IL42735A - Compositions containing (cyclo) alkyl alkyl sulfones and sulfoxides having a physiological cooling effect - Google Patents

Description

42735/3 COMPOSITIONS CONTAINING (CYCLO) ALKYL ALKYL SULFONES AND SULFOXIDES HAVING A PHYSIOLOGICAL COOLING EFFECT Field of Invention This invention relates to topical and other compositions having a physiological cooling effect on the skin and on the mucous membranes of the body, particularly the nose, mouth, throat and gastrointestinal tract.

Background of the Invention Menthol is well known for its physiological cooling effect on the skin and mucous membranes of the mouth and has been extensively used as a flavouring agent (menthol being a major constituent of oil of peppermint) in foodstuffs, beverages, dentifrices, mouthwashes, etc. and as a component in a wide range of toiletries, liniments and lotions for topical application. Menthol is also a well known tobacco additive for producing a "cool" sensation in the mouth when smoking.

It is well established that the "cooling" effect of menthol is a physiological effect due to the direct action of menthol on the nerve endings of the human body 1 responsible for the detection of hot or cold and is not due to latent heat of evaporation. It is believed that the menthol acts as a direct stimulus on the cold · receptors at the nerve endings which in turn stimulate the central nervous system.

Although menthol is well established as a physiological coolant its use, in some compositions, is circumscribed by its strong minty odour and its r ative volatilit .

Other compounds have been mentioned in the art as having a physiological cooling effect e.g. 2,4,6-tr1inethyl-4-heptanol (Parfums~Cosnet1ques-Savons, May 1956, pages 17-20) and N,N-diethyl-2-ethyl utanam1de (French Patent No. 1,572,332).

Summary of the Invention According to the Invention we have found a group of su hones and sulphoxides which are capable of stimulating the cold receptors of the nervous system of the body* 42735/2 Detai led Description of Invention The compounds having this physiological cooling effect and usable according to this Inve^lon are acyclic and cyclic sulphoxides and sulphones of the formula: RS0XR' where R' Is alkyl , optionally containing carboxy or al koxoy- carbonyl substituents ; x 1s 1 or 2; and R Is either Rl I ¾ - C - R3 where Rj 1s H or Cj-Cg alkyl ; R2 1s ^-Cg alkyl ; R3 Is Cj-Cg alkyl ; R^ , R2 and R3 together providing a total of from 3-15 carbon atoms, preferably 5-10 carbon atoms, and R- , R2« R3 and R1 together providing a total of from 6-18 carbon atoms; or where n 1s 0 or an Integer of from 1-4; R* 1s Cj-C5 alkyl , and where, when n Is greater than 1 , the R* groups may be the same or different; the total number of carbon atoms provided by R* and R1 taken together being from 2-12 inclusive, Preferred acyclic compounds are sulphoxides and sulphones of the formula: where x is 1 or 2, R is alkyl and contains up to 8 carbon atoms, R^ is hydrogen or C^-C^ alkyl, and and R-j are each C^-Cg alkyl, R , R^ , R2 and R^ t providing a total of from 8-14 carbon atoms.

The preferred cyclic compounds are those where n alkyl ©r- ¾ydr-oxyalky-l or o 6 carbon atoms.

Particularly preferred cyclic compounds made and used according to this invention are p-menth-3-yl n-butyl sulphoxide, n-butyl 1-isobutylcyclohexyl sulphoxide, n-hexyl 1-isobutylcyclohexyl sulphoxide, n-butyl 1-iso-amylcyclohexyl sulphoxide and n-hexyl 1 ,2-diethylcyclo-hexyl sulphoxide.

Generally speaking the sulphoxides, i.e. compounds where x is 1 , are to be preferred over the corresponding sulphones, i.e. the compounds where x is 2.

Broadly speaking, therefore, the invention provides compositions, in particular ingestible compositions and compositions for topical application, capable of stimulating the cold receptors of the nervous system of the human body comprising an effective amount of a cold receptor stimulant and a carrier therefor, the stimulant comprising one or more of the above defined sulphoxides or sulphones.

The sulphoxides and sulphones used in the invention may be readily prepared by conventional methods, such as by the oxidation of the corresponding sulphide, e.g. with hydrogen peroxide in glacial acetic acid.

Many of the compounds used in this invention exhibit geometric and/or optical isomerism and, depending on the starting materials and the methods used, the compounds used in this invention may be isomerically pure, i.e. consisting of one geometric or optical isomer, or they may' be a mixture of isomers. In those compounds where isomerism occurs the degree of cooling produced by the compounds will differ ά between isomers, in which case one or other isomer will be preferred.

