Description:
FIELD OF THE INVENTION
The present invention relates to blend of menthol isomers and related compounds that contribute to sensory and odor profile compared to L-Menthol, in no aroma impact cosmetic products.

BACKGROUND OF THE INVENTION
Menthol is a naturally occurring (C10H20O; molecular weight, 156) cyclic terpene alcohol, always a big research of perfume industry. Being a major constituent of peppermint oil, menthol has been used extensively in foodstuff, beverages, dentifrices, oral-care, skin-care and hair-care preparations, confectionary, tobacco and pharmaceutical products. The three unsymmetrical carbons are arranged in the menthol molecule, therefore, can have eight optically active isomers to exist. These 8 optically active isomers are L-menthol, D-menthol, L-isomenthol, D-isomenthol, L-neomenthol, D-neomenthol, L-neoisomenthol, D-neoisomenthol. The natural abundant isomers are L-menthol, D-neomenthol, D-neoisomenthol and D-isomenthol, present in various Mentha species.

Chandan S Chanotiya et al. in Journal of Essential Oil Research (2020) reported that D-menthol and L-neomenthol were not present in natural source. Isopulegol is a precursor molecule of L-menthol in biosynthetic pathway. It is also an intermediate molecule while synthesizing L-menthol.

A strong initial cooling sensation can be achieved if products containing L-menthol are applied to the skin and/or mucous membrane. However, the very similar sensory and odour profiles of various products persist when it is used with a unique blend of menthol isomers and isopulegol.

There have been reports in the literature where menthol and its related structures have been used in the same formulation by adding these in a blend or separately.

WO 00/42983 discloses a cosmetic composition based on menthol and menthyl lactate, having little odor and being non-irritating. The cosmetic composition comprises 0.01 % to 2 % by weight menthol and 0.1 % to 10 % by weight menthyl lactate, the menthol/menthyl lactate ratio lying in the range 1/1 to 1/10, and being such that the odor of the menthol is barely perceptible, said composition not being irritating, in particular for the sensitive parts of the human body, while conserving the various beneficial effects of menthol.

JP 06329528 discloses a cosmetic which can maintain refresh feeling. The cosmetic contains a clathrate prepared from one or more refreshing agents, one or more menthol derivatives and a cyclodextrin derivative. The cooling agents are selected from menthol, camphor, mint or eucalyptus oil, wherein the menthol derivative is menthyl lactate, menthoxypropane diol, menthyl hydroxybutyrate, menthoxyfuran, and menthyl glucoside.

JP10231238 discloses a cosmetic excellent in refreshing feeling and persistence thereof by including a refreshing agent, ethanol and isopropyl alcohol therein. This cosmetic is prepared by including 0.001-10.0wt.% refreshing agent [e.g. menthol (especially L-menthol), a camphor, a mint and a eucaryptus oil capable of providing immediately effective refreshing feeling and preferably at least one slow-acting menthol derivative (menthyl lactate, menthoxypropanediol, menthyl hydroxybutyrate, menthoxyfuran or menthyl glucoside)], ≥ 0.1wt.%, preferably ≥1.0wt.% ethanol and ≥ 0.05wt.%, preferably 0.1-10wt.% isopropy alcohol therein.

US5663460 discloses a liquid l-n-menthol composition containing 30 to 80% by weight of (-)-n-isopulegol and a process for preparing a liquid l-n-menthol composition comprising mixing 20 to 70 parts by weight of liquid menthol at a temperature of notlower than 42° C. The liquid-n-menthol composition of the present invention is less expensive than convention ally available menthol and yet has an improved feeling of coolness (particularly, the bitterness is reduced) and can be used in place of conventional menthol.

ES2488634T3 discloses a refreshing composition that provides a cooling sensation significantly similar to that provided by menthol. The composition comprises: chin in an amount of about 10 to about 25% by weight; isomenthone in an amount of about 10 to about 25% by weight; isopulegol in an amount of about 2.5 to about 15% by weight; monomentile succinate in an amount of about 15 to about 25% by weight; and mentyl lactate in an amount of about 5 to about 30% by weight.

JP5912482B2 discloses menthol-containing mixture based on the total weight of the mixture, consist of the following components: Racemic d, l-menthol and 72.0 to 85.0% by weight in total Optional additional l-menthol; • 7.5 to 20.0% by weight of d, l-isomenthol; • Overall 7.0 to 11.0% by weight of the first alkylene diol and optional and one or more additional alkynene diols; and... 0 to 2.0 wt.%, wherein the mass ratio of d, l-menthol to the l-menthol is greater than 1: 4.

