• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    TERNARY ANTIMICROBIAL MIXTURES OF SYNERGISTIC ACTION. The invention relates to synergistically effective ternary antimicrobial mixtures.
    公开号:BR102012028255B1
    申请号:R102012028255-0
    申请日:2012-11-05
    公开日:2020-12-08
    发明作者:Ravikumar Pillai；Antje Kohler；Gerhard Schmaus
    申请人:Symrise Ag；
    IPC主号:
    专利说明:

    [0001] The present invention relates to the area of antimicrobial active substances and, in particular, certain mixtures, preparations and foods comprising 2-phenoxyethanol and at least two different alkanediols, selected from the group consisting of 1,2-decanediol, 1, 2-octanodiol, 1,2-hexanediol and 1,2-pentanediol. The invention also relates to the use of 2-phenoxyethanol for synergistic enhancement of the antimicrobial effectiveness of mixtures of at least two of the above-mentioned alkanodiols, to a method of preserving or antimicrobial treatment of a perishable product, to a method of cosmetic treatment of certain microorganisms and the use of a mixture according to the invention for the therapeutic treatment of certain microorganisms.
    [0002] In the cosmetics, pharmaceutical and food industries, there is a constant demand for agents with antimicrobial properties, in particular for the preservation of otherwise perishable products (for example, cosmetics, pharmaceuticals or food), but also for the treatment direct cosmetic or therapeutic use of microorganisms, which may have an adverse influence on the human body or the body of an animal. As an example, reference is made to microorganisms that can cause body odor, acne, mycoses or others.
    [0003] A large number of active antimicrobial substances are already admittedly used in the technical areas mentioned above, but additional alternatives are still being sought in order to be able to perform special targeted treatments and / or to reduce side effects. When looking for alternative agents with antimicrobial action and, in particular, preservative, it must be kept in mind that the substances used in the cosmetic, pharmaceutical and / or food fields must be: - toxicologically harmless, - well tolerated by the skin, - stable (in particular, in the usual cosmetic and / or pharmaceutical formulations), - very and preferably completely odorless and / or - produced at low cost (that is, using standardized processes and / or starting from standardized precursors).
    [0004] Furthermore, it is desirable to have to use as little as possible of the active antimicrobial substances in the corresponding agents to achieve a certain antimicrobial effect.
    [0005] The search for suitable (active) substances that have one or more of the above properties in sufficient degree is difficult for those skilled in the art, because there is no clear relationship between the chemical structure of a substance, on the one hand, and its activity biological protection against certain microorganisms (microbes) and their stability, on the other hand. In addition, there is no predictable relationship between antimicrobial action, toxicological safety, compatibility with the skin and the stability of a substance.
    [0006] The objective to be achieved by the present invention was, therefore, to present agents that meet several or all of the requirements mentioned above and / or have a desirable combination of the properties mentioned above.
    [0007] This objective is achieved by a mixture comprising or consisting of: (a) 2-phenoxyethanol and (b1 + b2) at least two different alkanedioles, selected from the group consisting of 1,2-decanediol, 1,2-octanodiol, 1,2-hexanediol and 1,2-pentanediol.
    [0008] The invention is based on the surprising discovery that ternary mixtures according to the invention can have a synergistically enhanced antimicrobial effect against at least selected microbes, in particular against Aspergillus niger, a fungus that is very difficult to control.
    [0009] In particular, the mixtures according to the invention have been found to be excellent for use as an antimicrobial mixture, in particular for the preservation of otherwise perishable articles (see above).
    [0010] Both experts have already conducted extensive investigations of the antimicrobial properties of 1,2-alkanediols and 2-phenoxyethanol, there was previously no indication that the ternary mixtures of these compounds according to the invention possessed, at least in an isolated case, definitely better antimicrobial action (at least against selected microbes).
    [0011] The antimicrobial action of 2-phenoxyethanol, a widely used condom, is known and is described, for example, in the "Handbuch der Konservierungsmittel" [Publishes Handbook] (Publ .: Deutsche Gesellschaft für wissenschaftliche und angewandte Kosmetik, Verlag für chemische Industrie, H. Ziolkowsky GmbH, D-86150 Augsburg, 1995). So far, however, research into the synergistically enhanced efficacy of a ternary combination with 1,2-decanediol and 1,2-hexanediol, in particular against Aspergillus niger, has not been presented in any document.
    [0012] The antimicrobial action of polyols, particularly of aliphatic 1,2-diols and combinations of 1,2-diols with other substances with antimicrobial action is described in several documents. Mention may be made, for example, of JP5191327, JP11322591, EP1206933, WO 03/069994. However, the search for synergistically enhanced efficacy against Aspergillus niger in combination with 2-phenoxyethanol is not presented in any of these documents.
    [0013] Polyols and, in particular, 1,2-alkanediols are, in most cases, inadequately effective against fungi such as Aspergillus niger. With respect to individual polyols or mixtures of polyols, there is therefore a gap in effectiveness in the case of fungi (for example, the "problem germ" Aspergillus niger). Consequently, a complete inhibition of fungi until now required the use of high concentrations of individual polyols or mixtures of polyols.
    [0014] Therefore, it was particularly surprising that the mixtures according to the invention had a highly synergistic efficacy. For example, in the treatment of Aspergillus niger: - 2-phenoxyethanol individually dosed, - 1,2-decanediol individually dosed, - 1,2-hexanediol individually dosed, - 1,2-octanediol individually dosed, - 1,2-pentanediol individually dosed,
    [0015] as well as a mixture containing two or more of these diols are already much higher after 48 hours with respect to the reduction in microbial count, when they are contained at the same concentration of use in the final products that must be protected against microbial attack. In particular, at given concentrations, only said ternary mixtures according to the invention already achieved a reduction in microbial count of almost 2-log after 48 h.
    [0016] Due to the particularly significant intensification of the action of its constituents, mixtures according to the invention are suitable, in particular, to combat Aspergillus niger, even at a low dosage of the mixture according to the invention.
