Fragrances as urease inhibitors.

Abstract

It is proposed to use at least one fragrance having a molecular weight between 95 and 225 g / mol as a urease inhibitor.

Description

[Technical field]

[0001] <Field of the Invention> The present invention relates to the field of functional perfumery, in particular to the prevention of the formation of ammonia malodour, and more particularly to fragrances having the ability to inhibit the enzyme urease. [Background technology]

[0002] <Background of the invention> Fragranced products, such as perfumes, deodorants, and other fragrance-containing personal care, home care, pet care, and cosmetics, have been widely used to mask unpleasant odors. However, overcoming the malodor of ammonia is a major challenge due to its ability to activate the olfactory system as well as trigger trigeminal chemosensation. The latter is known as a warning system upon exposure to chemical danger (in this case due to changes in pH), which makes the perception highly unpleasant and difficult to mask with conventional fragrances. As a result, the best way to prevent ammonia odor is to prevent its production.

[0003] The most common form of ammonia production in biological systems and the environment is the enzymatic degradation of urea by bacterial urease. As a result, antimicrobial agents can be used to reduce the amount of urease-positive bacteria or the enzyme urease can be chemically inhibited to prevent the production of ammonia.

[0004] The inhibition of urease has been thoroughly studied from a pharmaceutical point of view, but also in agricultural products, especially in urea-containing fertilizers. In both areas, very potent small molecule inhibitors have been developed that are highly specific and effective against urease. Unfortunately, these compounds are not suitable for use in consumer products for several reasons, e.g. safety and cost. Summary of the Invention [Problem to be solved by the invention]

[0005] Consequently, it was an object of the present invention to provide a cost-effective, safe and fragrance compatible urease inhibitor that can be easily used in consumer products to address the problem of ammonia malodour production. [Means for solving the problem]

[0006] <Details of the Invention> Thus, according to the present invention there is provided at least one fragrance for use as a urease inhibitor, in particular as a urease inhibitor, having a molecular weight of 95 to 225 g / mol.

[0007] The inventors have surprisingly found that fragrances having a molecular weight between 95 and 225 g / mol inhibit the activity of urease, in particular bacterial urease, thereby reducing the amount of ammonia produced from ammonia precursors such as urea.

[0008] Urea functionally belongs to the amidohydrolase and phosphotriesterase superfamily. Urea is present in many bacteria, fungi, algae, plants, and some invertebrates, and is also present in soil as a soil enzyme. Urease is a high molecular weight nickel-containing metalloenzyme. These enzymes catalyze the hydrolysis of urea to carbon dioxide and ammonia: [ka] The hydrolysis of urea occurs in two steps. In the first step, ammonia and carbamate are produced. The carbamate spontaneously and rapidly hydrolyzes to ammonia and carbonic acid. To produce ammonia, which is basic, urease activity increases the pH of the environment.

[0009] The fragrances used according to the invention further advantageously are easily accessible or readily available or easily prepareable, have high effectiveness even at low concentrations, especially at concentrations where the fragrance is odorless or at least has only a barely perceptible odor, are largely or completely colorless, have high stability in various mixtures or preparations, and have no toxic and / or allergenic effects on humans.

[0010] The fragrances of the present invention also have the advantage that they can be combined with different fragrances other than those according to the invention, and with perfume oils or the usual components of perfume oils, in order to perfuming a product with any desired fragrance, so that a wide variety of fragrances can be offered to the consumer by the present invention. [Brief description of the drawings]

[0011] [Figure 1] Results from a urease enzyme screening assay. [Diagram 2] FIG. 2 is a graph showing the relative ammonia production (%) in cat litter (compared to the negative control). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] "Urease inhibitors" or "urease inhibitors" according to the present invention are chemical compounds, particularly fragrances, that reduce or completely block the activity of the enzyme urease.

[0013] In a preferred embodiment according to the present invention, the amount of at least one fragrance is not enough to impart a specific odor when added to the composition or product.Fragrances according to the present invention have the advantage that, especially when used according to the use according to the present invention, they are already active for the purpose of the present invention at such low concentrations that the essential odor of fragrance is not imparted or at least not perceived.This allows these fragrances to be optionally combined with different fragrances (not according to the present invention) as well as with further components of perfume oils to produce particularly advantageous fragrance mixtures or to further perfume products with any desired scent.

[0014] In a preferred embodiment according to the present invention, the composition or product is a consumer product. A "consumer product" according to the present invention is a product that is purchased by an individual or household for personal use. In other words, a consumer product is an item that is purchased for consumption by a general consumer. Preferred consumer products according to the present invention are personal care, especially toilet care, especially perfume and / or fragrance compositions, home care, pet care, especially cat toiletry, and cosmetics.