CN101346073B discloses a composition that does not contain menthol, and provides substantially the same physiological sensation that provides the composition comprising menthol. The composition comprisesmenthone in an amount of about 10 to about 25% by weight; Isomenthone in an amount of about 10 to about 25% by weight; Isopulegol in an amount of about 2.5 to about 15% by weight; Monomenthyl succinate in an amount of about 15 to about 25% by weight; and Menthyl lactate in an amount of about 5 to about 30% by weight.

WO2007115593A1 discloses application of a mixture of menthyl lactate, neomenthol and menthol as cooling agent or flavoring agent. In particular, this invention relates to a coolant composition comprising menthyl lactate, neomenthol and menthol having a solidification point below +5°C, wherein the weight ratio of neomenthol to menthol is in the range from 1:1.25 to 1:2.5. The invention further discloses using a) l-menthyl l-lactate or l-menthyl d-lactate, more preferably l-menthyl l-lactate, and/or b) racemic neomenthol, and/or c) l-menthol, d-menthol or racemic menthol, more preferably racemic menthol, as preferred components of the cooling composition.

CN1805728B discloses a shampoo and body detergent composition which comprises (A) a refrigerant substance selected among menthol, menthone, camphor, pulegol, isopulegol, cineole, Japanese peppermint oil, peppermint oil, spearmint oil, and eucalyptus oil, (B) a substance giving a cool feeling and comprising an N-substituted p-menthane-3-carboxamide derivative, (C) an anionic surfactant, and (D) a water-soluble polymer and/or polyhydric alcohol. It optionally contains (E) a substance which gives a warm feeling. The composition is satisfactory in the effect of giving a refrigerant feeling and cool feeling during use and in the retention of that effect thereafter.

The isomers of menthol have similar but not identical odour and cooling profiles. In these isomers, (L)-menthol has the strong effect of cooling, is widely used in spices and medicine industry. The other isomers of L-menthol also have different sensory and odour profiles. The next most cooling efficacy after L-menthol is D-neomenthol and D-menthol and then followed by L-neoisomenthol, D-isomenthol and isopulegol.

Neomenthol, neoisomenthol, menthol and isomenthol differ slightly in their boiling points with a range of 211.7-218.6 0C. The isomers also differ in their physical characteristics, as at room temperature, D-neomenthol is a colourless liquid and isomenthol and menthol are white crystals. Isopulegol is a colourless liquid and have characteristic odour.

Mans H. Boelens et. al. in Perfumer and Flavorist (1993), Volume 18, No. 6 reported that opically active stereoisomers, optical antipodes or enantiomers can have different sensory qualities. The sensory properties of (d)- and (1)-menthol have been reviewed by Doll and Bournot andin more detail by Embergerand Hopp. According to Doll and Bournot the intensity for L-menthol was 3.3-3.5 timesgreater than the intensity for D-menthol. The cooling tasteeffect was significantly stronger for L-menthol than for D-menthol.An excellent study on the sensory qualities of the enantiomersof menthol, its epimers and acetates, was carriedout by Emberger and Hopp. They determined the sensoryqualities of the enantiomers of all menthol isomers,menthone, isomenthone and menthyl acetate and foundaclear difference between the odor qualities of the enantiomersof menthol. The differences in flavor thresholdsof the various pairs of enantiomers are small. Greaterdifferences can be seen in the cooling effect thresholds ofthe various enantiomer pairs.

Further, according to a review conducted by Leffingwell and Associates about Menthol-A cool place, reported the difference in cooling, fragrance and flavors for optical isomers of menthol. The review reported a large difference in the organoleptic properties between optical isomers of menthol. For example, the cooling threshold for L-Menthol is calculated as 0.8 ppm, while the D-menthol shows a high threshold value of 3.0 ppm. Similarly, L-Neomenthol shows a value of 25 ppm, whereas D-Neomenthol shows a value of only 2.5 ppm. Further, the flavor profile of L-Menthol shows a high value for mint flavor, whereas D-menthol shows maximum of bitter flavor.

The present inventors aim to develop a composition comprising reduced amount of L-Menthol in the composition and still having the cooling and odor profile of 99.0% L-Menthol in the composition by including some of the isomers of Menthol in the composition.

OBJECTS OF THE INVENTION
Accordingly, the main object of the present invention is to provide a unique composition of L-menthol in reduced amount and menthol isomers that maintains cooling initiation, cooling intensity and long lasting cooling sensation similar to 99% L-menthol in the composition.

