MXPA00012704A - Method of reducing or preventing malodour - Google Patents

Abstract

Cosmetic method for reducing or preventing body malodour by topically applying to human skin an active agent capable of inactivating body malodour-causing microorganisms comprising corynebacteria, characterised in that the agent is capable of inactivating, of the corynebacteria, only those corynebacteria capable of catabolising fatty acids.

Description

METHOD TO REDUCE OR PREVENT BAD ODOR This invention relates to a cosmetic method for reducing or preventing bad body odor. In particular, it relates to a cosmetic method for reducing or preventing body odor by the topical application to human skin of an active agent capable of inactivating the bad body odor caused by microorganisms comprising corinabacteria, characterized in that the agent it is capable of selectively inactivating, of the corinabacteria, only those corinabacteria capable of catabolising the fatty acids. It is well known that the newly secreted sweat is sterile, and that the bad body odor is the result of the biotransformation of sweat by the microorganisms that live on the surface of the skin, to produce volatile odoriferous compounds. There are three types of compositions used as a routine to combat body odor: perfumes, antiperspirants, and deodorants. The perfumes are designed simply to mask the bad body odor. The antiperspirant activates the work by blocking the sweat glands, thus reducing perspiration. However, even the best cosmetically acceptable antiperspirant actives rarely reduce sweat production by more than 50 percent. Deodorant actives, on the other hand, are designed to reduce the population of microorganisms that live on the surface of the skin. Typical deodorants include ethanol and triclosan (2, 4, 4'-trichloro-2'-hydroxy diphenylether), which is a well-known antimicrobial agent. The skin is host to a number of microorganisms, some of which are beneficial, and others of which are not. The use of common deodorant actives results in the indiscriminate annihilation of most of the natural microflora of the skin, including beneficial species. This is considered an undesirable side effect of these deodorant formulations. Many disclosures describe compositions comprising antimicrobials that are designed to eliminate bad odor by reducing the microfloral population. International Publication Number WO 95/16429 (Henkel) discloses deodorant compositions comprising fat-soluble partial esters of hydroxycarboxylic acids. International Publications Nos. WO 95/07069; WO 91/11988, and WO 91/05541 (all of Gillette) describe deodorant compositions comprising inhibitors of pyridoxalphosphate-dependent amino acid lyase.

International Publication Number WO 94/14934 (Unilever) describes a method for reducing the perceptibility of an odoriferous substance, using an antibody or an antibody fragment. These antibodies could be used in deodorant compositions. Intentional Publication Number WO 93/07853 (Monell) describes the use of imitations of odoriferous 3-methyl-2-hexenoic acid, to reduce body odor. The Patent Number DD 29 39 58 (Medezinische Fakultaet (Charité) der Humboldt Universitaet zu Berlin) describes the use of lipoxygenase inhibitors to act biochemically to reduce the production of sweat, and to inhibit, to different degrees, the action of the bacteria of The skin or its enzymes on the decomposition of sweat to form substances with unpleasant odor. German Patent Number DE 43 43 265 (Henkel) describes deodorant compositions comprising saturated dioic acid esters (from 3 to 10 carbon atoms). The active inhibits an esterase that breaks down sweat, and it is said that the compositions do not alter the natural microflora of the. skin . German Patent Number DE 43 43 264 (Henkel) describes the use of lipid-soluble partial esters of hydroxycarboxylic acids in deodorant compositions. International Publication Number WO 94/07837 discloses unsaturated aliphatic dicarboxylic acids and their use for medical or cosmetic purposes. MIC is given a number of diacids against bacterial species, including Corynebacterium minutissimum. Extract Number AN1998-045392 from Derwent, discloses a biphenyl compound for the treatment and prevention of axillary odor. U.S. Patent No. 5,641,475 discloses topical compositions for, among other things, the contaminating odor of the body, containing aryl- or diaryl-2-acetoxyethoxy acids, containing the aryl group of 6 to 13 carbon atoms. carbon. The MIC for phenyl-2-acetoxyethanoic acid is given against a number of bacteria, including Corynebacterium minutissium. US Pat. No. 4,356,190 discloses a method for inhibiting the formation by Corynebacterium of fatty acids of 4 to 18 carbon atoms by applying a composition containing an aminocarboxylic acid to the skin. or your salts, keeping the composition the viability of the Coryn ebacterium. European Patent Number EP-A-750903 discloses a deodorant composition for preventing or combating the odor of the human body by using at least one fatty acid ester of sugar as the active ingredient. The inhibitory action is against a number of bacteria, including Corynebacterium xerosis and Corynebacterium minutissimum. German Patent Number DE 19620644 discloses the use of complexing agents containing nitrogen, for deodorization and antimicrobial treatment of the skin. The test microorganisms comprise Corynebacterium xerosis and Cor nejacterium minutissimum. German Patent Number DE 4321753 discloses cosmetic deodorants containing an alpha-omega-alkanedioic acid, which is not aminated, and the use of these acids to counteract gram-positive bacteria, including corynteria. European Patent Number EP 636359 discloses cosmetic deodorants containing mixtures of an alpha-omega-alkanedioic acid and wool wax acids. The Patent of the United States of America Number US 5,683,682 discloses aromatic benzoates as inhibitors of esterase producing microorganisms. The benzoates are hydrolyzed to obtain arylic acid and aryl alcohol products. The Patent of the United States of America Number US 4,089,942 discloses deodorant compositions to prevent the formation of unpleasant odors due to bacterial decomposition of perspiration, using a weak organic carboxylic acid, a hydroxycarboxylic acid, or a dicarboxylic acid, and a salt thereof.