[0015] In a preferred embodiment according to the invention, the at least one fragrance is selected from fragrances having a molecular weight between 95 and 225 g / mol, in particular from alcohols, carbonyls, aldehydes, ketones, ethers and esters. More preferably, the at least one fragrance is selected from fragrances having a molecular weight between 95 and 225 g / mol, in particular from α,β-unsaturated carbonyls, β-unsaturated alcohols and γ-unsaturated esters.

[0016] In a further preferred embodiment according to the present invention, the at least one fragrance comprises cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal); 2,6-octadien-1-ol 3,7-dimethyl (mixed or isolated isomers); geraniol (mixed or isolated isomers);Geraniol), trans-2-hexenol, cis-3-hexenol, trans-2-hexenal, 3,7-dimethylocta-2,6-dienal (Citral FF), cis-3-hexenyl butyrate, (E)-1-(2,6,6-trimethyl-1-cyclohex-1,3-dienyl)but-2-en-1-one (Damascenone total), (E)-1-(2,6,6-trimethyl-1-cyclohex-2-enyl)but-2-en-1-one (Damascone alpha alpha), cis-3-hexenyl propionate, cis-3-hexenyl acetate, cis-3-hexenyl hexanoate, cis-3-hexenyl isovalerate, cis-3-hexenyl isobutyrate, (2E)-3-phenylprop-2-en-1-ol (cinnamic alcohol alcohol), alpha-methylcinnamaldehyde, cis-3-hexenyl salicylate, 4-hydroxy-2,5-dimethyl-3-furanone (Furaneol), methylcyclopentenolone-3,2,2,methylethylhydroxyfuranone, 2-ethoxy-4-methylphenol (Ultravanil), 2-methoxyphenol (Guaiacol), 2-methoxy-4-(prop-2-en-1-yl)phenol (Eugenol), 3-(1,3-benzodioxol-5-yl)-2-methylpropanal (Helional), dimethyl-3,6-benzo-2(3H)-furanone (Furaminton / Tonkalactone®). (Furaminton / Tonkalactone), (2Z)-3,7-Dimethylocta-2,6-dien-1-ol (Nerol 900), 2,6-Nonadien-1-ol, Methylionone Alpha, Methylionone Gamma, or mixtures thereof;

[0017] In a more preferred embodiment according to the present invention, the at least one fragrance is selected from the group consisting of cis-3-hexenyl salicylate, cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal), trans-2-hexenal, methylethylhydroxyfuranone, cis-3-hexenyl butyrate or mixtures thereof. More preferably, the at least one fragrance is selected from trans-2-hexenal and / or methylethylhydroxyfuranone. Most preferably, the at least one fragrance is selected from trans-2-hexenal.

[0018] In a further preferred embodiment, the at least one fragrance is selected from the group consisting of 2,6-octadien-1-ol 3,7-dimethyl (mixed or isolated isomers; geraniol) and / or 3,7-dimethylocta-2,6-dienal (citral FF).

[0019] In other words, in a further preferred embodiment according to the present invention, the at least one fragrance is selected from the group consisting of: TIFF2025515248000002.tif190164 TIFF2025515248000003.tif237164 TIFF2025515248000004.tif188164 TIFF2025515248000005.tif181164 TIFF2025515248000006.tif182164 TIFF2025515248000007.tif209164 TIFF2025515248000008.tif194164 TIFF2025515248000009.tif182164 TIFF2025515248000010.tif185164 TIFF2025515248000011.tif242164 TIFF2025515248000012.tif245164 TIFF2025515248000013.tif182165 TIFF2025515248000014.tif168164

[0020] In another embodiment according to the invention, the at least one fragrance, when added to the composition or product, is used in an amount of 0.01-10% by weight, calculated on the total weight of the composition or product. More preferably, the at least one fragrance is used in an amount of 0.05-5% by weight; more preferably, in an amount of 0.05-1% by weight, most preferably, in an amount of 0.05-0.5% by weight; all weight percentages are calculated on the total weight of the composition or product.

[0021] Particularly advantageous is the use according to the invention, in which the ratio of the total mass of the at least one fragrance to the total mass of the at least one ammonia precursor is between 1:1 and 1:5, more preferably between 1:2 and 1:4.

[0022] A "precursor" according to the present invention is a compound that participates in a chemical reaction that produces another compound. In the present invention, an "ammonia precursor" refers to a compound that participates in a chemical reaction that produces ammonia. In one embodiment according to the present invention, the ammonia precursor is urea.

