MXPA02007033A - Antimicrobial compositions - Google Patents

Abstract

An antimicrobial composition comprising:(i) a C1 to C4 monohydric alcohol carrier fluid, present at a level of at least 25%by weight of the total composition (excluding any volatile propellant present);(ii) an iron (III) chelator having an iron (III) binding constant of 1023 or greater;(iii) a solubility promoter selected from the group consisting of:(a) water;(b) an organic amine;(c) a polyhydric alcohol or derivative thereof;(d) a volatile propellant having fluorinecarbon or oxygencarbon bonds;(e) any combination of (a) to (d). The transitional metal chelator serves as an active antimicrobial, whilst the carrier fluidsolubility promoter mixture enables the formation of a stable composition. Preferred compositions are homogeneous solutions.

Description

ú or COM ANTI-MICROBIAL POSITIONS FIELD OF THE INVENTION This invention relates to the field of antimicrobial compositions and methods for reducing microbial numbers. In particular, this invention concerns reducing the microbial numbers on the surface of the human body or on used articles in close proximity thereto, thereby reducing malodor. The compositions and methods involved use particular iron chelators (11) as anti-microbial agents in compositions also comprising a short chain alcohol and a solubility promoter. When used in the human body, the compositions and methods of the invention are of greatest benefit when used in the most odorous areas of the human body, for example, the armpit and foot areas.

Background Anti-microbial agents can function through a variety of means. When used on the human body, such agents can significantly reduce microbial numbers either by reducing perspiration or by directly affecting the microorganisms on the surface of the body as represented herein by the skin. It is with this last class of agents, often called deodorant agents, that this invention is greatly interested. Most deodorant agents reduce the number of viable microorganisms on the surface of the skin. It is well known that sweat is usually odorless until it has been degraded by the microflora of the skin. Normal deodorants include ethanol and triclosan (2 ', 4,4'-trichlor, 2-hydroxy-diphenyl ether), which is a well-known anti-microbial agent. However, the deodorizing effect obtained with such deodorants wears with time and the microflora progressively recovers its figures. Consequently, there is a continual requirement for effective, durable deodorant compositions for the market. The problem to solve is not simply to reduce the microbial number in the corporal surface; It is equally important to maintain low microbial numbers (particularly low bacterial numbers) on the body surface (particularly in the areas of most bad odor, for example, the armpits). Certain iron chelators (III) have previously been incorporated into deodorant compositions. US 4, 356, 1 90 (Personal Products Co.) discloses the use of selected aminopolycarboxylic acid compounds to inhibit the formation of short chain fatty acids by Corynebacterium on the surface of the skin. For topical application, it is stated that alkanolamine salts are preferred. Especially preferred are di- and trialkanolamine salts, such as triethanolamine, diethanolamine and triisopropanolamine salts. It is also stated that a solvent compatible with the system can be used, in which the chelator is incorporated; however, products that comprise mixed solvent systems are not described.

WP 97/02010 (Procter and Gamble Co.) describes the use of chelators selected from the classes of succinic acid, glutaric acid and phosphonic acid as bactericidal compounds. WP 97/44006 (Ciba Specialty Chemicals Holding, I nc.) Claims the use of particular nitrogen-containing complexing agents for the anti-microbial treatment of skin and textile fiber materials. The above-mentioned complexing agents include those formed from neutralizing N, N-ethylenediamine disuccinic acid (EDDS) with ethanolamine or laurylamine. Deodorant compositions comprising EDDS, ethanol and water are also described. EDDS has an iron binding constant (III) of 1022 ("Critical Stability Constants, Volume 1: Amino Acids" (Critical Stability Constants, Volume 1: Amino Acids), p92, Martell and Smith, Plenum Press, 1974) . WO97 / 01360 (Concat Ltd.) claims a method for inhibiting bacterial growth using particular substituted polyaza compounds showing affinity for their first transition series. It is stated that compatible salts can be formed by neutralization with inorganic or organic bases, including primary, secondary and tertiary amines, notably ethanolamine, diethanolamine, morpholine, glucamine, N, N-dimethylglucamine and N-methylglucamine. Other patents indicate that iron chelators (11) can improve the effectiveness of particular known anti-microbials. WO 89/1 2399 (Public Health Research I nstitute of the City of New York) describes improved performance of bacteriocins containing lanthionine in compositions that also comprise an iron chelator (11). WO 97/09974 (Laboratoire Medix) describes compositions comprising chlorhexidine and a chelant. EP 0019670 B1 (Glyco Chemicals, Inc.) discloses anti-microbial compositions comprising a condensation product of 5, 5-dimethyl hydantoin and formaldehyde in combination with a water-soluble chelating agent selected from ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid ( DTPA) or the alkali metal salts thereof. US 4, 199,602 (Economics Laboratory, Inc.) describes the potentiation of antimicrobial nitroalkanes by aminocarboxylic chelating agents. US 5,688,516 (University of Texas System et al) discloses compositions comprising non-glycopeptide anti-microbials (other than vancomycin), in combination with a selection of components, including a chelating agent. WO 99/10017 (University of Texas System et al) describes a method for controlling the growth of microorganisms using a chelating agent and an anti-microbial agent. GB 1, 420,946 (Beecham Group Ltd.) discloses that the activity of selected phenolic antimicrobials can be greatly increased by certain chelating agents, in particular the disodium salt of E DTA.

BRIEF DESCRIPTION OF THE INVENTION This invention concerns the formulation of stable, long-acting antimicrobial compositions. The compositions of the invention comprise a fluid carrying alcohol, an iron chelator.

(III) having an iron binding constant (III) 1023 or greater, and a solubility promoter selected from a specific group of materials. The particular iron chelators (11) of the invention lead to prolonged anti-microbial activity upon application. The alcohol carrier fluid and the solubility promoter allows the chelant to be formulated in an anti-microbial, preferably homogeneous, stable composition. Prolonged anti-microbial activity often manifests itself as a lasting deodorant benefit, for example, lasting for a day. Additionally, in compositions comprising fragrance material, the anti-microbial activity may manifest itself as increased fragrance intensity. The stability of the compositions of the invention is a result of good compatibility between the components - this can also lead to benefits in terms of performance and aesthetics. The preferred compositions of the invention are homogeneous solutions. Such solution compositions have advantages over many of the problems associated with alternative suspension compositions; for example, valve blockage, settling and cake formation of suspended solids, and uneven application can all be reduced. Thus, according to a first aspect of the present invention, there is provided an anti-microbial aerosol composition comprising: (i) a fluid carrying monohydric alcohol from C1 to C, present at a level of at least 25% by weight of the total composition (excluding any present volatile propellant); (ii) an iron chelator (11) having an iron binding constant (11) of 1023 or greater; (iii) a solubility promoter selected from the group consisting of: (a) water; (b) an organic amine; (c) a polyhydric alcohol or derivative thereof; (d) a volatile propellant having fluorine-carbon or oxygen-carbon linkages; (e) any combination of (a) to (d). According to a second aspect of the present invention, there is provided a method for controlling the microbial numbers, said method comprising applying to a substrate an anti-microbial aerosol composition as provided according to the first aspect of the invention. An application of this aspect of the invention is the control of microbial figures on the surface of the human body or on articles used in close proximity thereto.

