Antifungal composition

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Wearing apparel – fabric – or cloth

Reexamination Certificate

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Details

C424S439000, C424S755000, C424S776000, C424S725000, C435S069100, C530S350000, C530S370000

Reexamination Certificate

active

06599514

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a composition showing enhanced antifungal activity comprising one or more antifungal agents and one or more food additives, to the use of food additives to enhance the antifungal properties of an antifungal agent and to a method of inhibiting fungal growth using a composition according to the invention.
BACKGROUND OF THE INVENTION
Contamination in foodstuffs due to the presence of common food spoilage organisms is a recurring problem in the food industry. Most surprisingly we have observed an enhancement of antifungal activity when antifungal agents are combined with commonly used food additives. Furthermore, where the food additive shows antifungal activity we have observed an enhanced effect whereby the antifungal activity of the mixture is greater than would be expected. This enhancement or synergistic effect makes it possible to use a reduced amount of antifungal compound and/or food additive present in a foodstuff. This is particularly advantageous since it is highly desirable to minimise the amount of any additive present in foodstuffs both for human and animal consumption.
SUMMARY OF THE INVENTION
Accordingly in a first aspect the invention provides an antifungal composition comprising one or more antifungal agents and one or more food additives with the proviso that said composition does not contain nisin, lactoferrin and derivatives thereof, trichorzianine or lysozyme; the relative amounts of the antifungal agent(s) and the food additive(s) being such as to enhance the overall antifungal activity of the composition.
The food additive may also exhibit some antimicrobial activity especially antifungal activity when used in isolation as is observed, for example with food preservatives, and in this case the combination of the antifungal agent and the food additive will result in a synergistic effect where the antifongal activity of the mixture will be greater than that observed for each in isolation and compared to the sum of the individual results. It will be readily apparent to the man skilled in the art that in this case the antifumgal agent and the food additive present in the composition are not the same i.e. are different. The invention therefore extends to an antifungal composition comprising one or more antifungal agents and one or more food additives; the relative amounts of the antifungal agent(s) and the food additive(s) being such as to produce a synergistic effect. The invention further extends to the use of the synergistic composition in the methods of the invention hereinafter described further herein.
In a preferred embodiment the invention provides an antifungal composition comprising one or more antifungal agents and one or more food additives wherein one or more of said food additive(s) shows antimicrobial activity with the proviso that said composition does not contain nisin, lysozyme, or lactoferrin and derivatives thereof; the relative: amounts of the antifungal agent(s) and the food additive(s) being such as to produce a synergistic effect on the overall antifungal activity of the composition.
In a further preferred embodiment the invention provides a composition comprising one or more antifungal agents and one or more food additives selected from the group consisting of metal chelating agents, wetting agents, adjuvants, antioxidants, colourants, emulsifiers, stabilisers, surfactants, bleaching agents, pH control agents, flavours and flavour enhancers, sequestrants or food preservatives with the proviso that said composition does not contain nisin, lactoferrin and derivatives thereof, trichorzianine or lysozyme; the relative amounts of the antifungal agent and the food additive being such as to enhance the overall antifungal activity of the composition.
In a further aspect the invention provides the use of a food additive to enhance the antifungal properties of an antifungal agent.
As used herein the term enhance is used to denote an improvement in antifungal activity and this may be evidenced by, for example, an observed reduction in the concentration of antifungal agent required to give strong fungal growth inhibition e.g. more than 90% fungal growth inhibition. As used herein the term synergistic is used to denote an improvement in antifungal activity which can be demonstrated to be synergistic for example by application of the Colby Formula (Colby S. R. (1967) Weeds 15, 20-22) or in graphical representation in isobolograms as described by Parrish and Davidson (1993) (In: Antimicrobials in foods. Ed. By P. M. Davidson and A. L. Branen. Marcel Dekker, Inc. New York Examples of food additives include the following commonly used food additives: sorbic acid and sorbates (E200-E203), benzoic acid and benzoates (E210-E213), hydroxy-benzoates (E214-E219), sulphur dioxide and sulphites (E220-E228), biphenyl and derivatives (E230-E232), nitrites (E249-E250), nitrates (E251-E252), lactic acid (E270), lactates (E325-E327), citric acid and citrates (E330-E333), tartaric acid and tartrates (E334-E337), orthophosphoric acid and orthophosphates (E338-E341), malates (E350-E352), adipic acid (E355), succinic acid (E363), 1,4-heptonolactone (E370), nicotinic acid (E375), triammoniun citrate (E380), ammonium ferric citrate (E381), calcium disodium EDTA (E385), glycerol (E422), di-, tri- andpolyphosphates (E450a, E450b, E450c), fatty acids (E470), mono- and diglycerides of fatty acids (E471), esters of mono- and diglycerides of fatty acids (E472a-E472f), carbonates (E500, E501, E503, E504), gluconates (E576-E578), chlorine (E925), sodium hexametaphosphate, butylated hydroxyanisole (BHA)(E320), butylated hydroxytoluene (BHT)(E321), t-butyl hydroquinone (THBQ), propyl gallate, calcium heptonate, calcium phytate, diethyl ether, EDTA, disodium dihydrogen EDTA, ethyl acetate, glycerol mono-, di- and triacetates, glycine, oxystearin, propan-1,2-diol and propan-2-ol and sodium heptonate.
Particularly preferred food additives include sorbic acid and sorbates (E200-E203), benzoic acid and benzoates (E210-E213), hydroxy-benzoates (E214-E219), acetic acid and acetates (E260-E263), lactic acid (E270), lactates (E325-E327), citric acid and citrates (E330-E333), tartaric acid and tarttates (E334-E337), orthophosphoric acid and orthophosphates (E338-E341), malates (E350-E352), adipic acid (E355), succinic acid (E363), nicotinic acid (E375), calcium disodium EDTA (E385), fatty acids (E470), mono- and diglycerides of fatty acids (E471), esters of mono- and diglycerides of fatty acids (E472a-E472f), EDTA, disodium dihydrogen EDTA, ethyl acetate, glycerol mono-, di- and triacetates.
Further preferred additives include butylated hydroxy anisole, butylated hydroxytoluene and tertiary butyl hydroquinone.
We have found that when antifungal agents are used in the presence of calcium ions a significant reduction in the activity of the antiflngal agent is observed. This observation could restrict the usefulness of the technology in foods rich in calcium such as dairy products. We have now found that the problem associated with high calcium levels may be overcome by the use of chelating agents in association with the antifungal agent and most surprisingly that the presence of the chelating agent enhances the activity of the antifungal agent. Furthermore, we have found that it is possible to achieve this with levels of chelating agents, especially EDTA and salts thereof which are substantially lower than that recommended in the literature to obtain effective chelation.
Examples of particularly preferred food additives are metal chelating agents such as EDTA and its use as the disodium or calcium disodium salts; solvents and wetting agents such as organic acids e. g. lactic acid; adjuvants; and food preservatives including membrane permeabilising agents such as, for example, sorbic acid and its use as the calcium, sodium or potassium salts, benzoic acid and its use as the sodium potassium or calcium salts, antioxidants such as propyl gallate and C1-6 alkyl ethers such as butylated hydroxy anisole, butylated hydroxytoluene and tertiary butyl hydr

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