WO2015061829A1

WO2015061829A1 - Cooling solution and methods of use

Info

Publication number: WO2015061829A1
Application number: PCT/AU2014/000986
Authority: WO
Inventors: Amanda Merrin HAMER
Original assignee: Magna Carta Pty Ltd
Priority date: 2013-10-30
Filing date: 2014-10-20
Publication date: 2015-05-07

Abstract

The present disclosure relates to a cooling fluid comprising menthol oil which is suitable for providing relief to a person experiencing one or more symptoms of a condition involving a hot flush. The disclosure also relates to a cooling wipe impregnated with the cooling fluid, and to methods of using such wipes to treat a person experiencing a hot flush.

Description

COOLING SOLUTION AND METHODS OF USE

RELATED APPLICATIONS

[001] The present application relates to Australian Provisional Patent Application

No 2013904195, titled 'Cooling Wipe', filed on 30 October 2013, and Australian Provisional Patent Application No 2014902622, tided 'Cooling Wipe', filed on 7 July 2014, the entire contents of which are hereby incorporated by reference as if fully set forth herewith.

TECHNICAL FIELD

[002] The present disclosure relates to a cooling fluid suitable for providing relief to a person experiencing one or more symptoms of a condition, including a hot flush, and to methods of treating a hot flush.

BACKGROUND

[003] Menopause is a natural part of die ageing process in women. Many women suffer discomfort and often distressing symptoms of menopause. Sometimes men also suffer from similar symptoms and while the description herein is directed to women it is also applicable to men suffering from those symptoms. Symptoms may vary among individuals and may range from mild to severe. In some cases symptoms are absent Hot flushes, which also commonly referred to asなot flashes', are the most common symptom of menopause and perimenopause. A hot flush is a quick feeling of heat, sometimes accompanied by a red, flushed face and swearing. During the hot flush, the woman may feel an intense and sudden feeling of heat starting on the forehead and rapidly spreading down through the body. Usually, during a hot flush, blood vessels near the skin's surface dilate, and the flush may be accompanied by sweating, rapid heart rate or chills. Hot flushes may also occur during the night and are sometimes called night flushes.

[004] The intensity and duration of hot flushes in women may vary. Typically a menopausal woman may suffer an average of seven hot flushes every day for about four years.

[005] Hormone Replacement Therapy (HRT) is the most common treatment for hot flushes associated with menopause. However, the long term use of HRT has been shown to significantly increase the risk of heart disease, heart attack, stroke, pulmonary embolism, breast cancer and endometrial cancer. Side effects of HRT may include breakthrough bleeding, bloating, breast tenderness and nausea. HRT is only recommended for women under the age of 51 years, as these risks have been shown to increase after this age. It is

recommended that HRT be used for no more than approximately 5 years. Further, there is a 50% likelihood of hot flushes returning after ceasing HRT, whether the HRT is suddenly stopped, or tapered off.

[006] Bio-identical hormones such as phytoestrogens from soy or red clover have been recommended as a safe alternative to HRT. However, there is no evidence to suggest that phytoestrogens are effective for the treatment of menopausal symptoms.

[007] Hot flushes are not only associated with menopause, and may occur in response to alcohol, caffeine, spicy food, tight clothing, heat, cigarette-smoke, stress, etc. For example, alcohol flush reaction (also referred to as Asian flush) is a condition in which an individual develops flushes after consuming alcohol. The hot flush is a result of the accumulation of acetaldehyde after consumption of alcohol due to acetaldehyde dehydrogenase deficiency.

[008] Thus, a need exists to provide a method for treating a person suffering from one or more symptoms of a medical condition, such as a hot flush.

SUMMARY

[009] The present invention broadly relates to a cooling fluid comprising menthol oil which is suitable for providing relief to a person experiencing one or more symptoms of a condition involving a hot flush. In various preferred aspects die invention relates to a cooling wipe impregnated with the cooling fluid, and to methods of using such wipes to treat a person experiencing a hot flush.

[010] A first aspect of the present invention relates to a cooling fluid comprising 40% to 80% v/v isopropyl alcohol, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1% v/v surfactant. In preferred embodiments the cooling fluid comprises a surfactant in an amount of 0.01% v/v to 1% v/v. The cooling fluid may be a single phase liquid solution or a mtcrocmulsion. In preferred embodiments the cooling fluid is clear.

[011] A second aspect of the present invention relates to a cooling wipe comprising an absorbent substrate, and a cooling fluid, wherein die cooling fluid comprises 40% to 80% v/v of a topically acceptable solvent, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1% v/v surfactant; wherein the substrate is impregnated with the cooling fluid. In preferred embodiments the cooling fluid comprises a surfactant in an amount of 0.01% v/v to 1% v/v.

[012] In preferred embodiments the absorbent substrate is a deformable or flexible substrate selected from the group consisting of a towellette, a towel, a cloth, and a tissue.

[013] In preferred embodiments the cooling fluid is a cooling fluid as defined in the first aspect of the invention.

[014] A third aspect of the present invention relates to a method of treating a person experiencing a hot flush, the method comprising the step of applying a cooling fluid comprising 40% to 80% v v of a topically acceptable solvent, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1% v/v surfactant, or a cooling wipe according to the second aspect of the invention to an area of skin of the person so as to provide relief from one or more of symptoms of the hot flush.

[015] A fourth aspect of the present invention relates to the use of a cooling fluid comprising 40% to 80% v/v of a topically acceptable solvent, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1 % v/v surfactant, in the manufacture of a medicament for treating a person experiencing a hot flush.

[016] A fifth aspect of the present invention relates to a cooling fluid comprising 40% to 80% v/v of a topically acceptable solvent, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1 % v/v surfactant, or a cooling wipe according to the second aspect of the invention, for use in die treatment of a person experiencing a hot flush.

[017] In preferred embodiments of the third, fourth and fifth aspects of the invention, the cooling fluid comprises a surfactant in an amount of 0.01% v/v to 1% v v. In further preferred embodiments the topically acceptable solvent is isopropyl alcohol or ethanol or a mixture thereof. In other preferred embodiments the cooling fluid is the cooling fluid as defined in the first aspect of the invention. In alternative preferred embodiments the cooling fluid comprises isopropyt alcohol, ethanol, menthol oil and water.