It is another object of the present invention to provide a cost effective economic menthol composition having reduced percentage weight of L-menthol in the composition.

BRIEF DESCRIPTION OF FIGURES
Figure 1 illustrates comparative odour/perfume evaluation of Composition A, B, C, D and E with L-menthol (99.0%) in Balm (ZB)
Figure 2 illustrates comparative odour/perfume evaluation of Composition A, B, C, D and E with L-menthol (99.0%) in Cooling hair oil (NRO).
Figure 3 illustrates comparative sensory evaluation of Composition A, B, C, D and E with L-menthol (99.0%) in Balm (ZB).
Figure 4 illustrates comparative sensory evaluation of Composition A, B, C, D and E with L-menthol (99.0%) in Cooling Hair Oil (NRO).

SUMMARY OF THE INVENTION
Accordingly, in an aspect of the present invention, there is provided a menthol composition having sensory and odor profiles of 99% wt. ofL-menthol comprising L-menthol in an amount less than 98%, DL-Menthol, optionally isopulegol and optionally other menthol isomers.

In another aspect of the present invention there is provided a menthol composition having sensory and odor profiles of 99% wt. of L-menthol, comprising 96.3% wt. of L-menthol and 3.66% wt. of DL-menthol.

DETAILED DESCRIPTION OF THE INVENTION
The following description with reference to the accompanying drawings is provided to assist in a comprehensive understanding of various embodiments of the present disclosure as defined by the claims and their equivalents. It includes various specific details to assist in that understanding but these are to be regarded as merely exemplary. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the various embodiments described herein can be made without departing from the scope and spirit of the present disclosure. In addition, descriptions of well-known functions and constructions may be omitted for clarity and conciseness.

It is to be understood that the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component surface" includes reference to one or more of such surfaces.

The terminology used herein is for the purpose of describing particular various embodiments only and is not intended to be limiting of various embodiments. It will be further understood that the terms "comprises" and/or "comprising" used herein specify the presence of stated features, integers, steps, operations, members, components, and/or groups thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, members, components, and/or groups thereof. Also, expressions such as "at least one of," when preceding a list of elements, modify the entire list of elements and do not modify the individual elements of the list.

The invention is directed to the development of a cost effective economic menthol composition having cooling and odor profile of 99.0 % wt of L-Menthol in a composition having reduced amount of L-menthol in the composition.

In an embodiment of the present invention there is provided a menthol composition having reduced amount of L-Menthol providing sensory and odor profiles of 99.0% wt of L-menthol.

The menthol composition essentially comprises L-menthol and DL-Menthol.

The menthol composition essentially comprises L-menthol in an amount less than 98% wt., DL-Menthol in an amount ranging from about 0.3% wt. to about 6% wt.
DL-menthol is a racemic mixture of menthol isomers and contains 51.69% L-Menthol, 46.65% D-Menthol along with 0.2% Isopulegol, and traces of D-Neomenthol and D-Isomenthol.

The present menthol composition although comprises L-menthol in an amount less than 99.0%, but exhibits sensory and odor profiles of 99.0% wt. L-menthol.

The menthol composition optionally comprises other menthol isomers, in an amount of 0.45% wt., wherein the other menthol isomers are selected from D-Menthol, D-Neomenthol and D-Isomenthol and combinations thereof.

The menthol composition optionally comprises Isopulegol in an amount ranging from about 3.5-0.25% wt.

In a preferredembodiment the menthol composition comprises 95.0-98.0% L-Menthol, DL-Menthol in an amount ranging from about 0.3% wt to about 6% wt; and optionally menthol isomers in an amount of 0.45% wt.

In a more preferred embodiment the menthol composition comprises 96.3%wt of L-menthol and 3.66% wt. of DL-menthol.

There is further provided a method for preparation of the menthol composition comprising reduced amount of L-Menthol and having sensation and odorprofile similar to 99.0% of L-menthol.

The method for preparation of the menthol composition comprises mixing of L-Menthol in an amount less than 98% with DL-menthol in an amount ranging from about 0.3% wt. to about 6% wt.

The method for preparation of the menthol composition comprises optionally adding menthol isomers and optionally adding isopulegol in the composition.

The menthol composition comprises adding of L-menthol in reduced amount furtherreduces the cost of production of any perfumed formulation by Rs. 10 -30/- per Kg.

The present invention therefore provides a method to reduce the developmental cost of a cooling and perfumed formulation without affecting the quality of the formulation.

The present invention is further illustrated with examples.

