SOLUBILIZATION OF POORLY SOLUBLE COOLING SUBSTANCES

Abstract

The present invention relates to a cooling composition for producing cooling particles comprising a solvent component and dissolved therein (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide. The present invention further relates to cooling particles comprising a cooling composition according to the invention, oral preparations comprising cooling particles, new uses of cooling particles, a process for the production of cooling particles as well as the use of a solvent component for dissolving cooling agents.

Claims

1. A cooling composition for producing cooling particles comprising: (A) a solvent component or comprising: i) 2-hydroxypropyl (2-isopropyl-5-methyl-cyclohexyl) carbonate, and/or ii) (2-isopropyl-5-methyl-cyclohexyl) 2-hydroxypropanoate; and (B) 0.5 to 12% by weight, based on the total weight of the composition, of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide (CAS number 68489-09-8; FEMA number 4681) as a cooling agent dissolved in the solvent component.

2. The composition according to claim 1, wherein the composition comprises: A) 0.5 to 6% by weight, based on the total weight of the composition, of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide (FEMA 4681) as cooling agent, or B) 6 to 12% by weight, based on the total weight of the composition, of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide (FEMA 4681) as cooling agent.

3. The composition according to claim 1, wherein the composition further comprises N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide.

4. The composition according to claim 1, wherein 2-hydroxypropyl (2-isopropyl-5-methyl-cyclohexyl) carbonate is 2-hydroxypropyl [(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl] carbonate (CAS number 260781-16-6).

5. The composition according to claim 1, wherein N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide is (1R,2S,5R)-N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide (CAS number 68489-00-9).

6. The composition according to claim 1, wherein (2-isopropyl-5-methyl-cyclohexyl) 2-hydroxypropanoate is [(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl] (2S)-2-hydroxypropanoate (CAS number 61597-98-6).

7. The composition according to claim 1, wherein the solvent component comprises 2 to 20% by weight, based on the total weight of the solvent component, of 2-hydroxypropyl (2-isopropyl-5-methyl-cyclohexyl) carbonate.

8. The composition according to claim 1, wherein the solvent component comprises 15 to 35% by weight, based on the total weight of the solvent component, of N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide.

9. The composition according to claim 1, wherein the solvent component comprises 55 to 75% by weight, based on the total weight of the solvent component, of (2-isopropyl-5-methyl-cyclohexyl) 2-hydroxypropanoate.

10. The composition according to claim 1, wherein the composition contains 88 to 99.5% by weight, based on the total weight of the solvent component, of the solvent component (A).

11. The composition according to claim 1, wherein the composition additionally comprises 0.5 to 8% by weight, based on the total weight of the solvent component, of medium-chain triglycerides.

12. The composition according to claim 11, wherein the composition comprises 80 to 99% by weight, based on the total weight of the solvent component, of the solvent component (A).

13. (canceled)

14. Cooling particles comprising a composition according to claim 1.

15. The cooling particles according to claim 14, wherein the particles have an average particle diameter D50 in the range of 10 to 2000 μm as determined by laser light diffraction according to ISO ISO13320:2009-10.

16. An oral preparation comprising cooling particles according to claim 14.

17. (canceled)

18. The oral preparation according to claim 16, comprising: a) 5 to 95% by weight of chewing gum base, b) 5 to 95% by weight of fillers and sweeteners, c) 0.1 to 15% by weight of flavours, and d) 0.2 to 4% by weight of the cooling particles.

19. (canceled)

20. (canceled)

21. A process for producing cooling particles comprising: providing a composition according to claim 1, storing the provided composition, providing matrix materials, mixing the composition with the matrix materials, and carrying out an encapsulation process resulting in cooling particles in which the composition is encased by the matrix materials.

22. The process according to claim 21, wherein the encapsulation process is spray drying, spray granulation, melt granulation, coacervation, coagulation, extrusion, melt extrusion, an emulsion process, coating, or other suitable encapsulation process.

23. The process according to claim 21, wherein the matrix materials are starch, starch derivatives, cellulose or cellulose derivatives, other polysaccharides, natural fats, natural waxes, proteins, and/or other natural products.

24-28. (canceled)

29. A method for imparting a feeling of freshness to an oral preparation comprising incorporating the cooling particles according to claim 14 into the oral preparation.

Description

EXAMPLES

Example 1

[0090] 96 g of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate were put in a 250 mL beaker and 4 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide were added. The mixture was stirred and heated in 20° C. steps until a clear solution was formed. After each heating by 20° C., the solution was stirred for at least 20 minutes. Afterwards the mixture was cooled down to a room temperature of about 25° C. The produced solution was stable for 8 hours even after cooling and no crystals were formed.

Example 2

[0091] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate (2-isopropyl-5-methyl-cyclohexyl)2-hydroxypropanoate was used as solvent. The produced solution was stable even after cooling and no crystals were formed.

Example 3

[0092] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate a mixture of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate and (2-isopropyl-5-methyl-cyclohexyl)2-hydroxypropanoate was used as solvent. The produced solution was stable even after cooling and no crystals were formed.