[0023] Thus, in a preferred embodiment according to the invention, at least one fragrance is used as a urease inhibitor in a composition or product, in particular in a consumer product, together with at least one ammonia precursor. Thus, it is possible that, when in contact with, for example, bacterial urease, the fragrance of the invention completely, but at least partially, blocks the production of ammonia.

[0024] It will be appreciated that one or more fragrances having a molecular weight of 95-225 g / mol can be used to inhibit urease activity. Thus, for example, fragrances 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 having a molecular weight of 95-225 g / mol can be used to inhibit urease activity in a consumer product.

[0025] Examples of other fragrances which in principle can be advantageously used as further components together with the at least one fragrance having a molecular weight of 95 to 225 g / mol according to the invention can be found, for example, in S. Arctander, Perfume and Flavor Chemicals, Vol. I and II, Montclair, NJ, 1969, Selbstverlag oder H. Surburg, J. Panten, Common Fragrance and Flavor Materials, 5th Ed., Wiley-VCH, Weinheim 2006.

[0026] Another embodiment of the present invention comprises: (a) a fragrance composition comprising at least one fragrance having a molecular weight of 95 to 225 g / mol as a urease inhibitor; and (b) at least one ammonia precursor This report relates to consumer products, including:

[0027] As already explained above, fragrances having a molecular weight between 95 and 225 g / mol inhibit the activity of urease, in particular bacterial urease, thereby reducing the amount of ammonia produced from ammonia precursors such as urea.

[0028] In a preferred embodiment according to the invention, the consumer product comprises: (c) at least one emulsifier selected from the group consisting of cetearyl ethylhexanoate, cetearyl alcohol, potassium cetyl phosphate, sodium cetyl sulfate, and PEG-40 stearate; Further includes:

[0029] In a preferred embodiment according to the invention, the consumer product does not comprise a further urease inhibitor.As mentioned above, preferred consumer products according to the invention are personal care, especially toilet care, especially perfume and / or fragrance compositions, home care, pet care, especially cat litter and cosmetics.

[0030] Preferably, the at least one fragrance is present in an amount of 0.01 to 10% by weight, calculated on the total weight of the consumer product. More preferably, the at least one fragrance is present in an amount of 0.05 to 5% by weight, calculated on the total weight of the consumer product. Even more preferably, the at least one fragrance is present in an amount of 0.05 to 1% by weight, calculated on the total weight of the consumer product.

[0031] In a preferred embodiment, the ratio of the at least one fragrance having a molecular weight between 95 and 225 g / mol and the at least one ammonia precursor is between 1:1 and 1:5, more preferably between 1:2 and 1:4.

[0032] In a further preferred embodiment according to the present invention, the at least one fragrance is selected from the group consisting of cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal), 2,6-octadien-1-ol 3,7-dimethyl (mixed or isolated isomers; geraniol), trans-2-hexenol, cis-3-hexenol, trans-2-hexenal, 3,7-dimethylocta-2,6-dienal (citral FF), cis-3-hexenyl butyrate, (E)-1-(2,6,6-trimethyl-1-cyclohexa-1,3-dienyl)but-2-en-1-one (damascenone). Total), (E)-1-(2,6,6-trimethyl-1-cyclohex-2-enyl)but-2-en-1-one (damascone alpha), cis-3-hexenyl propionate, cis-3-hexenyl acetate, cis-3-hexenyl hexanoate, cis-3-hexenyl isovalerate, cis-3-hexenyl isobutyrate, (2E)-3-phenylprop-2-en-1-ol (cinnamic alcohol), alpha-methylcinnamaldehyde, cis-3-hexenyl salicylate, 4-hydroxy-2,5-dimethyl-3-furanone (furaneol) ), methylcyclopentenolone-3,2,2, methylethylhydroxyfuranone, 2-ethoxy-4-methylphenol (Ultravanil), 2-methoxyphenol (Guaiacol), 2-methoxy-4-(prop-2-en-1-yl)phenol (Eugenol), 3-(1,3-benzodioxol-5-yl)-2-methylpropanal (Helional), dimethyl-3,6-benzo-2(3H)-furanone (Furaminton / Tonkalactone®), (2Z)-3,7-dimethylocta-2,6-dien-1-ol (Nerol 900), 2,6-nonadien-1-ol, methylionone alpha, methylionone gamma, or mixtures thereof.