According to a third aspect of the present invention, there is provided a method for inhibiting malodor generation comprising topical application to the human body to garments worn in close proximity thereto of a composition as provided in accordance with a first aspect of the invention. This method can also be used to deliver increased fragrance intensity from a fragrance-containing composition according to the invention.

According to a fourth aspect of the present invention, there is provided a method for the manufacture of an antimicrobial composition, said method comprising the formation of a solution of an iron chelator (III) having an iron binding constant (III) of 1023 or greater in a carrier fluid of monohydric alcohol from Ci to C, present at a level of at least 25% by weight of the total composition (excluding any volatile propellant present), and also comprising a solubility promoter selected from the group consists of: (a) water; (b) an organic amine; (c) a polyhydric alcohol or derivative thereof; (d) a volatile propellant having fluorine-carbon bonds or oxygen-carbon bonds; any combination of (a) to (d).

DETAILED DESCRIPTION The novel anti-microbial compositions of the present invention perform unexpectedly well in terms of anti-microbial efficacy and maintenance of low odor, particularly when applied to the human body. Without wishing to join a theory, the hypothesis is formulated that after the reduction of microbial figures by other agents co-applied and / or by some external treatment similar to washing, the chelator effectively inhibits the uptake of nutrients from metal ions of transition, in particular iron (lll), by the remaining microbes, thus minimizing their re-growth. The above anti-microbial and deodorant benefits are particularly significant when the composition is applied to a particularly malodorous area of the human body or to garments worn in close proximity thereto. Thus, it is particularly advantageous to apply the compositions of the present invention to the areas of armpits, feet and socks and shoes. Benefits have been observed for fragrance-containing compositions of the present invention that include increased fragrance intensity, particularly when many hours have passed after application. It is believed that this benefit is an aspect of the benefit of deodorance, deriving both benefits from the excellent anti-microbial properties of the compositions of the invention. The stability benefit of the compositions of the invention results from making the iron chelator (11) compatible with the alcohol carrier fluid in the composition. This is done using particulate solubility promoters (vide infra). This aspect of the invention also allows the formulation of the preferred homogeneous compositions. It is particularly preferred that the aerosol compositions are homogeneous solutions, because valve blockage can be a severe problem in such products. When compositions according to the invention are applied to the surfaces, any volatile propellant present evaporates, leaving the chelator, generally dissolved in the carrier fluid and solubility promoter, on the surface being treated. This aspect of solution can lead to significant benefits, both in terms of performance and aesthetics, for example, lack of dusty deposits. Preferred compositions comprise a chelator solution in the carrier fluid and solubility promoter. Preferably, such solutions have an absorbance, relative to the carrier fluid, of less than 0.2, especially less than 0. 1 (during a path length of 1 cm to 600 nm) measured using a Pharmacia Biotech Ultrospec 200 spectrophotometer or similar instrument. The preferred compositions are homogeneous solutions. It is preferred that such composition solutions also meet the absorbance criteria set forth above: less than 0.2, especially less than 0.1, measured at 600 nm. The compositions of the invention can also be applied to the surface that requires treatment by any means. Although direct application is probably the most common method used by most products, pre-application on a carrier matrix similar to paper, cloth or sponge and application when contacting said carrier matrix with the surface is also a possibility.

Carrier Fluid The compositions of the present invention comprise more than %, preferably more than 50%, and more preferably more than 65%, of a carrier fluid of monohydric alcohol of d to C4, by weight of the total composition (excluding any volatile propellant present). The exclusion of volatile propellant during the calculation of the previous values is equivalent to saying that the aforementioned levels are related to the "base" composition when the composition concerned comprises a volatile propellant. Within the base composition of aerosol compositions, it is further preferred that the alcohol carrier fluid is present at a level in the base composition of more than 90% by weight, more preferably greater than 95% by weight. The compositions of the invention preferably have a weight ratio of C! -C4 monohydric alcohol carrier fluid to water of more than 65:35, more preferably more than 90: 1. In certain particularly preferred compositions, notably aerosol compositions, the weight ratio of C? -C monohydric alcohol carrier fluid to water is between 95: 5 and 99: 1. In other particularly preferred compositions, notably aerosol compositions, the weight ratio of C 1 -C 4 monohydric alcohol carrier fluid to water is greater than 99: 1. The carrier fluid of monohydric alcohol is preferably an alcohol of C2 or C3 or a mixture of the same. Particularly preferred alcohols are ethanol and isopropanol, with ethanol being most preferred.

Iron chelators (11) The chelants of the invention have an iron binding constant (11) of 1023 or greater. Chelants that have lower iron binding constants (11) are, in general, less effective in anti-microbial compositions. Chelants having an iron binding constant (11) of 1026 or greater are preferred, with chelators having an iron binding constant being particularly preferred (11). of 1 028 or greater. The "iron binding constant (11)" is the absolute stability constant for the chelant-iron complex (11). Such values are pH independent and consider only the most anionic, completely deprotonated form of the chelator. Potentiometric measurements can be made, and in a variety of different ways. Full details of suitable methods can be found in "Determination and Use of Stability Constants", A.E. Martell and R.J. Motekaitis (VCH, New York, 1989). Tables of such values can be found in numerous sources, for example "Critical Stability Constants", R. M. Smith and A. E. Martell (Plenum Pub. Corp., 1977). Iron chelators (l l l) are, in general, acidic. They can be used as such in the compositions of the invention, although they are preferably used as their salts or acid salts. In certain preferred compositions of the invention, notably compositions (particularly aerosol compositions) having a monohydric alcohol ratio of C! -C4 to water of more than 90: 1 0, it is preferred to have the chelator in the form of a salt, or acid salt, with an organic cation. The protonated or quaternized minerals are normal for such cations. More information is given in relation to the amines used to form such salts in the part of the specification that discusses amine solubility promoters. The salts or salts of acid from which they have a mixture of Associated cations, including mixtures of both organic and inorganic cations, can also be employed. The iron chelators (III) used in the present invention preferably have acid forms with at least two, preferably at least four, and most preferably at least five, ionizable acid groups. The acid groups are preferably carboxylic and / or phosphonic, but can be sulfonic or phosphinic, or any mixture of these groups. Particularly suitable chelants with acid forms that have carboxylic acid groups are polycarboxylate compounds, in particular aminopolycarboxylate compounds. The acid forms of the aminopolycarboxylate compounds include acid . { ethylenediaminetetraacetic fljfc (EDTA) and trans-1,2-diaminocyclohexane-N, N, N ', N'-tetraacetic acid (CDTA). The aminopolycarboxylate chelators more Preferred are the N, N'-ethylenebis [2- (2-hydroxyphenyl) glycine] (EDDHA), triethylenetetramhexacetic acid (TTHA) and diethylenetriaminepentaacetic acid (DTPA) forms. The chelants have, preferably, only moderate molecular weight, by which is meant that the chelants, in their acid forms, have a molecular weight of less than 1,000, more preferably 200 to 800, and most preferably 290 to 580, and in their salt form they have a molecular weight of less than 2000, more preferably 300 to 1400 and most preferably 500 to 1000. The chelant is preferably incorporated in the composition at a level of 0.01% to 10%, more preferably at a level of 0.05% a 1 %, and most preferably at a level of 0.3% to 3% by weight of the composition, excluding any volatile propellant present. Mixtures of chelators can also be used.

