Macrocyclic ketone as malodor counteracting ingredient

Abstract

The present invention relates to the field of perfumery. More particularly, it concerns malodor masking compositions and/or ingredients, as well as method for counteracting or masking malodors and perfuming compositions having odor masking properties.

Claims

1. A method of reducing malodor, comprising treating a malodor source with a malodor counteracting composition comprising a compound of formula (I) in an amount sufficient to inhibit the growth of at least one bacteria selected from the group consisting of S. aureus, S. haemolyticus, M. morganii, and S. agalactiae, ##STR00007## wherein one R group is a hydrogen atom and the other is a hydrogen atom or a C.sub.1-3 alkyl group; and each carbon-carbon double bond of said compound, independently from each other, can be in a configuration Z or E or a mixture thereof.

2. The method of claim 1, wherein both R's are a hydrogen atom.

3. The method of claim 1, wherein the compound of formula (I) is selected from the group consisting of (4E,8E)-4,8-cyclododecadien-1-one, (4Z,8E)-4,8-cyclododecadien-1-one, (4E,8Z)-4,8-cyclododecadien-1-one, (4E,8E)-1 2-methylcyclododeca-4,8-dienone, (4E,8Z)-12-methylcyclododeca-4,8-dienone, (4Z,8E)-12-methylcyclododeca-4,8-dienone, 2-methylcyclododeca-4,8-dienone and mixtures thereof.

4. The method of claim 1, wherein the compound of formula (I) is: 4,8-cyclododecadien-1-one in the form of a mixture comprising about 99%, w/w of (4E,8E)-4,8-cyclododecadien-1-one and about 1% w/w of the (4Z,8E)-4,8-cyclododecadien-1-one and (4E,8Z)-4,8-cyclododecadien-1-one stereoisomer; or 4,8-cyclododecadien-1-one in the form of a mixture comprising at least 90% w/w of (4E,8Z)A,8-cyclododecadien-1-one and (4Z,8E)-4,8-cyclododecadien-1-one stereoisomers and about 5% w/w of the (4E,8E)-4,8-cyclododecadien-1-one stereoisomer.

5. The method of claim 1, wherein the inhibition of the growth of at least one bacteria selected from the group consisting of S. aureus, S. haemolyticus, M. morganii, and S. agalactiae, is sufficient to modify, suppress, reduce, decrease or mask the sensory perception of a body, residential or pet malodor.

6. The method of claim 5, wherein the malodor is selected from the group consisting of kitchen, bathroom, tobacco, pet, and body malodor.

7. The method of claim 1, wherein the amount sufficient to inhibit the growth of at least one bacteria selected from the group consisting of S. aureus, S. haemolyticus, M. morganii, and S. agalactiae is from 300 to 3500 ppm.

Description

EXAMPLES

(1) The invention will now be described in further detail by way of the following examples, wherein the abbreviations have the usual meaning in the art, the temperatures are indicated in degrees centigrade (° C.); the NMR spectral data were recorded in CDCl.sub.3 (if not stated otherwise) with a 360 or 400 MHz machine for .sup.1H and .sup.13C, the chemical shifts δ are indicated in ppm with respect to TMS as standard, the coupling constants J are expressed in Hz.

Example 1

(2) MOC Activity of the Compounds of Formula (I) as Such

(3) The Compound 1, as defined above, was tested, using current sensory analysis methods, for its ability to reduce the perception of bathroom, tobacco, kitchen, pet and body malodors.

(4) A) To this End, First Various Malodor Model were Prepared, by Admixing Various Ingredients as Per the Below Tables, or According to the Protocol Described:

(5) TABLE-US-00002 Bathroom Malodor Ingredient % w/w Dipropylene glycol 62.82 Skatole 0.91 2-Naphthalenethiol 0.91 Thioglycolic acid 21.18 n-Caproic acid 6.00 4-Methylphenyl 3-Methylbutanoate 2.18 n-Methylmorpholine 6.00 Total 100.00

(6) TABLE-US-00003 Kitchen Malodor Ingredient % w/w Diacetyl 3.85 Pyridine 3.85 Allyl sulfide 9.23 Methyl sulfide 40.00 Heptaldehyde 3.85 Paraldehyde 1.90 Propionic acid 36.92 Acetic acid, glacial 0.40 Total 100.00

(7) TABLE-US-00004 Body Malodor Ingredient % w/w n-Caproic acid 30.00 Isovaleraladehyde 30.00 Phenylacetic acid 3.00 Butyric acid 0.25 Indole 1.50 p-Cresyl isovalerate 1.50 p-Cresyl phenyl acetate 2.75 Thioglycolic acid 5.00 Dipropylene glycol 26.00 Total 100.00