    Accordingly, it is preferred, according to the invention, a mixture according to the invention comprising or consisting of (a) 2-phenoxyethanol, (b1) 1,2-decanediol, and (b2) 1,2- hexanediol and / or 1,2-pentanediol.
    [0018] The mixture according to the invention in which the weight ratio of component (a) to component (b1 + b2) is 0.3 - 1.2 to 0.06 - 0.7, and in particular , wherein the weight ratios of components (a) to (b1) to (b2) are 0.3 -1.2 to 0.05 - 0.4 to 0.01 - 0.3, is particularly preferred.
    [0019] The mixture according to the invention in which the weight ratios of the components (a) to (b1 + b2) and / or (a) to (b1) to (b2) are adjusted so that the antimicrobial action is synergistically enhanced is particularly preferred.
    [0020] By properly selecting the concentrations of the components (a), (b1) and (b2) and selecting the mixing ratios of the components with each other, therefore, a synergistic effect with respect to the antimicrobial action can be achieved. As mentioned above , that was surprising. The synergistic effect has the advantage that, for the same effectiveness, less antimicrobial active substance needs to be used, or, with the same amount of active substance, a better antimicrobial effect can be achieved.
    [0021] In case of doubt, the antimicrobial efficacy in the sense of this text is present when adequate conservation is established in accordance with the European Pharmacopoeia (ISBN 3-76922768-9; Supplement 2001 to 3rd Edition, pages 421-422, chapter 5.1. 3). The microbe to be preferably used is Aspergillus niger ATCC16404. For more information on the procedure for testing antimicrobial efficacy, reference is made in particular to example 1 given below.
    [0022] Synergistic intensification (of antimicrobial action) is present when the synergy index (SI value) of the test mixture according to Kull (literature: FCKull et al., Applied Microbiology Vol.9, pp. 538-541 (1961); DCSteinberg, Cosmetics & Toiletries Vol.115 (11), 59-62 (2000)) gives a value <1. For more information on the calculation of the synergy index, reference is made again to the example 1 given below. Once again, the microbe to be preferably used to determine the synergy index is the Aspergillus niger strain presented above.
    A particularly preferred mixture according to the invention is one in which component (b1) consists of 1,2-decanediol, and component (b2) consists of 1,2-hexanediol. A particularly large synergistic effect with respect to antimicrobial efficacy can be achieved in the resulting ternary system prepared with 2-phenoxyethanol, 1,2-decanediol and 1,2-hexanediol.
    [0024] The antimicrobial mixtures according to the invention are suitable for the preservation and antimicrobial treatment of perishable products, for example, cosmetics, pharmaceuticals or food. The perishable product is contacted with an amount of a mixture according to the invention that is antimicrobially effective, preferably effective against Aspergillus niger. However, due to their synergistically enhanced antimicrobial efficacy, the mixtures according to the invention can also be used: (a) for cosmetic treatment (in particular also topical) of microorganisms that cause body odor, (b) for cosmetic treatment ( in particular also topical) of microorganisms that cause acne, (c) for cosmetic treatment (in particular also topical) of microorganisms that cause mycoses and (d) for the treatment of microorganisms on or in inanimate matter.
    [0025] The mixtures according to the invention develop their synergistically enhanced antimicrobial action against a large number of Gram-positive bacteria, Gram-negative bacteria, fungi and yeasts. There is a particularly good action against Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, against yeasts, such as Candida albicans and - as mentioned above - also against fungi, such as Aspergillus niger. The very good effectiveness of the mixtures according to the invention against Aspergillus niger, a fungus that is very difficult to control, must be considered as particularly advantageous.
    [0026] The invention also relates to the use of the mixture according to the invention for the therapeutic treatment of (i) microorganisms that cause body odor, (ii) microorganisms that cause acne and / or (iii) microorganisms that cause mycoses,
    [0027] or as agents for the therapeutic treatment of (i) microorganisms that cause body odor, (ii) microorganisms that cause acne and / or (iii) microorganisms that cause mycoses.
    [0028] The present invention therefore relates to the corresponding methods for cosmetic and / or therapeutic treatment of microbes, and indeed in particular (a) microorganisms that cause body odor, (b) microorganisms that cause acne and / or (c) microorganisms that cause mycoses, comprising the topical application of an antimicrobially effective amount of the mixture according to the invention, wherein, preferably, the proportions of said diols in the mixture are preferably adjusted so that their antimicrobial action is synergistically enhanced.
    [0029] Preferred forms of the methods according to the invention correspond to the preferred forms of use according to the invention described above.
    [0030] Human skin is colonized by a large number of various microorganisms, including the microorganisms already mentioned above and others. Most of these microorganisms are not pathogenic and have no relevance to the physiological state of the skin and its odor. Others, however, can have a decisive influence on the health status of the skin.
    [0031] As our own investigations have shown, the synergistically active mixtures according to the invention are very effective not only against the microbes already mentioned above, but also against Staphylococcus epidermidis, Corynebacterium xerosis, Brevibacterium epidermidis, Propionibacterium acnes and against Trichophyton and Epidermophyton, species so that they can also be used as agents for the treatment (control) of underarm and foot odor or body odor in general, as agents for fighting acne, as anti-dandruff agents and for the treatment of mycoses (in particular dermatomycoses).
    [0032] "Treatment" means, in the context of this text, any form of therapeutic or non-therapeutic influence on the relevant microorganisms, in which the multiplication of said microorganisms is inhibited and / or the microorganisms are killed.
    [0033] The invention relates to a cosmetic or pharmaceutical preparation or a food, comprising: - an antimicrobially effective mixture according to any one of the preceding claims and - additional usual constituents.
    [0034] A cosmetic or pharmaceutical preparation according to the invention or a food according to the invention is preferred, in which the total quantity of components (a) and (b1 + b2) and / or the total quantity of components (a ), (b1) and (b2) are in the range of 0.01 to 10% by weight, with respect to the total mass of the preparation or food.
