Use of isosorbide monoesters as antimicrobial active substances

Abstract

The use of one or more compounds of the formula (I) ##STR00001## in which R is a straight-chain or branched saturated alkyl group having 5 to 11 carbon atoms or a straight-chain or branched mono- or polyunsaturated alkenyl group having 5 to 11 carbon atoms
as antimicrobially active compound is described. The use is preferably in cosmetic, dermatological or pharmaceutical compositions, in crop protection formulations, in washing or cleaning compositions or in paints or coatings.

Claims

1. A method for destroying fungus or inhibiting fungal growth, comprising the step of contacting at least one fungi with a composition comprising at least one compound of the formula (I) ##STR00005## in which R is a straight-chain or branched saturated alkyl group having 5 to 11 carbon atoms or a straight-chain or branched mono- or polyunsaturated alkenyl group having 5 to 11 carbon atoms.

2. The method as claimed in claim 1, wherein the radical R in formula (I) is a straight-chain saturated alkyl radical having 7 to 9 carbon atoms.

3. The method as claimed in claim 2, wherein the radical R in formula (I) is a straight-chain saturated alkyl radical having 7 carbon atoms.

4. The method as claimed in claim 1, wherein the composition further comprises at least one substance selected from the group consisting of sorbitol, sorbitol esters, sorbitan, sorbitan esters, isosorbide, isosorbide diesters and carboxylic acids.

5. The method as claimed in claim 4, wherein the composition further comprises I) isosorbide and II) at least one isosorbide diester of the formula (II) ##STR00006## where R is a straight-chain or branched saturated alkyl group having 5 to 11 carbon atoms or a straight-chain or branched mono- or polyunsaturated alkenyl group having 5 to 11 carbon atoms.

6. The method as claimed in claim 1, wherein the composition further comprises I) from 0.05 to 0.7 part by weight of isosorbide and II) from 0.1 to 1.0 part by weight of the one or more isosorbide diesters of the formula (II), in each case based on 1.0 part by weight of the at least one compound of the formula (I).

7. The method as claimed in claim 4, wherein the composition further comprises at least one sorbitan ester of sorbitan and carboxylic acid R.sup.aCOOH, where R.sup.a is a straight-chain or branched saturated alkyl group having 5 to 11 carbon atoms or a straight-chain or branched mono- or polyunsaturated alkenyl group having 5 to 11 carbon atoms, and where the weight ratio of the at least one compound of the formula (I) to the at least one sorbitan ester is from 70:30 to 100:0.

8. The method as claimed in claim 7, wherein the carboxylic acid R.sup.aCOOH is selected from the group consisting of caprylic acid.

9. The method as claimed in claim 4, wherein the hydroxyl value of the mixture of the at least one compound of the formula (I) and the at least one compound selected from the group consisting of sorbitol, sorbitol esters, sorbitan, sorbitan esters, isosorbide, isosorbide diesters and carboxylic acids in the composition is less than or equal to 320.

10. The method as claimed in claim 4, wherein the composition comprises the at least one compound of the formula (I) in an amount of at least 30% by weight, in each case based on the total weight of the finished composition.

11. The method as claimed in claim 1 for preventing fungal growth in a cosmetic, dermatological or pharmaceutical composition, in a crop protection formulation, in a washing or cleaning composition or in a paint or coating.

12. The method as claimed in claim 11, wherein the cosmetic, dermatological or pharmaceutical composition, the crop protection formulation, the washing or cleaning composition or the paint or coating comprise the at least one compound of the formula (I) in an amount of from 0.01 to 10.0% by weight, in each case based on the total weight of the finished cosmetic, dermatological or pharmaceutical composition, crop protection formulation, washing or cleaning composition or paint or coating.

13. The method as claimed in claim 11, wherein the cosmetic, dermatological or pharmaceutical composition, the crop protection formulation, the washing or cleaning composition or the paint or coating is formulated on an aqueous or aqueous-alcoholic basis or are present as emulsion or dispersion.

14. The method as claimed in claim 11, wherein the cosmetic, dermatological or pharmaceutical composition, the crop protection formulation, the washing or cleaning composition or the paint or coating has a pH of from 2 to 11.

15. The method as claimed in claim 11, wherein the cosmetic, dermatological or pharmaceutical composition, the crop protection formulation, the washing or cleaning composition or the paint or coating is formulated as an emulsion.

Description

EXPERIMENTAL EXAMPLES

A) Preparation of Isosorbide Caprylate

(1) In a stirred apparatus with distillation head, 190.0 g (1.3 mol) of isosorbide (“Sorbon” from Ecogreen Oleochemicals) and 187.5 g (1.3 mol) of octanoic acid (caprylic acid) are initially charged at 80° C. together with 0.38 g of aqueous sodium hydroxide solution (18% by weight strength, aqueous) as catalyst. With stirring and under a flow of nitrogen (10-12 liters per hour), the reaction mixture is initially heated to 180° C., where the water of reaction begins to distill off. The reaction is then heated to 190° C. over a period of 1 hour and to 210° C. over a further 2 hours. After 210° C. is reached, the esterification is continued until an acid value of <1 mg KOH/g is reached. This gives 345.7 g of amber isosorbide caprylate (97% of theory). The pH (5% by weight in ethanol/water 1:1) is 5.9. The pH was measured according to DIN EN 1262.