(8) TABLE-US-00005 Pet Malodor Ingredient % w/w Skatole 0.91 Isovaleric acid 2.18 Methyl mercaptan (10% w/w in 0.12 triethylcitrate) Indole (0.5% w/w in Dipropylene 1.50 glycol) Urea 1.00 n-Caproic acid 2.18 Dipropylene glycol 92.11 Total 100.00
Tobacco Malodor

(9) The tobacco malodor was prepared by extraction of cigarette debris, comprising: ash; filter; and, paper. The debris from 30 smoked Marlboro Red cigarettes (origin: Philip Morris International) was collected in a 500 ml glass powder jar with a screw closure. 300 ml of ethanol was added. The combination was mixed in a Turbula mixer for 8 hours and then filtered through a Whatman Grade 4 filter paper. The filtrate was used as the tobacco malodor.

(10) B) Sample Preparation

(11) In the following description, the test concentration of the malodor sample used in each case was selected so as to provide a perceived malodor intensity, when evaluated in Sniffin' Sticks odor pens as described below, that was approximately of the order of 6 units on the scale described under Section C below.

(12) The malodor concentrations that were perceived as comprising a malodor intensity rating of approximately 6 when evaluated in Sniffin' Sticks odor pens were as follows:

(13) Bathroom malodor: 0.3% by weight in propylene glycol

(14) Kitchen malodor: 30% by weight in propylene glycol

(15) Body malodor: 0.5% by weight in propylene glycol

(16) Pet malodor: 0.5% by weight in propylene glycol

(17) Tobacco malodor: 50% by weight in propylene glycol

(18) The test concentration of the Compound 1 used in each of the malodor reduction tests was selected so as to provide a perceived intensity, when evaluated in Sniffin' Sticks odor pens as described below, that was approximately of the order of 6 units on the scale described under Section C below. The concentration of Compound 1 that was perceived as comprising an odor intensity of about 6 when evaluated in Sniffin' Sticks odor pens was 16% by weight in propylene glycol.

(19) Stock solutions were prepared as follows:

(20) Compound 1 32% by weight: 12.8 g of Compound 1 was mixed with 27.2 g of propylene glycol. Bathroom malodor 0.6% by weight: 0.6 g of bathroom malodor was mixed with 99.4 g of propylene glycol. Kitchen malodor 60% by weight: 12.0 g of kitchen malodor was mixed with 8.0 g of propylene glycol. Body malodor 1% by weight: 1.0 g of body malodor was mixed with 99.0 g of propylene glycol. Pet malodor 1% by weight: 1.0 g of pet malodor was mixed with 99.0 g of propylene glycol. The tobacco malodor was used as is.

(21) Each sensory test comprised 3 samples: a malodor only sample; a test sample comprising a combination of Compound 1 and the test malodor; and, a Compound 1 only sample. The samples for the sensory tests were prepared as follows: Malodor only sample: in a separate beaker 3.0 g of malodor stock solution was mixed with 3.0 g of propylene glycol. Once fully homogenized, 2.0 g of the resulting solution was applied to the absorbent fiber in the body of a Sniffin' Stick odor pen (origin: Burghart Messtechnik GmbH). The odor pen was immediately capped and allowed to equilibrate for 24 hours before use.

(22) Compound 1 only sample: in a separate beaker 3.0 g of Compound 1 stock solution was mixed with 3.0 g of propylene glycol. Once fully homogenized, 2.0 g of the resulting solution was applied to the absorbent fiber in the body of a Sniffin' Stick odor pen (origin: Burghart Messtechnik GmbH). The odor pen was immediately capped and allowed to equilibrate for 24 hours before use.

(23) Test samples: in a separate beaker 3.0 g of Compound 1 stock solution was mixed with 3.0 g of malodor stock solution. Once fully homogenized, 2.0 g of the resulting solution was applied to the absorbent fiber in the body of a Sniffin' Stick odor pen (origin: Burghart Messtechnik GmbH). The odor pen was immediately capped and allowed to equilibrate for 24 hours before use.

(24) C) Sensory Test Procedure

(25) The samples were assessed by a panel of 19 trained panelists. By “trained panelists” we mean here individuals that had previously been screened for olfactive acuity and were experienced in rating the perfume and malodor intensity. Moreover, the panelists were prior acquainted with the malodor sample before carrying out the malodor reduction efficacy test.

(26) Each test comprised a malodor only sample, a Compound 1 only sample, and a test sample that comprised Compound 1 and the malodor. The samples were presented to the panelists in Sniffin' Sticks odor pens, prepared according to the description in Section B above. Each Sniffin' Stick was labeled with a randomly generated 3 digit code. Sample presentation was blind, balanced, randomized and sequential monadic.