    [0035] Therefore, a cosmetic or pharmaceutical preparation according to the invention or a food according to the invention is particularly preferred, comprising: from 0.30 to 1.20% by weight of 2-phenoxyethanol, from 0.05 to 0.40% by weight of 1,2-decanediol, and from 0.01 to 0.30% by weight of the total amount of 1,2-hexanediol and / or 1,2-pentanediol,
    [0036] in each case with respect to the total mass of the preparation or food.
    [0037] In addition, a cosmetic or pharmaceutical preparation according to the invention or a food according to the invention comprising 2-phenoxyethanol as component (a), 1,2-decanediol as component (b1) and 1, is also preferred. 2-hexanediol and / or 1,2-pentanediol as component (b2), with a proportion of (a) 70% by weight of 2-phenoxyethanol, (b1) 0.20% by weight of 1,2-decanediol and 0 , 1% by weight of the total amount of 1,2-hexanediol and / or 1,2-pentanediol, with respect to the total mass of the preparation or food.
    [0038] For the preparations according to the invention or foods according to the invention that have just been described, more preferably, the particular antimicrobial effects and, in particular, the synergistic enhancement of these effects are, in each case, further enhanced.
    [0039] Therefore, in addition, a cosmetic or pharmaceutical preparation according to the invention or a food according to the invention, in which the concentration of each of the components (a), (b1) and (b2) is very particularly preferred by itself it is below the antimicrobially effective concentration, but the total concentration of components (a), (b1) and (b2) is antimicrobial effective. In this regard, it is particularly preferable that the proportions of component (a) are in the range of 0.5 to 1% by weight, those of component (b1) are in the range of 0.1 to 0.3% by weight, and those of component (b2) are in the range of 0.05 to 0.2% by weight.
    [0040] Likewise, in a preferred method according to the invention for cosmetic and / or therapeutic treatment of (a) microorganisms that cause body odor, (b) microorganisms that cause acne and / or (c) microorganisms that cause mycoses, the concentration to be used of the synergistically active mixtures according to the invention is in the range between 0.01 and 10% by weight and, particularly preferably, in the range between 0.05 and 5% by weight, in each case with respect to the total mass of the cosmetic or pharmaceutical product that the mixture comprises.
    [0041] Synergistically active mixtures can be used (a) prophylactically or (b) when necessary.
    [0042] The concentration of the amount of active substance, for example, to be applied daily varies and depends on the subject's physiological state and specific parameters of the individual, such as age or body weight. The synergistically active mixtures according to the invention can be used alone and in combination with other substances with antimicrobial action.
    [0043] It should be noted that the 1,2-alkanedioles to be used according to the invention in the context of the present text can be in the form of the corresponding 2S configuration enantiometer and the 2R configuration enantiometer, or in the form of any mixtures these 2S and 2R configuration enantiometers. For commercial reasons, it is, in fact, particularly advantageous to use mixtures of racemates of the respective 1,2-alkanediols to be used according to the invention for the control of microorganisms, as these are synthetically accessible in a particularly easy way, but pure enantiomers or non-racemic mixtures of these enantiometers are also suitable for the purposes according to the invention.
    [0044] Additional uses / methods and mixtures / compositions according to the invention can be seen in the following report and in the attached patent claims.
    [0045] Preparations containing a mixture according to the invention are, particularly if used against microbes that cause body odor, as a rule applied topically in the form of solutions, creams, lotions, gels, sprays or others. For other purposes, oral application (tablets, capsules, powder, drops), intravenous, intraocular, intraperitoneal or intramuscular or application in the form of an impregnated dressing is appropriate in some cases.
    [0046] The mixtures according to the invention can be incorporated without difficulty in common cosmetic or dermatological formulations (preparations) such as, among others, pump sprays, aerosol sprays, creams, ointments, tinctures, lotions, nail care products ( for example, nail polishes, nail polish removers, nail balms) and others. It is also possible and, in some cases, advantageous to combine the (synergistic) mixtures according to the invention with additional active substances, for example, with other substances with antimicrobial, antimycotic or antiviral action. Cosmetic and / or dermatological / keratolytic formulations containing the (synergistic) mixtures according to the invention can also be formulated in the usual way and be used for the treatment of skin and / or hair in the sense of a dermatological treatment or a treatment in the sense of cosmetic care. However, they can also be used in makeup products in decorative cosmetics.