[018] in preferred embodiments the hot flush is associated with menopause, alcohol flush reaction, caffeine consumption, spicy food consumption, wearing of tight doming, heat, cigarette smoke, or stress. In particularly preferred embodiments the hot flush is associated with menopause.

[019] Preferably, the area of skin mat is treated is the forehead of the person, particularly the forehead just below the hairline.

[020] Other aspects of the invention are described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[021] One or more embodiments of the present disclosure are described by way of specific examples) with reference to the accompanying drawings, in which:

[022] FIGS 1A-1C are schematic representations illustrating various shapes of a wipe, in accordance with various embodiments of the present disclosure.

[023] FIG.2 is a schematic representation of a sachet used for packaging the wipes of FIGS 1 A-1C, in accordance with another embodiment of the present disclosure.

[024] Features in the accompanying drawings that have the same reference numerals are to be considered to have the same unction(s) or operations), unless the contrary intention is expressed or implied. The following description is intended only by way of example, and illustrates certain selected embodiments of products and methods that are consistent with the disclosed subject matter.

DETAILED DESCRIPTION

[025] It will be readily understood that the components of the disclosed embodiments, as generally described and illustrated in the accompanying drawings, may be arranged and designed in a wide variety of different configurations. Thus, the following detailed description of the embodiments of the product and method of the disclosed subject matter, as presented in the drawings, is not intended to limit the scope of the disclosed subject matter, as claimed, but is merely representative of selected embodiments of the disclosed subject matter.

[026] The presen invention broadly relates to a cooling fluid comprising menthol oil and a topically acceptable solvent, which is suitable for providing relief to a person experiencing one or more symptoms of a condition involving a hot flush. In various preferred aspects the invention relates to a cooling wipe impregnated with the cooling fluid, and to methods of administering the cooling fluid to treat a person experiencing a hot flush.

[027] The cooling fluid comprises menthol oil and a topically acceptable solvent, such as isopropyl alcohol, ethanol or mixtures thereof. In various embodiments the cooling fluid may further comprise water, surfactant, or bom.

[028] A first aspect of the present invention relates to a cooling fluid comprising: 40% to 80% v/v isopropyl alcohol, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1% v/v surfactant. In preferred embodiments the cooling fluid comprises 0.01% v/v to 1% v/v surfactant.

[029] In a preferred embodiment, the cooling fluid comprises 60% to 70% v/v isopropyl alcohol, 5% to 15% v/v menthol oil, 25% to 35% v/v water, and 0.05% to 0.5% v/v surfactant. In another preferred embodiment the cooling fluid comprises 60% to 65%v/v isopropyl alcohol, 5% to 12% v/v menthol oil, 25% to 30% v/v water, and 0.1% v/v surfactant. In a further preferred embodiment the cooling fluid comprises about 63%v/v isopropyl alcohol; about 10% v/v menthol oil; about 27% v/v water, and about 0.1% v/v surfactant.

[030] The menthol oil may comprise an extract from at least one Mentha species or Mentha sub-species. In various embodiments the menthol oil comprises an extract from the leaves of at least one of Mentha arvensis, Mentha aquatica, Mentha haplocalyx, Mentha pulegium, Mentha spicata, Mentha X cardiaca, Mentha X piperita, and Mentha X piperita subspecies citrate. In another embodiment the menthol oil comprises an extract from one or more leaves of Mentha arvensis. Thus, the precise composition of the menthol oil may vary in terms of components and proportions. However, utility can be achieved across the range of menthol oil extracts.

[031] The surfactant may be polysorbate 80 or any other pharmaceutically acceptable or topically acceptable surfactant. More than one surfactant may be used.

[032] When water is included in the cooling fluid, it may be present in an amount ranging from about 0.1% v/v to about 40% v/v. For example, water may be present in an amount of about 1% v v, about 5% v/v, about 10% v/v, about 15% v/v, about 20%v/v, about 25% v/v, about 30% v/v, about 35% v/v or about 40% v/v. In preferred embodiments, water is present in an amount of 20% to 40% v/v, 25% to 35% v/v, or about 25% to 30% v/v

[033] The water is preferably distilled water or deionized water.

[034] When a surfactant is included in the cooling fluid, it may be present in an amount ranging from about 0.01%v/v to about l%v/v. For example, the surfactant may be present in an amount of about 0.01%v/v, about 0.02%v/v, about 0.03%v/v, about 0.04%v/\\ about 0.05%v/v, 0.075%v/v, 0.1% v/v, 0.2% v/v, 0.3% v/v, 0.4% v/v, 0.5% v/v, 0.6% v/v, 0.7% v/v, 0.8% v v, 0.9% v/v or 1% v/v. Preferred surfactants are pharmaceutically acceptable for topical application. An example of a presently preferred surfactants is polysorbate 80 (Tween), which is a commercially available hydrophilic nonionic surfactant derived from

polyethoxylated sorbttao and oleic acid. Other pharmaceutically and topically acceptable surfactants will be known to those skilled in the art and include, for example, surfactants listed in the European Pharmacopoeia, the US Pharmacopoeia (USP) or National Formulary ( F), die British Pharmacopoeia (BP), and so on.

[035] A second aspect of the invention relates to a cool ing wipe comprising: an absorbent substrate; and a cooling fluid, wherein the cooling fluid comprises: 40% to 80% v v of a topically acceptable solvent, 5% to 25% v/v menthol oil, 0% to 40% v/v water, and 0% to 1% v/v surfactant; wherein die substrate is impregnated with the cooling fluid. In preferred embodiments the cooling fluid comprises 0.01% v/v to 1% v/v surfactant.

[036] In a preferred embodiment die cooling wipe comprises an absorbent substrate; and a cooling fluid comprising about 60%v/v ethanol, aboutlO%v/v menthol oil extracted from leaves of Mentha arvemis by steam distillation, about 30% v/v water, and about 0.1% v/v poh/sorbate 80.