(27) After smelling an identified malodor only reference sample first to familiarize themselves with the malodor, the panelists were asked to rate the malodor intensity and the overall odor intensity of each sample using a linear, labeled line scale, where 0=no odor and 10=extremely strong odor.

(28) The data generated from the panel's evaluations was statistically analyzed in each case using variance analysis (ANOVA) with Duncan's post-hoc analysis (α=0.05).

(29) D) Sensory Test Results

(30) The following tables list the Average Perceived Malodor Intensity (APMI) and Average Perceived Overall Odor Intensity (APOOI) for each of the sensory tests. N.S.D next to the APMI or APOOI indicates that the rating is not statistically different from the same rating for the malodor only sample. An asterisk (*) next to the APMI or APOOI indicates that the rating is statistically different (at the 95% confidence level). It must be noted that the APOOI is not related to the pleasantness of the overall odor.

(31) TABLE-US-00006 Bathroom malodor Sample Odor Pen Content APMI APOOI Malodor Only 0.006 g bathroom malodor and 5.02  5.68 1.994 g propylene glycol Compound 1 + 0.006 g bathroom malodor, 1.61 * 5.99 Malodor 0.320 g Compound 1 and NSD 1.674 g propylene glycol Compound 1 Only 0.320 g Compound 1 and 0.91 * 5.75 1.680 g propylene glycol NSD

(32) The Compound 1 was efficient at reducing the perceived intensity of bathroom malodor. The average perceived malodor intensity of the “Compound 1+Malodor” sample was significantly lower than the “Malodor Only” sample; meanwhile, there was no significant increase in the average perceived overall odor intensity.

(33) TABLE-US-00007 Kitchen malodor Sample Odor Pen Content APMI APOOI Malodor Only 0.60 g kitchen malodor and 6.02  6.35 1.40 g propylene glycol Compound 1 + 0.60 g kitchen malodor, 2.49 * 5.51 Malodor 0.32 g Compound 1 and NSD 1.08 g propylene glycol Compound 1 Only 0.32 g Compound 1 and 0.95 * 5.78 1.68 g propylene glycol NSD

(34) The Compound 1 was efficient at reducing the perceived intensity of kitchen malodor. The average perceived malodor intensity of the “Compound 1+Malodor” sample was significantly lower than the “Malodor Only” sample; meanwhile, there was no significant increase in the average perceived overall odor intensity.

(35) TABLE-US-00008 Body Malodor Sample Odor Pen Content APMI APOOI Malodor Only 0.01 g body malodor and 6.37  6.55 1.99 g propylene glycol Compound 1 + 0.01 g body malodor, 2.78 * 5.61 Malodor 0.32 g Compound 1 and NSD 1.67 g propylene glycol Compound 1 Only 0.32 g Compound 1 and 0.83 * 6.39 1.68 g propylene glycol NSD

(36) The Compound 1 was efficient at reducing the perceived intensity of body malodor. The average perceived malodor intensity of the “Compound 1+Malodor” sample was significantly lower than the “Malodor Only” sample; meanwhile, there was no significant increase in the average perceived overall odor intensity.

(37) TABLE-US-00009 Pet Malodor Sample Odor Pen Content APMI APOOI Malodor Only 0.01 g pet malodor and 6.33  6.59 1.99 g propylene glycol Compound 1 + 0.01 g pet malodor, 4.84 * 6.70 Malodor 0.32 g Compound 1 and NSD 1.67 g propylene glycol Compound 1 Only 0.32 g Compound 1 and 0.93 * 6.01 1.68 g propylene glycol NSD

(38) The Compound 1 was efficient at reducing the perceived intensity of pet malodor. The average perceived malodor intensity of the “Compound 1+Malodor” sample was significantly lower than the “Malodor Only” sample; meanwhile, there was no significant increase in the average perceived overall odor intensity.

(39) TABLE-US-00010 Tobacco Malodor Sample Odor Pen Content APMI APOOI Malodor Only 1.00 g tobacco malodor and 6.06  6.25 1.00 g propylene glycol Compound 1 + 1.00 g tobacco malodor, 3.35 * 5.85 Malodor 0.32 g Compound 1 and NSD 0.68 g propylene glycol Compound 1 Only 0.32 g Compound 1 and 1.27 * 6.07 1.68 g propylene glycol NSD

(40) The Compound 1 was efficient at reducing the perceived intensity of tobacco malodor. The average perceived malodor intensity of the “Compound 1+Malodor” sample was significantly lower than the “Malodor Only” sample; meanwhile, there was no significant increase in the average perceived overall odor intensity.

