PERFUME COMPOSITIONS

Abstract

A fragrance suitable as a substitute for Citral (3,7-dimethyl-2,6-octadienal) and fragranced products, essentially free of Citral but reminiscent of the odor and performance of Citral nevertheless.

Claims

1. A perfume composition comprising 2,4,7-trimethyl-2,6-octadienal, characterized in that the perfume composition is essentially free of 3.7-dimethyl-2,6-octadienal.

2. The perfume composition according to claim 1, wherein the perfume composition comprises I) 2,4,7-trimethyl-2,6-octadienal; and II) at least one compound selected from the group (A) consisting of 2,6-dimethyloct-7-en-2-ol, 6,6-dimethoxy-2,5,5-trimethylhex-2-ene, methyl 3-oxo-2-pentylcyclopentaneacetate, (E)-3,7-dimethylnona-1,6-dien-3-ol, 3-(4-isobutyl-2-methylphenyl)propanal, 2,4,7-trimethyloct-6-en-1-ol, and mixtures thereof; and III) optionally at least one compound selected from the group (B) consisting of 3,7-dimethylnona-2,6-dienenitrile, 3,7-dimethyloct-6-enenitrile, 3,7-dimethyl-6-octen-1-ol, 2,4-dimethyl-4-phenyltetrahydrofuran, 1-methyl-4-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbaldehyde, and mixtures thereof.

3. The perfume composition according to claim 2 wherein the weight ratio of 2,4,7-trimethyl-2,6-octadienal to the total amount of group (A) compounds is at least 1:3.

4. A fragranced product comprising the perfume composition according to claim 1.

5. The fragranced product according to claim 4, wherein the product is intended to be applied to the skin.

6. A perfume composition essentially free of 3,7-dimethyl-2,6-octadienal, comprising 2,4,7-trimethyl-2,6-octadienal, characterized in that said perfume composition has a reduced sensitizing potential compared with an identical perfume composition in which 2,4,7-trimethyl-2,6-octadienal has been replaced by an equal weight of 3,7-dimethyl-2,6-octadienal.

7. A method of substituting 3,7-dimethyl-2,6-octadienal in a perfume composition comprising the step of admixing to a perfume composition, which is essentially free of 3,7-dimethyl-2,6-octadienal, I) 2,4,7-trimethyl-2,6-octadienal; and II) at least one compound selected from the group (A) consisting of 2,6-dimethyloct-7-en-2-ol, 6,6-dimethoxy-2,5,5-trimethylhex-2-ene, methyl 3-oxo-2-pentylcyclopentaneacetate, (E)-3,7-dimethylnona-1,6-dien-3-ol, 3-(4-isobutyl-2-methylphenyl)propanal, 2,4,7-trimethyloct-6-en-1-ol, and mixtures thereof; and III)optionally at least one compound selected from the group (B) consisting of 3,7-dimethylnona-2,6-dienenitrile, 3,7-dimethyloct-6-enenitrile, 3,7-dimethyl-6-octen-1-ol, 2,4-dimethyl-4-phenyltetrahydrofuran, 1-methyl-4-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbaldehyde, and mixtures thereof.

8. A method of providing a perfume composition with reduced skin sensitization potential by providing a perfume composition which is essentially free of 3,7-dimethyl-2,6-octadienal, and wherein the perfume composition comprises 2,4,7-trimethyl-2,6,-octadienal.

9. A method of producing a fresh, natural, juicy odor characteristic to a perfume composition comprising the step of adding to said perfume composition 2,4,7-trimethyl-2,6,-octadienal.

10. The method according to claim 9 characterized in that the perfume composition is essentially free of 3,7-dimethyl-2,6-octadienal.

11. (canceled)

12. A fragranced product comprising the perfume composition according to claim 2.

13. A fragranced product comprising the perfume composition according to claim 3.

14. A method of imparting freshness and naturalness to a fragranced product, said method comprising the step of incorporating into said product a perfume composition comprising 2,4,7-trimethyl-2,6,-octadienal, and at least one compound selected from group (A) consisting of 2,6-dimethyloct-7-en-2-ol, 6,6-dimethoxy-2,5,5-trimethylhex-2-ene, methyl 3-oxo-2-pentylcyclopentaneacetate, (E)-3,7-dimethylnona-1,6-dien-3-ol, 3-(4-isobutyl-2-methylphenyl)propanal, and 2,4,7-trimethyloct-6-en-1-ol.

