Food or edible material: processes – compositions – and products – Inhibiting chemical or physical change of food by contact... – Biocidal or disinfecting chemical agent
Reexamination Certificate
1999-08-06
2001-05-08
Pratt, Helen (Department: 1761)
Food or edible material: processes, compositions, and products
Inhibiting chemical or physical change of food by contact...
Biocidal or disinfecting chemical agent
C426S044000, C426S323000, C426S334000, C426S580000, C426S583000, C426S601000, C426S634000, C426S656000
Reexamination Certificate
active
06228408
ABSTRACT:
The present invention relates to the preparation of compositions which comprise natamycin and the use of such compositions to treat foods such as cheeses and sausages or agricultural products such as fruits, grains and seeds. Also said products treated with compositions of the invention are disclosed.
For more then 20 years natamycin has been used to prevent fungal growth on cheeses and sausages.
Cheeses are treated by immersion in a suspension of natamycin in water or covered by an emulsion of a polymer in water, mostly polyvinyl acetate. Sausages are mainly treated by immersion or by spraycoating with a suspension of natamycin in water. Usually aqueous suspensions for immersion treatments contain 0.1% to 0.2% w/v of natamycin, while polymer emulsions for coating purposes contain 0.01% to 0.05% w/v of natamycin.
These treatments can be highly effective in preventing fungal growth on the surface of cheeses and sausages. However because of the low solubility of natamycin, mould species which are less susceptible to natamycin sometimes are not fully inhibited. Thus some fungal spoilage still may occur. Examples of fungal species which are more tolerant towards natamycin are
Verticilium cinnabarinum, Botrytis cinerea
and Trichophyton species. More tolerant species may also be found among those of the genii Aspergillus, Fusarium and Penicillium. An example of such a species which sometimes causes mould problems in cheese industry is
Penicillium discolour.
Due to the low solubility of natamycin a food product treated with this antimycotic will be protected against fungal growth for a longer period. only the natamycin which is in solution will be available to exert anti-fungal activity.
Natamycin has a MIC (Minimal Inhibitory Concentration) of less than 10 ppm for most foodborn fungi, while its solubility in water is from 30 to 50 ppm (Brik, H.; “Natamycin” Analytical Profiles of Drug Substances 10, 513-561, (1981)). After many years of continuous use of this antimycotic natamycin-resistant fungi have never been found (De Boer, E.; Stolk-Horsthuis, M.; “Sensitivity to natamycin (pimaricin) of fungi isolated in cheese warehouses” J. of Food Prot. 40, 533-536, (1977)). Under normal conditions natamycin will protect food products such as cheese fully against fungal spoilage for a short period of time. However, sometimes the amount of fungi present in the surroundings is high, for example in a cheese factory, such that the dissolved fraction of natamycin is insufficient to prevent fungal growth on cheese, or the production or storage conditions in factories are particularly favourable for fungal growth. An example of an important factor which enhances fungal growth is an insufficient control of the relative humidity.
In such cases the more tolerant mould species will grow on natamycin treated products.
Spoilage by moulds can cause considerable economic losses and a more efficient antifungal system is necessary to protect food products such as cheese against spoilage by more natamycin-tolerant mould species.
The present invention relates to a process seeking to improve the activity of natamycin towards fungi and to compositions prepared according to said process. In particular such compositions can be useful for combatting moulds and yeasts which are normally relatively less sensitive to the action of natamycin.
In the case of fungi with relatively low susceptibility to natamycin solubilisation and diffusion may have a more limiting effect on its antifungal activity. When a conventional fungicide preparation containing natamycin is employed, at the state of equilibrium the average amount of dissolved natamycin may drop below the effective concentration because elimination will not be adequately compensated by dissolution and diffusion of the antifungal compound.
Modification of the polymorphic form of polyene antifungal compounds, such as natamycin, may also lead to an improved activity of these compounds towards less susceptible species European Patent Application No. 670676, (1995)). Examples of such modified forms are solvates of natamycin, such as the methanol solvate and crystal modifications of natamycin. The activity of polyene fungicides can also be enhanced by converting the compound into an earth alkaline metal salt, such as the calcium and barium salts.
Another method to enhance the activity of polyene fungicides is to first dissolve the antifungal compound in a solvent and then incorporate the dissolved fungicide in an aqueous composition (European Application No. 670676). Examples of suitable solvent systems are lower alcohols such as methanol, ethanol and propanol; glycerol and glycol; methoxy ethanol and ethoxy ethanol; glacial acetic acid and aqueous acid and alkaline solutions; also suitable solubilizers can be used.
These modified polyene antibiotics can also be applied on a carrier by well known methods; e.g. by spray coating techniques using a solution of the antifungal composition on a carrier or by evaporating the solvent from a mixture of a solution of the antifungal and the carrier.
The solution of the antifungal compound may be incorporated into the final composition by adding the solution to a preparation or vice versa.
Enhancing the activity could be achieved by improving the availability of the antifungal compound as a result of improved dissolution (EP 670676). The solubility in water can be increased using alkaline or acidic conditions. The solubility can also be enhanced by using solvents. However it is well known that dissolved natamycin is rapidly decomposed under such conditions (Brik, vide supra). Further dissolved natamycin is known to be less stable compared with the crystal form. Natamycin for instance may be deactivated by decomposition through the action of light or by hydrolysis.
It can be concluded that all known methods to enhance the activity of polyene fungicides by enhancing the vailability leads to a rapid decomposition of the polyene fungicide.
Unexpectedly it has been found that the activity of natamycin towards moulds and yeasts can be markedly enhanced if natamycin is complexed to a suitable compound.
Moreover it has been found that the complexes described in this document are very stable under aqueous conditions, eg. cheese coating or a dipping/spraying solution.
The present invention provides a complex, comprising natamycin complexed to one or more proteins or amino acids, when present in water, does not produce crystals visible at 400×magnification.
Advantageously this complex does not substantially lose activity within 60 days. In general, the ratio of natamycin to the total amount of protein or amino acid is 10,000:1 to 1:10, preferably this ratio is 100:1 to 1:1.
Preferably at least one of the proteins is a milk protein, more preferably a whey protein, casein or caseinate.
The complex can be produced by the following method:
(1) dissolving natamycin in an aqueous liquid by increasing or reducing the pH, such as by using well known methods;
(2) mixing the (dissolved) natamycin with the suitable compound (or complexing agent);
(3) adhering natamycin to the suitable compound by adjusting the pH to the required level using well known methods; and optionally
(4) isolating the complex of natamycin adhered to the suitable compound from the liquid fraction using known methods.
The complex can also be produced using the following method:
(1) dissolving natamycin in a suitable solvent system;
(2) adhering the natamycin to the suitable compound by mixing the dissolved natamycin with that compound; and
(3) optionally isolating the complex of the natamycin adhered to the suitable compound from the liquid fraction using methods known per se. This compound can be present in an aqueous solution or suspension.
The complex of natamycin adhered to a suitable compound can be used for different applications including to prevent fungal infection and growth on natural products e.g. cheeses or sausages.
Before application the formed and optionally purified complex can also be mixed with aqueous systems, such as water or cheese coating, or with
Geijp Edith Magda Lucia
Stark Jacobus
van Rijn Ferdinand Theodorus Jozef
DSM Patents and Trademarks
Murashige Kate H.
Pratt Helen
LandOfFree
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