[037] In another preferred embodiment the cooling wipe comprises an absorbent substrate; and a cooling fluid comprising about 20%v/v to 30 v/v isopropyl alcohol, about 20%v/v to 30%v/v ethanol, about5%v/v to 15%v/v (eg, about 10 v/v) menthol oil extracted from leaves of Mentha arvensis by steam distillation, about 30% v/v water, and about 0.1% v/v polysorbatc 80.

[038] The absorbent substrate is preferably flexible. In preferred embodiments the absorbent substrate is selected from the group consisting of a towellette, a towel, a cloth, and a tissue. Preferably, the absorbent substrate is a towellette made from alcohol resistant woven towel or paper. The towel may be made from any suitable fabric or material, including for example, cotton or bamboo, among others.

[039] The topically acceptable solvent comprises an alcohol selected from isopropyl alcohol, ethanol and mixtures thereof.

[040] In preferred embodiments the menthol oil comprises an extract from at least one Mentha species or Mentha sub-species. In various embodiments the menthol oil comprises an extract from the leaves of at least one of Mentha arvensis, Mentha aquatica, Mentha haplocalyx, Mentha pulegium, Mentha spicata, Mentha cardiaca, Mentha X piperita, and Mentha X piperita subspecies citrate. In a particularly preferred embodiment the menthol oil comprises an extract from one or more leaves of Mentha arvensis. Preferably, the mentha oil is extracted by steam distillation.

[041] in a preferred embodiment, the cooling wipe comprises a cooling fluid as defined in the first aspect of die invention.

[042] The cooling wipe may be housed within a dispensing container selected from the group consisting of sealed sachet, resealable packet, and resealable towellette dispenser. Preferably, the dispenser is configured to retain volatile material and to prevent the cooling wipe from drying out. The dispenser may contain one or more cooling wipes and may be resealed after use.

[043] A third aspect of the invention relates to a method of treating a person experiencing a hot flush, the method comprising the step of applying a cooling fluid as defined in the first aspect of the invention, or a cooling wipe as defined in the second aspect of the invention to an area of skin of the person so as to provide rel ief from one or mote of symptoms of the hot flush. The hot flush may be associated with one or conditions or causes, including menopause, alcohol flush reaction, caffeine consumption, spicy food consumption, wearing of tight clothing, heat, cigarette-smoke, and stress. In a preferred embodiment the hot flush is associated with menopause. In another preferred embodiment the hot flush is associated with alcohol flush reaction.

[044] To ach ieve relief from a hot flush, the cooling fluid or cooling wipe is applied to the forehead of the person requiring treatment. In preferred embodiments this may invol ve wiping the cooling wipe across the forehead of the person one or more times. Preferably, the cooling fluid or cooling wipe is applied to the forehead just beneath the hairline of a person being treated.

[045] The cooling fluid and cooling wipe of die present invention have the advantage of providing two cooling phases to provide relief from a hot flush. The first cooling effect is associated with evaporation of the topical solvent from the skin surface. The second cooling affect is associated with the action of menthol oil on cold receptors of the skin. Thus, in presently preferred embodiments the use of a combination of menthol oil and isopropyl alcohol is intended to induce a cooling action. Initial cooling may be induced by isopropyl alcohol, which volatile and rapidly evaporates from the skin. A second cooling sensation may be induced by the menthol oil, which stimulates die cold receptors of the skin by interfering with the movement of calcium across cell, membranes. The initial cooling effect typically lasts around 3 minutes, while the effect of the menthol oil may typically last up to 20 minutes.

[046] The effect of menthol oil when combined with different vehicles varies widely. It has been found mat different aqueous and organic vehicles used for the application of menthol influence the biological activity of menthol. Furthermore there is evidence that there are significant differences in sensitivity between different body surfaces for the cooling action of menthol. Gradation of sensitivity is thought to be related to density of thermo-receptors of these surfaces (Watson, H.R, Hems, R., Rowsell, D.O., Spring, D.J. (1978) New compounds with menthol cooling effect. J.Soc.Cosmet.Chem. 29:185-200). Accordingly, the effect of menthol oil when combined with volatile solvent, in particular isopropyl alcohol, in accordance with this invention was not predictable.

Overview

[047] Some embodiments of the present disclosure relate to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition. The medical condition may be a hot flush associated with menopause, or another condition or cause, including a hot flush in response to the consumption of alcohol, caffeine, spicy food, tight clothing, heat, cigarette-smoke, stress, among others. In preferred embodiments the invention relates to the use of a cooling wipe for providing relief to a person experiencing a hot flush associated with menopause, or in response to alcohol consumption.

[048] The cooling wipe comprises a predefined quantity of fluid comprising isopropyl alcohol, a menthol oil and water. About 40% to 80% of the predefined quantity of fluid includes isopropyl alcohol, 5% to 25% of die predefined quantity of fluid includes the menthol oil and at least 0.02% of the predefined quantity of fluid includes a surfactant.

[049] The presence of surfactant in the cooling fluid is optional. When present, the surfactant is preferably included in the cooling fluid in an amount ranging from about 0.01 %v/v to about l%v/v. For example, die surfactant may be present in an amount of about 0.0l%v/v,

0.02%v/v, 0.03%v/v, 0.04%v/v, 0.05%v/v, 0.075%v/v, 0.1% v/v, 0.2% v/v, 0.3% v/v, 0.4% v/v, 0.5% v/v, 0.6% v/v, 0.7% v/v, 0.8% v/v, 0.9% v/v or 1% vN. Preferred surfactants are pharmaceutically acceptable for topical application . An example of a presently preferred surfactants is polysorbate 80 (T een), which is a commercially available hydrophilic nonionic surfactant derived from polyethoxylated sorbitan and oleic acid.