Examples
RawMaterials: Natural L-Menthol and DL-Menthol were procured from Norex Flavours Pvt. Ltd., while DL-Menthol is also manufactured by BASF India Pvt. Ltd.

Example 1: Preparation of menthol composition having L-menthol in reduced amount
Five compositions A, B, C, D and E were prepared by homogenisation of menthol isomers and isopulegol at 45-60oC, having varied amount of L-menthol. The isomers and isopulegol were procured from various commercial sources.

Sample A is prepared by blending 98.25% wt of L-Menthol, and 1.67% wt of DL-Menthol at 55oC.

Sample B is prepared by blending 98.89% wt of L-Menthol, 0.316% wt of Isopulegol and 0.45% wt of D-Neomentholat 55oC.

Sample C is prepared by blending 97.73% wt of L-Menthol, 1.17% wt. of DL-Menthol, 0.316% wt of Isopulegol and 0.45% wt of D-Neomentholat 55oC.

Based on sensory evaluation and odour profile in Balms and Hair Oils, Sample A was taken up as standard for further cost benefit purpose. Menthol Sample D and E were prepared on the basis of raw materials used in Sample A.

Sample D is prepared by blending 96.33% wt of L-Menthol, 3.66% wt of DL-Menthol at 55oC.

Sample E is prepared by 94.88%% wt of L-Menthol, and 5.12% wt of DL-Menthol at 55oC.

All the components of the sample were identified by GC-MS spectra, elution pattern of compounds in GC chiral column, compared with the literature data of isomers present in M. arvensis&M. piperita and structural (Chair conformation) stability of isomers.All the samples were analyzed by GC with chiral column, CP-Chirasilof Agilent J&W GC columns (part number: CP7502).

All the isomersof menthol were identified by having different Cooling and Odor profilesas per literature data as illustrated in Table 1. Table 1 shows the percentage of the isomers of menthol identified in different samples of the Menthol composition along with their costs, cooling and odor profile.

Table 1A. Composition Charts of Sample A-E (GC analysis data, Cooling and Odour profile of isomers)
GC Analysis of samples A-E
Samples L-Menthol (%) D-Menthol (%) Isopulegol (%) D-Neomenthol (%) D-Isomenthol (%)
Menthol Sample A 99.25 0.38 0.16 0.13 0.08
Menthol Sample B 98.92 -- 0.4 0.50 0.27
Menthol Sample C 98.95 0.19 0.36 0.46 0.20
Menthol Sample D 97.73 1.75 0.19 0.1 0.05
Menthol Sample E 97.22 2.36 0.19 0.11 0.06
L-Menthol D-Menthol Isopulegol D-Neomenthol D-Isomenthol
Cost of Isomers (Rs/Kg) 1270/- 500/- 2750/- 950/- 1000/-
# Cooling Profile
(Threshold in ppm) 0.8 3 * Cooling potency < D-menthol 2.5 7
# Odour Profile Fresh, Sweet, Minty Fresh, Sweet-Minty with Musty, Bitter, Phenolic and Herbaceous notes Fresh, Minty, Herbaceous Sweet, Musty, Fresh, Minty Musty, Sweet, Herbaceous, Earthy-Camphoraceous,
#http://www.leffingwell.com/chirality/menthols.htm
* The cooling potency of Isopulegol is < D-Menthol (by Cell Based assay) -Sourced from: British Journal of Pharmacology, 141, 2004, 737-745.

The composition Samples A, D and E although do not contain menthol isomers like Isopulegol, D-Neomenthol and D-Isomenthol, but traces are found during GC-MS analysis, which may be due to impurity of the compounds.

The Samples A, D and E contains only L-menthol along with the racemic mixture of menthol, i.e., DL-Menthol. The composition samples A, D and E shows presence of L-Menthol isomers due to the presence of racemic mixture of Menthol isomers.
The major chemical constituents in composition A in the decreasing order are L-menthol, D-menthol, Isopulegol and D-neomenthol. In composition B, it is L-menthol, isopulegol, D-neomenthol and D-isomenthol whereas in composition C, it is L-menthol, D-neomenthol, isopulegol, D-isomenthol. In composition D, the chemical constituents in decreasing order are L-menthol, D-menthol, isopulegol and D-neomenthol, and in composition E, it is L-menthol, D-menthol, isopulegol and D-neomenthol.

The least threshold value of the composition samples represents highest cooling capability of the compositions. The threshold values of L-Menthol, D-Neomenthol, D-Menthol and D-isomenthol are in the order of 0.8<2.5<3.0<7.0. The cooling potency is in the order of L-Menthol