U.S. Patent No. 5,433,943 discloses a deodorant composition containing, among other things, benzyl alcohol. Corinaphoresis bacteria are a group of bacteria that include Actinomyces, Arachnia, Arcanobacterium, Arthobacter, Bacterionema, Bifidobacterium, Brevibacterium, Cellulomonas, Corynebacterium, Eyrsipelothrix, Eubacterium, Kurthia, Listeria, Mycobacterium, Nocardia, Oerskovia, Propioni -bacterium, Rhodococcus and Rothia. (The Skin Microflora and Microbial Skin Disease, W. C. Noble, Cambridge University Press 1992). It is believed that corynaform bacteria contribute to the formation of bad body odor. We have now found that the genus of Corynebacterium can be subdivided into two subgroups according to its ability to catabolize fatty acids, and that one of these subgroups, referred to hereinafter as "corinteria A", is able to catabolize the acids fatty, contributes a lot to the formation of bad body odor, in particular the axillary bad smell, while the other subgroup, referred to hereinafter as "corinteria B", which catabolizes fatty acids much less or not at all, contributes much less or even not substantially to the formation of bad odor. We have also found that it is possible to selectively inactivate corinteria A, compared to corybacteria B.

We have also found that, on average, there is a difference between the axillary microflora of men and women, and in the strength and typical nature of the masculine and feminine malodor, in particular the axillary bad smell. Although for women corinteria A tend to comprise a smaller proportion of axillary microflora, we find that for many men the formation of bad odor is largely caused by corybacteria A. Corinteria means all strains of the genus Corynebacterium. The deodorants available in the market tend to be insufficiently effective or to substantially reduce the numbers of all bacteria in the microflora in an indiscriminate manner. The present invention offers the opportunity to provide deodorant products which, for many women, will substantially reduce malodour formation, while inactivating only a minor portion of the microflora. For many men, malodour formation can be substantially reduced, or even largely eliminated, while only a subset of the microflora, corinteria A, is inactivated. In addition, we find a range of specific active ingredients preferred to inactivate selectively the corinteria A, while leaving other bacteria, notably corinteria B, much less affected, or even notoriously affected at all. In accordance with the foregoing, the invention provides a cosmetic method to reduce or prevent body odor, by means of the topical application to the human skin, of an active agent capable of inactivating the bad body odor caused by the microorganisms comprising corinabacteria, characterized in that the agent is capable of selectively inactivating, of the corinabacteria, only those corinabacteria capable of catabolizing the fatty acids. The invention also provides the use of an active agent capable of inactivating the body odor caused by microorganisms comprising corinabacteria, in the manufacture of a cosmetic composition to reduce or prevent body odor, characterized in that the agent is capable of selectively inactivating , of the corinabacteria, only those corinabacteria capable of catabolising the fatty acids. According to the invention, the inactivation of microorganisms is any sub-lethal effect that results in a reduction or elimination of the production of sweat metabolites, for example by modification of the bacterial metabolism, in particular the metabolism of the fatty acid. Sub-lethal means a significant inhibition of metabolism, for example the use of pentadecanoic acid (inhibition of <; 60 percent), without concomitant reductions in cell viability (reduction of <1 log10 CFU / milliliter), and glucose utilization (reduction = .10 percent). By selective inactivation of corinabacteria, it means that only corinabacteria A capable of metabolizing fatty acids to a significantly higher degree than corinabacteria B are inactivated. Preferably, it means inactivating corinabacteria A to a significantly higher degree than most , preferably at least 75 percent, more preferably at least 90 percent of the bacteria other than corinabacteria A, which constitute the microflora of the skin. The active agent employed in the present invention can suitably be an agent that is more active against corinabacteria A than against corinabacteria B. Preferably, the agent is more active against corinabacteria A than against most of the other bacteria that make up the microflora of the skin, including corinabacteria B. The following is a non-exhaustive list of the active agents according to the invention: 1. inactivating agents directed to corybacteria A by antibodies, antibody fragments, and hydrophobic proteins; and 2. Agents capable of modifying the metabolism, in particular the metabolism of the fatty acid of the malodor producing microorganisms comprising corinabacteria, but, of the corinabacteria, only those corinabacteria capable of catabolizing the fatty acids, resulting in a reduction or elimination of the production of odoriferous compounds. It should be noted that the active agents according to the invention do not include the perfume components. A perfume component means an ingredient that is added to a perfume to contribute to the olfactory properties of perfume. Perfume means a mixture of perfume components, and optionally a suitable diluent, which is added to a product to provide a pleasant fragrance. 