Example 4

[0093] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate a mixture of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate, (2-isopropyl-5-methyl-cyclohexyl)2-hydroxypropanoate and N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide was used as solvent and 10 g of (1 R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexanecarboxamide were dissolved. The produced solution was stable even after cooling and crystals were formed only after more than 24 hours.

Example 5

[0094] Example 4 was repeated, but 8 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide were dissolved. The produced solution was stable for more than 24 hours even after cooling and no crystals were formed.

Example 6

[0095] Example 4 was repeated, but 6 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide were dissolved. The produced solution was stable for more than 24 hours even after cooling and no crystals were formed.

Example 7

[0096] Example 4 was repeated, but 4 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide were dissolved. The produced solution was stable for more than two weeks even after cooling and no crystals were formed.

Example 8

[0097] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate a mixture of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate, (2-isopropyl-5-methyl-cyclohexyl)2-hydroxypropanoate, N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide and 6% by weight of medium-chain triglycerides were used as solvents and 6 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide were dissolved. The produced solution was stable for more than two weeks even after cooling and no crystals were formed.

Example 9: Production of Granular Particles with a Cooling Composition According to the Invention by Spray Granulation

[0098] A cooling composition according to invention from example 8 was produced and stored at approx. 20° C. A mixture of 50 parts by weight of modified starch, 25 parts by weight of gum arabic (Senegal) and 10 parts by weight of mannitol as carrier component was then provided. The cooling composition and the carrier component were mixed in a weight ratio of 1 to 4 and spray granulated.

[0099] Cooling particles with an average particle diameter D50 of 600 μm, determined by laser light diffraction according to ISO ISO13320:2009-10, are obtained, which comprise approx. 20% by weight of the cooling composition according to the invention.

[0100] By varying the process parameters of the spray granulation process, it is also possible to produce particles with a size of, for example, 200 μm, 300 μm, 400 μm, 800 μm, 1400 μm, 1800 μm or 2000 μm.

Example 10: Production of Particles with a Cooling Composition According to the Invention by Spray Drying

[0101] A cooling composition according to invention from example 8 was produced and stored at approx. 20° C. A mixture of 60 parts by weight of modified starch, 25 parts by weight of gum arabic (Senegal) and 10 parts by weight of sugar alcohol as carrier component was then provided. The cooling composition and the carrier component were mixed in a weight ratio of 3 to 7 and spray dried.

[0102] Cooling particles with an average particle diameter D50 of 80 μm, determined by laser light diffraction according to ISO ISO13320:2009-10, are obtained, comprising approximately 27% by weight of the cooling composition according to the invention.

[0103] By varying the process parameters of the spray drying process, it is also possible to produce particles with a size of, for example, 10 μm, 20 μm, 75 μm, 125 μm, 150 μm, 175 μm or 200 μm.

Example 11: Production of a Mouthwash

[0104]

TABLE-US-00001 Part Ingredient Use in % by weight A Ethanol 10.00 Cremophor ® CO 40 (BASF, detergent) 1.00 Benzoic acid 0.12 Solution of example 8 1.00 B Demineralised water 82.71 Sorbitol, 70% 5.00 Sodium saccharin 450 0.07 L-Blue 5000 e.c., 1% in water (dye) 0.10

[0105] The ingredients of parts A and B were each mixed separately. Part B was slowly stirred into part A until the mixture was homogeneous.

[0106] When using the mouthwash produced in this way, a very high cooling effect was observed.

Example 12: Production of a Sugar-Free Chewing Gum

[0107]

TABLE-US-00002 Part Ingredient Use in % by weight A Chewing gum base, Company “Jagum T” 30.00 B Sorbitol, powdered 39.00 Isomalt ® (Palatinit GmbH) 9.50 Xylitol 2.00 Mannitol 3.00 Aspartame ® 0.10 Acesulfam ® K 0.10 Emulgum ® (Colloides Naturels, Inc.) 0.30 C Sorbitol, 70% 14.00 Glycerin 1.00 D Granules of example 9 1.00

[0108] Parts A to D were mixed and intensively kneaded. The raw mass was processed e.g. in the form of thin strips into ready-to-eat chewing gums.

[0109] When using the chewing gum produced in this way, a considerable cooling effect was observed.

Comparative Example 1

[0110] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate ethanol was used as solvent. The produced solution crystallised already during cooling to room temperature.

Comparative Example 2

[0111] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate medium-chain triglycerides were used as solvent and 1 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide was dissolved. No solution could be prepared. (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide is insoluble in medium-chain triglycerides even at 60° C.

Comparative Example 3

[0112] Example 1 was repeated, but instead of 2-hydroxypropyl(2-isopropyl-5-methyl-cyclohexyl)carbonate N-ethyl-2-isopropyl-5-methyl-cyclohexanecarboxamide was used as solvent, 1 g of (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexane-carboxamide was dissolved and the mixture was heated until both substances were melted. Both substances crystallised during cooling.