(2) Further analytical characteristics of the isosorbide caprylate: Acid value: 0.9 mg KOH/g, measured according to DIN EN ISO 2114 Hydroxyl value: 206 mg KOH/g, measured analogously to DIN 53240-2 according to method OHV-A Saponification value: 204 mg KOH/g, measured according to DIN EN ISO 3681

(3) The isosorbide caprylate has the following composition:

(4) TABLE-US-00001 Substance % by weight caprylic acid 0.4 isosorbide 18.1 isosorbide monocaprylate 50.9 isosorbide dicaprylate 30.6

(5) Hereinbelow, this composition is referred to as “isosorbide caprylate 1”.

B) Determination of the Antimicrobial Efficacy of Isosorbide Caprylate 1

(6) Below, the antimicrobial efficacy of isosorbide caprylate 1 in butyl polyglycol against bacteria, fungi and yeasts is examined. For the tests with bacteria, isosorbide caprylate 1 was diluted with butyl polyglycol and then, at 50° C., added to liquid CASO agar (casein-peptone agar) buffered to pH 7 (+1-0.2) in various concentrations (hereinbelow referred to as compositions B1, B2, etc.). For the tests with fungi and yeasts, isosorbide caprylate 1 was diluted with butyl polyglycol and then added to liquid Sabouraud 4% dextrose agar buffered to pH 5.6 (+1-0.2) in various concentrations (hereinbelow referred to as compositions PH1, PH2, etc.). The compositions B1, B2, etc. and PH1, PH2 etc. were each poured into Petri dishes and each inoculated with identical amounts of bacteria, fungi and yeasts. The minimum inhibitory concentration (MIC) is the concentration at which inhibition of the growth of the bacteria, fungi and yeasts in the compositions B1, B2, etc. and PH1, PH2, etc. occurs.

(7) The values determined for the minimum inhibitory concentrations of isosorbide caprylate 1, stated in Table 1 below, have already been corrected for the dilution effect of the butyl polyglycol.

(8) TABLE-US-00002 TABLE 1 Minimum inhibitory concentrations (MIC) of isosorbide caprylate 1 MIC of isosorbide Bacteria (B), fungi (F) or yeasts caprylate 1 (Y) examined [ppm] Staphylococcus aureus (B) 2500 Pseudomonas aeruginosa (B) 10000 Escherichia coli (B) 7500 Enterobacter aerogenes (B) 10000 Klebsiella pneumoniae (B) 10000 Proteus vulgaris (B) 5000 Pseudomonas oleovorans (B) 10000 Citrobacter freundii (B) 10000 Candida albicans (Y) 600 Aspergillus brasiliensis (F) 800 Penicillium minioluteum (F) 600 Aspergillus terreus (F) 600 Fusarium solani (F) 600 Penicillium funicolosium (F) 400

(9) The results listed in Table 1 show that isosorbide caprylate 1 is antimicrobially active, in particular against the yeast Candida albicans and the fungi tested.

C) Antimicrobial Activity of the Constituents of Isosorbide Caprylate 1

(10) Caprylic acid is antimicrobially effective. However, since in the composition “isosorbide caprylate 1” caprylic acid is present in an amount of only 0.4% by weight, its antimicrobial efficacy in this composition is so low that it can be neglected. In addition, caprylic acid has no antimicrobial activity at a pH of 6 or above.

(11) Analogously to the determination of the antimicrobial activity of isosorbide caprylate 1, the antimicrobial activity firstly of a mixture comprising 89.6% by weight of isosorbide dicaprylate and 9.4% by weight of isosorbide monocaprylate (remainder: 1% by weight) (hereinbelow referred to as “isosorbide dicaprylate”) and, secondly, pure isosorbide was determined in further test series. The results are shown in Table 2:

(12) TABLE-US-00003 TABLE 2 Minimum inhibitory concentrations (MIC) of isosorbide dicaprylate and isosorbide MIC of isosorbide MIC of Bacteria (B), fungi (F) or dicaprylate isosorbide yeasts (Y) examined [ppm] [ppm] Staphylococcus aureus (B) 10000 10000 Pseudomonas aeruginosa (B) 10000 10000 Escherichia coli (B) 10000 10000 Enterobacter aerogenes (B) 10000 10000 Klebsiella pneumoniae (B) 10000 10000 Proteus vulgaris (B) 10000 10000 Pseudomonas oleovorans (B) 10000 10000 Citrobacter freundii (B) 10000 10000 Candida albicans (Y) 10000 10000 Aspergillus brasiliensis (F) 10000 10000 Penicillium minioluteum (F) 10000 10000 Aspergillus terreus (F) 10000 10000 Fusarium solani (F) 5000 10000 Penicillium funicolosium (F) 5000 10000

(13) As shown by the results of Table 2, neither isosorbide nor isosorbide dicaprylate is antimicrobially active.