Solubility Promoter A solubility promoter selected from the aforementioned alternatives is an essential component of the invention. The choice of solubility promoter is influenced by the nature of the composition and the other components therein. A guide as to the selection of the solubility promoter is given below.

Water Water is a preferred solubility promoter in compositions comprising a chelant which is in the form of an acid salt or salt having an inorganic cation or an organic cation formed from a water soluble amine. Water serves as a solubility promoter by increasing the polarity of the total solvent system. In compositions for use in roll-on dispensers, squeeze atomizer or pump atomizer, water is preferably present at a level of from 5 to 50% and more preferably at a level from 1 to 40% by weight. In aerosol compositions, water is preferably present at less than 25%, preferably less than 10%, by weight of the base composition and is preferably used in combination with an organic amine solubility promoter. In aerosol compositions, it is preferred that the weight ratio of C-C4 monohydric alcohol carrying fluid to water is greater than 65:35, more preferably greater than 90: 10. Certain preferred aerosol compositions comprising water, have a weight ratio of carrier fluid of monohydric alcohol of C! -C4 to water of 95: 1 to 99: 1 and an organic amine solubility promoter. Other preferred aerosol compositions have a weight ratio of carrier fluid of C 1 -C 4 monohydric alcohol to water of more than 99: 1 and particular organic amine and / or other solubility promoter (s) present (s) ( vide infra). Compositions with relatively low levels of water may be of particular value in products applied to the human body. When such compositions contain relatively high levels of water, they can sometimes cause an undesirable moisture sensation on the application. The relatively low level of water compositions can also be of benefit with respect to the choice of container: such compositions allow the metal containers to be used with less risk of corrosion. An additional benefit of compositions having relatively low water levels is their compatibility with additional hydrophobic components, for example, fragrance components (see "Perfumery: practice and principles" (Perfumery: practice and principles), RR Calkin and S. Jellinek, [Wiley, 1 994, p 1 71]).

Organic amines An organic amine is a preferred solubility promoter in compositions comprising a weight proportion of carrier fluid of monohydric C1-C alcohol to water of more than 75:25 by weight, in particular in aerosol compositions. The organic amine can serve as a solubility promoter by neutralizing or partially neutralizing groups of acids in the chelator, thereby increasing the solubility of the chelator in the monohydric alcohol carrying fluid of C! -C4. The quaternized amines can also be used for this purpose, these amines being added conveniently to their hydroxide salts. The amine is preferably used, at a level sufficient to neutralize at least 40%, more preferably at least 60%, of such acid groups. In this way, the amount of preferred amine to be added is dependent on the amount of the chelator present, the relative molecular weights of the amine and the chelator, and the stoichiometry of the neutralization reaction. For example, it is preferred that at least 2 molar equivalents of a monobasic amine, or at least 3 molar equivalents of a monobasic amine, be added to a chelator having 5 acid groups, in order to achieve at least 40%, or at least 60%, neutralization of the acid groups. Preferably when an organic amine is used, the amount added is that which would lead to an aqueous solution of the chelating salt having a pH of between 6 and 8 (at a molar concentration of a chelating salt equal to that present in the composition) . Preferred amines are liquids at 20 ° C and atmospheric pressure. This may be of advantage with respect to formulation and processing. Preferred amines have a relatively low odor. This is of potential benefit during manufacturing and during the selection and use of compositions comprising amine solubility promoters. Regarding this point, preference is given to amines having relatively low volatility: a boiling point of 130 ° C or more is preferred at atmospheric pressure. The normal amine solubility promoters of the invention comprise at least one terminal hydrocarbyl group of C ^ C KJ; containing such a group only carbon and hydrogen atoms. Preferred amines of such type are isopropanolamine, 2-amino-2-ethyl-1,3-propanediol, 2- (N, N-dimethylamino) -2-methyl-1-propanol (DMAMP) and N, N-dimethylaminoethanol. Particularly preferred amines are 2-amino-2-methyl-1-propanol (AMP), diisopropanolamine, 2-aminobutan-1-ol, cyclohexylamine and mixtures thereof. Such relatively hydrophobic amines are of particular benefit in aerosol compositions having a weight ratio of Ci-C4 monohydric alcohol carrier fluid to water of more than 90: 10, in particular between 95: 5 and 99: 1. The benefit is of particular value in aerosol compositions comprising more than 40% by weight of volatile propellant and of even more value in aerosol compositions comprising more than 50% by weight of volatile propellant. When the proportion of monohydric alcohol carrier fluid C? -C4 to water is greater than 99: 1, it is preferred that the amine is free of any N-H bond and / or free of any O-H bond (thereby promoting the solubility of the chelant in such a hydrophobic system). Such amines can alternatively be described as tertiary amines and / or non-hydroxylated amines. Particularly preferred methods for such compositions are DMAMP, cyclohexylamine, diisopropylamine, tert-butylamine, N, N-diethylhexylamine and mixtures thereof. This preference is particularly valuable in aerosol compositions, especially those comprising more than 40% by weight of volatile propellant and even more especially those comprising more than 50% by weight of volatile propellant.