[050] Another embodiment of the present disclosure provides a cooling wipe for providing relief to a person having one or more symptoms of a medical condition, such as, but not limited to, a hot flush (also known as a hot flash). The cooling wipe typically includes a predefined quantity of cooling fluid comprising isopropyl alcohol, menthol oil and water. In the cooling fluid, about 40% to 80% of the predefined quantity of cooling fluid includes the isopropyl alcohol, 5% to 25% of the predefined quantity of fluid the menthol oil, and/or 0% to 40% of the predefined quantity of cooling fluid includes the water. In addition, 0.01% to 1% of die predefined quantity of fluid may include a surfactant. Yet another embodiment of the present disclosure relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition. The cooling wipe may include a predefined quantity of cooling fluid comprising isopropyl alcohol, menthol oil and water. In the predefined quantity of cooling fluid, about, 60% to 70% of the predefined quantity of fluid includes the isopropyl alcohol, 5% to 15% of the predefined quantity of cooling fluid includes the menthol oil, and 20% to 35% of the predefined quantity of cooling fluid includes water. Further, 0.01% to 1% of the predefined quantity of cooling fluid may include a surfactant.

[051] A further embodiment of the present disclosure provides a method for treating a person suffering from one or more symptoms of a medical condition, such as a hot flush. The method includes providing a cooling wipe impregnated with a predefined quantity of cooling fl uid comprising isopropyl alcohol, a menthol oil, and water. The method also includes applying the cooling wipe to skin on a forehead just beneath the hairline of a person being treated so as to provide at least some relief from one or more symptoms.

[052] Yet another embodiment of the present disclosure relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition. The cooling wipe comprises at least one towellette made from at least one of an alcohol resistant woven towel or a paper. The cooling wipe includes a predefined quantity of cooling fluid comprising isopropyl alcohol, a menthol oil, and water. Further, the at least one towellette may be impregnated with about 1 mL to 2 mL of the fluid before sealing the at least one towellette in a sachet.

[053] A further embodiment of the present disclosure provides a cooling wipe for providing relief to a person having one or more symptoms of a medical condition. The cooling wipe includes a predefined quantity of cooling fluid including ethanol, a menthol oil, and water. In the fluid, about 40% to 80% of the predefined quantity of fluid includes the ethanol, 5% to 25% of the predefined quantity of fluid includes the menthol oil. The cooling fluid may Anther comprise a surfactant in an amount of about 0.01% to 1% of the predefined quantity of cooling fluid.

[054] Another embodiment of the present disclosure relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition. The cooling wipe includes a predefined quantity of cooling fluid including isopropyl alcohol, ethanol, a menthol oil, and water.

[055] A further embodiment of the present disclosure provides a method for treating a person suffering from one or more symptoms of a hot flush condition. The method includes providing a cooling wipe including a predefined quantity of cooling fluid. The predefined quantity of cooling fluid includes isopropyl alcohol, ethanol, a menthol oil, and water. The method also includes applying the cooling wipe to skin on a forehead just beneath the hairline of a person being treated.

Description of Embodiments

[056] The present disclosure provides a cooling fluid that includes menthol, in particular menthol oil, and is suitable for providing relief to a person having one or more symptoms of a medical condition, such as hot flushes. The cooling fluid may be applied to the person by any convenient means, such as a cooling wipe, a spray, o a roll-on dispenser. Cooling wipes are especially preferred. It is preferred that the roll-on dispenser is configured so as to minimize loss of volatile solvent via evaporation. Sprays have a risk that cooling fluid may be sprayed into eyes and so are less preferred.

[057] In one aspect, the present disclosure provides a cooling wipe including a predefined quantity of fluid. Various embodiments of the present disclosure relate to different composition of the predefined cooling fluid. In some embodiments, the cooling fluid includes isopropyl alcohol, menthol oil, water, and/or surfactant. In alternative embodiments, the cooling fluid includes ethanol, isopropyl alcohol, menthol oil, water, and or surfactant. In further embodiments, the cooling fluid includes ethanol, menthol oil, water, and or surfactant. The cooling wipe may be used for providing relief to a person having one or more symptoms of a medical condition.

[058] FIGS 1 A-IC illustrates cooling wipes 102A-102C including a predefined quantity of cooling fluid. Hereinafter, the cooling wipes 102A-102C may be collectively referred to as a cooling wipe 102. The predefined quantity of fluid may include isopropyt alcohol, a menthol oil, and water. The predefined quantity of fluid may also include a surfactant The predefined quantity of fluid may include about 40% to 80% of isopropyl alcohol, 5% to 25% of the menthol oil, and 0.01% to 1% of a surfactant. Further, the predefined quantity of fluid may include 40% to 80% of the isopropyl alcohol, 5% to 25% of the menthol oil, 0% to 40% of the water, and/or at least 0.01% to 1% of the surfactant. In some embodiments, the predefined quantity of fluid includes 60% to 70% of the isopropyl alcohol, 5% to 15% of the menthol oil. 20% to 35% of the water, and or 0.01% to 1 % of the predefined quantity of fluid comprises a surfactant. In some embodiments, the surfactant includes polysorbate 80. In preferred embodiments the fluid may be a single phase liquid solution or a microemulsion. The fluid is preferably clear. For convenience, reference in this specification to a 'solution' or 'clear solution' includes a single phase liquid solution and a microemulsion.

[059] In some embodiments, the predefined quantity of fluid may include ethanol, the menthol oil, water and/or the surfactant. Further, the predefined quantity of fluid may include 40% to 80% of the ethanol, 5% to 25% of the menthol oil, and/or at least 0.01% to 1% of the predefined quantity of fluid may include a surfactant. In some embodiments, the predefined quantity of fluid includes equal quantity of the ethanol, water, and menthol oil. In alternative embodiments, the emanol, the menthol oil and the water may be in same or equal proportion with respect to each other in die predefined quantity of fluid. In further embodiments, 60% to 70% of the predefi ned quantity of fluid includes the ethanol, 5% to 15% of the predefined quantity of fluid includes the menthol oil, 20% to 35% of the predefined quantity of fluid includes the water, and/or at least 0.01% to 1 % of the predefined quantity of fluid comprises the surfactant.

[060] In further embodiments, the predefined quantity of fluid includes the ethanol, the isopropyl alcohol, the menthol oil, the water, and or surfactant.

