WO2000044346A1

WO2000044346A1 - Lowering skin temperature

Info

Publication number: WO2000044346A1
Application number: PCT/US1999/002372
Authority: WO
Inventors: Gerard Hassler
Original assignee: Gerard Hassler
Priority date: 1999-02-03
Filing date: 1999-02-03
Publication date: 2000-08-03
Also published as: AU3286299A

Abstract

Compositions and methods for controlled lowering of skin temperature of a human subject are disclosed. The method includes: providing a cooling solution comprising about 60-90 % water, about 40-10 % alcohol, 0.02-2.0 % menthol, and 0.02-2.0 % camphor; contacting the cooling solution with a region of the skin of the subject for 10 to 60 minutes, thereby cooling the skin. This controlled skin cooling stimulates a localized thermal response. Stimulation of the thermal response at appropriate time intervals can be used to achieve localized fat reduction or to reduce localized inflammation.

Description

LOWERING SKIN TEMPERATURE

Field of the Invention

The field of the invention is human anatomy, physiology, metabolism, fat reduction and cosmetic formulation.

Background of the Invention

Excess body fat can detract from personal appearance, reduce athletic performance, and even result in risks to health. Human health problems associated with excess body fat include diabetes and cardiovascular disease. In many situations, excess body fat can be reduced by increasing physical activity, reducing caloric intake, or both. Nevertheless, these traditional approaches are often impractical or insufficient, for example due to physical injury or metabolic disorder. In addition, methods based solely on exercise or diet cannot be targeted effectively to achieve fat loss in specific locations on the body. An alternative method of reducing body fat is stimulating metabolic rate by administration of pharmacologically active agents. Examples of drugs used to stimulate metabolism are hormones, e.g., human growth hormone or insulin-like growth factor, and stimulants, e.g., ephedrine or caffeine. Disadvantages of using drugs to reduce body fat include the need for medical supervision and the risk of unwanted side effects.

Summary of the Invention

The invention features a method for controlled, localized lowering of skin temperature of a human subject. The method includes providing a cooling solution comprising (by weight) : about 60-90% water, about 40-10% alcohol, 0.02-2.0% menthol, and 0.02-2.0% camphor; and contacting the cooling solution with a region of the skin of the subject for 10 to 60 minutes.

The amount of water can be about 75% to about 90%, while the amount of alcohol is about 25% to about 10%. In some embodiments, the preferred amount of water is about 84% and the amount of alcohol is about 15%. Preferred alcohols are ethanol, isopropanol, or a mixture thereof. In some embodiments, the amount of menthol is 0.10% to 0.15%, for example, about 0.13%. In some embodiments, the amount of camphor is 0.10% to 0.15%, for example, about 0.13%. In some embodiments, the cooling solution includes a skin conditioning agent, for example, an emollient. A suitable emollient is PEG-7 glyceryl cocoate (Cetiol HE; Henkel) . In some embodiments, the cooling solution is contacted with the skin for 10-40 minutes, for example, about 25 minutes. The cooling solution can be applied to the skin by a woven or nonwoven fabric wrap wetted with the solution. A suitable fabric wrap is an elastic cotton crepe bandage. For use on arms, a bandage width of about 5 to 12 cm is suitable, with a width of about 10 cm being preferred. For use on the legs and body, a bandage width of about 15-20 cm is suitable, with about 20 cm being preferred. The controlled lowering of skin temperature in the region of skin contacted with the cooling solution can be a decrease of 3°C to 12°C, with respect to the pre- treatment skin temperature. Preferably, the decrease is 4°C to 8°C, more preferably 5°C to 7°C, and most preferably about 6°C, when the skin cooling treatment is used for fat reduction. This decrease is produced over a period of 4 minutes to 10 minutes. Preferably it is produced over a period of 5 minutes to 9 minutes, more preferably over a period 6 minutes to 8 minutes, and most preferably over a period of about 7 minutes. The invention also provides a first composition (cooling solution) to be contacted with the skin in the method of the invention. The composition contains (by weight) : about 15% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; about 84% water; about 0.13% menthol; and about 0.13% camphor. In some embodiments, the solution includes a skin conditioning agent, for example, an emollient. A suitable emollient is PEG-7 glyceryl cocoate, and a suitable amount of PEG-7 glyceryl cocoate is about 0.9%. The invention also provides a second composition (cooling solution) to be contacted with the skin in the method of the invention. The composition contains (by weight) : about 18% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; about 80.5% water; about 0.16% menthol; and about 0.16% camphor. In some embodiments, the second composition includes a skin conditioning agent, for example, an emollient. A suitable emollient is PEG-7 glyceryl cocoate, and a suitable amount of PEG-7 glyceryl cocoate is about 1.1%.

The invention also provides a cooling solution concentrate that can be diluted with water to obtain a cooling solution suitable for contacting with the skin in the method of the invention. The concentrate contains (by weight) 85% to 95% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; 0.1% to 10% menthol; and 0.1% to 10% camphor. A preferred embodiment of the concentrate contains: about 60% ethanol; about 31% isopropanol; about 0.8% menthol; and about 0.8% camphor. Optionally, the concentrate contains about 1% to 4% water. The concentrate also can contain a skin conditioning agent, for example an emollient. A suitable emollient is PEG-7 glyceryl cocoate, and a suitable amount of PEG-7 glyceryl cocoate in the concentrate is about 5.5%. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present application, including definitions will control. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference.

Although methods and materials similar or equivalent to those described herein can be used in the practice of testing of the present invention, the preferred methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting. Other features and advantages of the invention will be apparent from the detailed description, and from the claims.

