1. Field of the Invention It is believed that a vast majority, perhaps as much as 80 percent, of women experience the discomfort of the"hot flash/flush"associated with menopause. A hot flash is believed to be the result of the hormonal changes, particularly the decline in estrogen levels, that occur during menopause. (Although some sources differentiate between a"hot flash" and"hot flush,"both conditions will be referred to herein collectively as"hot flash"or"hot flashes.") A hot flash is marked by an increase in body temperature accompanied by an intense feeling of unbearable heat, particularly internally radiating body heat. A hot flash may also be accompanied by an increase in heart rate, dizziness, anxiety, faintness, a sense of unease, tingling sensations, pressure in the head, nausea, perspiration, and feelings of breathlessness. The feeling of heat is often concentrated in the area of the face and neck, and sometimes spreads to the area of the upper chest. Although a hot flash may last for as short as a minute, a hot flash usually lasts as long as two to three minutes, and may last as long as an hour. Regardless of the duration of the hot flash, the discomfort due to the

intense feeling of heat is extremely uncomfortable and disconcerting to a woman experiencing the hot flash.

2. Description of the Related Art Perhaps the most common treatment of a hot flash is Hormone Replacement Therapy (HRT), more specifically Estrogen Replacement Therapy (ERT). Some sources recommend vitamin supplements, such as vitamin E and bioflavonoids, to treat a hot flash. These treatments are systemic methods of treatment that require foresight. In addition in the case of HRT/ERT, one needs a prescription from a medical professional.

U. S. Patent No. 5,730,957 to Rizk describes the use of a cooling composition having dimethyl ether and water to alleviate the discomfort associated with heat. This cooling composition utilizes the latent heat of vaporization to provide its cooling action and also requires that the cooling composition be at a temperature below ambient temperature and higher than the freezing point of water. This patent also provides a method of maintaining the cooling composition at such a temperature that requires a pressurized dispensing container. In addition, the sole embodiment described in the Rizk patent is a water-dimethyl ether composition contained within an aerosol dispenser (col. 3, line 51 et seq.). In addition to the fact that maintaining the composition at a cold temperature is an inconvenient and impractical requirement, the use of dimethyl ether has known safety issues.

Some prior art provides for topical cooling of the skin. For example, U. S. Patent No. 5,703,123 to Peizer et al. describes the use of compositions having asymmetric carbonates, thiocarbonates and/or carbonates to create a physiologic cooling effect on the skin and on mucosae in compositions such as food stuffs (e. g. beverages, jams,), cosmetic agents (e. g. shaving products, skin care products, etc.), household products (e. g. fabric softeners) and pharmaceutical preparations

(e. g. antiseptic ointments, cough mixtures). U. S. Patent No. 5,266,692 to Grub et al. provides that ketals, such as 1-methone glycerol ketal or 3,3,5- trimethylcyclohexanone glycerol ketal, have a physiological cooling effect when applied to the skin or mucous membranes in preparations, such as dentifrices, mouth washes, perfumes and shaving foams. In addition, U. S.

Patent No. 5,688,497 to Lozeau et al. discloses shaving aids that provide a physiological cooling effect.

U. S. Patent No. 5,451,404 to Furman, the disclosure of which is incorporated herein by reference, provides coolant compositions that may be administered topically. Also, U. S. Patent No. 4,661,476 to Lane et al. describes a method of cooling skin overheated by exposure to heat, sun or wind that is the topical application of an aqueous gel having a starch- polyacrylamide graft copolymer.

U. S. Patent No. 5,595,970 to Garfield et al. describes the use of a nitric oxide substrate and/or nitric acid donor, either alone or in combination with a progestin or estrogen to alleviate climacterium symptoms such as hot flashes. However, the compositions disclosed in Garfield et al. require systemic administration.

Until now, there has not been a method of alleviating the discomfort of hot flashes experienced by women that is non-systemic, easy to use and relatively inexpensive.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a method of alleviating the discomfort associated with a hot flash.

It is another object of the present invention to provide such a method for alleviating the feeling of intense heat associated with a hot flash.

It is a further object of the present invention to provide such a method that includes the topical application of a composition having a cooling agent.