Polyhydric alcohol or derivative thereof. The solubility promoters which are polyhydric alcohols or derivatives thereof are particularly useful in compositions having a weight ratio of C T-CJ monohydric alcohol carrying fluid to water of more than 90: 1., in particular in aerosol compositions. The polyhydric alcohol or derivative thereof generally serves as a solubility promoter by increasing the polarity of the total solvent system. The amount of polyhydric alcohol or derivative thereof employed is preferably between 1% and 20% by weight, more preferably between 5% and 15% by weight, of the composition, excluding any volatile propellant present. This form of solubility promoter is preferably used in combination with a promoter of organic solubility. Particularly large benefits were found in aerosol compositions, especially those having a weight ratio of C1-C4 monohydric alcohol carrier fluid to water of more than 95: 5, more particularly when said ratio is greater than 99: 1. The benefits of polyhydric alcohols or derivatives thereof as well they are quite worthwhile in aerosol compositions comprising more than 49% or by weight of volatile propellant and of even greater value in aerosol compositions comprising more than 50% by weight of volatile propellant. The polyhydric alcohols of the invention are materials having at least two hydroxyl groups in a carbon skeleton (optionally interrupted by hetero atoms). The derivatives are esters, ethers and carbonates, including ethers and partial esters. Preferred polyhydric alcohols are alkane diols, such as 1,2-diols of C 2 to C 12 alkanes. Preferred derivatives are esters, such as C2 to C12 di esters of 1,2-diols of C2 to C3 alkanes, and carbonates, such as cyclic carbonates such as propylene carbonate. Preferred polyhydric alcohols and derivatives thereof are of molecular weight from 60 to 500. Particularly preferred materials are 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, propylene glycol, propylene glycol dicaprate / caprylate, and mixtures thereof. thereof.

Volatile propellant having C-O or C-F bonds When these materials are used in aerosol compositions according to the invention, the solubility of the chelant is substantially promoted. Such propellants are generally used in combination with an organic amine solubility promoter and usually in compositions comprising a weight ratio of CrC monohydric alcohol carrying fluid to water of more than 90: 10. The amount used is usually 1 5. % to 99% and preferably of 35% to 87% by weight of the composition. Mixtures of volatile propellants that have carbon-oxygen or carbon-fluorine bonds can also be used, such as mixtures with volatile propellants that do not have carbon-oxygen or carbon-fluorine bonds (vide infra). Preferred volatile propellants of this disclosure are dimethyl ether, 1,1-difluoroethane, 1-trifluoro-2-fluoroethane, carbon dioxide and mixtures thereof. Dimethyl ether and 1,1-difluoroethane are particularly preferred.

Additional components Volatile propellants Aerosol compositions are a preferred form of the present invention, and preferably comprise from 30 to 99% by weight, and in particular 35 to 87% by weight, of a volatile propellant. Said volatile propellant may include one having C-F or C-O bonds, as previously described as a solubility promoter. In addition to such materials, the volatile propellant may be selected from liquefied nitrogen or liquefied hydrocarbon gases, having a boiling point below 10 ° C and especially that with a boiling point below 0 ° C. The liquefied hydrocarbon gas is preferably a C3 to C6 hydrocarbon, including propane, isopropane, butane, isobutane, pentane and isopentane and mixtures of two or more thereof. Particularly preferred volatile propellants are isobutane, isobutane / isopropane, isobutane / propane and mixtures of isopropane, isobutane and butane.

When the volatile propellant is present at a level greater than 40% by weight of the composition, and in particular when it is greater than 50% by weight of the composition, it is preferred that the solubility promoter be selected from the group comprising: (a) ) organic amine free of any NH bond and / or OH bond; (b) an organic amine and a polyhydric alcohol or derivative thereof; (c) an organic amine and a volatile propellant having fluorine-carbon or oxygen-carbon bonds. The prior preference for solubility promoters is particularly valid in compositions having a weight ratio of d-C monohydric alcohol carrier fluid, to water between 95: 5 and 99: 1, and when said ratio is greater than 99: 1. The amounts of solubility promoters desirably present are as previously described herein.

Additional anti-microbial agents An additional component that can sometimes increase the effectiveness of a composition of the invention is an additional anti-microbial agent. Most classes of agents commonly used in the art can be incorporated into compositions of the invention. The levels of incorporation are preferably from 0.01% to 3%, more preferably from 0.03% to 0.5% by weight of the composition, excluding any volatile propulsive present. The preferred additional antimicrobial agents have an inh ibitory concentration minimum (MIC) of mg.ml "1 or less, in particular 200 μg.ml" 1 or less, and especially 100 μg.ml "1 or less The MIC of an anti-microbial agent is the minimum concentration of the required agent To inhibit significantly the microbial growth, the inhibition is considered "significant" if a reduction of 80% or greater in the growth of an inoculum of a relevant microorganism is observed, in relation to a control medium without an anti-microbial agent, on a period of 16 to 24 hours at 37 ° C. The "relevant microorganism" used for testing should be representative of those associated with the substrate to be treated.When the substrate to be treated is human skin, a relevant microorganism is Stpahylococcus epidermidis Details of suitable methods for determining MICs can be found in "Antimicrobial Agents and Susceptibility Testing", C. Thornbsberry, (in "Manual of Clinical Microbiology" (Manual of clinical microbiology), 5th edition, Ed. A. Balows et al, American Society for Microbiology, Washington D.C., 1991). A particularly suitable method is the macrocalcium dilution method as described in chapter 110 of the previous publication (pp. 1101-1111) by D.F. Sahn and J.A. Washington II. The MICs of anti-microbials suitable for inclusion in the compositions of the invention are triclosan: 0.01-10 μg.ml "1 (J. Regos et al., Dermatological (1979); 158: 72-79) and farnesol: ca. 25 μg.ml "1 (K. Sawano, T. Sato and R. Hattori, Proceedings of the 17th, IFSCC International Conference, Yokahama (1992) pp. 210-232) By contrast ethanol and similar alkanols have MICs of more than 1 mg mi "1. Preferred anti-microbials are bactericidal, particular organic bactericides, for example, quaternary ammonium compounds, such as cetyltrimethylammonium salts; chlorhexidine and salts thereof; and diglycerol monocaprate, diglycerol monolaurate, glycerol monolaurate and similar materials, as described in "Deodorant Ingredients" (I ngredientes deodorants), S.A. Makin and MR Lowry, in "Antiperspirants and Deodorants", Ed. K. Laden (1999, Marcel Dekker, New York) The most preferred antimicrobials for use in the compositions of the invention are polyhexamethylene biguanide salts ( also known as polyaminopropyl biguanide salts), an example being Cosmocil CQM R available from Zeneca PLC, preferably used up to 1% and more preferably at 0.03% to 0.3% by weight; 2 ', 4,4'-trichloro-2, -hydroxy diphenyl ether (triclosan), preferably used up to 1% by weight of the composition and more preferably at 0.05-0.3%; and 3, 7, 1 1 -trimethyldodeca-2,6, 10 -trienol (farnesol), preferably used up to 1% by weight of the composition and more preferably up to 0.5% The inorganic anti-microbial agents can also be used in the compositions of the invention Such materials frequently also function as anti-perspirant agents Examples are selected, with frequency a, of astringent active salts, including in particular aluminum, zirconium and alumiumium / zirconium salts, including both inorganic salts, salts with organic anions and complexes. Its use should consider local regulations concerning the incorporation of zirconium compounds in cosmetic or aerosol products. The astringent salts Preferred include aluminum halides, zirconium and aluminum / zirconium halides and halohydrate salts, such as hydrochlorides. When included, preferred levels of incorporation are from 0.5% to 60%, in particular from 5% to 30% or 40% and especially from 5% or 10% to 30% or 35% by weight of the composition. Especially preferred aluminum halohydrate salts, known as activated aluminum chlorohydrates, are described in EP 6,739 (Unilever PLC and NV). The assets of circoium aluminum chlorohydrate are also preferred materials, since they are the so-called ZAG complexes (zirconium-aluminum-glycine), for example, those described in US 3, 792068 (Procter and Gamble Co.). Zinc phenol sulfate can also be used, preferably up to 3% by weight of the composition. It should be noted that the incorporation of amphoteric or cationic anti-microbial agents makes it particularly important to use the compositions of the present invention comprising an organic amine solubility promoter. This is particularly true of organic anti-microbial agents, of cationic anti-microbial agents, and especially certain of organic polycationic anti-microbial agents. In this context, "polycationic" means that it possesses more than one positive charge, although the importance of the use of chelating salts according to the present invention is even greater in the presence of organic polycationic antimicrobial agents that possess more than five positive charges per molecule.