[061] Further, the cooling wipe 102 may include at least one toweltette made from at least one of an alcohol resistant woven towel or a paper. Further, the cooling wipe 102 may have different sizes and shapes. As shown in FIG. 1 A, the cooling wipe 102A have a rectangular shape. Further, the rectangular shaped cooling wipe 102A may have a length of 100 millimeters and a breadth (or width) of 150 mm.

[062] Further as shown in FIG. IB, the cooling wipe 102B have a square shape and the cooling wipe 102B may have a length and a breadth (width) in a range of 30 mm to 40 mm. In some embodiments, the cooling wipe 102C may have any suitable regular or irregular shape as shown in FIG. IC.

[063] Further, the cooling wipe 102 may comprise at least one towellette made from at least one of an alcohol resistant woven towel or a paper. The cooling wipe 102 may also comprise a predefined quantity of fluid, wherein the fluid comprises isopropyl alcohol, a menthol oil and water. In some embodiments, the predefined quantity of the fluid does not include water. In alternative embodiments, the predefined quantity of fluid includes 0% to 40% of water.

[064] The menthol oil used in the predefined quantity of fluid may be obtained by distillation of a number of leaves of at least one of Mentha species and Mentha sub-species. In alternative embodiments, the menthol oil may be obtained by the steam distillation of one or more leaves of Mentha arvensis.

[065] In some embodiments, the cooling wipe 102 is moistened with a liquid or fluid comprises isopropyl alcohol and menthol oil, the liquid/fluid being free of water or having a water content of less than 40%.

[066] Further, the at least one towellette may be impregnated with about 1 mL to 2 mL of the fluid before sealing the at least one towellette in a sachet. FIG.2 illustrates an image of an exemplary sachet 200 in which the cooling wipe 102 ca be packed or sealed. In some embodiments, the cooling wipe 102 is pre-moistened with the predefined quantity of fluid and wrapped in the sachet 200. Hereinafter, the terms liquid and fluid are used interchangeably without changing its meaniog. The sachet 200 may be a bleached paper that is laminated with an aluminum foil. Further, a length and a breadth or width of the sachet 200 is in accordance with a length and a breadth of the cooling wipe 102. m an exemplary scenario, the sachet 200 has a length and a breadth in a range of SO mm to 60 mm when the sachet 200 is sealed. In an embodiment, the cooling wipe 102 may be pie-moistened and may be wrapped in a foil lined individual packet i.e. the sachet 200, which can be opened by a user shortly before the cooling wipe 102 is used.

[067] According to another embodiment of the invention a method of treatment of hot flushes is provided. The method includes applying the fluid including the isopropyl alcohol and the menthol oil to the skin on die forehead beneath the hairline. The fluid may be free of water or may have a water content of less than 40%

[068] The cooling wipe 102 may be may be applied to a forehead of a person suffering fro the symptoms of hot flushes or night flushes. The hot flushes may be treated by the use of the cooling wipe 102. Further, the hot flushes may be the hot flushes of menopause and/or hot flushes associated with alcohol flush reaction, heat reaction, and so forth.

[069] This present disclosure provides a convenient method of alleviating or reducing the symptoms of the hot flushes. In particular the present disclosure provides methods and cooling wipes (such as cooling wipe 102) that are intended for the treatment of hot flushes associated with menopause etc. in women and/or men. However the disclosed cooling wipes (such as cooling wipe 102) may also be used to alleviate the symptoms of ho flushes associated with other conditions including alcohol flush reaction, heat, etc.

[070] Isopropyl alcohol is considered to be safe for external application to the skin, and menthol oil is a naturally occurring compound of plant origin which is also safe for application to the skin. The menthol oil leaves a pleasant minty smell and counters the drying effects on the skin potentially caused by the isopropyl alcohol.

[071] Alternative means of application of the fluid have been considered. Spray packs run the risk of spraying the liquid into the eyes, while roll-on applicators are not necessarily well adapted to retaining volatile liquids. Hence, a cooling wipe including the cooling fluid is safe and convenient to be used. Accordingly, the preferred method of applying the cooling fluid is by a wipe.

[072] The use of a combination of menthol oil and isopropyl alcohol is intended to induce a cooling action. Initial cooling may be induced by isopropyl alcohol, which volatile and rapidly evaporates from the skin. A secondary cooling sensation may be induced by the menthol oil, which stimulates the cold receptors of the skin by interfering with the movement of calcium across cell membranes. The initial cooling effect typically lasts around 3 minutes, while the effect of the menthol oil may typically last up to 20 minutes.

[073] The menthol oil may be obtained by extraction from the leaves of Mentha species. In a preferred embodiment the menthol oil is extracted from the leaves of Mentha arvensis. In an alternative embodiments, the menthol oil is extracted from the leaves of Mentha aquatica, Mentha haplocalyx, Mentha pulegium, Mentha spicata, Mentha X cardiaca, Mentha X piperita, or Mentha X piperita subspecies citrate, or other species and subspecies of Mentha. Preferably, the mode of extraction is steam distillation, although other extraction methods known to those skilled in the art may also be used.

[074] In a preferred embodiment the menthol oil extracted from Mentha arvensis typically contains L-menthol as well as menthone, menthyl acetate, limonene, neomenthol, isomenthone and traces of 1,8 cineol, piperitone, camphene, linalool, (J-caryophyllene, β-caryophylleoe epoxide, pulegone, a-pinene, pinene, germacrene D, mejithofurane, and β hexenytphenyl acetate.

[075] In alternative embodiments, substantially pure L-menthol obtained from other sources, including synthetic sources and other biological sources, may be used.

[076] The term "menthol oil" as used in this specification, including the claims, includes L-menthol, as well as L-menthol-containing oils such as those deri ved from Mentha species and subspecies as hereinbefore described.

[077] The cooling fluid may be formed by emulsifying the isopropyl alcohol, water and menthol oil, before application or use to moisten a wipe. The cooling fluid is preferably a clear liquid solution. The solution may be an emulsion, including a microemulsion. A clear solution can be achieved by addition of a surfactant, preferably at a level between about 0.0l%v/v and l%v/v.

[078] The effect of menthol oil when combined with different vehicles varies widely. It has been found that different aqueous and organic vehicles used for the application of menthol oil influence the biological activity of the menthol oil.