The present invention, in brief summary, is a method of alleviating the discomfort associated with hot flashes that comprises the step of applying to the body, particularly to the chest, face and neck area and/or to the wrist and arm area, a topical cooling composition having at least one cooling agent.

DETAILED DESCRIPTION OF THE INVENTION Hot flashes are most commonly associated with the discomforting symptom of an intense feeling of heat that begins in the face, neck, or chest regions and then radiates to other parts of the body. However, prior to the intense feeling of heat, many women experience a premonition of an impending hot flash that is accompanied by symptoms, such as a feeling of unease or anxiety, a feeling of pressure in the head, or tingling sensations.

During this time, there is a concurrent increase in heart rate, digital blood flow, and vasodilation of blood vessels of the skin. At this point, women will experience an intense feeling of heat and. which may further be accompanied by feelings of dizziness, nausea and breathlessness.

For most women who experience hot flashes, these foregoing symptoms are very unpleasant. Indeed, for some women the extent of these symptoms experienced during a hot flash can be downright unbearable.

The first detectable change is an increase in finger blood flow with a concomitant enhancement of skin conductance, as well as a change in temperature of the skin of the face and neck. The increase in skin conductance is followed rapidly by a sharp rise (1-7°C) in finger temperature. The degree to which finger temperature rises during a hot flash is inversely proportional to the base-line finger temperature before the

flash. Thus, a 0.5°C increase in finger temperature in a woman with a base-line finger temperature of 35°C may be as good a measure of the occurrence of a hot flash as a 5°C increase in finger temperature in a woman with base-line finger temperature of 29°C, because of the non- linear relationship between skin temperature and blood flow.

As vasodilation and sweating ensue, internal body temperature drops. The magnitude of decrease in core temperature ranges from 0.1°C to 0.9°C. The onset of sweating is rapid and is particularly profuse in the face and scalp. It may occur in five minute bursts accompanying short, discrete hot flashes, or continue in waves for more than thirty minutes during prolonged hot flashes.

A hot flash is the inverse of a fever. In mammals, the control of body temperature resembles a negative feedback system in which a set point temperature serves as reference for the themoregulatory mechanism. A fever can be understood as the upward adjustment of this temperature set point. In a febrile episode, the set point is first elevated, initiating vasoconstruction, shivering and behavorial modifications, such as the addition of blankets. This results in an elevation of body temperature to a level that is maintained for a period of time. A hot flash, on the other hand, is a transient downward adjustment of the set point, which results in the sensation of heat. At the end of a hot flash, the set point returns to normal.

The trigger for a change in set point may be a series of nerve impulses. A fever, even with a rapid onset, may last for hours, days or even weeks. In contrast, the duration of a hot flash is in the order of minutes.

The present invention provides a method of alleviating discomfort experienced by a woman during a hot flash that occurs during menopause including alleviating the feeling of intense heat. The present invention further provides a method of alleviating symptoms of physical discomfort resulting from increased heart rate and digital blood flow associated with

hot flashes. The method of the present invention includes the step of applying topically to the woman a cooling composition having at least one cooling agent.

Although to practice the method of the present invention, a woman experiencing a hot flash may apply the topical cooling composition to any part of her body that feels overheated, it is preferred that the cooling composition is applied topically to the head and/or neck areas. It is more preferred that the cooling composition is applied topically to the face and neck areas. It is most preferred that the cooling composition is applied topically to the temples.

To practice the present invention, the cooling composition, which is considered a topical composition, may be a solution, gel, cream, lotion, emulsion, solid stick, towelette or spray. It is preferred that the topical cooling composition is a stick, spray or a towelette. However, the topical cooling composition may be any form that may be quickly and easily applied to the head and neck areas.

To practice the present invention, the topical composition must have at least one cooling agent. The cooling agent must be suitable for topical application. As stated above, U. S. Patent No. 5,730,957 to Rizk discloses a cooling mixture of water and dimethyl ether. The cooling agents of the present invention are not a mixture of dimethyl ether and water. In addition, the cooling mixture of the Rizk patent must be delivered at a temperature less than ambient temperature and higher than the freezing point of water. The cooling agents suitable and contemplated for use in the present invention do not have any such temperature requirements. Also, the cooling mixtures of the Rizk patent achieve their cooling effect through the latent heat of transformation, or evaporation, of both the dimethyl ether and the water components. The cooling agents of the present invention, in contrast, stimulate the cold receptors of the nervous system, and, thus,

achieve a cooling effect that is not dependent upon the temperature of the cooling agent relative to ambient temperature.