(14) From the lack of antimicrobial activity of the compounds caprylic acid, isosorbide and isosorbide dicaprylate present in the composition isosorbide caprylate 1 on the one hand and from the antimicrobial activity of the composition “isosorbide caprylate 1” evident from the results of Table 1 on the other hand, it can be concluded that the compound isosorbide monocaprylate likewise present in the composition isosorbide caprylate 1 has significant antimicrobial activity, in particular as fungicide against fungi and yeasts.

(15) For this reason, it is also thought that the low activity of the composition isosorbide dicaprylate with respect to the fungi Fusarium solani and Penicillium funicolosium is due to the compound isosorbide monocaprylate present therein.

D) Use Examples

(16) The use according to the invention can take place, for example, in the following formulations.

Formulation Example 1: Revitalising Moisturizing Cream

(17) TABLE-US-00004 % by Phase Ingredient weight A Hostacerin ® SFO 2.0 sunflower seed oil sorbitol esters Velsan ® CCT 4.5 caprylic/capric triglyceride Cetiol ® OE 4.5 dicaprylyl ether Lanette ® 22 4.0 behenyl alcohol Lanette ® 18 4.0 stearyl alcohol Fucogel ® 1000 1.0 biosaccharide gum-1 B Coenzyme ® Q 10 0.1 ubiquinone C water ad 100 glycerol 10.0 Hostaphat ® CK 100 0.6 potassium cetyl phosphate D phenoxyethanol 1.0 isosorbide caprylate 1 1.0 E NaOH (10% by weight in water) q.s. Preparation: I The components of A are mixed and the mixture is heated to 80° C. II The components of C are mixed and the mixture is heated to 80° C. III B is added to I. IV II is added to III and the mixture is stirred until it has cooled to room temperature. V D is added to IV. VI The pH is adjusted to 5.5 using E.

Formulation Example 2

(18) TABLE-US-00005 % by Phase Ingredient weight A Hostacerin ® EWO 16.0 polyglyceryl 2-sesquiisostearate (and) cera alba (and) carnauba wax (and) ethylhexyl stearate (and) magnesium stearate (and) aluminum stearate isopropyl palmitate 10.0 avocado oil 2.0 Velsan ® CCT 2.5 caprylic/capric triglyceride B Octopirox ® 0.05 piroctone olamine propylene glycol 1.0 C water ad 100 glycerol 4.0 magnesium sulfate * 7 H.sub.2O 0.7 allantoin 0.5 D tocopheryl acetate 0.5 Rosmarinus officinalis (rosemary) leaf oil 0.1 urea 10.0 isosorbide caprylate 1 1.0 phenoxyethanol 0.8 Preparation: I The components of A are mixed and the mixture is heated to 80° C. II The components of B are mixed until all substances have been dissolved (if required with gentle heating). III II is added to I. IV The components of C are mixed and the mixture is heated to 50° C. V IV is stirred into I at high speed until the mixture has cooled to 35° C. VI D is added to V at 35° C.

Formulation Examples 3 and 4: Crop Protection Formulations

(19) TABLE-US-00006 Formulation No. 3 4 Amount of the respective Ingredient ingredient [% by weight] atrazine 43.6 43.6 Dispersogen ® PSL 100 — 1.7 Genapol ® LSS — 1.6 Dispersogen ® LFS 2.1 — propylene glycol 4.3 4.3 Defoamer ® SE 57 0.6 0.6 Kelzan ® S (2% by weight in water) 7.3 7.3 isosorbide caprylate 1 0.3 0.2 benzyl alcohol 1.0 1.0 Water ad 100 ad 100 Preparation: The active compound is pre-dispersed with the other ingredients (except for the Kelzan ® S solution) and then subjected to fine grinding until the mean particle size is < 2 micrometers. The Kelzan ® S solution is then stirred in.

Formulation Example 5: Dishwashing Liquids

(20) TABLE-US-00007 Ingredient % by weight Hostapur ® SAS 60 40.0 (alkanesulfonate, 60% by weight in water) Hostapur ® OS liquid 11.0 (sodium C14-16 alkyl sulfonate, 40% by weight in water) Genaminox ® LA 3.0 (dimethyllauramine oxide, 30% by weight in water) Genagen ® CAB 3.0 (cocoamidopropyl betaine, 30% by weight in water) isosorbide caprylate 1 0.8 benzyl alcohol 0.8 Water ad 100

Formulation Example 6: Surface Cleaners (All-Purpose Cleaners)

(21) TABLE-US-00008 % by Ingredient weight Hostapur ® SAS 60 5.0 (alkanesulfonate, 60% by weight in water) Genapol ® UD 080 2.0 (undecanol + 8 EO) Genaminox ® LA 2.0 (dimethyllauramine oxide, 30% by weight in water) methylisothiazolinone 0.01 isosorbide caprylate 1 1.0 Water ad 100

Preparation of Formulation Examples 5 and 6

(22) Half of the amount of water is initially charged and the components are stirred in in the same order as listed in the tables given for formulation examples 5 and 6. The remaining water is then added. This gives clear aqueous compositions.