The compounds of the above formulae find utility in a wide variety of compositions for consumption by or application to the human body. Broadly speaking, these compositions can be divided into comestible and topical compositions, both terms being taken in their broadest possible sense. Thus comestible is to be taken as including not only foodstuffs and beverages taken into the mouth and swallowed, but also other orally ingested compositions taken for reasons other than their nutritional value, e.g. indigestion tablets, antacid preparations, laxatives etc. Comestible compositions are also to be taken to include edible compositions taken by mouth, but not necessarily swallowed, e.g. chewing gum. Topical compositions are to be taken as including not only compositions such as perfumes, powders i and other toiletries, lotions, liniments, oils and ointments applied to the external surfaces of the human body, whether for medical or other reasons, but also compositions applied to, or which, in normal usage, come in contact with, internal mucous membranes of the body, such as those of the nose,mouth, or throat, whether by direct or indirect application or inhalation, and thus include nasal and throat sprays, dentifrice, mouthwash and gargle compositions. Also included within the present invention are toilet articles such as cleansing tissues and toothpicks"impregnated or coated with the active cooling compound; A further class of compositions included within the scope of this invention are tobacco and associated articles e.g. pipe and cigarette filters, especially filter tips for cigarettes.

The compositions of this invention will contain an amount of the sulphone or sulphoxide sufficient to stimulate the cold receptors in the areas of the skin or mucous membrane with which the compositions come into contact and thereby promote the desired cold sensation. The degree and longevity of cooling sensation varies from compound to compound and therefore the quantity of stimulant used in each composition will vary widely. As a guide, it may be said that, with the more active compounds of the invention, a significant cooling sensation is achieved upon application to the skin of as little as 0.05 ml. of a 0.5 weight percent solution of the active ingredient in ethanol. For the less active compounds a significant cooling effect is achieved only with more concentrated solutions, e.g. containing 5.0% by weight or more of the active ingredient.

Typical acyclic sulphoxides and sulphones falling within · the above formulae and utilisable in the compositions of this invention are indicated in the following Table 1 together with an indication of their relative activities as a stimulant for the _cold receptors of the nervous system of the human body. The greater the number of stars, the greater the activity, i.e. the greater the cooling effect produced by application of a given quantity of the compound. Typical cyclic compounds are listed in Table 2.

Table 1 C2¾ n-C^ * * * X R1 R2 R1 Activity 1 II II It * * 1 II It II * * n"C6H 3 CH, 1 II II tl -CH(CH2)2CH3 * * C2H5 1 II It II -CHCH2CH2CH3 1 II sec-C^Hg tt * ·* 1 II iso-CjHy n-CjHy It * * 1 n-C3H? n-CjHy II n-C3Hy * * 1 iso-C^H^ It II II * * 1 CH, CH2CH C02C H^ 5 °2H5 C2H5 x R1 R2 R3 R Activity †--CHj- - - -¾¾ eHgSHgGH * -I—« —11— i) —eii^Gii^OH *. 1 " C2H5 n-C Hg * 1 II n II iso-C5H1n * 1 CH3 - CH, * C2H5 2 II II n-C6H13 C2¾ 2 It iso- II It * 2 II * C2¾ C2¾ C2H5 Table 2. n-hexyl 1-isobutylcyclohexyl sulphoxide ·* ·* * ■¾■ n-butyl 1-isobutylcyclohexyl sulphoxide * # * n-butyl 1-isoamylcyclohexyl sulphoxide * * * p-menth-3-yl n-butyl sulphoxide * # * n-hexyl 1 , 2-diethylcyclohexyl sulphoxide * * # p-menth-3-yl ethyl sulphoxide p-menth-3-yl isopropyl sulphoxide * * p-menth-3-yl methyl sulphone * * ethoxycarbonylmethyl p-menth-3-yl ethylcailraxym^ hyl sulphoxide * * ethoxycarbonylmethyl p-menth-3-yl et¾yiearb«xyme-tnyi sulphone * * isopropyl 2,5-dimethylcyclohexyl sulphoxide * * isopropyl 2-methylcyclohexyl sulphoxide * * n-propyl 2-methylcyclohexyl sulphoxide * * isopropyl 3-methylcyclohexyl sulphoxide * * isopropyl 4-methylcyclohexyl sulphoxide * * 3,3,5-trimethylcyclohexyl sec.-butyl sulphoxide * * p-rmenth-3-yl methyl sulphoxide * p-aeftth—3—yl--3—hy^ex-^yl--sulphoxitte- *— p-menth-3-yl isopropyl sulphone * methyl 2,5-dimethylcyclohexyl sulphoxide * methyl 2,5-dimethylcyclohexyl sulphone * isopropyl 2,5-dimethylcyclohexyl sulphone * methyl 2,6-dimethylcyclohexyl sulphoxide * methyl 2,6-dimethylcyclohexyl sulphone v * isopropyl 2-methylcyclohexyl sulphone * n-octyl 2-methylcyclohexyl sulphoxide * isopropyl 3-methylcyclohexyl sulphoxide * n-butyl .1-isobutylcyclohexyl sulphone * isobutyl 2-n-butylcyclohexyl sulphoxide * n-hexyl 2-n-butylcyclohexyl sulphoxide * isobutyl 2-n-butylcyclohexyl sulphone * n-hexyl 2-n-butylcyclohexyl sulphone * n-butyl -isoamylcyclohexyl sulphone * n-propyl 3,3,5-trimethylcyclohexyl sulphone * tert-butyl 3,3, 5-trimethylcyclohexyl sulphone * n-hexyl 1,3-dimethylcyclohexyl sulphone * n-hexyl 1,2-diethylcyclohexyl sulphone * p-menth-3-yl carboxymethyl sulphoxide * In formulating the compositions of this invention the sulphoxide or sulphone will usually be incorporated into a carrier which may be completely inert or which may be or contain other, active ingredients. A wide variety of carriers will be suitable, depending upon the end use of the composition, such carriers including solids, liquids, emulsions, foams and gels. Typical carriers for the sulphoxides and sulphones include aqueous or alcoholic solutions; oils and fats such as hydrocarbon oils, fatty acid esters, long chain alcohols and silicone oils; finely divided solids such as starch or talc; cellulosic materials such as paper tissue; tobacco; low-boiling hydrocarbons and halohydrocarbons used as aerosol propellants; gums and natural or synthetic resins.

