0072] Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.
[0073] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, and L-cysteine hydrochloride.
[0074] Examples of the colorant include inorganic pigments and natural dyes.
[0075] Examples of the pearl luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate.
[0076] Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether / maleic anhydride crosslinked copolymer, and organic acids.
[0077] Examples of the chelating agent include EDTA disodium salt, EDTA calcium disodium salt, and the like.
[0078] Examples of the pH adjuster include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.), etc. Among these, inorganic bases and / or organic bases are preferred, and potassium hydroxide and triethanolamine are more preferred.
[0079] Examples of the cooling agent include terpenes such as menthol, camphor, borneol, geraniol, cineol, anethole, limonene, eugenol, etc. (which may be in the d-, l- or dl-form); essential oils such as eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil, cinnamon oil, rose oil, and turpentine.
[0080] Examples of the preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, and phenoxyethanol.
[0081] Examples of the thickener include vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymers; cellulose thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose; guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, xanthan gum, acrylates / alkyl methacrylate copolymers, polyethylene glycol, bentonite, alginic acid, propylene glycol alginate, macrogol, sodium chondroitin sulfate, hyaluronic acid, sodium hyaluronate, (hydroxyethyl acrylate / Na acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, and the like. Of these, vinyl-based thickeners and cellulose-based thickeners are preferred, and carboxyvinyl polymers, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and carboxyethyl cellulose are more preferred.
[0082] Examples of the irritation reducer include licorice extract, sodium alginate, gum arabic, polyvinylpyrrolidone, and the like.
[0083] The BF destruction effect of the BF destruction composition of the present invention can be confirmed by measuring the biofilm survival rate (hereinafter sometimes abbreviated as "BF survival rate") using the BF destruction test described below. EXAMPLES
[0084] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.
[0085] <Test 1: BF Destruction Test> The biofilm destruction effect is confirmed by measuring the BF residual rate after adding a sample of the example product to a medium on which P. acnes has formed a biofilm. Specifically, 10 P. acnes suspensions were cultured anaerobically at 37°C for 3 days on Reinforced Clostridia (RCM) slant medium in a 48-well round-bottom well plate. 9 Dispense 500μL of each test solution into each well, inoculated to a bacterial solution (CFU / mL). Culture anaerobically at 37℃ for 28 hours to allow the bacteria to attach to the wells and form a biofilm. Discard the bacterial solution and wash each well twice with 500μL of phosphate-buffered saline (PBS).
[0086] Dispense 500 μL of each sample into each well and culture anaerobically for 24 hours. After culture, wash each well twice with 500 μL of PBS. Dispense 500 μL of methanol (manufactured by Wako Pure Chemical Industries, Ltd.) into each well and leave for 15 minutes, then remove the methanol and dry.
[0087] Each well was stained with 100 μL of 0.5 wt% crystal violet (Kanto Chemical) for 20 minutes. The crystal violet solution was removed, and each well was washed twice with 500 μL of purified water. The attached crystal violet was dissolved with 150 μL of 33 wt% acetic acid (Wako Pure Chemical Industries), and the wells were shaken at 300 rpm for 5 minutes using a shaker (Shaking Incubator SI-300, AS ONE). The extract from each well was dispensed into a 96-well flat plate at 100 μL per well, and the absorbance at 590 nm, at which crystal violet shows absorbance, was measured using a microplate reader (Molecular Devices, Versa max) to obtain the sample OD. 590 value.
[0088] An RCM medium containing 2.5% by weight of dimethyl sulfoxide (DMSO, manufactured by Wako Pure Chemical Industries, Ltd.) was prepared as a control, and the biofilm survival rate was calculated using the ratio to the amount of biofilm formed using the following formula (1).
[0089] Equation (1): Biofilm survival rate (%) = sample OD 590 Value / Control OD 590 Value x 100
[0090] Statistical significance was tested using Dunnett test to calculate P value. The experiment was performed with an n number of 6.
[0091] <Test 2: Bacterial viability measurement> Bacterial viability is measured using a Cell Titer-Blue Cell Viability Assay kit (Promega). Specifically, 10 P. acnes suspensions were cultured anaerobically at 37°C for 3 days in RCM slant medium in a 48-well round-bottom well plate. 9 Dispense 500μL of each test solution into each well, inoculated to a bacterial solution (CFU / mL). Culture anaerobically at 37℃ for 28 hours to allow the bacteria to attach to the wells and form a biofilm. Discard the bacterial solution and wash each well twice with 500μL of PBS.