Phenolic anti-oxidants These materials can also increase the effectiveness of compositions of the invention. Preferred materials for incorporation into compositions of the invention are butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). Such agents are preferably used at 0.05% up to 5%, more preferably 0.075% up to 2.5%, and most preferably 0.1% up to 1% by weight of the composition, excluding any volatile propellant present.

Sensory modifiers Certain sensory modifiers are additional desirable components in the compositions of the invention. Emollients, humectants, volatile oils and non-volatile oils are all suitable classes of sensory modifiers. Examples of such materials include cyclomethicone, dimethicone, dimethiconol, isopropyl myristate, isopropyl palm itoate, C 1 2 -C 1 1 alcohol benzoate, PPG-3 myristyl ether, octyl dodecanol, C 7 -C 14 isoparaffins, di-adipate. isopropyl, isosorbide laurate, PPG-15 butyl ether, glycerol, hydrogenated polyisobutene, polydecene, phenyl trimethicone, dioctyl adipate and hexamethyl disiloxane.

Fragrance, etc. The fragrance is also a desirable additional component in the compositions of the invention. Suitable materials include conventional perfumes, such as perfume oils and also include so-called deo-perfumes, as described in E P 545, 556 and others publications. The levels of incorporation are preferably up to 4% by weight, in particular from 0. 1% to 2% by weight, and especially from 0.7% to 1.7% by weight of the composition, excluding any volatile propellant present. A fragrance solubilizer is also a desirable component in many compositions. Such materials are emulsifiers that aid in the dissolution / dispersion of a fragrance material in a composition. Preferred levels for incorporation are from 0.05% to 2%, preferably from 0.1% to 0.5%, by weight of the composition, excluding any volatile propellant present. These materials are of particular value when the ratio of water to monohydric alcohol carrier fluid from C to C4 is greater than 25:75 and especially when it is greater than 35:65. Preferred materials are non-ionic surfactants of HLB from 5 to 20 and particularly preferred materials include ethoxylated fatty alcohols, ethoxylated fatty acids, and ethoxylated oils, one example being the last hydrogenated castor oil of PEG-40.

Other additives Other additional components that may be included are colorants, preservatives, for example, C 1 -C 3 alkyl parabens, and anticoagulant agents, in conventional concentrations. It should be noted that certain components of compositions play more than one function. Such components are particularly preferred additional ingredients, their use often saving both money and formulation space. Examples of such components include isopropyl myrist.

MANUFACTURING METHODS The compositions of the invention are generally manufactured by forming a solution of the iron chelator (11) in the carrier fluid plus solubility promoter. A particularly preferred method comprises the addition of the chelator and an organic amine to water to form an aqueous solution, followed by dilution with the monohydric alcohol carrier fluid from C, to C to form an aqueous solution of alcohol, optionally followed by pressurization with a liquefied volatile propellant. Further details of specific anti-microbial compositions are given in the Examples.

Examples (Note that the "letter" codes refer to Comparative examples) Example 1: Preparation of an aerosol deodorant composition 0.52 g of DTPA was added as a powder of 65.91 g of 96% (w / w) ethanol. To this mixture was added (in the form of drops, with stirring) 0.38 g of AMP. The resulting mixture was stirred, with gentle heating (50 ° C) for 30 minutes. 0.34 g of isopropyl mistamine was added to the resulting solution and mixed. The reusable mixture was sealed in a conventional aluminum deodorant can, having valve access, and 36.16 g of liquefied propulsifier (CAP 40, eg Heat) was introduced into the can from a "transfer can" of propeller, via the valve, using a polyethylene transfer device. Finally, the can was equipped with a suitable actuator to allow an application of effective atomization of the product.

Deodorance Test 1 An anti-microbial composition according to the current invention (Example 1) and a control composition (Comparative Example A - lacking chelator and amine solubility promoter, see Table 1 for compositions), were prepared according to the method described. The deodorant performances of the two compositions were tested according to the following protocol. The results, presented in Table 1, illustrate the benefit of deodorance obtained from using an example prepared according to the invention. This benefit is a direct result of the anti-microbial performance of the composition.

Deodorant Protocol The panel employed included 50 individuals who had been instructed to use control ethanolic deodorants during the week prior to the test. At the start of the test, panelists were washed with unscented soap and test product (1.20 g) was applied to one axilla and control product to the other (1.20 g). (The product application was random to consider any left / right deviation). The panelists were instructed not to consume spicy foods or alcohol and not to wash under their armpits for the duration of the test. At least three expert advisers determined the intensity of axillary malodor at 5 hours and 24 hours after application, recording the intensity on a scale of 1 -5. After each 24 hour assessment, the panelists were washed again, and the products were reapplied as before. The procedure was repeated 4 times. At the end of the test, the data was analyzed using standard statistical techniques.

Table 1: Salt of DTPA-AMP vs. Control All components are expressed as percent by weight of the total components added. 1 . Diethylenetriaminepentaacetic acid. 2. 2-amino-2-methyl-1-propanol, used to form the amine salt of the chelant. 3. Emollient. 4. Propeller, patented mixture of butane, isobutane and propane, ex. Hot.

. The differences in malodor between the compositions were significant at the 99% level, after both 5 hours and 24 hours. (The minimum differences required for significance at the 95% and 99% confidence levels were: After 5 hours: 0.14 for the 95% level, 0.19 for the 99% level, After 24 hours: 0.17 for the the 95% level, 0.22 for the 99% level).