In most compositions according to the invention the carrier will be or contain as an adjuvant one or more of the following: an antacid, antiseptic or analgesic, a flavourant, colourant, or odourant, or a surfactant.

The following illustrate the range of compositions into which the compounds of this invention can be incorporated: 1. Edible or potable compositions including alcoholic and non-alcoholic beverages, confectionery, chewing gum; cachous; ice cream; jellies; 2. Toiletries including after shave lotions, shaving soaps, creams and foams, toilet water, deodorants and antiperspirants, "solid colognes", toilet soaps, bath oils and salts, shampoos, hair oils, i 1 talcum powders, face creams, hand creams, sunburn lotions, cleansing tissues, dentifrices, toothpicks, mouthwashes, hair tonics, eyedrops; 3. Medicaments including antiseptic ointments, hemorrhoidal p±ie ointments, liniments, lotions, decongestants, counter-irritants, cough mixtures, throat lozenges, antacid and indigestion preparations, oral analgesics; k. Tobacco preparations including cigars, cigarettes, pipe tobacco, chewing tobacco and snuff; tobacco filters, "especially filter tips for cigarettes. 5. Miscellaneous compositions such as water soluble adhesive compositions for envelopes, postage stamps, adhesive labels etc.

. Particular preparations according to the invention are discussed in more detail below.

Edible and Potable Compositions The edible and potable compositions of this invention will contain the active cooling compound in combination with an edible carrier and usually a flavouring or colour^ ing agent. The particular effect of the compounds of the invention is to create a cool or fresh sensation in the mouth, and in some cases, even in the stomach, and therefore they find particular utility in sugar-based confectionery such as chocolate, boiled sweets, mints and candy, in ice cream and jellies and in chewing gum. The formulation of such confections will be by ordinary techniques and according to conventional recipes and as such forms no part of this invention. The active compound will be added to the recipe at a convenient point and in amount sufficient to produce the desired cooling effect in the final product. As already indicated, the amount will vary depending Upon the particular compound, the degree of cooling effect desired and the strength of other flavourants in the recipe. For general guidance, however, amounts in the range 0.05 to 2.5% by weight based on the total composition will be found suitable.

Similar considerations apply to the formulation of beverages. Generally speaking the compounds will find most utility in soft drinks e.g. fruit squashes, lemonade, cola etc., but may also be used in alcoholic beverages. The amount of compound used will generally be in the range 0.02 to 0.5% by weight based on the total composition.

Toiletries Because of the cooling sensation imparted to the skin, a major utility of the compounds of this invention will be in a wide range of toilet preparations and toilet articles. The particular preparations discussed below are to be taken as exemplary.

A major utility will be in after shave lotions, toilet water etc., where the compound will be used in I alcoholic or aqueous alcoholic solution, such solutions usually also containing a perfume or mild antiseptic I or both. The amount of sulphoxide or sulphone added to the formulation will usually be in the range 0.1 to 5.0%' by weight based on the total composition.

Another field of utility will be in soaps, shampoos, bath oils etc. where the compound will be used in combination with an oil or fat or a natural or synthetic surfactant e.g. a fatty acid salt or a lauroylsulphate salt, the composition usually also containing an essential oil or perfume. The range of soap compositions will include soaps of all kinds e.g. toilet soaps, shaving soaps, shaving foams etc. Usually the active compound will be added to the formulation in amount of from 0.1 to .0% by weight.

A further class of toilet compositions into which the compounds of this invention may be incorporated includes cosmetic creams and emollients, such creams and emollients usually comprising a base emulsion and optionally a range of ingredients such as wax, preservative, perfume, antiseptics, astringents, pigments etc. Also included within this class are lipstick compositions such compositions usually comprising an oil and wax base into which c other - , the compound can be incorporated along with the IrrmniH--<_i>nvJi?K -vc.MJ ingredients ΐΐϋϊΐ of such compositions, apart from the incorporation of the active compound, usually in an amount of from 0.05 Compositions or oral hygiene containing the cold 10 receptor stimulants of this invention include mouthwash, gargle and dentifrice compositions. The first two may be considered togethe _and will usually comprise an aqueous, alcbholic or aqueous-alcoholic solution of an antiseptic often coloured or flavoured for palatability, to which 15 the compound is added in an amount of from 0.05 to 0.5% by weight.