[0092] After dispensing 500 μL of each sample per well, the plate is anaerobically cultured for 24 hours. Each well is washed twice with 500 μL of PBS. After dispensing 500 μL of physiological saline (Otsuka Pharmaceutical) and 100 μL of Cell Titer blue (Promega) into each well, the plate is anaerobically cultured at 37°C for 1 hour, and then the fluorescence is measured (Ex: 560 nm, Em: 590 nm) using a fluorescence microplate reader (Molecular Devices, Flex station).
[0093] An RCM medium containing 2.5% by weight DMSO (manufactured by Wako Pure Chemical Industries, Ltd.) was prepared as a control, and the bacterial survival rate was calculated using the ratio to this fluorescence value according to the following formula (2).
[0094] Equation (2): Bacterial viability (%) = sample fluorescence value / control fluorescence value x 100
[0095] Statistical significance was tested using Dunnett test to calculate P value. The experiment was performed with an n number of 6.
[0096] First, prior to the Examples, Reference Example 1 (control) shown below was prepared, and Examples and Comparative Examples containing this and component (A) and, if necessary, component (B) were prepared.
[0097] [Reference example 1] As a control, 2.5 wt % DMSO was prepared.
[0098] [Example 1, Comparative Example 1] A BF destruction composition was prepared by mixing the control of Reference Example 1 with the component (A) in the amount shown in Table 1 below.
[0099] [Table 1]
[0100] The above-mentioned BF destructive test and bacterial viability measurement were carried out for the above Reference Example 1, Example 1, and Comparative Example 1. The results of the BF destructive test are shown in Table 1 and in Figure 1(a), and the results of the bacterial viability measurement are shown in Figure 1(b).
[0101] As a result of the bacterial survival rate measurement, as shown in FIG. 1(b), the bacterial survival rate of Example 1 and Comparative Example 1, which are conventionally known as bactericidal components, was nearly 0%, confirming their bactericidal effect.
[0102] On the other hand, as a result of the BF destruction test, from Table 1 and FIG. 1(a), it was found that the BF remaining rate of the product of Example 1 was reduced to 29%, and BF destruction was effectively performed. In contrast, the BF remaining rate of the product of Comparative Example 1, which contained azelaic acid, known as an acne bactericide, was 89%, and it was found that it had almost no BF destruction effect. As such, even if it is an acne bactericide, there are some that are not BF destruction ingredients (A), and it can be seen that the inventors, as a result of intensive research, have found a BF destruction ingredient (A) that can destroy BF for the fundamental treatment of acne from among many ingredients.
[0103] <Test 3: BF fracture state observation> The results of Reference Example 1 (control) and Example 1 after staining the biofilm with crystal violet used in the BF destruction test in Test 1 above were observed under an optical microscope (Carl Zeiss) at a magnification of 50x (eyepiece x10, objective x5). An optical microscope photograph of Reference Example 1 is shown in Figure 2(a), and an optical microscope photograph of Example 1 is shown in Figure 2(b).
[0104] As a result, as can be seen from Figure 2, biofilm stained with crystal violet was present over a wide area in Reference Example 1, whereas the amount of crystal violet staining in Example 1 was significantly reduced, indicating that the biofilm had been destroyed.
[0105] [Examples 2 to 9, Comparative Example 2] Next, BF destruction compositions were prepared by mixing the above control with the component (A) in the amounts shown in Table 2 below.
[0106] [Table 2]
[0107] The BF destruction test of Test 1 was carried out for the above-mentioned Examples 2 to 9 and Comparative Example 2. The results are shown in Table 2 and FIG. 3. From Table 2 and FIG. 3, it was found that Comparative Example 2 had a BF residual rate of 98% and almost no reduction in biofilm, and that, like Comparative Example 1, Comparative Example 2 is known as an effective acne ingredient, but has no BF destruction effect. In contrast, the BF residual rate of all of the Examples 2 to 9 was below 60%, and it was found that they exhibited a BF destruction effect.
[0108] Next, we investigated the BF-destroying effect of changing the concentration of isopropyl methylphenol (IPMP), one of the BF-destroying components (A).
[0109] [Examples 1-1 to 1-4] To the above control, a BF destruction composition was prepared by blending IPMP (A) to obtain the content shown in Table 3 below.