    [0047] If the mixtures according to the invention are used as active substances for the conservation of organic material, then, in addition, an additional preservative or several additional preservatives can be advantageously used. It is preferable to select preservatives such as benzoic acid, its esters and salts, propionic acid and its salts, salicylic acid and its salts, 2,4-hexadiene acid (sorbic acid) and its salts, formaldehyde and paraformaldehyde, 2-hydroxybiphenyl ether and its salts , 2-zinc sulfidopyridine-N-oxide, inorganic sulfites and bisulfites, sodium iodate, chlorobutanol, 4-ethyl mercury (II) -5-amino-1,3-bis (2-hydroxybenzoic), their salts and esters , dehydroacetic acid, formic acid 1,6-bis (4-amidino-2-bromophenoxy) -n-hexane and its salts, the sodium salt of ethyl mercury (II) -thiosalicylic, phenyl mercury and its salts, 10-undecylenic acid and its salts, 5-amino-1,3-bis (2-ethylexyl) -5-methyl-hexahydropyrimidine, 5-bromo-5-nitro-1,3-dioxane, 2-bromo-2-nitro-1,3 - propanediol, 2,4-dichlorobenzyl alcohol, N- (4-chlorophenyl) -N '- (3,4-dichlorophenyl) -urea, 4-chloro-m-cresol, 2,4,4'-trichloro-2 ether '- hydroxydiphenyl, 4-chloro-3,5-dimethylphenol, 1,1'-methylene-bis (3- (1-hydroxymethyl-2,4-dioximidazolidin-5-yl) u reia), poly- (hexamethylenediguanide) hydrochloride, 2-phenoxyethanol, hexamethylenetetramine, 1- (3-chloroallyl) -3,5,7-triaza-1-azonia-adamantane chloride, 1 (4-chlorophenoxy) 1 (1H -imidazol-1-yl) -3,3-dimethyl-2-butanone, 1,3-bis (hydroxymethyl) -5,5-dimethyl-2.4-imidazolidinedione, benzyl alcohol, octopirox, 1,2-dibromo-2, 4-dicyanobutane, 2,2'-methylene-bis (6-bromo-4-chlorophenol), bromochlorophen, mixture of 5-chloro-2-methyl-3 (2H) - isothiazolinone and 2-methyl-3 (2H) isothiazolinone with magnesium chloride and magnesium nitrate, 2-benzyl-4-chlorophenol, 2-chloroacetamide, chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, 1-phenoxy-propan-2-ol, N-alkyl bromide (C12- C22) trimethylammonium and chloride, 4,4-dimethyl-1,3-oxazolidine, N-hydroxymethyl- N- (1,3-di (hydroxymethyl) -2,5-dioxoimidazolidin-4-yl) -N ' -hydroxymethylurea, 1,6-bis (4-amidino-phenoxy) -n-hexane and its salts, glutaraldehyde, 5-ethyl-1-aza-3,7-dioxabicyclo (3.3.0) octane, 3- (4- chlorophenoxy) -1,2-propanediol, hiamines, chloride alkyl- (C8-C18) -dimethylbenzylammonium, alkyl- (C8-C18) -dimethylbenzylammonium bromide, alkyl- (C8-C18) -dimethylbenzylammonium, benzylemiformal, 3-iodo-2-propynyl-butylcarbamate hydroxyacetamino hydroxy sodium or sodium hydroxymethyl-aminoacetate [sic].
    [0048] If the mixtures according to the invention are used mainly for inhibiting the growth of undesirable microorganisms on or in animal organisms, the combination with additional substances with antibacterial or antimycotic action is also advantageous in some cases. To that extent, as additional active substances, in addition to the large group of classic antibiotics, mention may be made in particular of products relevant to cosmetics, such as triclosan, climbazol, octoxiglycerol, octopirox (1-hydroxy-4-methyl-6- (2 , 4,4-trimethylpentyl) -2 (1H) -pyridone, 2-aminoethanol), chitosan, farnesol, glycerol monolaurate, aliphatic and aromatic hydroxamic acids, tropolon, hypoquitiol or combinations of the substances mentioned above, which, among other things, are used against armpit odor, foot odor or dandruff.
    [0049] The mixtures according to the invention can, particularly in cosmetic preparations, be advantageously combined with additional usual constituents, for example:
    [0050] Other preservatives, other antimicrobial agents, for example, other antibacterial or fungicidal agents, abrasives, anti-acne agents, anti-aging agents, anti-cellulite agents, anti-dandruff agents, anti-inflammatory agents, irritation-preventing agents, anti-inflammatory agents irritation, antioxidants, astringents, sweating inhibitors, antiseptic agents, antistatic agents, binders, tampons, vehicle materials, chelating agents, cellular stimulants, cleaning agents, care agents, depilatory agents, surfactants, deodorants, antiperspirants, plasticizers, emulsifiers, enzymes, essential oils, fibers, film-forming agents, fasteners, foam-forming agents, foam stabilizers, anti-foaming substances, foam reinforcers, gelling agents, gel-forming agents, hair care agents , hair styling agents, hair styling agents to soften hair, moisturizing agents, humidifiers, humectants, bleaching agents, reinforcing agents, stain removing agents, optical brighteners, impregnating agents, dirt repellants, friction reducing agents, lubricants, wetting creams, ointments, opacifiers, plasticizing agents , opacifying agents, enamels, shine agents, polymers, powders, proteins, over-greasing agents, abrasive agents, silicones, skin calming agents, skin cleansing agents, skin care agents, skin healing agents, agents skin lightening agents, skin protecting agents, skin softening agents, cooling agents, skin cooling agents, heating agents, skin heating agents, stabilizers, UV absorbers, UV filters, detergents, fabric softeners, suspending agents, skin tanning agents, thickeners, vitamins, oils, waxes, fats, phospholipids, sa fatty acids fatty acids, single or multiple unsaturation fatty acids, a-hydroxy acids, polyhydroxy fatty acids, blenders, dyes, color protective agents, pigments, anti-corrosion agents, flavors, flavoring materials, odorants, polyols, surfactants, electrolytes, solvents organic or silicone derivatives.
    [0051] In addition, the mixtures according to the invention can also be used in combination with active substances that inhibit perspiration (antiperspirants), in a particularly advantageous way to combat body odor. Aluminum salts, such as aluminum chloride, hydrochloride, nitrate, sulfate, acetate and other aluminum are mainly used as antiperspirants. In addition, however, the use of zinc, magnesium and zirconium compounds can also be advantageous. Essentially, aluminum salts and - to a lesser extent - aluminum / zirconium salt combinations have been shown to be suitable for use in cosmetic and dermatological antiperspirants. In addition, aluminum hydroxychlorides that are partially neutralized and therefore better tolerated by the skin, but not as effective, can also be mentioned.
    [0052] If the mixtures according to the invention are used for antimicrobial treatment of a surface (for example, of a human or animal body), in some cases, a combination with chelating agents (of metal) is advantageous. Preferred (metal) chelating agents for use are, among others, α-hydroxy fatty acids, phytic acid, lactoferrin, α-hydroxy acids, such as, among others, citric acid, lactic acid and malic acid and humic acids, bile acids, bile extracts, bilirubin, biliverdin or EDTA, EGTA and its derivatives.
    [0053] For use, the mixtures according to the invention with cosmetic and / or dermatological action are applied in a sufficient amount on the skin and / or hair in the manner that is usual for cosmetic and skin remedies. Particular advantages are provided by cosmetic and dermatological preparations which contain a mixture according to the invention and, in addition, act as sunscreen agents. Advantageously, these preparations contain at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment. The preparations can be in various forms, for example, as those normally used for sunscreen preparations. For example, they can be in the form of a solution, a water-in-oil (W / O) or oil-in-water (W / O) type emulsion, or a multiple emulsion, for example, water-in-oil in water type (W / O / W), a gel, an aqueous dispersion, a solid stick or also an aerosol.