Dentifrice compositions may be of the solid block, powder, paste or liquid type and will usually comprise a finely divided abrasive or polishing material, e.g. 20 precipitated chalk, silica, magnesium silicate, aluminium hydroxide or ether similar materials well known in the art, and a detergent or foaming agent. Optional ingredients which may also be included are flavouring agents and colourants, antiseptics, lubricants, thickeners, 2 emulsifiers or plasticizers. The amount of active compound added in such compositions will generally be from 0.1 to 2.5% by weight based on the total composition.

Medicaments Because of their cooling effect on the skin and on the mucous membranes of the mouth, throat and nose and of the gastrointestinal tract the compounds of this invention may be used in a variety of oral medicines, nasal and throat sprays, and topical compositions, particularly where a counter-irritant is required. In particular the compounds of the invention may be formulated into antacid and indigestion remedies, in particular those based on sodium bicarbonate, magnesium oxide, calcium or magnesium carbonate, aluminium or magnesium hydroxide or magnesium trisilicate. In such compositions the compounds will usually be added in an amount of from 0.05 to 1.0?o by weight.

The compounds of the invention may' also be included in oral analgesic compositions e.g. with acetylsalicylic acid or its salts, and in nasal decongestants e.g. those containing ephedrine.

Tobacco Preparations The compounds of this invention may be incorporated directly into tobacco to give a cool effect when smoking but without the attendant strong and characteristic odour which is associated with mentholated tobacco and cigarettes. However, a more advantageous utilisation of the compounds of- this invention is in pipe or cigarette filters, in particular, filter tipped cigarettes. The pad of filter material, which may be of any of the well known types, e.g. cellulose acetate, paper, cotton Compositions according to the invention are illustra ted by the following Examples.

Example 1 After Shave Lotion An after shave lotion was prepared according to the following recipe by dissolution of the ingredients in the liquid and cooling and filtering: Denatured Ethanol ' 75% Diethy^ hthalate 1.0% Propylene Glycol 1.0% Lactic Acid 1.0% Perfume 3.0% Water to 100% Into a sample of the base, lotion was added 2.0% by weight based on the weight of the sample of 3-methylpent-3-yl isopropyl sulphoxide.

When the final solution was applied to the face a clearly noticeable cooling effect became apparent after EXAMPLE 2 Toilet Water A toilet .water was prepared according to the following recipe: Denatured Ethanol 75.0% Perfume 5.0% Water to 100% To the recipe was added 3·0%, based on the total composition, of 3-methylhex-3-yl isopropyl sulphoxide.

As with the after shave lotion, a cooling effect was clearly noticeable on the skin well after the termination of any cooling effect attributable to the evaporation of the alcoholic carrier.

EXAMPLE 3 Eye Lotion An eye lotion was prepared containing the following ingredients: Witch Hazel 12.95% Boric Acid 2.00% Sodium Borate 0.50% Allantoin 0.05% Salicylic Acid 0.025% Chlorobutol 0.02% Zinc Sulphate 0.004% Water to 100% To the formulation was added 0.005%, based on the (ethoxycarbonyl )- J total composition, of 3-methylpent-3-yl 2-et«^-b©ai!l©xy-- J ethyl sulphoxide. When used to bathe the eyes a cool fresh sensation is apparent on the eyeball and eyelids.

EXAMPLE 4 Antiseptic Ointment An ointment was prepared according to the following formulation: Cetyltrimethyl ammonium 4.0% bromide Cetyl Alcohol 6.0% Stearyl Alcohol 6.0% White Paraffin 14.0% Mineral Oil 21.0% Water to 100% The ingredients were mixed, warmed to 40°C and emulsified in a high speed blender. Added to the mixture during blending was 3.0% of 3-methylhex-3-yl n-octyl sulphoxide." The final ointment when applied to the skin gave rise to a cooling effect.

EXAMPLE 5 Antipruritic Ointment The following ingredients were warmed together to form a homogeneous melt: Methyl salicylate 50,20% White Beeswax 25.0% Anhydrous Lanolin 25.0% To the melt was added 3.0% of 3-methylpent-3-yl pent-2-yl sulphoxide and the mixture then allowed to solidify. A soft ointment resulted having a soothing effect on the skin accompanied by a cooling effect.

EXAMPLE 6 Cleansing Tissue A cleansing liquid was prepared having the formulation: Triethanolamine Lauryl 1.0% Sulphate Glycerol 2.0% Perfume .95% Water to 100% To this liquid was added 3.0% of n-hexyl 2,3-dimethylbut-3-yl sulphoxide. A paper tissue was then soaked in the liquid.

When the impregnated tissue was used to wipe the skin a fresh cool sensation developed on the skin after a short interval.

EXAMPLE 7 Cigarette Tobacco A proprietary brand of cigarette tobacco was sprayed with an ethanolic solution of hex-3-yl isopropyl sul-phoxide and was rolled into cigarettes each containing approximately .05 mg. of active compound. Smoking the impregnated cigarettes produced a cool effect in the mouth characteristic of mentholated cigarettes but without any attendant odour other than that normally i associated with tobacco.