[0110] [Table 3]
[0111] The BF destruction test of the above Test 1 was carried out for the above Examples 1-1 to 1-4. The results are shown in Table 3 and Fig. 4. From Table 3 and Fig. 4, it was found that the BF remaining rates of the products of Examples 1-1 to 1-4 were 30%, 29%, 11%, and 10%, respectively, and a certain BF destruction effect was exhibited.
[0112] We also investigated the BF-destroying effect of changing the concentration of ethanol, which is one of the BF-destroying components (A).
[0113] [Examples 2-1 to 2-5] A BF destruction composition was prepared by blending the above control with the ethanol (A) content shown in Table 4 below.
[0114] [Table 4]
[0115] The above-mentioned Examples 2-1 to 2-5 were subjected to the BF destruction test of Test 1. The results are shown in Table 4 and Fig. 5. It is clear from Table 4 and Fig. 5 that the BF remaining rate of all of the Examples 2-1 to 2-5 was below 60%, and a certain degree of BF destruction effect was exhibited.
[0116] Furthermore, the BF destruction effect of changes in resorcinol concentration, one of the BF destruction components (A), was examined.
[0117] [Examples 3-1 to 3-5] To the above control, a BF destruction composition was prepared by blending resorcin (A) to obtain the content shown in Table 5 below.
[0118] [Table 5]
[0119] The above-mentioned Examples 3-1 to 3-5 were subjected to the BF destruction test of Test 1. The results are shown in Table 5 and Fig. 6. It is clear from Table 5 and Fig. 6 that all of the Examples 3-1 to 3-5 exhibited a BF residual rate of 40% or less, and thus exhibited a certain BF destruction effect.
[0120] The BF breaking effect of a BF breaking composition containing a BF breaking component (A) and a breaking assistant component (B) was examined.
[0121] [Examples 10 to 13] To the above control, a BF destruction composition was prepared by blending the components (A) and (B) in the amounts shown in Table 6 below.
[0122] [Table 6]
[0123] The BF destruction test of Test 1 was carried out on the products of Examples 10 to 13. The results are shown in Table 6 and Fig. 7. It is clear from Table 6, Fig. 7 and Fig. 4 that even a low-concentration IPMP-containing composition of 0.025 wt % exhibits a BF destruction effect equivalent to that of a 0.1 wt % IPMP-containing composition, which exhibits an excellent BF destruction effect, when used in combination with the destruction aid component (B).
[0124] [Examples 14 to 16] To the above control, a BF destruction composition was prepared by blending the components (A) and (B) in the amounts shown in Table 7 below.
[0125] [Table 7]
[0126] The BF destruction test of the above Test 1 was carried out for the above Examples 14 to 16. The results are shown in FIG. 8 together with the above Table 7. It was found from Table 7, FIG. 8 and FIG. 6 that even a low-concentration resorcin-containing composition of 0.25 wt. % which tends to have an insufficient BF destruction effect can exhibit a BF destruction effect equivalent to that of a 0.5 wt. % resorcin-containing composition which exhibits an excellent BF destruction effect by using the above destruction aid component (B) in combination.
[0127] (Formulation example) Formulation examples of the Propionibacterium acnes biofilm disrupting composition of the present invention are shown in Tables 8 and 9 below.
[0128] [Table 8]
[0129] [Table 9] [Industrial Applicability]
[0130] Since the BF-destroying composition of the present invention can destroy biofilms, it is extremely effective as an external composition such as an external medicine, an external quasi-drug, or a cosmetic that is effective in fundamentally treating acne.
Claims
1. An acne bacteria biofilm destroying composition comprising an acne bacteria biofilm destroying component (A) consisting of benzoyl peroxide.
2. An acnes biofilm disrupting agent for use in a topical composition applied to the skin for the treatment or prevention of acne, the composition containing benzoyl peroxide as an active ingredient.
3. A composition for external use for treating or preventing acne, comprising the Propionibacterium acnes biofilm disrupting agent according to claim 2.
4. 3. An external composition for fundamentally treating or preventing acne, comprising the Propionibacterium acnes biofilm disrupting agent according to claim 2.
5. 3. A composition for external use for treating or preventing acne caused by acne bacteria protected by the formation of a bacteria biofilm, comprising the acne bacteria biofilm disrupting agent according to claim 2.
Citation Information
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