1. Agents targeted with antibodies or hydrophobic proteins: Antibody means any complete antibody or fragment thereof that has a selective affinity for corybacteria A. Antibodies or antibody fragments can be used to deliver active agents to target sites, with provision of fixing to these white sites. In the present invention, the target sites are the cell surface antigens of the Corynebacterium A species. The active agent can be connected to the antibody or to the antibody fragment by a variety of means, for example chemical conjugation. Examples of the hydrophobic proteins include oleosins. Agents means any active agent according to the invention. 2. Examples of active substances capable of inhibiting metabolism, in particular fatty acid metabolism, include: Fatty acids which may be saturated or unsaturated, and may optionally be substituted, in particular those containing from 6 to 24 carbon atoms, example palmitic and stearic acids, and also including: hydroxy fatty acids, for example ricinoleic acid, and juniperic acid; Alkyl sulfates of alkali metals, wherein alkyl is from 8 to 20 carbon atoms, for example sodium dodecylsulfate, sodium 7-ethyl-2-methyl-4-undecylsulfate, and sodium primary alkyl sulphates (from 9 to 13 carbon atoms) ). Dicarboxylic acids, which may be saturated or unsaturated, for example C18 dioic acid: C18: 2 dioic acid, and medium chain length, saturated or unsaturated dioic acids, for example azelaic acid, suberic acid, sebacic acid, undecanoic acid, dodecanoic acid, and mixtures thereof; aryl / phenyl alcohols, for example benzyl alcohol, t-butylhydroquinone, pyrocatechol, 2-amino-4-nitrophenol, salicylic alcohol, 3-hydroxybenzyl alcohol, 2,3-dimethoxybenzyl alcohol, 2,4-dimethoxybenzyl alcohol, 3, 5 alcohol -dihydroxybenzyl, 3-hydroxy-4-methoxybenzyl alcohol, 2-hydroxy-3-methoxybenzyl alcohol, coniferyl alcohol, and 4-hydroxy-3-methoxyphenethyl alcohol; aryl / phenyl acids, for example gallic acid, benzoic acid, salicylic acid, cinnamic acid, 3-methoxycinnamic acid, 4-methoxycinnamic acid, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, 4-hydroxycinnamic acid, 4-methoxybenzene propionic acid , 3,4-dihydroxybenzene propionic acid, 4-hydroxybenzene propionic acid, ferulic acid, and 2-methoxycinnamic acid; phenylesters, for example benzyl cinnamate; monoterpene derivatives, for example geranic acid; osmotic agents, for example sodium chloride; sterols, for example cholesterol, and ergosterol; steroids, for example testosterone, and andros-tenodione; - flavonoids, for example naringenin, isosacurane-tina, eriodictiol, and genistein; steryl esters, for example amyrin cinnamate; 2, 7-naphthalenediol, and oxyquinoline. aryl- / phenyl ketones, for example 4-hydroxy-3-methoxyphenylacetone, and 4- (4-hydroxy-3-methoxyphenyl) -3-buten-2-one. 2 or more of the active agents described hereinbefore may be employed. The active agent according to the present invention can preferably be used in a composition that can be applied to human skin for the reduction or elimination of body odor. Examples of products comprising an active agent according to the invention include antiperspirants, deodorants, shampoos, conditioners, skin cleansers, detergents, hair conditioners, sunscreens, tanning lotions, skin conditioners, and the like. It should be understood that this non-exhaustive list with respect to the suitable products comprising the active agents according to the invention. Typical deodorant compositions comprising an active agent according to the invention may also comprise other materials commonly found in compositions under the arm, such as deodorant or antiperspirant compositions, for example cosmetically acceptable vehicles; deodorant active; perfumes; perspiring assets; skin benefit agents; colorants; water, humectants, and other cosmetic adjuvants conventionally employed in these compositions. The use of these substances depends on the form of the composition, which can be an aerosol, a bar, a roll-on, gel, lotion, cream, ointment, powder, suspension, or soap. The active agent can be used in an amount effective to inactivate, from corybacteria, only those corybacteria capable of catabolising fatty acids. Normally, the active agent may be present in an amount of 0.001 to 10 weight percent of the composition, preferably 0.01 to 2 weight percent.