15. The method according to claim 14 wherein the weight ratio of 2,4,7-trimethyl-2,6-octadienal to the total amount of group (A) compounds is 1:3 to 1:50.

Description

[0061] The invention is now further described with reference to the following non-limiting examples. These examples are for the purpose of illustration only, and it is understood that variations and modifications can be made by one skilled in the art.

[0062] The perfume compositions of the Examples 5-7 have been smelled at 5 weight % in an alcoholic solution (alcohol)85.

[0063] FIG. 1: shows the gene-induction and cell viability curves for Citral in the KeratinoSens assay, in which the black diamonds indicate the induction of the luciferase activity and the open squares cellular viability.

[0064] FIG. 2: shows gene-induction and cell viability curves for 2,4,7-trimethyl-2,6,-octadienal in the KeratinoSens assay, in which the black diamonds indicate the induction of the luciferase activity and the open squares cellular viability.

[0065] FIG. 3: shows the gene-induction and cell viability curves for composition (a) (comparison) and (b) of Table 3. The filled black diamonds indicate the induction of the luciferase activity for the composition (a) containing Citral and the open diamonds show gene induction for the composition (b) containing 2,4,7-trimethyl-2,6,-octadienal instead of Citral. Filled black squares indicate cellular viability for the formulations with Citral and open squares indicate cellular viability for composition containing 2,4,7-trimethyl-2,6,-octadienal, respectively.

[0066] FIG. 4: shows the gene-induction and cell viability curves for composition (c) (comparison) and (d). The filled black diamonds indicate the induction of the luciferase activity for the composition (c) containing Citral and the open diamonds show gene induction for the composition (d) containing 2,4,7-trimethyl-2,6,-octadienal instead of Citral. Filled black squares indicate cellular viability for the formulations with Citral and open squares indicate cellular viability for composition containing 2,4,7-trimethyl-2,6,-octadienal, respectively.

[0067] FIG. 5: shows the gene-induction and cell viability curves for composition (e) (comparison) and (f). The filled black diamonds indicate the induction of the luciferase activity for the composition (e) containing Citral and the open diamonds show gene induction for the composition (f) containing 2,4,7-trimethyl-2,6,-octadienal instead of Citral. Filled black squares indicate cellular viability for the formulations with Citral and open squares indicate cellular viability for composition containing 2,4,7-trimethyl-2,6,-octadienal, respectively.

EXAMPLE 1

Skin Sensitization Test of 2,4,7-trimethyl-2,6,-octadienal in Comparison with Citral in a Cell-Based Assay

[0068] Compounds were tested using the commercial KeratinoSens assay for skin sensitization. The KeratinoSens test compares the potential skin sensitization risk of chemicals. The KeratinoSens cell line contains a stable insertion of a Luciferase gene under the control of the ARE-element of the gene AKR1C2 and induction of luciferase is indicative of skin sensitization potential (R. Emter, G. Ellis, A. Natsch, Toxicol. Appl. Pharmacol. 2010, 245, 281-290). The assay was performed as described by the OECD test guideline 442d. KeratinoSens cells were grown for 24 h in 96-well plates. The medium was then replaced with medium containing the test chemical and the solvent dimethylsulfoxide (DMSO) at a final level of 1% (v/v). Each compound was tested at 12 binary dilutions in the range from 0.98 to 2000 M. Cells were incubated for 48 h with the test agents, and then luciferase activity and cytotoxicity were determined. This full procedure was repeated three times for each chemical. For each chemical in each repetition and at each concentration, the gene induction compared to DMSO controls and the wells with statistically significant induction over the threshold of 1.5 (i.e. 50% enhanced gene activity) were determined. Furthermore, the maximal fold-induction (I.sub.max) and the EC1.5 value (concentration in M for induction above the threshold) were calculated. Chemicals are rated as positive (i.e. likely skin-sensitizers) in the assay if the following three criteria are fulfilled: [0069] (i) EC1.5 value is below 1000 M. [0070] (ii) At the lowest concentration with a gene induction above 1.5 fold, the cellular viability is above 70%. [0071] (iii) There is an apparent overall dose-response for luciferase induction, which is similar between the repetitions.

