Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-05-26
1998-10-13
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 65, 536 185, A61K 3170, C07H 1708
Patent
active
058212337
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the preparation of compositions which comprise an antifungal compound of the polyene type such as natamycin, and the use of such compositions to treat foodstuffs or agricultural products or for pharmaceutical purposes.
BACKGROUND OF THE INVENTION
For more than 20 years, natamycin has been used to prevent the growth of mold on cheese and sausages. (Ref. 1-12)
Cheeses are treated by immersion in a suspension of natamycin in water or by coating with a natamycin-containing aqueous emulsion of a polymer, commonly an aqueous emulsion of polyvinyl acetate. Sausages are mainly treated by immersion or by spray coating with a suspension of natamycin in water. Usually aqueous suspensions of natamycin for immersion treatments contain 0.1 to 0.2% w/v of natamycin, while polymer emulsions for coating purposes containing natamycin have a natamycin content of 0.01 to 0.05% w/v.
Mostly these treatments are highly effective in preventing spoilage by mold. However, because of the low solubility of natamycin, spoilage by some fungi which have relatively low susceptibility to natamycin may still occur due to lack of full inhibition.
The present invention relates to a process for improving the activity of polyene antifungal compounds, in particular natamycin, towards mold, and to compositions prepared according to said process. In particular, such compositions are useful for combatting yeasts and fungi which are normally relatively resistant to the action of antifungal compounds of the polyene type.
SUMMARY OF THE INVENTION
Unexpectedly, it has been found that the activity of antifungal compounds of the polyene type, such as natamycin, towards yeast and fungi can be markedly enhanced by one of the following methods.
(1) By modifying the polymorphic form.
Firstly the polyene antifungal compound can be converted into a solvated form by contacting the compound with a solvent. An example of such a solvate is natamycin methanol solvate.
Secondly the solvated solvent molecules may be removed from the crystal lattice of the solvate. An example of such a compound is .delta.-natamycin, which can be obtained by subjecting natamycin methanol solvate to diminished pressure over phosphorous pentoxide.
Thirdly the "empty" room of the crystal lattice may be refilled with other solvent molecules; e.g. by contacting the "empty" compound with a solvent or the vapor thereof. Examples of such compounds are the solvates of natamycin with the following solvents; methanol, ethanol, n-propanol, n-butanol, methoxy-ethanol, dichloromethane, 1,2-dichloro-ethane, methyl formate, ethyl formate, acetonitrile, formamide, N,N-dimethyl formamide and dimethyl sulide.
Finally new polymorphic forms of polyene antifungal compounds may be obtained by subjecting the compound with the "empty" crystal lattice to a humid condition. For example when 67-natamycin is subjected to 76% RH a new trihydrated crystal modification is obtained. This new compound, which is named y-natamycin, has an enhanced activity towards species which are normally relatively resistant to the action of the original .alpha.-natamycin, which is also a trihydrated form of natamycin (see Ref. 14, p. 520).
(2) Prior to incorporating the antifungal compound into a food treatment composition or into a pharmaceutical preparation the antifungal compound is dissolved in a suitable solvent system.
Suitable solvent systems for dissolving the fungicide are lower alcohols, e.g. a lower alcohol having 1 to 4 carbon atoms, glacial acetic acid, aqueous acid and alkaline solutions, and appropriate mixtures thereof. Examples of suitable alcohols are methanol, ethanol, n-propanol, isopropanol, ethylene glycol, ethoxy ethanol, propylene glycol and glycerol. Examples of suitable acidic solutions are aqueous solutions of hydrochloric acid, citric acid and acetic acid. Examples of suitable aqueous alkaline solutions are aqueous solutions of ammonia, alkali metal hydroxides and ethanolamine.
(3) By preparing an alkaline-earth salt. Examples are the barium and the calcium salt of n
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Barendse Nicolaas Cornelis
Stark Jacobus
Tan Hong Sheng
Van Rijn Ferdinand Theodorus
Van Zoest Willem Johan
Gist-brocades, N.V.
Peselev Elli
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