EXAMPLE 1 The demonstration of fatty acid catabolism in a particular bacterial strain was determined in vi tro using the following method: The in vi tro model system, which reproduces fatty acid catabolism by the axillary bacteria, consisted of shaking flasks with 250 milliliter screen, to which 30 milliliters of a semi-synthetic medium was added, (see below) supplemented with fatty acid substrate (2.0 milligrams / milliliter of pentadeca-noic acid), and non-fatty acid substrate (0.5-1.0) milligrams / -mililiter of glucose). This system was used - to evaluate the selected potential deodorant assets (see below). The flasks were inoculated with fresh bacterial biomass, previously cultured for 24 hours in TSBT (see below), to give the starting optical densities (A590) of 1.0-2.0. Following inoculation, the flasks were incubated aerobically at 35 ° C with shaking (130 rpm), and analyzed after 24 hours. The viability / purity of the culture was determined by TVC analysis on TSAT plates (see below), followed by serial dilution in a Ringers solution at a one-quarter concentration. The fatty acids were determined by capillary gas chromatography (GC) (see below). Residual glucose concentrations were measured with blood glucose test strips (BM-Test 1-44, Boehringer Mannheim) used in conjunction with a ReflofluxMRS glucose meter (Boehringer Mannheim). The fatty acid levels in the flasks were determined by capillary GC analysis. Initially, 5.0 milliliter aliquots were rapidly transferred from each flask to universal tubes; an internal standard (1.0 milligram / milliliter of lauric acid) was added to each universal tube, and the culture medium was acidified (pH of about 2) by the addition of hydrochloric acid. Then the liquid-liquid extraction was performed using two volumes (10 milliliters) of ethyl acetate; The organic and aqueous phases were resolved by centrifugation (2,000 rpm, 3 minutes). Then, 2.0 milliliters of each organic phase (upper) was transferred to a sampling tube, before analysis in a Perkin Elmer 8,000 (Series 2) of GC, adapted with a silica capillary column (0.25 micron film thickness) (Quadrex) fused with FFAP (PEG / siloxane copolymer modified with nitroterephthalic acid), 15 meters x 0.32 millimeters (internal diameter). This column was connected to the divided injector-no division, and to a flame ionization detector (FID) of the GC; the injector and detector temperatures were each 300 ° C. The carrier gas for the column was helium (0.42 kg / cm2), while hydrogen (1.19 kg / cm2) and air (1.61 kg / cm2) were supplied to the FID. The temperature program for the fatty acid analysis was 80 ° C (2 minutes); 80-250 ° C (20 ° C / minute); 250 ° C (5 minutes). The sample size for the injection was 0.5 to 1.0 microliters. The fatty acid levels in the flasks were quantified by comparing the peak areas with the known levels of both the internal standard (lauric acid) and the externally tested standard (pentadecanoic acid).