Cooling agents that may be used in the present invention include menthol, and the alkyl-substituted methanols disclosed in U. S. Patent No.

4,069,345 to Gascoyne et al. The cooling agent may also be acyclic sulphones or acyclic sulphoxides, phoshine oxides, alkyl-substituted alicyclic carboxylic acids, esters and amides, cyclohexan-amides, cyclic and acyclic amides, substituted ureas and sulphonamides. Examples of the foregoing are disclosed in U. S. Patent Nos. 4,318,900; 4,296,093; 4,136,164; 4,070,496; and 4,070,449 to Rowsell et al. Further, the cooling agent may also be N-hetero substituted-p-menthane-3-carboxamides as disclosed in U. S. Patent No. 4,190,643 to Watson et al. Still further, the cooling agent may be monomenthyl succinates, alkali metal salts of monomenthyl succinate, alkaline earth metal salts of monomenthyl succinate, and mixtures thereof. Examples of the foregoing are disclosed in U. S. Patent Nos. 5,725,865 and 5,843,466 to Mane et al. Yet further, the cooling agent can be an asymmetric carbonate, thiocarbonate or urethate as disclosed in U. S. Patent No. 5,703,123 to Pelzer et al. The cooling agent can also be a 2-(2-alkoxy-1-methylethyl)-5-methyl cyclohexanol derivative as disclosed in U. S. Patent No. 5,756,857 to Kuribayashi et al.

Each patent cited in this paragraph is incorporated herein by reference.

When the cooling agent is a ketal, such as menthone glycerin acetal and the ketals disclosed in U. S. Patent No. 5,266,692 to Grub et al., which is incorporated herein by reference, the onset and duration of the effect of the cooling agent may be affected by manipulating the substituents on the ketal.

When the cooling agent is menthol lactate, the topical cooling composition preferably comprises an alkali metal carbonate and/or bicarbonate and/or alkaline earth metal carbonate as set forth in U. S.

Patent No. 5,783,725 to Kuhn et al., which is also incorporated herein by reference, to improve stability of the topical cooling composition.

It is believed that when the cooling composition comprises two or more of the cooling agents, the cooling effect achieved by the cooling composition is enhanced. For example, U. S. Patent No. 5,451,404 to Furman discloses cooling compositions that are suitable for use in practicing the present invention. One example of a topical cooling composition of the Furman'404 patent comprises an effective amount of a first cooling component that is a ketal of the formula in which R'represents a C2-C6-alkylene radical having at least 1, but not more than 3, hydroxyl group (s) and either R2 and R3 independently of one another represent Cr-Cr0-alkyl which is optionally substituted by 1 to 3 radicals selected from the group comprising hydroxyl, amino and halogen, or C5-C7-cycloalkyl, or C6-Cr2-aryl, with the proviso that the total of the C atoms of R2 and R3 is not less than 3, or R2 and R3 together represent an alkylene radical which, together with the carbon atom which carries the radicals R2 and R3, forms a 5-7-membered ring, and a second coolant component selected from the group consisting of menthol, carboxamides and mixtures thereof.

The preferred cooling agents for the present invention include menthol, menthone glycerin acetal (a non-limiting example of the foregoing is available from Haarmann & Reimer GmbH under the trademark FRESCOLATs MGA), menthyl lactate (a non-limiting example of the foregoing is available from Haarmann & Reimer GmbH under the trademark FRESCOLAR ML), menthyl pyrrolidane carboxylic acid (PCA)

(a non-limiting example of the foregoing is available from Quest International under the tradename QUESTICE L), N-2,3,-Trimethyl-2- isopropyl butanamide (a non-limiting example of the foregoing is available from ChiRex, Inc. under the tradename WS-23), N-ethyl-p-menthan-3- carboxamide (a non-limiting example is available from ChiRex, Inc. under the tradename WS-3), 3-1-methoxypropane-1,2-diol, (1- (2- hydroxyphenyl) 4- (3-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-2-one), C, to C5 derivatives of 2-(2-alkoxy-1-methylethyl)-5-methyl cylcohexanols, 1- menthanyl carbonates and mixtures of the foregoing. Menthone glycerin acetal is the most preferred cooling agent. One reason why menthyl pyrrolidane carboxylic acid is a preferred cooling agent is because it exhibits moisturizing properties as well as coolant properties.