[0072] 2,4,7-trimethyl-2,6,-octadienal was compared with Citral (3,7-dimethyl-2,6-octadienal). The results can be found in Table 1 below, and FIGS. 1 and 2.

TABLE-US-00001 TABLE 1 Results of KeratinoSens I II I.sub.max (fold maximal gene induction) 22.3 1.40 Concentration for 1.5-fold gene induction (EC 1.5 7.7 n.i. in M) Concentration for 50% Cytotoxicity (in M) 95.5 317.8 n.i. = no induction above threshold of 1.5, indicating negative rating in the assay I = Citral (3,7-dimethyl-2,6-octadienal) II = 2,4,7-trimethyl-2,6,-octadienal

[0073] Citral is highly active (induces the luciferase gene at about 7.7 M) whereas 2,4,7-trimethyl-2,6,-octadienal is clearly negative with no induction above the threshold of 1.5 fold and is thus rated as non-sensitizing by this assay.

[0074] Accordingly 2,4,7-trimethyl-2,6,-octadienal can be used, e.g. in perfume compositions, for reduced sensitization risk to the consumer.

EXAMPLE 2

Skin Sensitization Test 2,4,7-trimethyl-2,6,-octadienal in Comparison with Citral (3,7-dimethyl-2,6-octadienal) in a Peptide Reactivity Assay

[0075] Another method to determine allergenic potential of chemicals is the Direct Peptide Reactivity Assay (DPRA; OECD TG 442c). It is based on the fact that allergenic chemicals must react with a peptide/protein in order to be immunogenic.

[0076] A modification of the peptide reactivity assay (A. Natsch, H. Gfeller, Toxicol. Sci. 2008, 106, 464-478) was conducted similarly to the DPRA, but including an LC-MS based detection of peptide adducts: The test chemicals were dissolved to a final concentration of 4 mM in acetonitrile and 250 l of this solution were added to 2 ml HPLC vials. The test peptide Cor1C-420 with the sequence Ac-NKKCDLF (Genscript Inc., Piscataway, N.J., USA), was dissolved at 0.133 mM in 20 mM phosphate buffer at pH 7.5, and 750 l of this solution were added to each test vial (final concentrations: 1 mM of test chemical and 0.1 mM of peptide; ratio 1:10 as in the DPRA). The samples were incubated for 24 h at 37 C. and analysed by LC-MS analysis on a VELOS PRO Mass spectrometer (Thermo SCIENTIFIC, San Jose, Calif., U.S.A.) operated in the ESI(+) mode.

[0077] Mass spectra were recorded from 200-2000 amu. A ZORBAX Eclipse XDB-C18 column, 2.1 mm ID, 150 mm, 5-Micron (Agilent Technologies) was used. The mobile phase consisted of H.sub.2O (A) and methanol (B) each containing 0.1% formic acid (v/v). The solvent flow was 250 l/min and the following gradient (ratio A:B) was used: 0 min, 95:5; 2 min, 40:60; 10 min, 2:98; 12 min, 2:98. The integration was performed with Xcalibur Quan Browser.

[0078] In order to detect formation of modified peptides, the specific ion trace for a new adduct with the mass of the test chemical added to the test peptide is extracted, and the peak of the peptide-adduct is integrated. Peptide adduct formation is a particular sensitive endpoint to determine reactive, and thus allergenic nature of compounds.

[0079] As can be observed in Table 2, modified peptides were observed with both Citral (I) and 2,4,7-trimethyl-2,6,-octadienal (II). However, only traces were formed in the case of 2,4,7-trimethyl-2,6,-octadienal, and this amount is 27-fold lower as compared to Citral, indicating a strongly reduced reactivity and hence sensitization potential for 2,4,7-trimethyl-2,6,-octadienal.