Anti-microbial test 1 Example 2, indicated in Table 2, was prepared in a manner similar to Example 1 and subjected to the following in vivo test for anti-microbial activity, together with Comparative Example A. The panel employed included 27 men who had been instructed to use control ethanolic deodorants during the week before the test. During the first week of the test, the armpits of panelists were washed every morning with soap without fragrance and deodorant products were not applied. During the second week of the test, the washing procedure was followed by the application of the test product (1.20 g) to one axilla and control product (1.20 g) to the other. (The product application was random to consider any left / right deviation). The panelists were instructed not to consume spicy foods or alcohol and not to wash under the armpits for the duration of the test. During the second week, samples of microflora were extracted axillary of each of the panelists just before the morning wash (on one of the days of the week different from the first). The axillary microflora was extracted by washing with a phosphate buffer. The extract was subjected to serial dilution and plated on selective media. This allowed the determination of the colony forming units of number (CFU) of Coryneform bacteria, Staphylococci bacteria and total aerobic bacteria per square centimeter of axillary skin. At the end of the test, the data was analyzed using standard statistical techniques.

Table 2: Anti-microbial results All components are expressed as percent by weight of the total components added. These results illustrate the anti-microbial benefit of compositions according to the invention. Each of the reductions in bacterial numbers was significant at the 99% level. (The result of Staphylococci was significant at the 99.9% level.) Deodorance test 2 The deodorance protocol described above was also used to test the performance of Examples B and 3 (see Table 3). These Examples were prepared in a manner similar to Examples A and 1, with the modification that a fragrance material was added to the compositions shortly before introduction into conventional aluminum deodorant cans. The results indicate that the benefit of the compositions of the invention is also found in fragrance-containing compositions.

Table 3: Salt of DTPA-AMP with fragrance vs. control with fragrance All components are expressed as percent by weight of the total components added. The differences in malodor between the compositions were significant at the 99% level, after both 5 hours and 24 hours. (The minimum differences required for significance at the 95% and 99% confidence levels were: After 5 hours: 0. 1 0 for the 95% level, 0.1 3 for the 99% level, After 24 hours : 0.1 0 for the 95% level, 0. 1 3 for the 99% level).

Anti-microbial test 2 The chelants indicated in Table 4 were subjected to the following in vitro test for anti-microbial activity against Staphylococcus epidermidis. An axillary isolate of S. epidermidis was grown overnight at 100 ml tryptone soy broth (TSB, eg Oxoid Ltd.). 10 ml of this culture were taken and subjected to centrifugation. The separated cells were re-suspended in 10 ml of phosphate-buffered saline and the centrifugation procedure was repeated. The washed cells were resuspended in 10 ml of phosphate buffered saline to give the inoculum. 100 ml of semi-synthetic medium (SSM) [containing (NH4) 2SO4 (0.066 g), MgSO4.7H2O (0.012 g), KCl (0.1 g), KH2PO4 (0.27 g), Na2HPO4 (1.43 g), fc Thiamine (0.1 mg), biotin (0.05 mg), Peptone P (0.05 g), glucose (2.0 mmol)] was sterilized by autoclaving at 121 ° C for 20 minutes. After sterilization, the pH was adjusted to 6.7 with HCl to give the control medium. The chelating test media were prepared in a similar manner, the chelator being introduced at a concentration of 5 x 10 0"5 mol.dm" 3, before adjusting the pH with HCl. 100 μl of the inoculum were introduced into each of the test means and the control medium. The cultures were incubated at 37 ° C (with shaking at 200 rpm) for 16 hours. After this time, the optical density of the cultures was measured at 600 nm to determine the degree of bacterial growth. When comparing the optical density of the culture in the presence of the chelating agent with the control one, the percentage of inhibition of growth was established for each of them. the chelators. (Optical density measurements were made in 1 in 4 dilutions of the cultures with 0.9% (w / v) saline, using 1-cm path length specimens, in a Pharmacia Biotech Ultrospec 200 spectrophotometer.) Table 4: Results in the anti-microbial activity test 1 . Ethylene glycol-O, O'-bis- (2-aminoethyl) -N, N, N ', N'-tetraacetic acid 2. Nitrilotriacetic acid Table 4 also indicates the iron binding constant (11) (K) of the tested chelators. The results show that only chelators having an iron binding constant (11) of more than 1022 have acceptable anti-microbial activity. Although the lower iron affinity chelates (11) have some anti-microbial activity in this test, the inhibition values obtained clearly indicate the inferiority of these materials.

Examples 4 to 7: Additional aerosol compositions DTPA salt compositions were prepared according to Table 5. The solutions of 76 mmol. kg '1 of the amine-chelator salts indicated in 96: 4 (w / w) ethanol / water, also counting perfume (1.5% w / w) and isopropyl myristate (0.33% w / w), were pressurized to approximately 2.7 x 105 Pa with a patented mixture of propane, isobutane and N-butane (CAP40, 22:24:54, eg Heat). The resulting pressurized systems contained liquefied propellant: base in the weight ratio of 35:65, with DTPA present at approximately 13 mmol.kg "1, based on the total weight of all the components present, including the propellants. products were homogeneous solutions Table 5: DPTA salts in 96% ethanol and CAP40 All components are expressed as percent by weight of the total components added.

Compositions in roll-on Examples 8 to 11, illustrated in Table 6, were prepared in the following manner. The indicated chelating acid (1 g or 0.5 g) was added to 20 g of water. The pH was adjusted to approximately 7.0 by the addition in the form of droplets of 1 M sodium hydroxide solution. Separately, hydroxypropylcellulose (HPC) (0.65 g) was added to ethanol (60 g), while mixing at a rate of approximately 8000 rpm in a Silverson L4RT mixer (eg Silverson, Ch'esham, Bucks.). The resulting homogeneous solution was allowed to cool to room temperature and then fragrance oil and fragrance solubilizer were added with stirring. The ethanolic HPC solution was then mixed with the aqueous solution of the chelating salt and the total weight was adjusted to 100 g with water.

Table 6: Compositions in roll-on of 60% ethanol 1 . Fragrance solubilizer (hydrogenated castor oil from PEG-40, eg BASF). The amount of chelator indicated is the amount of free acid added - this was adjusted to pH 7.0 with NaOH. All components are expressed as percent by weight of the total composition. Examples 1 2 to 1 5, see Table 7, were prepared in a manner analogous to Examples 8 to 11; the only differences were the use of ethanolamine (EA) to bring the aqueous chelating solution to pH 7.0, the omission of the perfume solubilizer and the incorporation of 70% ethanol in the final composition.