    [0054] As already mentioned, preparations containing a mixture according to the invention can be advantageously combined with substances that absorb UV radiation, wherein the total quantity of the filter substances is, for example, 0.01% by weight at 40% by weight, preferably from 0.1% to 10% by weight, in particular from 1.0 to 5.0% by weight, with respect to the total weight of the preparations, to provide cosmetic preparations that protect the hair or hair. skin against ultraviolet radiation.
    [0055] In formulations containing mixtures according to the invention for topical prophylactic or cosmetic treatment of the skin, a high proportion of care substances is regularly advantageous. According to a preferred embodiment, the compositions contain one or more animal and / or vegetable fats and oils, such as olive oil, sunflower oil, refined soy oil, palm oil, sesame oil, rapeseed oil, almond, borage oil, evening primrose oil, coconut oil, shea butter, jojoba oil, sperm whale oil, beef tallow, mocotó and lard oil, for maintenance care and, optionally, other constituents for maintenance care, for example, fatty alcohols with 8 - 30 carbon atoms.
    [0056] Care substances that can be combined in an excellent way with the synergistic mixtures according to the invention also include: - ceramides, in which ceramides are to be understood as N-acylsphingosines (sphingosine fatty acid amides) or synthetic analogs of these lipids (called pseudoceramides), which greatly improve the water retention capacity of the stratum corneum; - phospholipids, for example, soy lecithin, egg lecithin and cephalins; - petroleum jelly, paraffin oils and silicone oils; the latter include, but are not limited to, dialkyl and alkaryl siloxanes, such as dimethylpolysiloxane and methylphenylpolysiloxane, and their alkoxylated and quaternized derivatives.
    [0057] Cosmetic preparations containing mixtures according to the invention can also contain antioxidants, in which all antioxidants that are suitable or usual for cosmetic and / or dermatological applications can be used.
    [0058] Cosmetic preparations containing mixtures according to the invention can also contain vitamins and vitamin precursors, in which all vitamins and vitamin precursors that are suitable or usual for cosmetic and / or dermatological applications can be used. Mentioned, in particular, vitamins and vitamin precursors such as tocopherols, vitamin A, nicotinic acid and nicotinamide, other B vitamins, in particular biotin and vitamin C, panthenol and its derivatives, in particular the panthenic esters and ethers and panthenically derivatized, for example, panthenol triacetate, panthenol monoethyl ether and its monoacetate and cationic panthenic derivatives.
    [0059] Cosmetic preparations containing mixtures according to the invention may also contain anti-inflammatory agents or active substances to relieve redness or itching. Any anti-inflammatory agents or active substances for relieving redness and itching that are suitable or usual for cosmetic and / or dermatological applications can be used.
    [0060] Cosmetic preparations containing mixtures according to the invention may also contain active substances with a skin lightening or tanning action. According to the invention, all active substances for skin whitening or skin tanning which are suitable or usual for cosmetic and / or dermatological applications can be used.
    [0061] Cosmetic preparations containing mixtures according to the invention may also contain anionic, cationic, nonionic and / or amphoteric surfactants, particularly when crystalline or microcrystalline solids, for example, inorganic micropigments, must be incorporated into the preparations.
    [0062] The invention is explained in greater detail below with reference to examples. Unless otherwise stated, data refer to weight. Example 1: Synergistic effectiveness of ternary mixtures according to the invention
    [0063] A comparison of the proper preservation of cosmetic formulations containing 2-phenoxyethanol (product A, not according to the invention), 1,2-decanediol (product B, not according to the invention), 1,2- hexanediol (product C, not according to the invention), a binary mixture of 2-phenoxyethanol and 1,2-hexanediol (product D, not according to the invention), a binary mixture of 2-phenoxyethanol and 1,2- decanediol (product E, not according to the invention), a binary mixture of 1,2-decanediol and 1,2-hexanediol (product F, not according to the invention) and a ternary mixture of 2-phenoxyethanol, 1, 2-decanediol and 1,2-hexanediol (product G, according to the invention).
    [0064] The proper conservation test was carried out in accordance with the European Pharmacopoeia.
    [0065] Thus, the test consists of contamination of the preparation, if possible in its final proportions, with a specified inoculum of suitable microorganisms, storage of the inoculated preparation at a specified temperature, removal of samples from the container at specified time intervals and determination the number of microorganisms in the samples removed. The preservation properties are adequate if, under the conditions of the test, there is a clear decrease or, optionally, no increase in the microbial count in the inoculated preparations after the specified times at the specified temperatures. Experimental details of the test procedure are described in the European Pharmacopoeia (ISBN 37692-2768-9; Supplement 2001 to the 3rd Edition, p. 421-422, chapter 5.1.3). TEST BODIES:
    [0066] The following strains of microorganisms were used for the tests of proper conservation: A: Escherichia coli ATCC 8739 B: Pseudomonas aeruginosa ATCC 9027 C: Staphylococcus aureus ATCC 6538 D: Candida albicans ATCC 10231 E: Aspergillus niger ATCC 16404
    [0067] The initial microbial count (UFC / g; ColonyForming Units / g; value "0") was in the range of 1,000,000 to 1,200,000 in the various test series. FORMULATION:
    [0068] For the tests of adequate conservation, the combination of active substances according to the invention (product G) was incorporated in an amount defined in an O / A emulsion. For comparison, the comparative products (products A to F) were incorporated into separate O / W emulsions. TABLE 1: Formulations with products A to G

    RESULTS:
    [0069] The results of the condom stress tests for Aspergillus niger for the combinations of active substances investigated, consisting of the mixture according to the invention (product G) or the comparative systems (products A and F), are compared in Table 2. The synergistic effect of the mixture according to the invention (product G) can be seen in the residual microbial counts after just 48 hours for Aspergillus niger. As can be seen in the table, in the case of Aspergillus niger, a microbe particularly problematic in relation to the conservation of industrial products, the microbial count was reduced by 48 hours using the mixture according to the invention at a dosage of 1% in weight from 1,200,000 to 14,000. In contrast, comparative products A to F that have been tested to compare at a dosage of 1% by weight, in the case of Aspergillus niger, do not allow this significant reduction in the number of colony forming units (CFU). This series of tests therefore shows, for example, that ternary mixtures of active substances according to the invention have an action that is synergistically better with respect to products A to G.