EXAMPLE 2 A demonstration of sub-lethal inactivation of fatty acid metabolism was performed with the following in vi tro methods. Prior to inoculation, the flasks were supplemented with selected materials, in a range of concentrations, to determine their ability to sub-lethally inhibit the catabolism of fatty acid by corinobacteria A. Active solutions / emulsions were prepared from supply in a semi-synthetic medium (see below), supplemented with gum arabic (5.0 milligrams / milliliter); emulsions were formed by ultra homogenization at 24,000 rpm for about 1 minute. At the end of each experiment, viability was compared, the levels of fatty acid and the residual glucose concentrations in the experimental flasks, with those in a control flask. The sub-lethal inhibition of fatty acid catabolism was defined as the significant inhibition of the use of pentadecanoic acid, without concomitant reductions in cell viability or in the utilization of glucose. Composition of broth / agar of Trypta soya supplemented with. Tween (TSBT, TSAT) used for the growth / maintenance of axillary bacteria grams / li-tro): Tryptone Soy Broth (30.0) (Merck), Yeast Extract (10.0) (Beta Lab), Tween 80 (1.0) (Tween is a registered trademark of ICI Specialty Chemicals), ± agar (20.0). Composition of the semi-synthetic medium used in laboratory systems that simulate the catabolism of fatty acid by axillary bacteria (grams / liter): KH2P04 (1.6), (NH4) 2HP04 (5.0), Na2S04 (0.38), Nitrogen Base of Yeast (Difco) (3.35), Yeast Extract (0.5), Tween 80 (0.2, Triton X-100 (Registered Trade Mark of Union Carbide) (0.2), MgCl2.6H20 (0.5), Glucose (0.5-1.0) , Pentadecanoic acid (2.0) The effect of azelaic acid and benzoic acid on viability, the use of glucose (initial concentration of 1.0 grams / liter), and of pentadecanoic acid (initial concentration of 2.0 grams / liter), part of corinabacteria A (NCIMB 40928) after a 24-hour incubation is presented in Table 1. The initial biomass levels in each trial were identical.

TABLE 1 The results in Table 1 clearly demonstrate that both azelaic acid, at a concentration of 2.5 milligrams / milliliter, and benzoic acid, at 2.5 and 5.0 milligrams / milliliter, inhibit sub-lethally in fatty acid catabolism, is say, inactivates corinabacteria A, as defined in the invention.

EXAMPLE 3 The following are typical formulations comprising an agent capable of inactivating the bad body odor caused by microorganisms comprising corinabacteria, characterized in that the agent is capable of inactivating, of the corinabacteria, only those corinabacteria capable of catabolising the fatty acids. They are made by methods common in the art.

TAB1, A 2 Ingredient Content,% by weight Ethanol 56.5 Benzyl alcohol 1.00 Isopropyl myristate 1.0 Fragrance 1.5 Propylene 40.0 EXAMPLE 4 A further example of the sub-lethal inactivation of corinabacteria A The effect of ferulic acid on viability, glucose utilization (initial concentration 0.5 milligrams / milliliter), and pentadecanoic acid (initial concentration 2.0 milligrams / milliliter) ) by Corynebacterium A sp. NCIMB 40928 after a 24 hour incubation, is summarized in Table 3.

TABLE 3 The results of Table 3 clearly demonstrate that ferulic acid, at a concentration of 2.5 milligrams / milli-liter, inhibits in a sub-lethal way the catabolism of the fatty acid, without concomitant reductions in cell viability and utilization, of glucose, that is, inactivates corybacteria A according to the invention.

Claims (6)

1. A cosmetic method for reducing or preventing body odor by applying topically to human skin an active agent capable of inactivating the microorganisms that cause the bad body odor that comprise corinabacteria, characterized in that the agent is able to inactivate selectively, of the corinabacteria, only those corinabacteria capable of catabolising the fatty acids, and does not comprise a perfume component.

2. The cosmetic method according to claim 1, characterized in that the active is a fatty acid containing from 6 to 24 carbon atoms, an alkali metal alkyl sulphate containing from 8 to 20 carbon atoms, a saturated dicarboxylic acid or unsaturated containing at least 8 carbon atoms, a phenyl alcohol, a phenyl acid, a phenyl ester, a monoterpene derivative, an osmotic agent, a sterol, a steroid, a flavonoid, a steryl ester, naphthalene-2,7-diol, or oxyquinoline. The cosmetic method according to claim 2, wherein the active agent is selected from the group consisting of recinoleic acid, C18: l dioic acid, salicylic acid, benzyl alcohol, benzoic acid, ferulic acid, naringenin, alcohols hydroxybenzyl, hydroxymethoxybenzyl alcohols, and dimethoxybenzyl alcohols. The cosmetic method according to claim 2, characterized in that the active agent is selected from ricinoleic acid, hydroxybenzyl alcohols, hydroxymethoxybenzyl alcohols, and dimethoxybenzyl alcohols a phenyl ester, a monoterpene derivative, an osmotic agent, a sterol, a steroid, naringenin, a sterile ester, naphthalene-2,7-diol, oxyquinoline, and antibodies or fragments thereof, with the provision to bind to cell surface antigens of Corynebacterium A. 5. The use of an active agent according to any of the preceding claims, to reduce or eliminate body odor. 6. The use of an active agent according to any of claims 1 to 5, in the manufacture of a cosmetic composition to reduce or eliminate body odor.