Table 7: Compositions in roll-on of 70% ethanol The amount of chelator indicated is the amount of free acid added - this was then adjusted to pH 7.0 with EA. All components are expressed as percent by weight of the total composition. Examples 16 to 19, see Table 8, were prepared in a manner analogous to Examples 1 2 to 1 5; the only differences were the use of AMP to bring the aqueous chelate solution to pH 7.0 and the incorporation of 80% ethanol.

Table 8: Compositions in roll-on of 80% ethanol The amount of chelator indicated is the amount of free acid added - this was then adjusted to pH 7.0 with 2-amino-2-methyl-1-propanol (AMP). All components are expressed as percent by weight of the total composition.

Compositions for squeeze atomization / pump Examples 20 to 25, as illustrated in Table 9, were prepared in a manner similar to Examples 12 to 15. The chelating salts were formed by neutralizing the chelating acid to pH 7.0 with the base indicated (1 M sodium hydroxide solution or pure ethanolamine [EA]).

Table 9: Compositions for squeeze atomization / 70% ethanol pump The amount of base used was that required to neutralize the chelator at pH 7.0 in 20 g of water. All other components are expressed as percent by weight of the total composition. (The amount of chelator indicated is the amount of free acid added.) Analogous squeeze / pump spray compositions were prepared with a level of 80% ethanol and AMP salts of the above chelators at levels of 0.5% and 1.0. % by weight (of the chelator in the acid form) Additional analogous squeezing compositions / pumps were also prepared comprising 0.05% by weight of triclosan (2 ', 4,4'-trichloro-2'-hydroxydiphenyl ether).

Additional aerosol compositions For each of Examples 26 to 32 (Table 10), DTPA (2.00 g) was added as a powder to demineralized water (2.40 g). To each mixture, the indicated organic amines or amines were added, in the form of drops, with stirring. The weight in grams of the added organic amines or amines was four times the weight percentage indicated in Table 5. The resulting mixtures were each brought to 20 g with anhydrous ethanol and stirred until a homogeneous solution was obtained. Independently, for each Example, an anhydrous ethanol solution (30 g), isopropyl myristate (1 g) and butylated hydroxytoluene (0.1 g) was prepared. For each Example, this solution was mixed with 5 g of the solution containing the appropriate amine. To each mixture was then added fragrance (1.5 g) and anhydrous ethanol (up to 45 g). The resulting 45 g base compositions were made into aerosol products by the addition of 55 g of CAP40, using the same technique as described for Example 1.

Table 10: High propellant aerosol compositions All components are expressed as percent by weight of the total components added. 1 . 2- (N, N-dimethylamino) -2-methyl-1-propanol. 2. Cyclohexylamine. 3. Diisopropylamine. 4. Ter-butylamine. 5. N, N-diethylhexylamine. 6. Isopropyl myristate.

All of the above compositions were homogeneous solutions. A similar composition was prepared using only 0.37 g of AMP as the organic amine was nebulous and finally separated into two phases. These results illustrate the preference for tertiary or non-hydroxylated amines (ie, free amines of any O-H or N-H bond) in such hydrophobic systems. Examples 33 to 36 (Table 11) were prepared in a manner analogous to Examples 26 to 32. Please note that these compositions each comprise 45%) of hydrocarbon propellant.

Table 1 1: Additional high propellant aerosol compositions } 44 All components are expressed as percent by weight of the total components added. 1 . Dicaprate / propylene glycol caprylate, eg Condea.

Examples 33 to 36 were all homogeneous solution compositions. The ethanol and water in Examples 33 to 35 were added in the form of 96% w / w of ethanol, while the ethanol and water in Example 36 were added in the form of 99.4% w / w of ethanol. When the analogous compositions were prepared without the glycol or As a result thereof, the resulting compositions were nebulous and finally separated into two phases. These results illustrate the preference for a glycol or derivative thereof when present on 40% hydrocarbon propellant. In addition, Example 36 illustrates an aerosol composition of homogeneous solution comprising a carrier fluid of ethanol, DTPA, AMP and propylene carbonate, having a weight ratio of ethane water of more than 99: 1. Examples 37 to 40 (Table 12) were prepared in a manner analogous to Examples 26 to 32. Please note that these compositions each comprise 55% hydrocarbon propellant. twenty Table 12: Additional high propellant aerosol compositions All components are expressed as percent by weight of the total components added. Examples 37 to 40 were all homogeneous solution compositions. The ethanol and water in Example 40 were added in the form of 96% w / w ethanol, while in Examples 37 to 39, anhydrous ethanol was used. When the analogous compositions were prepared without the glycol or derivative thereof, the resulting compositions were separated into two phases. These results illustrate the preference for a glycol or derivative thereof when present on 50% hydrocarbon propellant. In addition, Examples 37 to 39 illustrate aerosol compositions of homogeneous solutions comprising a ethanol carrier fluid, DTPA, AMP and a glycol or derivative thereof, having a weight ratio of ethane water of more than 99: 1.

A tetraalkylammonium-DTPA aerosol compositions The tetraalkylammonium-DTPA salts compositions set forth in Table 13 were prepared in a manner similar to Examples 26 to 32. The indicated tetraalkylammonium hydroxide salts were used, instead of the amines of Examples 26 to 32, to form the DTPA salts according to the following equation: 3. 3R4N + OH "+ X (CH2COOH) 5? X (CH2COOH)? 7 (CH2COO" R4N +) 3 3 + 3.3H2O where R is methyl, ethyl or n-butyl and X is the skeleton group of DTPA, which binds the acetate groups.

Table 13: Tetrabutylammonium-DTPA aerosol composition All components are expressed as percent by weight of the total components added. 1 . The water level excludes that formed from the reaction between DTPA and tetraalkylammonium hydroxide.

Aerosol compositions with polar propellants Examples 44 to 46 (Table 14) were prepared in a manner similar to Examples 26 to 32, with tetrabutylammonium hydroxide being used in place of a free amine for Example 44.

Table 14: Aerosol compositions with polar propellants Deodorance test 3 The previously described protocol was used to compare the performance of Example 27 (vide supra) with that of Comparative Example C, whose composition is indicated in Table 15 (together with a reproduction of the composition of Example 27, for convenience) ). Comparative Example C was prepared in a manner analogous to Example 27.

Table 15: Example 27 vs. control fifteen All components are expressed as percent by weight of the total composition. The differences in malodor between the compositions were - * & significant at the 99% level after 5 and after 24 hours. 20 (The minimum differences required for significance at the 99% confidence levels were: After 5 hours: 0. 1 3; After 24 hours: 0. 14.) These results illustrate the excellent performance of deodorant achievable using a composition comprising a carrier fluid of ethanol, DTPA, organic amine and an additional anti-microbial agent.