[0033] In a more preferred embodiment according to the present invention, the at least one fragrance is selected from the group consisting of cis-3-hexenyl salicylate, cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal), trans-2-hexenal, methylethylhydroxyfuranone, cis-3-hexenyl butyrate or mixtures thereof. More preferably, the at least one fragrance is selected from trans-2-hexenal and / or methylethylhydroxyfuranone. Most preferably, the at least one fragrance is selected from trans-2-hexenal.

[0034] In a further preferred embodiment, the at least one fragrance is selected from the group consisting of 2,6-octadien-1-ol 3,7-dimethyl (mixed or isolated isomers; geraniol) and / or 3,7-dimethylocta-2,6-dienal (citral FF).

[0035] The fragrance composition according to the invention, which comprises at least one fragrance having a molecular weight between 95 and 225 g / mol, can be in liquid form either neat or diluted with a solvent, and is advantageously used in perfumery. Preferred solvents for this purpose are ethanol, isopropanol, diethylene glycol monoethyl ether, glycerol, propylene glycol, 1,2-butylene glycol, dipropylene glycol, diethyl phthalate, triethyl citrate, isopropyl myristate, triacetin, and diacetin.

[0036] Furthermore, the fragrance composition according to the invention may be adsorbed on a carrier that provides both a fine distribution of the fragrance in the product and a controlled release upon application. Such carriers may be porous inorganic materials, such as light sulfate, silica gel, zeolites, gypsum, clay, clay granules, aerated concrete, etc., or organic materials, such as wood, cellulosic materials, sugars, dextrins (e.g. maltodextrin), or plastics, such as PVC, polyvinyl acetate, polyurethane, etc. The resulting combination of the composition according to the invention and the carrier may also be understood as a fragrance composition according to the invention or may be present as an article according to the invention (as further described herein).

[0037] The fragrance compositions according to the invention may also be microencapsulated, spray dried, inclusion complexed or extruded and in this form can be added, for example, to the product to be perfumed.

[0038] If necessary, the properties of the composition can be further optimized in terms of a more targeted fragrance release by so-called "coating" with a suitable material; for this purpose waxy plastics such as polyvinyl alcohol are preferably used.

[0039] The other preferred embodiments and definitions mentioned above of course also apply to the consumer product according to the invention.

[0040] A further embodiment of the present invention relates to a method of inhibiting urease activity in a composition or product, wherein at least one fragrance having a molecular weight of 95 to 225 g / mol is added to the composition or product.

[0041] Preferably, the at least one fragrance is added in an amount of 0.01 to 10% by weight, calculated on the total weight of the consumer product. More preferably, the at least one fragrance is added in an amount of 0.05 to 5% by weight, calculated on the total weight of the consumer product. Even more preferably, the at least one fragrance is added in an amount of 0.05 to 1% by weight, calculated on the total weight of the consumer product.

[0042] More preferably, the composition or product is a consumer product.

[0043] The above mentioned preferred embodiments and definitions of course also apply to the method according to the invention.

[0044] A further embodiment of the present invention relates to cat litter comprising at least one fragrance as a urease inhibitor having a molecular weight of 95 to 225 g / mol.

[0045] Of course, all the above preferred embodiments and process definitions also apply to the cat litter according to the invention.

[0046] In the following, embodiments of the present invention are further characterized. EXAMPLES

[0047] [Urease inhibition screening] Urease-catalyzed ammonia production results in a change in pH (alkalinization). Therefore, the reaction can be monitored using pH indicators. The enzymatic screening assay is described below. Colorimetric measurements are performed in 96-well plates using phenol red as a pH-sensitive indicator in conjunction with a microplate spectrophotometer. Briefly, the substrate urea, fragrance raw material and urease are mixed in a well and the change in absorbance at 560 nm is observed for 1 hour. The resulting absorbance curve is compared to an untreated sample (negative control, no inhibitor) and a sample spiked with a commercially available NBPT inhibitor (positive control).

[0048] [Table 1]

[0049] The reaction rate is derived from the color change (Δabsorbance at 560 nm) over time:

number

[0050] The inhibitory effect is calculated as follows:

number

[0051] [Identifying positive hits] Figure 1 depicts typical results from a screening assay. The corresponding calculated results are shown in Table 2. In this case, the fragrance raw material (green trace) shows significant inhibition of the enzyme urease.

[0052] [Table 2]

[0053] [Positive hit] A total of 29 highly active compounds could be identified by in vitro screening. Interestingly, they share common structural features such as molecular weights between 95 and 225 g / mol, α,β-unsaturated carbonyls (e.g., damascones and ionones), various β-unsaturated alcohols, and γ-unsaturated esters. TIFF2025515248000019.tif165154

[0054] [Application to cat litter] The efficiency of reducing ammonia production in cat litter was tested using various fragrance ingredients as shown in the table below (Table 3). Briefly, litter was coated with 0.1% (w / w) active material on dry litter. In glass bottles with a total volume of 5 L, the litter was treated with artificial cat urine, consisting of an aqueous salt solution containing urea and urease. Ammonia evolution was measured by headspace sampling over a period of 5 days using an ammonia-sensitive detector.