    [0070] Excellent results were also obtained for the other test organisms, confirming the superiority of product G according to the invention.
    [0071] Calculation of the synergistic antimicrobial action of external mixtures containing 2-phenoxyethanol, 1,2-decanediol and 1,2-hexanediol
    [0072] To determine the potentially synergistically enhanced efficacy of ternary mixtures containing 2-phenoxyethanol, 1,2-decanediol and 1,2-hexanediol, the reducing properties of UFC were determined according to the test procedure described in example 1 for individual substances, for various binary mixtures and for ternary mixtures according to the invention. The test results are shown in Table 2. TABLE 2: Test for reducing CFU of Aspergillus niger to 2-phenoxyethanol (product A, not according to the invention), 1,2-decanediol (product B, not according to the invention), 1,2-hexanediol (product C, not according to the invention), a binary mixture of 2-phenoxyethanol and 1,2-hexanediol (product D, not according to the invention), a binary mixture of 2-phenoxyethanol and 1,2-decanediol (product E, not according to the invention), a binary mixture of 2-phenoxyethanol and 1,2-hexanediol (product F, not according to the invention) and a ternary mixture of 2-phenoxyethanol, 1,2-decanediol and 1,2-hexanediol (product G, according to the invention) and calculated synergy index values for selected binary and ternary mixtures

    RESULTS:
    [0073] The synergy index (SI values) of ternary mixtures according to the invention and binary mixtures not according to the invention according to Kull (literature: FCKull et al., Applied Microbiology Vol.9, p. 538- 541 (1961); DCSteinberg, Cosmetics & Toiletries Vol.115 (11), 59-62 (2000) was calculated using the following equations.
    [0074] Binary mixtures: SI = Z * D / A + Z * E / B
    [0075] Ternary mixture: SI = Z * D / A + Z * E / B + Z * F / C
    [0076] where:
    [0077] D, E, F: proportion factor of the individual constituents (for example, 70% by weight = factor 0.70)
    [0078] A, B, C: UFC of individual substances at the moment 48 h
    [0079] Z: UFC of the binary / ternary mixture at the moment 48 h
    [0080] A synergistic effect is present if values below 1.00 are obtained. Values above 1.00 show an antagonistic effect. At a value of exactly 1.00, there is neither synergistic nor antagonistic effect.
    [0081] The calculation of the synergy index for the ternary mixture according to the invention containing 0.70% by weight of 2-phenoxyethanol, 0.20% of 1,2-decanediol and 0.10% by weight of 1.2 -hexanediol is shown below.
    [0082] SI = 14,000 * 0.70 / 1,100,000 + 14,000 * 0.20 / 1,200,000 +14,000 * 0.10 / 1,000,000 = 0.0126
    [0083] The SI value of 0.0126 shows a highly significant synergistically intensified action of the mixture containing 2-phenoxyethanol, 1,2-decanediol and 1,2-hexanediol.
    [0084] The results presented in table 2 and, in particular, those for the calculated synergy indices clearly show that the ternary mixture according to the invention (product G) containing 2-phenoxyethanol, 1,2-decanediol and 1,2 -hexanediol has a definitely synergistically enhanced antimicrobial action. In the case of binary mixtures (products D - F), no significant synergy effect was detected; on the contrary, in some cases, even a negative synergy effect (enhanced microbial growth) was observed compared to the use of mixtures A, B and C.
    [0085] It can be concluded from this that the surprisingly clear effect of synergies in the ternary mixture once again, surprisingly, is not due to a mixing effect of just two components of the 3 component system.
    [0086] A synergistic effect as shown in example 1 was achieved in another example for the ternary mixture containing 2-phenoxyethanol, 1,2-decanediol and 1,2-pentanediol as a substitute for 1,2-hexanediol. The synergistic intensification of the action of these ternary mixtures can be attributed to the better availability of phenoxyethanol and 1,2-decanediol in the aqueous phase when adding 1,2-hexanediol or 1,2-pentanediol. Antimicrobially effective short-chain diols such as 1,2-hexanediol or 1,2-pentanediol can serve as solubilizers, which increases the concentration of the much more strongly antimicrobially effective substances 2-phenoxyethanol and 1,2-decanediol in the aqueous phase of emulsions, the living space of microorganisms. Example 2: Practical cosmetic / dermatological examples
    [0087] For application, ecologic cosmetic preparations containing synergistically effective ternary mixtures are applied in a sufficient amount in combination with other cosmetic active substances and additives to the skin and / or hair in the usual manner for cosmetics. Examples of advantageous preparations for some uses are given below:
    [0088] Creams to regulate skin moisture:


    [0089] Formulation of sunscreen:


    [0090] Shampoo formulation:


    [0091] Formulations for decorative cosmetics:


    Example 3: Additional formulations containing ternary antimicrobial mixtures according to the invention
    [0092] In the following table:
    [0093] 3.1 = O / A skin lightening cream for the day
    [0094] 3.2 = soothing skin lotion with plant extracts O / A
    [0095] 3.3 = balm for after the sun
    [0096] 3.4 = spray for the body
    [0097] 3.5 = sunscreen lotion (O / A), broadband protection
    [0098] 3.6 = A / O night cream
    [0099] 3.7 = shampoo
    [0100] 3.8 = self-tanning cream
    [0101] 3.9 = O / W barrier repair cream
    [0102] 3.10 = antiperspirant / deodorant stick













    权利要求:
    Claims (5)
    [0001]
    1. Use of a mixture characterized by the fact that the mixture comprises or consists of: (a) 2-phenoxyethanol, (b1) 1,2-decanediol, and (b2) 1,2-pentanediol, for preservation or antimicrobial treatment of a perishable product against Aspergillus niger, where the weight ratio of component (a) to component (b1 + b2) is 0.3 - 1.2 to 0.06 - 0.7.