Fragrance Intensity Test The compositions indicated in Table 16 were prepared in a manner analogous to Examples 26 to 32 (with the use of 96% v / v ethanol instead of anhydrous ethanol). The compositions were applied and evaluated in a manner analogous to the previously described deodorant protocol, the only difference being that the intensity of fragrance in the armpits was assessed, instead of the axillary bad smell.

Table 16: Benefit of fragrance intensity All components are expressed as percent by weight of , 51 the total components added. The differences in fragrance intensities observed were significant at the 95% level after 5 hours and were significant at the 99% level after 24 hours. These results illustrate that the anti-microbial benefit of compositions of the invention may manifest itself as improved fragrance intensity. ft

Claims (27)

1. - 52 REIVI NDICATIONS 1 . An anti-microbial composition comprising: (i) a carrier fluid of monohydric alcohol of C, a C, present at a level of at least 25% by weight of the total composition (excluding any volatile propellant present); (ii) an iron chelator (11) having an iron binding constant (11) of 1 023 or greater; (iii) a solubility promoter selected from the group consisting of: (a) water; (b) an organic amine; (c) a polyhydric alcohol or derivative thereof; (d) a volatile propellant having fluorine-carbon or carbon-oxygen bonds; (e) any combination of (a) to (d).
2. 2. An anti-microbial composition according to claim 1, wherein the solubility promoter is water or a volatile propellant selected from the group consisting of dimethyl ether, 1,1-difluoroethane, 1-20-trifluoro-2-fluoroethane, dioxide. of carbon and mixtures thereof.
3. 3. An anti-microbial composition according to claim 1 or 2, which is a deodorant composition for use in the human body or a garment used in close proximity thereto.
4. 4. An anti-microbial composition according to any of the preceding claims, which is a homogeneous solution.
5. 5. An anti-microbial composition according to claim 4, which is a homogeneous solution in aqueous ethanol.
6. 6. An anti-microbial composition according to any of the preceding claims, wherein the weight proportion of fluid 5 C 1 -C 4 monohydric alcohol carrier to water is greater than 65:35.
7. 7. An anti-microbial composition according to claim 6, wherein the weight proportion of monohydric alcohol carrier fluid of C? -C to water is greater than 75:25 and the composition comprises an organic amine.
8. 8. An anti-microbial composition according to claim 7, wherein the organic amine is present at a level sufficient to neutralize at least 60% of any acid group in the iron chelator (11).
9. 9. An anti-microbial composition according to claim 7 or 15, wherein the organic amine is present at a level sufficient to lead to an aqueous solution of the chelating salt having a pH of between 6 and 8 (at a concentration molar of chelating salt equal to that present in the composition).
10. 10. An anti-microbial composition according to any of the preceding claims, wherein the iron chelator (11) has a binding coefficient for iron (11) of more than 1026.1.
11. An anti-microbial composition according to any of the preceding claims, wherein the iron chelator (11) is a polyaminocarboxylic acid or salt thereof.
12. 12. An anti-microbial composition according to any of the preceding claims, wherein the iron chelator (11) has an acid form with at least five ionizable acid groups. 3.
13. An anti-microbial composition according to claim 12, wherein the iron chelator (I I I) is a diethylenetriaminepentaacetic acid or a salt thereof.
14. 14. An anti-microbial composition according to any of the preceding claims, wherein the chelant is present at a concentration of 0.01% up to 10% by weight of the composition, excluding any volatile propellant present. 5.
15. An anti-microbial composition according to any of the preceding claims, comprising an additional anti-microbial agent.
16. 16. An anti-microbial composition according to the claim

    1. Wherein the additional anti-microbial agent is a cationic bactericide.
17. 17. An anti-microbial composition according to any of the preceding claims, comprising fragrance material up to 4% by weight of the composition, excluding any volatile propellant present.
18. 18. An anti-microbial composition according to any of the preceding claims, comprising a volatile propulsor.
19. 1 9. An anti-microbial composition according to the claim 1 8. where the volatile propellant comprises from 30 to 99% by weight of the total composition.
20. 20. An anti-microbial composition according to the claim 18, comprising more than 40 wt.% Of volatile propellant and a solubility promoter selected from the group comprising: (a) an organic amine free of any N-H bond and / or O-H bond; (b) an organic amine and a polyhydric alcohol or derivative thereof; (c) an organic amine and a volatile propellant having fluorine-carbon or oxygen-carbon bonds. twenty-one .
21. An anti-microbial composition according to any of claims 18 to 20, wherein the weight ratio of fluid 10 C monohydric alcohol carrier! -C4 a ag ua is between 95: 5 and 99: 1.
22. 22. An anti-microbial composition according to any of claims 1 to 8, wherein the weight ratio of C port-C4 monohydric alcohol carrier fluid to water is greater than 99: 1.
23. 23. A method for controlling microbial numbers, said method comprising applying to a substrate an anti-microbial composition according to any of the preceding claims.
24. 24. A cosmetic method for inhibiting the generation of bad odor, comprising topical application to the human body or a garment used in close proximity to a body of agreement. 20 with any of claims 3 to 22
25. 25. A cosmetic method for delivering improved fragrance intensity comprising topical application to the human body or a garment used in close proximity thereto, of a composition according to any one of claims 1 to 7. to 22 which also comprises a fragrance material
26. 26. A method for the manufacture of an anti-microbial composition, said method comprising the formation of a solution of an iron chelator (11), having an iron binding constant (III) of 1023 or greater in a carrier fluid of C4 monohydric alcohol, present at 5 a level of at least 25% by weight of the total composition (excluding any volatile propellant present) and further comprising a solubility promoter selected from the group consisting of: (a) water; (b) an organic amine; (C) a polyhydric alcohol or derivative thereof; (d) a volatile propellant having fluorine-carbon or oxygen-carbon bonds; (e) any combination of (a) to (d). •
27. 27. A method for the manufacture of an anti-microbial composition 15 according to claim 26, comprising the addition of the chelator and an organic amine to water to form an aqueous solution, followed by dilution with the alcohol carrier fluid. monohydric of C to form an aqueous solution of alcohol, optionally followed by pressurization with a liquefied volatile propellant. # twenty - 57 a SUMMARY An anti-microbial composition comprising: (i) a carrier fluid of monohydric alcohol of Ci to C4, present at a level of at least 25% by weight of the total composition (excluding any volatile propellant present); (ii) an iron chelator (III) having an iron binding constant (III) of 1023 or greater, (iii) a solubility promoter selected from the group consisting of: (a) water; (b) an organic amine; (c) a polyhydric alcohol or derivative thereof; (d) a 10 volatile propellant having fluorine-carbon or oxygen-carbon bonds; (e) any combination of (a) to (d). The transition metal chelator serves as an active anti-microbial, while the carrier fluid-solubility promoter mixture allows the formation of a stable ft composition. The preferred compositions are homogeneous solutions. fifteen #