[0055] [Table 3]

[0056] The results showed that all fragrances tested produced less relative ammonia production compared to the negative (untreated) control, confirming the urease inhibitory effect of the fragrance ingredients, as shown in Figure 2.

Claims

1. Use of at least one fragrance having a molecular weight of 95 to 225 g / mol as a urease inhibitor.

2. 10. The use according to claim 1, wherein the amount of the at least one fragrance when added to the composition or product is not sufficient to impart a unique odor.

3. At least one fragrance may comprise any of the following: cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal), 2,6-octadien-1-ol 3,7-dimethyl (mixed or isolated isomers; geraniol), trans-2-hexenol, cis-3-hexenol, trans-2-hexenal, 3,7-dimethylocta-2,6-dienal (citral FF), cis-3-hexenyl butyrate, (E)-1-(2,6,6-trimethyl-1-cyclohexa-1,3-dienyl)but-2-en-1-one (damascenone). Total), (E)-1-(2,6,6-trimethyl-1-cyclohex-2-enyl)but-2-en-1-one (damascone alpha), cis-3-hexenyl propionate, cis-3-hexenyl acetate, cis-3-hexenyl hexanoate, cis-3-hexenyl isovalerate, cis-3-hexenyl isobutyrate, (2E)-3-phenylprop-2-en-1-ol (cinnamic alcohol), alpha-methylcinnamaldehyde, cis-3-hexenyl salicylate, 4-hydroxy-2,5-dimethyl-3-furanone (furaneol) ), methylcyclopentenolone-3,2,2, methylethylhydroxyfuranone, 2-ethoxy-4-methylphenol (Ultravanil), 2-methoxyphenol (guaiacol), 2-methoxy-4-(prop-2-en-1-yl)phenol (eugenol), 3-(1,3-benzodioxol-5-yl)-2-methylpropanal (Helional), dimethyl-3,6-benzo-2(3H)-furanone (Furaminton / Tonkalactone®), (2Z)-3,7-dimethylocta-2,6-dien-1-ol (Nerol 900), 2,6-nonadien-1-ol, methylionone alpha, methylionone gamma, or mixtures thereof.

4. 4. The use according to any one of claims 1 to 3, wherein the at least one fragrance is selected from the group consisting of cis-3-hexenyl salicylate, cis-1-(1-ethoxyethoxy)-3-hexene (leaf acetal), trans-2-hexenal, methyl ethyl hydroxyfuranone, cis-3-hexenyl butyrate or mixtures thereof.

5. The use according to any one of claims 1 to 4, wherein the at least one fragrance is selected from trans-2-hexenal and / or methylethylhydroxyfuranone.

6. The use according to any one of claims 1 to 5, wherein at least one fragrance is trans-2-hexenal.

7. Use according to any of the preceding claims, wherein the amount of the at least one fragrance, when added to the composition or product, is between 0.01 and 10% by weight, calculated relative to the total weight of the composition or product.

8. (a) a fragrance composition comprising at least one fragrance having a molecular weight of 95 to 225 g / mol as a urease inhibitor; and (b) at least one ammonia precursor Consumer products, including

9. 9. The consumer product of claim 8, wherein the consumer product does not contain an additional urease inhibitor.

10. 10. Consumer product according to claim 8 and / or 9, wherein the at least one fragrance is present in an amount of from 0.01 to 10% by weight, calculated on the total weight of the consumer product.

11. 10. Consumer product according to claim 8 and / or 9, wherein the at least one fragrance is present in an amount of from 0.05 to 1% by weight, calculated on the total weight of the consumer product.

12. A consumer product according to any of claims 8 to 11, wherein the ratio of the at least one fragrance having a molecular weight of 95 to 225 g / mol to the at least one ammonia precursor is from 1:1 to 1:

5.

13. A method for inhibiting urease activity in a composition or product, wherein at least one fragrance having a molecular weight of 95-225 g / mol is added to the composition or product.

14. The method according to claim 13, wherein the at least one fragrance is added in an amount of from 0.01 to 10% by weight, calculated on the total weight of the composition or product.

15. Cat litter comprising at least one fragrance having a molecular weight of 95 to 225 g / mol as a urease inhibitor.

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