    [0002]
    2. Use of a mixture, according to claim 1, characterized by the fact that the weight ratio of components (a) to (b1) to (b2) is 0.3 - 1.2 to 0.05 - 0.4 to 0.01 - 0.3.
    [0003]
    3. Cosmetic or pharmaceutical or food preparation characterized by the fact that it comprises a mixture consisting of: (a) 0.30% to 1.20% by weight of 2-phenoxyethanol, (b1) 0.05% to 0, 40% by weight of 1,2-decanediol, and (b2) 0.01% to 0.30% by weight of 1,2-pentanediol, in each case, with respect to the total mass of preparation or food.
    [0004]
    4. Use of 2-phenoxyethanol characterized by the fact that it enhances the antimicrobial efficacy of a mixture comprising components (b1) and (b2) against Aspergillus niger, in which the weight ratio of component (a) to component ( b1 + b2) is 0.3 - 1.2 to 0.06 - 0.7.
    [0005]
    5. Method for preservation or antimicrobial treatment of a perishable product against Aspergillus niger, the method being characterized by the fact that it comprises the following stage: - contact of the perishable product with an antimicrobially effective amount of a mixture that comprises or consists of (a) 2 -phenoxyethanol, (b1) 1,2-decanediol, and (b2) 1,2-pentanediol, where the weight ratio of component (a) to component (b1 + b2) is 0.3 - 1.2 to 0.06 - 0.7.
    类似技术:
    公开号 | 公开日 | 专利标题
    BR102012028255B1|2020-12-08|USE OF A MIXTURE, COSMETIC OR PHARMACEUTICAL OR FOOD PREPARATION, USE OF 2-PHENOXYETHANOL AND METHOD FOR THE PRESERVATION OR ANTIMICROBIAL TREATMENT OF A PERISHABLE PRODUCT AGAINST ASPERGILLUS NIGER
    EP1898952B1|2012-09-12|Synergistic mixtures of aromatic alcohols and derivatives thereof with tropolone
    EP1845776B1|2009-02-18|Synergistic mixtures of c6- to c12-alkanediols and tropolone
    US20070265352A1|2007-11-15|Synergistic mixtures of at least one 1,2 alkanediol such as 1,2-hexanediol and 1,2-octanediol with a further compound having antimicrobial properties
    WO2006045743A1|2006-05-04|Synergistic mixtures of 1,2-hexanediol and 1,2-octanediol and also a further preservative
    EP1478231B1|2006-08-30|Synergistic mixtures of 1,2-alkane diols
    JP5588435B2|2014-09-10|Compositions containing benzyl alcohol derivatives and other antimicrobial active compounds
    EP2051584A2|2009-04-29|Synergistic anti-microbial mixtures of tropolone | and selected compounds
    BRPI0720307B1|2020-12-01|personal care product and composition, use of at least one compound as well as methods of forming a preserved personal care product composition and manufacturing a preserved personal care product
    CN111050554B|2021-12-10|Antimicrobial mixture containing 4- | butan-2-one and cosmetic composition containing the same
    DE20221386U1|2005-10-06|Use of 1,2-alkanediol mixture as an antimicrobial agent, e.g. for treating body odor, acne or mycoses or preserving perishable products
    WO2012129630A1|2012-10-04|Deodorant and antiperspirant composition, method for producing a deodorant and antiperspirant composition, and method for preventing and/or reducing perspiration odour
    EP3644736A1|2020-05-06|Antimicrobial mixture containing 4-|butan-2-one and an arginate compound, and cosmetic composition containing same
    WO2016044903A1|2016-03-31|Chemical compositions for the elaboration of an organic antimicrobial spray
    CN113518614A|2021-10-19|Antibacterial activity of fatty acid esters and compositions thereof
    同族专利:
    公开号 | 公开日
    KR102043869B1|2019-11-12|
    EP2589291B1|2016-12-07|
    KR20130049729A|2013-05-14|
    DE102011085798A1|2013-05-08|
    CN108771637A|2018-11-09|
    EP2589291B2|2019-08-21|
    CN103083196A|2013-05-08|
    EP2589291A1|2013-05-08|
    BR102012028255A2|2013-11-26|
    JP2013095754A|2013-05-20|
    US9585388B2|2017-03-07|
    JP6337333B2|2018-06-06|
    US20130136709A1|2013-05-30|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JPH05191327A|1992-01-09|1993-07-30|Fujitsu Ten Ltd|Radio data communication method|
    JP5062708B2|1998-02-24|2012-10-31|株式会社マンダム|Antiseptic disinfectant and human body composition|
    EP1206933B1|2000-11-16|2006-05-17|Johnson & Johnson Consumer France SAS|Compositions comprising caprylyl glycol and iodopropynyl butylcarbamate|
    JP2003081736A|2001-09-14|2003-03-19|Lion Corp|Skin care preparation composition|
    DE10206759A1|2002-02-19|2003-08-28|Dragoco Gerberding Co Ag|Use of 1,2-alkanediol mixture as an antimicrobial agent, e.g. for treating body odor, acne or mycoses or preserving perishable products|
    DE20221386U1|2002-02-19|2005-10-06|Symrise Gmbh & Co. Kg|Use of 1,2-alkanediol mixture as an antimicrobial agent, e.g. for treating body odor, acne or mycoses or preserving perishable products|
    US20070265352A1|2002-02-19|2007-11-15|Joachim Roeding|Synergistic mixtures of at least one 1,2 alkanediol such as 1,2-hexanediol and 1,2-octanediol with a further compound having antimicrobial properties|
    JP2004323646A|2003-04-24|2004-11-18|Pola Chem Ind Inc|Copolymer for use in cosmetics and cosmetics containing the copolymer|
    JP4589050B2|2003-12-22|2010-12-01|日本精化株式会社|Diesters and oils, and cosmetics and skin external preparations|