TABLE-US-00002 TABLE 2 Result of a peptide reactivity assay I II Expected mass of a 908.5 + 152.1 = 908.5 + 166.1 = possible peptide adduct 1060.6 1074.6 Observed mass of 1060.6 1074.6 peptide adduct Peptide reactivity: Direct Michael Extremely low activity, quantification adduct observed, traces of direct adduct 8.1% of parent observed, 0.3% of parent peptide modified peptide modified

EXAMPLE 3

Skin Sensitization Test of Compositions Containing 2,4,7-trimethyl-2,6,-octadienal in Comparison to Compositions Containing Citral in a Cell-Based Assay

[0080] Perfume compositions containing 2,4,7-trimethyl-2,6,-octadienal or Citral and, in addition, materials selected from group A or from group A and B were formulated according to Table 3 (in parts by weight). These compositions were tested in the cell-based KeratinoSens assay as described in Example 1. All compositions were tested in the concentration range from 0.2-400 ppm (parts per million in weights per volume).

TABLE-US-00003 TABLE 3 Perfumery compositions Perfumery raw materials composition Group (a) (b) (c) (d) (e) (f) dihydro myrcenol (A) 30 30 30 30 20 20 Hedione (A) 30 30 30 30 20 20 Ethyllinalool (A) 20 20 30 30 20 20 Methyl- (A) 5 5 pamplemousse Citronellyl nitrile (B) 5 5 Rhubafuran (B) 10 10 Citral 20 10 20 2,4,7-trimethyl-2,6,- 20 10 20 octadienal Total 100 100 100 100 100 100

[0081] The results can be found in Table 4 below and FIGS. 3 to 5.

TABLE-US-00004 TABLE 4 KeratinoSens result for perfume compositions (a) to (f) (a) (b) (c) (d) (e) (f) I.sub.max (fold 9.43 1.35 3.50 1.13 11.49 1.26 maximal gene induction) Concentration 60.5 n.i. 83.3 n.i. 32.0 n.i. for 1.5-fold gene induction (EC 1.5 in ppm) Concentration 355.3 512.2 678.2 556.4 312.4 372.5 for 50% Cytotoxicity (in ppm) n.i. = no induction above threshold of 1.5, indicating negative rating in the assay (a)-(f) = Perfume compositions according to Table 3

[0082] Formulations containing 10-20 wt % of citral are highly active (they induce the luciferase gene at about 32-83 ppm) whereas 2,4,7-trimethyl-2,6,-octadienal containing formulations are clearly negative with no induction above the threshold of 1.5 fold and thus are rated as non-sensitizing formulations by this assay.

[0083] Accordingly, formulations with a citrus note containing 2,4,7-trimethyl-2,6,-octadienal and materials selected from group (A) and, optionally, group (B) can be used, e.g. in perfume compositions or consumer products, for reduced sensitization risk to the consumer.

EXAMPLE 4

Skin Sensitization Test of 2,4,7-trimethyl-2,6,-octadienal in Comparison with Citral by TIMES SS Model

[0084] The TIMES SS model is a computer model which predicts the sensitization potential based on all known structural features of skin sensitizers. This model was trained by all available expert knowledge on structural alerts over the years (Roberts, D. W., G. Patlewicz, et al. (2007). Chemical Research in Toxicology 20(9): 1321-1330). Recent improvements were described by Patlewicz, G., C. Kuseva, et al. (2014). SAR QSAR Environ Res 25(5): 367-391). The most updated model available is Version 20.24 obtained from OASIS, LMC.

[0085] 2,4,7-Trimethyl-2,6,-octadienal and Citral were run through the TIMES SS model (version 20.24). The results are given in Table 5 below.

TABLE-US-00005 TABLE 5 Result from TIMES SS 2,4,7-trimethyl- TIMES parameter Citral 2,6,-octadienal Predicted SkinSens Strong sensitizer Strong sensitizer Transformation Schiff base formation Michael type addition with disubstituted on ,-aldehydes ,-aldehydes Active alert Di-substituted ,- ,-Aldehydes unsaturated aldehydes Alert performance High, >=60% (n >= 5) High, >=60% (n >= 5) Amount Adduct/mol 0.3666 0.472

[0086] As can be seen from the results above (Table 5), both chemicals are predicted as strong skin sensitizers. For 2,4,7-trimethyl-2,6,-octadienal an even higher protein binding (Amount adduct/mol) is predicted. Accordingly, the in silico model indicates that based on the current general understanding of structural alerts for skin sensitization, 2,4,7-trimethyl-2,6,-octadienal would be expected to be an equally strong or stronger skin sensitizer as compared to Citral.