The cooling composition of the present invention comprises from about 0.01 wt% to about 10 wt% of the cooling agent, preferably from about 0.01 wt% to about 5 wt%, more preferably from about 0.1 wt% to about 2 wt%, even more preferably from about 0.1 wt% to about 1 wt%, and most preferably from about 0.2 wt% to about 0.8 wt%.

As stated above, the cooling composition is preferably a stick, spray or towelette. It is preferred that the cooling composition is a water-based system. In addition, it is preferred that the when the cooling composition is a water-based composition, the cooling composition further comprises an alcool, such as ethanol, isopropyl alcohol and propanol. Alcools act as a solvent and also exert a cooling effect that enhances the benefits of the present invention. When the cooling composition is a water-based system, it is preferred that the cooling composition comprises from about 5 wt% to about 15 wt% of an alcool. The remainder of the cooling composition may be water. When a water-based system is used, it is preferred that the cooling composition comprises from about 0.01 wt% to about 5 wt% of the cooling agent.

The cooling composition may also be an anhydrous system. In an anhydrous system comprising alcool, such as ethanol, isopropyl alcohol or propanol, it is preferred that the alcohol comprises the majority of the cooling composition other than the cooling agent. In an anhydrous, alcohol-free system, such as a cosmetic stick, the composition is comprised of esters, waxes and/or oils in place of the water and alcool.

When the cooling composition is an anhydrous system, the cooling composition may comprise up to 10 wt% of the cooling agent. It is more preferred that the cooling composition comprises from about 0.1 wt% to about 1 wt% of the cooling agent.

The cooling composition, whether a water-based system or an anhydrous system, may further include ingredients such as sunscreens, odor masking agents, natural/botanical extracts, alpha-hydoxy acids, polyhydroxy alpha-hydroxy acids, alpha-keto acids, vitamins, anti- mycobacterial agents, analgesics, lipidic compounds, moisturizers or lubricants.

When the cooling composition contains a natural/botanical extract, it is preferred that the natural/botanical extract comprises a soy extract, a black cohosh extract, or a ginseng extract, or mixtures thereof. More preferably, the natural/botanical extract will be a mixture of all three of the foregoing extracts.

Since many women experience feelings of anxiety during hot flashes, it is believed that when the cooling composition comprises a fragrant component, which is preferably a natural extract, the alleviation of the discomfort associated with hot flashes is augmente. It is believed that the aromatherapeutic benefits of the fragrant component will provide a calming effect, and thus synergistically enhance the cooling composition's effect on relieving the discomfort, both emotional as well as physiological, associated with hot flashes.

The cooling composition may also include emulsifiers, thickeners and preservatives. Emulsifiers (solubilizers) that can be used in the cooling compositions of the present invention can be cationic, anionic, non-ionic, amphoteric, zwitterionic, or combinations thereof. However, it is preferred that the emulsifier is a polysorbate emulsifier. Non-limiting examples of polysorbate emulsifiers are Polysorbate 20 and Polysorbate 80. Examples of thickeners that can be used are, xanthan gum, magnesium aluminum silicate (a non-limiting example of the foregoing is available under the tradename Veegum), cellulosic thickeners, and polymeric thickeners, such as CARBOPOL, PEMULENT" copolymers and acrylate copolymers. A non-limiting example of an acrylate copolymer that may be used in the present invention is an acrylate/C 0 to C30 alkyl acrylate copolymer.

It is preferred that the cooling composition also includes a neutralizer to adjust pH. The preferred neutralizer is sodium hydroxide. The pH of the cooling composition should be adjusted according to the cooling agent used. For example, it is preferred that when the cooling agent comprises menthone glycerin acetal that the pH of the cooling composition is greater than 7. In contrast, when the cooling agent comprises menthyl lactate, it is preferred that the pH of the cooling composition is less than 7.