    US7935732B2|2004-04-08|2011-05-03|Isp Investments Inc.|Antimicrobial compositions|
    CN102123585A|2008-07-10|2011-07-13|西姆莱斯有限公司|Compositions comprising benzyl alcohol derivatives and further antimicrobial active compounds|
    WO2011047420A1|2009-10-19|2011-04-28|Chemeq Ltd|Cosmetic compositions|GB2222890B|1988-09-19|1993-04-21|Asahi Optical Co Ltd|Exposure control apparatus of camera|
    US5253009A|1988-09-19|1993-10-12|Asahi Kogaku Kogyo Kabushiki Kaisha|Exposure control apparatus of camera having an auto-exposure bracket mode|
    US5164758A|1988-09-19|1992-11-17|Asahi Kogaku Kogyo Kabushiki Kaisha|Exposure control apparatus of camera having an automatic exposure bracket drive mode|
    PL2774481T3|2013-03-08|2019-03-29|Symrise Ag|Antimicrobial compositions|
    ES2807123T3|2014-03-25|2021-02-22|Basf Se|Mixtures of preservatives and polymer solutions stabilized therewith|
    US10039939B2|2014-10-01|2018-08-07|L'oreal|Sulfate-free cleansing composition with thickener|
    KR101788179B1|2014-10-24|2017-10-20|아이이씨코리아 주식회사|Low irritation skin external application composition with an improved antiseptic ability|
    KR101779131B1|2015-06-25|2017-09-19|주식회사 엑티브온|A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same|
    WO2017067620A1|2015-10-23|2017-04-27|Symrise Ag|Mixtures comprising climbazole|
    US20190060261A1|2016-01-29|2019-02-28|B.R.A.I.N Biotechnology Research And Information Network Ag|Active combinations of perillic acid and activity enhancing substances|
    KR101702648B1|2016-05-10|2017-02-03|주식회사 엑티브온|A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same|
    BR112019004784A2|2016-09-30|2019-06-04|Rohm & Haas|synergistic microbicidal composition, method for inhibiting the growth of microorganisms, and aqueous medium.|
    CN106720188B|2016-12-01|2020-10-23|江南大学|Preparation method of film coating preservative for refrigerated freshwater fish fillets, product and application thereof|
    KR20190110574A|2017-02-03|2019-09-30|가부시키가이샤 아데카|How to improve the storage stability of cosmetics|
    JP6988186B2|2017-06-16|2022-01-05|住友ベークライト株式会社|Antifungal agent, antifungal resin film, antifungal laminated film and antifungal packaging|
    ES2875543T3|2017-06-30|2021-11-10|Oreal|Antimicrobial mixture containing 4-butan-2-one and an aromatic alcohol, and cosmetic composition containing it|
    CN111133088A|2017-09-22|2020-05-08|西姆莱斯有限公司|Active substance sheet|
    KR102026810B1|2017-12-12|2019-09-30|주식회사 크로파세|A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same|
    US20210113442A1|2017-12-22|2021-04-22|Symrise Ag|Cosmetic emulsion comprising 1,2-decanediol|
    WO2019120572A1|2017-12-22|2019-06-27|Symrise Ag|Emulsions containing mixtures of 1,2-hexanediol and 1,2-octanediol|
    DE202017007256U1|2017-12-22|2020-05-08|Symrise Ag|Cosmetic emulsion comprising 1,2-hexanediol and 1,2-octanediol|
    WO2019174713A1|2018-03-12|2019-09-19|Symrise Ag|Active substance adhesive film|
    WO2019179597A1|2018-03-19|2019-09-26|Symrise Ag|Water-soluble release forms for an active substance|
    BR112021000739A2|2018-07-18|2021-04-13|Symrise Ag|DETERGENT COMPOSITION|
    CN109105476A|2018-08-13|2019-01-01|贵州省现代农业发展研究所|A kind of reduction dragon fruit fruit rot processing method and antistaling agent|
    EP3877494A1|2018-11-08|2021-09-15|Symrise AG|An antimicrobial surfactant based composition|
    WO2020256245A1|2019-06-21|2020-12-24|주식회사 엑티브온|Preservative for externally-applied dermal preparation, and cosmetic composition and pharmaceutical composition each comprising same|
    CN110575412A|2019-09-30|2019-12-17|广东丸美生物技术股份有限公司|a special skin caring liquid for pore containing medicinal extract of Fomitopsis pinicola layer, and its preparation method|
    WO2021073761A1|2019-10-16|2021-04-22|Symrise Ag|Compositions with antimicrobial properties|
    WO2021098950A1|2019-11-19|2021-05-27|Symrise Ag|Home care product or formulation|
    CN112063684B|2020-11-16|2021-02-02|广州智汇生物科技有限公司|Method and kit for detecting illegal addition of antibiotics in cosmetics|
    法律状态:
    2013-11-26| B03A| Publication of a patent application or of a certificate of addition of invention [chapter 3.1 patent gazette]|
    2014-04-22| B03H| Publication of an application: rectification [chapter 3.8 patent gazette]|Free format text: REFERENTE A RPI 2238 DE 26/11/2013, QUANTO AO ITEM (71). |
    2017-10-10| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|
    2018-03-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2018-07-24| B07E| Notice of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |
    2019-01-15| B06T| Formal requirements before examination [chapter 6.20 patent gazette]|
    2020-04-07| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2020-09-01| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2020-12-08| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 05/11/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    DE102011085798A|DE102011085798A1|2011-11-04|2011-11-04|Synergistically active ternary antimicrobial mixtures|
    DE102011085798.2|2011-11-04|
    [返回顶部]