EXAMPLE 5

Musk Perfume Composition for Fine Perfumery

[0087]

TABLE-US-00006 5(a) 5(b) geranyl acetate 10 10 2-phenylethan-1-ol 60 60 Ambermax.sup.1) @ 10 wt % in TEC 50 50 Ambrofix.sup.2) 10 10 ethylene brassylate 250 250 Damascenone giv 2 2 Galaxolide 238 238 Givescone.sup.3) 30 30 Hedione (group (A) compound) 130 130 Javanol 3 3 Mefrosol.sup.4) 50 50 Rose oxide @ 10 wt % in DEP 2 2 Thibetolide.sup.5) 150 150 Citral 15 2,4,7-trimethyl-2,6,-octadienal 15 Total 1000 1000 .sup.1)mixture of 2-(1,1,5,5-tetramethyl-1,3,4,5,6,8a-hexahydro-2H-2,4a-methanonaphthalen-8-yl)propan-1-ol and 2-(1,1,5,5-tetramethyl-1,3,4,5,6,7-hexahydro-2H-2,4a-methanonaphthalen-8-yl)propan-1-ol .sup.2)dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan .sup.3)ethyl 2-ethyl-6,6-dimethylcyclohex-2-ene-1-carboxylate .sup.4)3-methyl-5-phenyl-1-pentanol .sup.5)oxacyclohexadecan-2-one

[0088] In formula 5(a), 1.5 wt % Citral supports the freshness and performance of the accord, reinforcing the natural impression.

[0089] In formula 5(b), Citral was replaced by 2,4,7-trimethyl-2,6,-octadienal, which brings a very similar natural impression, and supports also both the freshness and performance.

EXAMPLE 6

Spicy-Citrus Perfume Composition

[0090]

TABLE-US-00007 6(a) 6(b) citronellyl acetate 80 80 decanal 3 3 Borneol (crystals) 1 1 lemon terpenes (citral free) 230 230 (E)-dec-4-enal 1 1 Elemi Oil 30 30 Ethyl Linalol (group (A) compound) 140 140 Eucalyptol (natural) 20 20 Mefrosol 120 120 Hedione (group (A) compound) 310 310 dihydroeugenol 5 5 Methyl Pamplemousse (group (A) comp.) 44 44 Vanillin @ 10 wt % in TEC 1 1 Citral 15 2,4,7-trimethyl-2,6,-octadienal 15 Total 1000 1000

[0091] In the formula 6(a), 1.5 wt % Citral supports the freshness and performance of the accord, reinforcing the natural impression.

[0092] In formula 6(b), Citral was replaced by 2,4,7-trimethyl-2,6,-octadienal, which brings a similar natural impression, and supports also both the freshness and performance

EXAMPLE 7

Rose Musk Perfume Composition

[0093]

TABLE-US-00008 7(a) 7(b) geranyl acetate 240 240 hexenyl-3-cis acetate @ 10 wt % in TEC 2 2 prenyl acetate 1 1 2-phenylethan-1-ol 210 210 decanal @10 wt % in TEC 3 3 dihydro myrcenol (group (A) compound) 50 50 Delta Damascone 2 2 dihydroeugenol 3 3 Galaxolide 130 130 Mefrosol 240 240 (Z)-hex-3-en-1-ol 1 1 Isoraldeine 40 40 3-(4-isobutyl-2-methylphenyl)propanal 30 30 (group (B) compound) Rose Oxide @10 wt % in DPG 3 3 Hexenyl-3-Cis Salicylate.sup.1) 30 30 Citral 15 2,4,7-trimethyl-2,6,-octadienal 15 Total 1000 1000 .sup.1)(Z)-hex-1-en-1-yl 2-hydroxy-3-methylbenzoate

[0094] In formula 7(a), 1.5 wt % citral supports the freshness and performance of the accord, reinforcing the natural impression.

[0095] In formula 7(b), Citral was replaced by 2,4,7-trimethyl-2,6,-octadienal, which supports the freshness and performance of the fragrance, and brought a slightly sweeter citrus character, more like a juicy lemon, but still fitting in the general character and original overall impression.