[079] Many individuals who are affected by hot flushes find that the feeling of heat begins on the forehead at the hairline and spreads down the body. Accordingly, m preferred

embodiments the cooling fluid or cooling wipe according to die present invention is applied to the forehead beneath the hairline at the beginning of a hot flush so as to stimulate cold receptors in this area of the forehead.

[080] The pre-moistened cooling wipe 102 may be small in size (for example, 5 cm in length and 5 cm in breadth or less) and packaged in a corresponding, small, individual, waterproof foil packet, such as the sachet 200, for convenient use.

[081] All menthol isomers may have very low skin sensitivity and oral toxicity to humans. The water content of the fluid may be less than 40%. Essential oils (other than menthol oil) are avoided or added in small amounts only, for example for fragrance.

[082] In an embodiment, the water content in the disclosed fluid is between 20% and 35%. In further embodiments, the water content in the fluid is approximately 25%. In alternative embodiments, the water content in the fluid is 27%.

[083] Further, in an embodiment the fluid composition contains between .01% and 1% of a surfactant, and is in the form of a liquid solution or stable emulsion, such as a clear solution.

[084] Further, in some embodiments a composition of the liquid includes 60% isopropyl alcohol, 15% menthol oil derived by steam distillation of the leaves of Mentha arvensis and 25% water. EXAMPLES

The following examples illustrate the invention, but to not limited its scope. Example 1 - Cooling fluid

[085] A representative cooling fluid according to the present invention comprises:

63%v/v isopropyl alcohol,

I0%v/v menthol oil extracted from leaves of Mentha arvensis by steam distillation, 26.9% v v water, and

0.1% v/v polysorbate 80.

[086] The cooling fluid was prepared by mixing the polysorbate 80 and water, and then gradually adding first the menthol oil, followed by the isopropyl alcohol while continuously mixing until a clear solution was obtained.

Example 2 - Cooling fluid

[087] A representative cooling fluid according to the present invention comprises:

60%v/v ethanol,

10%v/v menthol oil extracted from leaves of Mentha arvensis by steam distillation, 29.9% v/v water, and

0.1% v v polysorbate 80.

[088] The cooling fluid was prepared by mixing the surfactant (polysorbate 80) and water, and then gradually adding first the menthol oil, followed by the ethanol while continuously mixing until a clear solution was obtained.

Example 3 - Use of cooling wipe impregnated with cooling fluid to relieve hot flushes

[089] An exemplary study was conducted using six female subjects suffering from menopausal hot flushes. All six female subjects experienced between 1 and 20 hot flushes per day. Each subject was given five wipes impregnated with the cooling fluid and five placebo ipes (impregnated with water) in a blind crossover study. Each subject was instructed to apply a wipe impregnated with the cooling composition to the forehead at the onset of a hot flush.

[090] All six subjects reported a sense of immediate cooling relief after applying wipes impregnated with the composition. All six subjects reported between 15 minutes to I hour cooling relief. AH six subjects recorded a score greater than 5 (maximum score - 10;

minimum score = 0) for the level of immediate relief after J minute, and five subjects recorded a score of 7 to 10 after 5 minutes, with 4 maintaining die score for the level of cooling between 7 and 10 at 20 minutes. All six female subjects reached maximum level of cooling relief after 2 minutes. Four subjects reported a decrease of symptoms of hot flushes after 4 days. No subject experienced any irritation. One subject complained of a mild headache developing after one hour due to "brain freeze' from the cold sensation. This subject also reported experiencing mild and infrequent flushes. The control (containing only water) was found to have no cooling effect in any cases except one, in which one subject reported an initial I minute cooling effect.

Further Embodiments

[091] As individual sensitivities to menthol oil vary, and reduced sensitively is associated with build-up of oil on the skin, cooling fluids having more or less menthol may be used for particular individuals, or at particular times of the day, or to suit different weather conditions.

[092] In this specification and the claims the term "wipe" or "cooling wipe" may be embodied as a towellette, a towel, a cloth, a tissue, and the tike. For example, a wipe embodied as a towellette may be made from alcohol resistant woven towel or paper. The dimensions of the towellette may be preferably about 30 millimeter to 40 millimeter square, with a thickness of 1 millimeter to 2 millimeter. Larger towellettes of thinner material, for example 100 millimeter x 150 millimeter, can be used and folded to these preferred dimensions.

[093] Turning back to FIG.2, the sachet 200 may be preferably bleached paper laminated with aluminum foil, the sachets being between about 50 millimeters and 60 millimeters in breadth and length, respectively, when sealed. Further, there is a perimeter seal of at least 5 millimeter on each side of the sachet 200. The sachet 200 may be sealed by using appropriate means such as heat sealing.

[094] An embodiment disclosed herein relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition, the cooling wipe comprising a predefined quantity of cooling fluid comprising isopropyl alcohol, a menthol oil and water, wherein 40% to 80% of the predefined quantity of fluid comprises the isopropyl alcohol, 5% to 25% of the predefined quantity of fluid comprises the menthol oil, further wherein at least 0.01% to 1% of the predefined quantity of fluid comprises a surfactant.

[095] The cooling wipe may comprise a towellette made from at least one of an alcohol resistant woven towel or a paper, wherein the towellette is impregnated with about 1 mL to about 2 mL of the cooling fluid before sealing the towellette in a sachet.

[096] The cooling wipe may comprise a cooling fluid in which 40% to 80% of the predefined quantity of cooling fluid comprises isopropyl alcohol, 5% to 25% of the predefined quantity of fl uid comprises menthol oil, and at least 0.01% to 1% of the predefined quantity of fluid comprises a surfactant. The surfactant may be polysorbate 80 or any other topically acceptable surfactant.

[097] The menthol oil may be extracted from one or more leaves of at least one of Mentha species and Mentha sub-species. Typically, the extraction process involves steam distillation. For example, th menthol oil may be obtained by the steam distillation of one or more leaves (typically a plurality of leaves) of Mentha arvensis.