; Impregnation of the filter tip of a proprietary brand of tipped cigarette with 0.01 mg. of the same sulphoxide produced a similar effect.

EXAMPLE 8 Toothpaste The following ingredients were mixed in a blender Dicalcium phosphate Sodium Lauryl Sulphate Glycerol Sodium carboxymethyl cellulose Citrus flavourant Sodium saccharin Water Shortly before completion of the blending operation 0.5% by weight of 3-methylpent-3-yl n-hexyl sulphoxide was added to the blender.

When applied as a toothpaste a pleasant cooling effect is noticed in the mouth.

EXAMPLE 9 After Shave Lotion An after shave lotion was prepared according to the following recipe by dissolution of the ingredients in the liquid and cooling and filtering:- Denatured Ethanol 75° Diethyl Phthalate 1.0% Propylene Glycol 1.0% Lactic Acid 1.0% Perfume 3.0% Water to 10096 Into the base lotion was added 3% by weight based on the total composition of n-butyl 3-methylhept- -yl sulphone.

When the final lotion is applied to the face a clearly .noticeable cooling effect becomes apparent after a short interval of time.

EXAMPLE 0 Eye Lotion An eye lotion was prepared containing the following ingredients :- Witch Hazel 12.95% Boric Acid 2.00% Sodium Borate 0.50% Allantoin 0.05% Salicylic Acid 0.025% Chlorobutol 0.02% Zinc Sulphate 0.004% Water to 100% To the formulation was added 0.005%, based on the total composition of 2-methylnon-3-yl propyl sulphone When used to bathe the eyes a cool fresh sensation is apparent on the eyeball and eyelids.

EXAMPLE 11 Toothpaste The following ingredients were mixed in a blender:- Dicalcium Phosphate 40% Dihydrate Sodium Lauryl Sarcosinate 1.5% Glycerol 30% Sodium carboxymethyl 1.5% Cellulose Saccharin Sodium 0.2% Sodium Benzoate 0.2% Water 26.6% Shortly before completion of the blending operation 0.5% by weight of n-butyl 2-methylhex-3-yl sulphone was added to the blender.

When applied as a toothpaste, a cooling effect is noticed in the mouth.

EXAMPLE 12 Soft Sweet Water was added to icing sugar at 40°C to form a stiff paste. 0.1% of 4-n-propylhept-4-yl n-propyl sulphoxide was then stirred into the paste and the mixture allowed to set. A soft sweet mass resulted having the characteristic cooling effect in the mouth of peppermint but without the minty flavour or odour.

EXAMPLE 13 Antiseptic Ointment An ointment was prepared according to the following formulation:- Cetyltrimethy!jQammonium 4.0% bromide Cetyl Alcohol 6.0% Stearyl Alcohol '6.0% White Paraffin 14.0% Mineral Oil * 21.0% Water to 100% The ingredients were mixed, warmed to 60°C and emulsified in a high-speed blender. Added to the mixture during blending was 4% of n-hexyl 3-methylpent-3-yl sulphone .

The final ointment when applied to the skin gave rise to a marked cooling effect.

EXAMPLE 14 Aerosol Shaving Soap according to the following recipe : Stearic Acid 6.3% Laurie Acid 2-796 Triethanolamine 4.6% Sodium Carboxymethyl Cellulose 0.1 Sorbitol 5.0% Water to 100% Perfume 0.5% The composition was prepared by fusing the acids in water, adding the triethanolamine, cooling and adding the other constituents. To the mixture v/as then added 0.5% of n-propyl 2-methylnon-3-yl sulphoxide. The composition was then packaged in an aerosol dispenser under pressure of a butane propellant.

When used in shaving a fresh cool sensation was distinctly noticeable on the face.

EXAMPLE 1 Toilet Water A toilet water was prepared according to the following recipe :- Denatured Ethanol 75.0% Perfume 5.0% Water to 100% To the recipe was added 4.0%, based on the total composition, of n-hexyl 2 , 3-dimethyl^but-2-yl sulphoxide.

As with the after shave lotion, a cooling effect was clearly noticeable on the skin well after the termination of any cooling effect attributable to the evaporation of the alcoholic carrier.

EXAMPLE 16 Deodorant Composition A deodorant composition suitable for formulation and dispensing as an aerosol under pressure of a suitable propellant was formulated according to the following recipe :- Denatured Ethanol 96.954 Hexachlorophene 2.0% Isopropyl myristate 1.0% Perfume 0, To the composition was added 3% by weight of n-butyl 3-ethylpent-3-yl sulphoxide. Application of the final composition gave rise to a definite coolin sensation on the skin.

EXAMPLE 7 Hair Shampoo .Sodium lauryl other sulphate, 10 g. , was dispersed in 90 g. water in a high speed mill. To the dispersion was added .5% by weight of n-butyl 3-methylhept-4-yl sulphoxide. When the hair is washed using the shampoo a fresh, cool sensation is noticed on the scalp.

EXAMPLE 18 Solid Cologne A solid cologne was formulated according to the following recipe :- Denatured Ethanol j Propylene Glycol 3.0% j Sodium Stearate 5.0% I Perfume 5.0% Water to 100% The sodium stearate was dissolved by stirring in a warm mixture of the ethanol, propylene glycol and water.