Example 2

(41) MOC Activity of the Compounds of Formula (I) as Such, Via Odor Suppression and Antibacterial Activity

(42) Preparation of Bacterial Solutions

(43) Bacterial solutions of four bacterial strains were prepared for MIC test as follows. Stock cultures stored at −80° C. were subcultured onto agar plate media, and incubated at 37° C. for 24 h to obtain single colonies. Single colonies of the primary cultures were inoculated into broth media and incubated at 37° C., 160 rpm overnight. Aliquots of overnight cultures were inoculated into 50 ml of fresh broth media, and incubated at 37° C., 160 rpm. When the OD reached the target value for each strain (see Table 1), cells were harvested by centrifugation at 5000 rpm for 10 min, and then resuspended in the same fresh broth media at the same volume before the centrifugation. Aliquots (1.1 ml) of each cell suspension were diluted in 200 ml of the same broth media as the bacterial solutions for the MIC test.

(44) TABLE-US-00011 TABLE 1 Media, aliquots of overnight culture, and target OD of broth cultures for the preparation of bacterial solutions Aliquots of Agar plate Broth Overnight Target Strains media Media Culture OD Staphylococcus TSA MH 1 ml 0.7-0.9 aureus DSMZ 1104 Staphylococcus TSA MH 1 ml 0.5-0.7 haemolyticus ATCC 114126 Morganella TSA MH 1 ml 0.3-0.5 morganii URI62 Streptococcus Schaedler + 5% WC.sup.c 1 ml 0.6-0.8 agalactiae URI3 sheep blood Note: .sup.aTSA, Tryptic Soy Agar (BD Cat No. 236950), .sup.bMH, Mueller Hinton Broth (BD Cat No. 211443), .sup.cWC, Wilkins-Chalgren (OXOID Cat No. CM0643).
Preparation of Test Material Sample Solutions

(45) Sample solutions of casmirone and reference material (N302) were prepared as follows. Stock solutions of 1% and 20% were prepared in ethanol, and then seven serial dilutions of each stock solution were prepared in ethanol to obtain a total of 16 solutions of casmirone or the reference material. Aliquot (10 μl) of each solution was used for MIC test. The tested final concentrations of each material were 29, 44, 66, 99, 148, 222, 333, 500, 590, 900, 1300, 2000, 3000, 4500, 6700, 10000 ppm.

(46) The test material control was trans-hexenal, a known material for MIC tests and control tests (e.g. see Int J Food Microbiol. 2010 Jan. 1; 136(3):304-9.).

(47) MIC Test

(48) MIC test were performed in 96 well plates. Table 2 shows the schematic positions of sample solutions in 96 well plates. Column 1 contained bacterial solution only (the positive growth control), and column 12 contained growth media only (the negative growth control). Aliquots (100 of sample solutions were mixed with 190 μl of bacterial solutions in growth media, at concentrations of 10.sup.5 to 10.sup.6 cfu/ml, in wells of the 96 well plates. Three replicates for solution.

(49) The 96 wells plates were incubated at 37° C., 160 rpm overnight. After incubation, wells of 96 well plates were examined. Turbid wells were regarded as an indication of microbial growth.

(50) Minimal inhibition concentration (MIC) was determined as the lowest concentration where no growth was observed. Average MIC value of the three replicates was calculated against each strain (see Table 3).

(51) TABLE-US-00012 TABLE 2 Schematic positions of samples in 96 well plates A Positive growth 590  29  590  29 Negative growth control ppm ppm ppm ppm control (no B 900  44  900  44 contamination) ppm ppm ppm ppm C 1300  66 1300  66 ppm ppm ppm ppm D 2000  99 2000  99 ppm ppm ppm ppm E 3000 148 3000 148 ppm ppm ppm ppm F 4500 222 4500 222 ppm ppm ppm ppm G 6700 333 6700 333 ppm ppm ppm ppm H 10000  500 10000 500 ppm ppm ppm ppm 1 2 3 4 5 6 7 8 9 10 11 12 Compound 1 trans-hexenal

(52) TABLE-US-00013 TABLE 3 MIC concentrations (in ppm) of the Compound 1 vs various strain of bacteria Bateria MIC of Compound 1 S.. aureus 333 (compound 1 is Associated with hygiene efficiently active in application) S.. haemolyticus 345 (compound 1 is Associated with body odor efficiently active in application) M. morganii 900 (compound 1 is Associated with urine/bathroom efficiently active in application) S. agalactiae 3433 (compound 1 is Associated with urine/bathroom moderately active in application)

(53) Compound 1 shows to be an effective antimicrobial ingredient in concentrations compatible with consumer products, as so able to participate to a MOC effect.