[098] The cooling wipe may be pre-moistened and wrapped in a foil lined individual sachet. The sachet is configured so that it may be opened by the person for using the cooling wipe. Typically the sachet may be opened by tearing or cutting the sachet. The sachet may be manufactured from bleached paper laminated with aluminum foil so that the sachet is effectively sealed so as to prevent evaporation of volatile material . The sachet may additionally have a perimeter seat of at least 5 ram on each side of the sachet.

[099] The sachets may be any convenient size or shape, typically suitable to be carried in a bag, wallet or pocket. For example, the sachet may be rectangular, square, round, oval or any other shape. The sachet typically may have an area of between about 50 mm and 60 mm in width and length (as measured between the most distal points) when sealed.

[0100] In preferred embodiments the cooling fluid comprises 0% to 40% of water. Tn other words, water is an optional ingredient of the cooling fluid.

[0101] In a preferred embodiment the cooling wipe is a towellette. The towellette may be any shape or size suitable for convenient use. In one embodiment the towellette is square or rectangular in shape having a length and a breadth in a range from about 30 mm to about ISO mm. In alternative embodiments, the towellette may be square in shape and have dimensions between about 30mm and 40mm in length and width. In other embodiments the towellette may be rectangular in shape and have a length of 100 mm and a breadth of 150 mm. The towellette may be folded when placed within the sachet.

[0102] A preferred embodimen disclosed herein relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition including a hot flush, comprising: a predefined quantity of cooling fluid comprising isopropyl alcohol, menthol oil and water, wherein 40% to 80% of the predefined quantity of fluid comprises the isopropyl alcohol, 5% to 25% of the predefined quantity of fluid comprises the menthol oil, further wherein 0% to 40% of the predefined quantity of fluid comprises the water. The cooling fluid may further comprise at least 0.01% to 1% of a surfactant

[0103] In an embodiment disclosed herein the cooling wipe may comprise a towellette impregnated with about 1 mL to 2 mL of the cooling fluid before being sealed within a sachet

[0104] The cooling wipe may be pre-moistened and wrapped in a foil-lined individual sachet, wherein the sachet can be opened (eg, by tearing or cutting) by a person to access die cooling wipe.

[0105] Another embodiment disclosed herein relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition involving a hot flash, comprising: a predefined quantity of cooling fluid comprising isopropyl alcohol, menthol oil and water, wherein 60% to 70% of the predefined quantity of fluid comprises die isopropyl alcohol, 5% to 15% of the predefined quantity of fluid comprises the menthol oil, and 20% to 35% of the predefined quantity of fluid comprises the water, further wherein at least 0.01 % to 1 % of the predefined quantity of fluid comprises a surfactant.

[0106] Another embodiment disclosed herein relates to a method for treating a person suffering from one or more symptoms of a medical condition, comprising: providing a cooling wipe comprising a predefined quantity of cooling fluid, wherein the predefined quantity of cooling fluid comprises isopropyl alcohol, menthol oil, and water; and applying the cooling wipe to skin on a person's forehead just beneath the hairline of the person being treated.

[0107] In embodiments disclosed herein, about 40% to 80% of the predefined quantity of cooling fluid comprises the isopropyl alcohol, about 5% to 25% of the predefined quanti ty of cooling fluid comprises the menthol oil, and abou 0% to 40% of the predefined quantity of die cooling fluid comprises water.

[0108] In other embodiments disclosed herein, about 60% to 70% of the predefined quantity of the cool ing fluid comprises the isopropyl alcohol, about 5% to 15% of the predefined quantity of die cooling fluid comprises the menthol oil, and about 20% to 35% of the predefined quantity of fl uid comprises the water .

[0109] In embodiments disclosed herein, the cooling fluid may comprise a surfactant such as polysorbate 80 or any other pharmaceutical topically acceptable surfactant.

[0110] In embodiments disclosed herein, menthol oil may be obtained by distillation of a plurality of leaves of at least one of Mentha species and subspecies. For example, a suitable menthol oil may be obtained by the steam distillation of a plurality of leaves of Mentha arvensis.

[01111 The cooling wipes disclosed herein are typically applied for the treatment of a hot flush. The hot flush may occur in a man or a woman. Typically the person receiving treatment receives partial or foil relief from one or more symptoms of the hot flush. The hot flush may be a menopausal hot flush. Alternatively, the hot flush may be associated with alcohol flush reaction.

[0112] An embodiment disclosed herein relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition involving a hot flush, comprising a towellette made from at least one of an alcohol resistant woven towel or a paper; and a predefined quantity of cooling fluid comprising isopropyl alcohol, menthol oil and water; wherein the towellette is impregnated with about I inL to 2 mL of die cooling fluid before the towellette is sealed in a sachet. Typically, 40% to 80% of the predefined quantity of cooling fluid comprises the isopropyl alcohol, and 5% to 25% of the predefined quantity of fluid comprises the menthol oil.

[0113] In alternative embodiments disclosed herein, about 60% to 70% of the predefined quantity of the cooling fluid in the cooling wipe comprises the isopropyl alcohol, about 5% to 15% of the predefined quantity of the fluid comprises the menthol oil, and about 20% to 35% of the predefined quantity of fluid comprises 0% to 40% water.

[01141 The cooling fluid may further comprise 0.01% to 1% of a surfactant. The surfactant may be polysorbate 80 or any other pharmaceutically or topically acceptable surfactant.

[0115] The cooling fluid may comprise a clear solution. The cooling fluid may be a clear monophasic liquid, or a clear microemulsion.

[0116] Alternative embodiments disclosed herein relate to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition involving a hot flush. The cooling wipe comprises a predefined quantity of fluid comprising ethanol, menthol oil and water, wherein 40% to 80% of the predefined quantity of fluid comprises the ethanol, 5% to 25% of the predefined quantity of fluid comprises the menthol oil, further wherein at least 0.01 % to 1 % of the predefined quantity of fluid comprises a surfactant.

[0117] In various embodiments disclosed herein the ethanol, menthol oil, and water may be in equal proportion with respect to each other in the predefined quantity of the fluid. [0118] In embodiments of a cooling wipe disclosed herein about 60% to 70% of the predefined quantity of cooling fluid comprises cthanol, about 5% to 15% of the predefined quantity of cooling fluid comprises menthol oil, and about 20% to 35% of the predefined quantity of fluid comprises water. The cooling fluid may further comprise 0.01% to 1% of surfactant.