To the solution was added the perfume and 4.0% of sec. butyl 2, 6-dimethylhept-4-yl sulphoxide and the mixture then allowed to solidify into a waxy cake.

When applied to the forehead a distinct cooling effe is noticeable.

EXAMPLE 19 Mouthwash A concentrated mouthwash composition was prepared according to the following recipe: Ethanol Borax Sodium Bicarbonate Glycerol Flavourant Thymol Water To the composition was added 0.2% of n-hexyl 3-methylpent-3-yl sulphoxide.

When diluted with approximately 10 times its own volume of water and used to rinse the mouth a cooling effect is obtained in the mouth.

EXAMPLE 20 Soft Drink A soft drink concentrate was prepared from the following recipe :- Pure orange juice 60% Sucrose 10% Saccharin 0.2% Orange flavouring 0.1% Citric acid 0.2% Sulphur dioxide trace amount Water to 100% To the concentrate was added 0.05% of methyl hex-3-yl sulphoxide.

The concentrate was diluted with water and tasted. An orange flavour having a pleasaily cool after-effect was obtained.

EXAMPLE 2 Boiled Sweet 99.5% sucrose and 0.5% citric acid were carefully fused together in the presence of a trace of water.

Just before casting the melt onto a chilled plate 0.1% of di-sec. butyl sulphoxide was rapidly stirred in. The melt was then cast. A boiled sweet resulted having a marked cooling effect on the mouth.

EXAMPLE 22 The following ingredients \ere ground together Magnesium carbonate 9. 55o Sorbitol ' 49Λ% Saccharin 0.~L% Talc 1.0% Added to the mixture during grinding was 0.1% of β -hydroxyethyl hept-3-yl sulphoxide. After mixing the mixture was pressed into tablets.

Taken by mouth and swallowed the tablets produced, after a short interval of time, a noticeable cooling effect in the stomach.

EXAMPLE 23 Cleansing Tissue A cleansing liquid was prepared having the formulation:- Triethanolamine Lauryl 1.0o Sulphate Glycerol 2.0% Perfume 0.95 Water to 100% To this liquid was added % of n-hexyl 3-methylpent-3-yl sulphone. A paper tissue was then soaked in the liquid.

When the impregnated tissue was used to wipe the skin a fresh cool sensation developed on the skin after a short interval.

EXAMPLE 24 Hydrophilic Ointment A hydrophilic ointment was prepared having the, following formulation: Propylene Glycol 12% -Octadecanol 25 White Soft Paraffin 25% Sodium Lauryl Sulphate 1% Water to 100% The sodium lauryl sulphate was added to the water and heated to 60°C. The paraffin was melted by heating to 60°C and was then added to the sodium lauryl sulphate mixture with stirring. Propylene glycol and 1-octadecanol were then added to this mixture.

To the resultant mixture was added 3% of 1-ethyl-butyl 3-methylpent-3-yl sulphoxide. The final ointment when applied to the skin gave rise to a marked cooling effect.

EXAMPLE 25 Liniment A liniment was prepared according to the following formulation:- Methyl salicylate 25% Eucalyptus Oil 10% Arachis Oil to 100% To the composition was added 4% of n-propyl 2-methylnon-3-yl sulphoxide.

When the final composition was applied to the skin a clearly noticeable cooling effect became apparent afte^. a short interval of time.

EXAMPLE 26 Toothpick The tip of a wooden toothpick was impregnated with an alcoholic solution containing n-hexyl 2, 3-dimethylbut- 3-yl sulphoxide in an amount sufficient to depositjf on the toothpick 0.10 mg. of the sulphoxide. The impregnated -toothpick was then dried. When placed against the tongue, a cooling effect is noticed after a short period of time.

EXAMPLE 27 After Shave Lotion An after shave lotion was prepared according to the following recipe by dissolution of the ingredients in the liquid and cooling and filtering: Denatured Ethanol 75° Diethy^hthalate .0% Propylene Glycol 1.0% Lactic Acid 1.096 Perfume 3.0% Water to 100% I Into separate, samples of the base lotion were added 2.0% by weight based on the weight of the sample of p-menth-3-yl methyl sulphoxide and p-menth-3-yl methyl sulphone.

When the final solutions were applied to the face a clearly noticeable cooling effect became apparent after a short interval of time.

EXAMPLE 28 Toilet Water A toilet water was prepared according to the following recipe: Denatured Ethanol 75.0% Perfume 5.0% Water to 100% To the recipe was added 3.0%, based on the total composition, of p-menth-3-yl isopropyl sulphoxide.

As with the after shave lotion, a cooling effect was clearly noticeable on the skin well after the termination of any cooling effect attributable to the evaporation of the alcoholic carrier.