It is preferred that the cooling composition of the present invention has a preservative. Suitable preservatives include disodium EDTA, methyl paraben and benzyl alcool. Other suitable preservatives include EDTA salts, EDTA fatty acid conjugates, alkanols, especially ethanol, isopropyl alcool, benzyl alcool, parabens, sorbates, phenoxyethanol, urea derivatives and isothiazolinone.

An example of a contemplated composition that would be suitable for practicing the present invention is as follows:

EXAMPLE 1 INGREDIENT Wt Percent of Total Composition Menthone glycerin acetal 0.01 to 5 Vehicle Polysorbates 0.01 to 5 Methylparaben 0.01 to 5 Acrylates copolymer 0.01 to 4 Sodium Hydroxide 0.01 to 2 Alcohol 5 to 15 Disodium EDTA 0.01 to 0.8 Water QS The cooling composition of the present invention described above is used to alleviate the physical symptoms experienced by a woman during a hot flash. It is contemplated that when the cooling composition may be applied immediately when the woman either senses a hot flash about to occur or after a hot flash begins. Although a woman may apply the cooling composition to any surface area of her body that requires relief, it is contemplated that the most useful areas for application will be the chest, face and neck areas, particularly the areas around the temple and at the base of the neck adjacent the spine. In addition, it is also believed that topically applying the cooling composition to the wrist and arm areas will be particularly useful in alleviating discomfort associated with a hot flash.

Although it is contemplated that the method of the present invention will be used most often to alleviate the discomfort of a hot flash on an as needed basis, it is believed that the method of the present invention may be extended to prophylaxis. For example, many women have their slumber disturbed by"night time"hot flashes. As stated above, the onset and duration of action of the cooling agent may be manipulated via changes in chemical structure. Accordingly, women who frequently experience such

night time hot flashes may apply, just prior to sleep, topical cooling compositions having cooling agents with either delayed onset or prolonged effect.

When the topical cooling composition is a spray (hereinafter"cooling spray"), it is believed that the optimum benefits of the present invention are achieved in the following manner. The user will spray the cooling spray onto the palm (s) of the hand (s) or onto the fingertips. The user will then transfer the cooling spray onto the skin. In order to avoid inhalation of the cooling composition and to avoid contact of the cooling composition with the eyes, it is recommended that the cooling composition should never be directly sprayed onto or near the face area. When the topical cooling composition is a stick, towelette, lotion, cream or gel, (hereinafter collectively referred to as"non-spray cooling composition (s)"), the consumer may also manually apply the non-spray cooling composition to the area of skin that feels uncomfortably warm or hot due to the hot flash.

It is preferred that the non-spray cooling composition is spread over the surface of the skin, but not rubbed deeply into the skin. Extensive rubbing of the skin may intensify the feeling of heat experienced by the consumer, and is preferably to be avoided.

EXAMPLE 2 A study was conducted to test the effectiveness of the present invention in alleviating discomfort and symptoms experienced by women during a hot flash.

Forty-five women between 40 and 60 years of age participated in the study. The participants experienced at least three to four hot flashes per day. Some participants experienced as many as ten hot flashes per day.

In addition to hot flashes, the participants also reported experiencing

headaches, sleeplessness, mood changes, night sweats and/or erratic or stopped menstrual periods.

The participants were given spray bottles containing Sample A.

Sample A comprised 0.65 wt% menthone glycerin acetal in a compatible vehicle made according to Example 1 above. During a two-week period, the participants applied Sample A to various parts of their body when experiencing a hot flash. Those parts of the body to which the participants applied Sample A included the face, chest, neck/throat, shoulders, back, stomach, legs, arms, wrists and hands.

Over sixty percent of the participants expressed that Sample A was effective in alleviating discomfort experienced during hot flash episodes. In addition, over sixty percent of the participants expressed that Sample A either met or exceeded their expectations of performance.

Various modifications and alterations to the present invention may be appreciated based on a review of this disclosure. These changes and additions are intended to be within the scope and spirit of the present invention as defined by the following claims.