[0119] Another embodiment disclosed herein relates to a cooling wipe for providing relief to a person having one or more symptoms of a medical condition involving a hot flush, comprising: a predefined quantity of cooling fluid comprising isopropyl alcohol, ethanol, menthol oil and water.

[0120] Another embodiment disclosed herein relates to a method for treating a person suffering from one or more symptoms of a hot flush condition, comprising: providing a cooling wipe comprising a predefined quantity of cooling fluid comprising isopropyl alcohol, ethanol, a menthol oil, and water; and applying the cooling wipe to skin on a forehead just beneath the hairline of a person being treated.

INDUSTRIAL APPLICABILITY

[0121 J The invention and related embodiments described herein are applicable to the healthcare industry.

[0122] The foregoing disclosure describes only some embodiments of the present invention, and modifications and/or changes can be made thereto without departing from the scope and spirit of the invention, the embodiments being illustrative and not restrictive.

[0123] As used throughout this specification, unless otherwise specified, the use of ordinal adjectives "first", "second", "third", "fourth", etc., to describe common or related objects, indicates that reference is being made to different instances of those common or related objects, and is not intended to imply that the objects so described must be provided or positioned in a given order or sequence, either temporally, spatially, in ranking, or in any other manner.

[0124] The word 'comprising^* and forms of the word 'comprising' as used in this description do not limit the invention claimed to exclude any variants or additions. In the context of this specification, the word "comprising" and its associated grammatical constructions mean "including principally but not necessarily solely" or "having^*" or "including", and not "consisting only of. Variations of the word "comprising", such as "comprise" and

"comprises" have correspondingly varied meanings.

[0125] Where in this specification and the claims quantities of fluids or liquids are expressed in percentages, the percentages are volume/volume (v/v).

[0126] Although the invention has been described with reference to specific examples, it will be appreciated by those skilled i the art that the invention may be embodied in many other forms, which are encompassed by the present disclosure.

Claims

CLAIMS:

1. A cooling fluid comprising:

40% to 80% v/v isopropyl alcohol,

5% to 25% v/v menthol oil,

0% to 40% v/v water, and

0% to 1 % v/v surfactant

2. The cooling fluid according to claim 1 comprising:

60% to 70% v/v isopropyl alcohol,

5% to 15% v/v menthol oil,

25% to 35% v/v water, and

0.05% to 0.5% v/v surfactant

3. The cooling fluid according to claim 2 comprising:

60% to 65%v/v isopropyl. alcohol,

5% to 12% v/v menthol oil,

25% to 30% v/v water, and

0.1 % v v surfactant.

4. The cooling fluid according to any one of claims I to 3, wherein the menthol oil

comprises an extract from at least one Mentha species or Mentha sub-species.

5. The cooling fluid according to claim 4, wherein the menthol oil comprises an extract from the leaves of at least one of Mentha arvensis, Mentha aquatica, Mentha haplocalyx, Mentha pulegium, Mentha spicata, Mentha X cardiaca, Mentha X piperita, and Mentha X piperita subspecies citrate.

6. The cooling fluid according to claim 5, wherein the menthol oil comprises an extract from one or more leaves of Mentha arvensis.

7. The cooling fluid according to any one of claims 1 to 6, wherein the surfactant is polysorbate 80.

8. A cooling wipe comprising:

an absorbent substrate; and

a cooling fluid, wherein the cooling fluid comprises:

40% to 80% v/v of a topically acceptable solvent,

5% to 25% v/v menthol oil,

0% to 40% v/v water, and

0% to 1% v/v surfactant

wherein the substrate is impregnated with the cooling fluid.

9. The cooling wipe according to claim 8, wherein the absorbent substrate is selected from the group consisting of a towellette, a towel, a cloth, and a tissue.

10. The cooling wipe according to claim 9, wherein die absorbent substrate is a towellette made from alcohol resistant woven towel or paper.

1 1. The cooling wipe according to any one of claims 8 to 10, wherein the topically

acceptable solvent comprises an alcohol selected from isopropyl alcohol, ethanol and mixtures diereof .

12. The cooling fluid according to any one of claims 8 to 11, wherein the menthol oil comprises an extract from at least one Mentha species or Mentha sub-species.

13. The cooling fluid according to claim 12, wherein the menthol oil comprises an extract from the leaves of at least one of Mentha arvensis, Mentha aquatica, Mentha haplocalyx, Mentha puteghim, Mentha spicata, Mentha X cardiaca, Mentha X piperita, and Mentha X piperita subspecies citrate.

14. The cooling fluid according to claim 13, wherein the menthol oil comprises an extract from one or more leaves of Mentha arvensis.

15. The cooling fluid according to any one of claims 8 to 14, wherein the surfactant is polysorbate 80.

16. The cooling wipe according to any one of claims 8 to 11 , wherein the cooling fluid is a cooling fluid as defined in any one of claims 1 to 7.

17. The cooling wipe according to any one of claims 8 to 16, housed within a dispensing container selected from the group consisting of sealed sachet, resealable packet, and resealable towellette dispenser.

18. A method of treating a person experiencing a hot flush, the method comprising the step of:

applying a cooling fluid according to any one of claims 1 to 7, or a cooling wipe according to any one of claims 8 to 17 to an area of skin of the person so as to provide relief from one or more of symptoms of the hot flush.

19. The method according to claim 18, wherein the hot flush is associated with menopause, alcohol flush reaction, caffeine consumption, spicy food consumption, wearing of tight clothing, heat, cigarette-smoke, and stress.

20. The method according to claim 19, wherein the hot flush is associated with menopause.

21. The method according to any one of claims 18 to 20. wherein the area of skin is the forehead of die person.

22. The method according to any one of claims 18 to 21 , comprising wiping the cooling wipe across the forehead of the person.

23. The method according to claim 21, comprising applying the cooling fluid or cooling wipe to the forehead just beneath the hairline of a person being treated.