EXAMPLE 29 Eye Lotion |An eye lotion was prepared containing the following Witch Hazel 12.95% Boric Acid 2.00% Sodium Borate 0.50% Allantoin 0.05% Salicylic Acid 0.025% Chlorobutol 0.02% Zinc Sulphate 0.004% Water to 100% To the formulation was added 0.005%, based on ethoxycarbony1methy1 the total composition, of e*hyl^pfe€5^9t4-yli-p-menth-3-yl sulphoxide. When used to bathe the eyes a cool fresh sensation is apparent on the eyeball and eyelids.

EXAMPLE 30 Antiseptic Ointment An ointment was prepared according to the following formulation:- Cetyltrimethyl ammonium bromide 4.0% Cetyl Alcohol 6.0% Stearyl Alcohol 6.0% White Paraffin 14.0% Mineral Oil 21.0% Water to 100% The ingredients were mixed, warmed to 40°C and emulsified in a high speed blender. Added to the mixture during blending was 3·0% of 3-methylcyclohexyl sulphoxide. final ointment when applied to the skin gave rise to a cooling effect.

EXAMPLE 31.

Antipruritic Ointment The following ingredients were warmed together to form a homogeneous melt:- Methyl salicylate .50.0% White Beeswax 25.0% Anhydrous Lanolin 25.0% To the melt was added 3·0% of n-butyl 1-isoamyl-cyclohexyl sulphoxide and the mixture then allowed to solidify. A soft ointment resulted having a soothing effect on the skin accompanied by a cooling effect.

EXAMPLE 32 Cleansing Tissue A cleansing liquid was prepared having the formulation: Triethanolamine Lauryl 1.0% sulphate Glycerol 2.0% Perfume .95% Water to 100% To this liquid was added 3·0>ο of 2, 5-dimeth lcyclo-hexyl methyl sulphoxide. A paper tissue was then soaked in the liquid.

When the impregnated tissue was used to wipe the skin a fresh cool sensation developed on the skin after a short interval.

EXAMPLE 33 Cigarette Tobacco A proprietary brand of cigarette tobacco was sprayed with an ethanolic solution of p-menth-3-yl methyl sulphoxide and was rolled into cigarettes each containing approximately .O^g. of active compound. Smoking the impregnated cigarettes produced a cool effect in the mouth characteristic of mentholated cigarettes but without any attendant odour other than that normally associated with tobacco.

Impregnation of the filter tip of a proprietary brand of tipped cigarette with 0.01 mg. of p-menth-3-yl methyl sulphoxide produced a similar effect.

EXAMPLE 3^ Toothpaste The following ingredients were mixed in a blender: Dicalcium Phosphate 48.0% Sodium Lauryl Sulphate 2.5% Glycerol 24.8% Sodium carboxymethyl cellulose 2.0% Citrus flavourant 1.0% Sodium saccharin 0.5% Water to 100?; Shortly before completion of the blending operation 0.5% by weight of p-menth-3-yl isopropyl sulphox-ide was added to the blender.

When applied as a toothpaste a pleasant cooling effect is noticed in the mouth.

EXAMPLE 35 Aerosol Shaving Soap An aerosol shaving soap composition was formulated according to the following recipe :- Stearic acid 6.3% Laurie acid 2.7% Triethanolamine 4.6% Sodium carboxymethyl Cellulose 0.1% Sorbitol 5.0% Water to 100% Perfume 0.5% The composition was prepared by fusing the acids in water, adding the triethanolamine, cooling and adding the other constituents. To the mixture was then added 0.5% of n-hexyl 1 , 2-diethylcyclohexyl sulphoxide. The composition was then packaged in an aerosol dispenser under pressure of a butane propellant.

EXAMPLE 36 Deodorant Composition A deodorant composition suitable for formulation and dispensing as an aerosol under pressure of a suitabl propellant was formulated according to the following recipe :- Denatured ethanol 96.9% Hexachlorophene 2.0% Isopropyl myristate 1.0% Perfume 0.1% To the composition was added 4% by weight of p-menth-3-yl methyl sulphone. Application of the final composition- gave rise to a definite cooling sensation on the skin.

EXAMPLE 37 Hair Shampoo Sodium lauryl -e£i¾er sulphate, 10g. , was dispersed in 90 g. water in a high speed mill. To the dispersion was added 4.5% by weight of p-menth-3-yl n-butyl sulphoxide. When the hair is washed using the shampoo a fresh, cool sensation is noticed on the scalp.

EXAMPLE B Solid Cologne A solid cologne was formulated according to the following recipe:- - Denatured ethanol 7 .5% •; Propylene Glycol 3·0% j ■ I Sodium Stearate 5·0% i Perfume 5.0% j Water to 100% The sodium stearate was dissolved by stirring in a warm mixture of the ethanol, propylene glycol and water.

To the solution was added the perfume, and 4.0% of n-butyl 1-isobutylcyclohexyl sulphox de and the mixture then allowed to solidify into a waxy cake.

Whem applied to the forehead a distinct cooling effect is noticeable.

-EXAMPLE 39 Mouthwash A concentrated mouthwash composition was prepared according to the following recipe :- Ethanol 3.0% Borax 2.0% Sodium Bicarbonate 1.0% Glycerol 10.0% Flavourant 0. % Thymol 0.03% Water ' to 100% To the composition was added 0.2% of isopropyl 4-methylcyclohexyl sulphoxide.

When diluted with approximately 10 times its own volume of water and used to rinse the mouth a cooling effect is obtained in the mouth.

EXAMPLE 40 Soft Drink A soft drink concentrate was prepared from the following recipe :- Pure orange juice 60% Sucrose 10% Saccharin 0.2% Orange flavouring 0.1 Citric acid . 0.2% Sulphur dioxide trace amount Water to 100% To the concentrate was added 0.05% of 2,5-dimethylcyclohexyl isopropyl sulphoxide.

The concentrate was diluted with v/ater and tasted. An orange flavour having a pleasantly cool after-effect was obtained.

EXAMPLE 41 Boiled Sweet 99.5% sucrose and 0.5% citric acid were carefully fused together in the presence of a trace of water.

Just before casting the melt onto a chilled plate 0.1% of p-menth-3-yl ethyl sulphoxide was rapidly stirred in. The melt was then cast. A boiled sweet resulted having a marked cooling effect on the mouth.

EXAMPLE 42.

Indigestion Tablet The following' ingredients were ground together Magnesium carbonate 49.5% Sorbitol 49.4% Saccharin 0.1% Talc 1.0% Added to the mixture during grinding was 0.1% of methyl 2,6-dimethylcyclohexyl sulphoxide. After mixing the mixture was pressed into 0.5 g. tablets.

Taken by mouth and swallowed the tablets produced, after a short interval' of time, a noticeable cooling effect in the stomach.

EXAMPLE 43 Hydrophilic Ointment A hydrophilic ointment was prepared having the following formulation:- Propylene Glycol 12% -Octadecanol 2 % White Soft Paraffin 25% Sodium Lauryl Sulphate 1% · Water to 100% The sodium lauryl sulphate was added to the water and heated to 60°C. The paraffin was melted by heating to 60°C and was then added to the sodium lauryl sulphate mixture with stirring. Propylene glycol and 1-octadecanol were then added to this mixture.

To the resultant mixture was added 3% of n-hexyl 1-isobutylcyclohexyl sulphoxide. The final ointment when applied to the' skin gave rise to a marked cooling effect.

EXAMPLE 44.

Liniment A liniment was prepared according to the following formulation: Methyl salicylate ■ 25% Eucalyptus 105* Arachis Oil , to W0% To the composition was added 3% of 3, 3, 5-trimethyl-cyclohexyl sec. butyl sulphoxide.

When the final composition was applied to the skin a clearly noticeable cooling effect became apparent after a short interval of time.

EXAMPLE 45 Toothpick The tip of a wooden toothpick was impregnated with an alcoholic solution containing p-menth-3-yl ethylcarbo., methyl sulphoxide in an amount sufficient to deposit on the toothpick 0.05 nig. of the compound. The toothpick was then dried. ■ When placed against the tongue a cool sensation is noticed after a short period of time.

The above Examples illustrate the range of compounds and the range of compositions included in the invention.\ However, they are not to be taken as limitin, the scope of the invention in any way. Other compounds within the general formula will be equally suitable for use in the compositions of j-xamples 1-45 and the physiological effect obtained with the compounds of the .invention will recommend their use in a wide variety of other compositions where the cooling effect will be of value .

Claims (1)

1. WHAT WE CLAIM A manufactured product for application to or consumption by the human body comprising a physiologically active ingredient capable of stimulating the cold receptors of the nervous system of the body and a carrier said carrier constituting or providing a vehicle by means of which said ingredient may be brought into contact with the skin or other surface tissue of the body upon use of the said said carrier comprising a manufactured article or preparation into which the said ingredient is incorporated by admixture or impregnation and being other than a liquid or mixture of liquids which serve merely as solvent for the said ingredient and which contain no other wherein said physiologically active ingredient is a cyclic or acyclic sulphoxide or phone of the RSO R X R is optionally containing carboxy or substituent x is 1 or 2 and R is either is H or is is and together provide a total of from carbon and together with a total of from carbon or where is alkyl and when n is greater than the groups may be the same or n 0 or of the of provided groupn i A product according to claim vherein the cold receptor is of the formula vhere is containing up to 8 carbon is selected from and and and are each and together providing a total of carbon atoms A product according to claim the cold receptor is of tho where in the formula represents a radi al selected from allcyl of up to carbon represents n is an integer frora inclusive and x an integer of from A product according to claim vherein the cold receptor stimulant is selected butyl butyl and A product according to claim vherein said edible preparation containing an edible Material a Λ of chewing A product according to orally or topically an orally o topically acceptable carrier and orally or topically active r is a A product according to claim carrier ie a A product according to claim carrier is a comprising an aqueous or solution of an orally acceptable A product according to vherein said carrier is a lotion for topical application to the body which an aqueous or and more the a a odourant or a A product according to wherein caid carrier is an cream or oil for topical application to the A product according to claim vherein carrier is a toilet coap or A product according wherein caid carrier or Λ to A according to any of cold ptor a to A product according to any of cold rccoptor a according to claim A product according to claim being a product as hereinbefore dcDcribcd in one of the insufficientOCRQuality