Brief Description of the Drawings

Fig. 1 is a graph showing skin temperature versus time, in a preferred embodiment of the invention used for fat reduction.

Fig. 2 is a graph showing skin temperature versus time, in a preferred embodiment of the invention used for reduction of localized swelling or inflammation.

Detailed Description of the Invention Controlled lowering of skin temperature according to the invention is useful for fat reduction, particularly fat reduction localized to one or more regions of the human body. Controlled lowering of skin temperature according to the invention is also useful for reduction of localized inflammation. The methods and compositions of the invention are safe and noninvasive.

Suitable rates of skin temperature decrease, and maintenance of suitably lowered skin temperatures, can be achieved with the methods and compositions of the invention, without skin temperature monitoring. If desired, however, skin temperature can be measured from time to time, or monitored continuously, using conventional devices and techniques.

Without intending to be bound by theory, it is believed that the skin temperature lowering results primarily from evaporation of the alcohol and water applied to the skin. Accordingly, the rate and extent of skin temperature lowering depends largely upon the water: alcohol ratio. Increasing the alcohol content accelerates and intensifies the cooling effect. The water : alcohol ratio can be adjusted, if necessary, to increase or decrease the rate and extent of cooling. Such adjustment can be made by a person of ordinary skill in the art, without undue experimentation. This controlled skin cooling stimulates a localized thermal response, which requires energy provided by metabolism. Stimulation of the thermal response at effective time intervals can be used to achieve localized fat reduction or to reduce localized inflammation.

Without intending to be bound by theory, it is also believed that mild vasodilation near the skin is stimulated by the menthol and camphor, and that this promotes the "spot reduction" of fat, when used in combination with the cooling provided by the alcohol/water mixture. The amount of menthol and camphor can be adjusted, as desired. Such adjustment can be made by a person of ordinary skill in the art, without undue experimentation.

In addition to stimulating vasodilation, the menthol and camphor display mild analgesic properties and antipruritic properties, cause a pleasant sensation when applied to the skin, and impart a pleasant odor to the solution. These sensual effects enhance the pleasurability of the skin cooling treatment. This increases the likelihood of regular use of the treatments, which maximizes achievement of the desired results . Various alcohols can be used in the cooling solution. Ethanol (ethyl alcohol) and isopropanol (isopropyl alcohol) are preferred, because of their suitable evaporation rate, nontoxicity in topical application, and mild odor. Because their evaporation rates are similar, ethanol and isopropanol can be substituted for each other as the sole alcohol in the cooling solution. Alternatively, ethanol and isopropanol can be mixed in any ratio, to achieve the desired total alcohol content in the cooling solution. Some subjects prefer ethanol over isopropanol because of the difference in odor. Suitable water: alcohol ratios are described in the Summary of the Invention (above) .

Because of its transdermal toxicity, methanol (methyl alcohol) is not suitable for use in the invention. Ethanol included in a cooling solution may contain small amounts of denaturing agents, i.e., agents used to render the ethanol unfit for human consumption. If a denaturing agent is present, preferably it is not methanol . Menthol and camphor are nontoxic when applied topically. Both compounds can be produced by well known methods and are commercially available in grades (purity) suitable for application to human skin. Amounts of menthol and camphor suitable for a cooling solution are described in the Summary of the Invention (above) .

One or more skin conditioning agents can be included in the cooling solution. PEG-7 glyceryl cocoate, available commercially as Cetiol HE (Henkel) , is preferred. Examples of other suitable skin conditioning agents are Estol E03GC 3606 (Unichema) , Fitester HE (Hispano Quimica) , Glycerox HE (Croda) , Hodag POE (7) GML

(Calgene) , Mazol 159 (PPG) , Rewoderm ES 90 (Witco) ,

Sterol LG 491 (Cesalpina) , Tegosoft CG (Goldschmidt) ,

Unimul HE (UPI) , and Unitolate HE (UPI) .

A cooling solution can be prepared initially to contain all components at a concentration desired for application to the skin according to the invention. For convenience, however, the cooling solution can be prepared, packaged, and transported as a concentrate, which is diluted with water prior to use. The components of a preferred concentrate are listed in Table 1.

Table 1 Concentrated Cooling Solution

Prior to use, the concentrate defined in Table 1 is diluted. For example, for use in fat reduction, it can be diluted with 5 parts water to 1 part concentrate, to obtain a final water : alcohol ratio of about 85:15. Variation in the final water : alcohol ration, e.g., for use in reducing inflammation, can be obtained by adjusting the dilution ration. For example, the concentrate defined in Table 1 can be diluted with 4 parts water to 1 part concentrate. Water need not be present in the concentrate. For convenience, however, it may be advantageous to include water in the concentrate. This may enable the desired final concentrations of the various components to be obtained by using a dilution ratio based on whole numbers, e.g., 1:4, 1:5, or 1:6.

To achieve controlled lowering of skin temperature, a film or layer of the cooling solution is contacted with a region of the skin for 10 to 60 minutes. The necessary contact between the skin and the cooling solution can be accomplished in any of various ways. Preferably, unhindered evaporative cooling takes place at the skin's surface throughout the skin cooling treatment, i.e., the period of 10 to 60 minutes when the solution is contacted with the skin.

During a skin cooling treatment, the solution can be intermittently poured or sprayed onto the treated region of skin. In preferred embodiments of the invention, a woven or nonwoven fabric is wrapped around a portion of the body and wetted with the cooling solution. A particularly suitable fabric wrap is an elastic cotton crepe bandage. For use on the arms, a suitable width is 8 cm to 12 cm, preferably about 10 cm. For use on the legs and torso, a suitable width is 18 cm to 22 cm, preferably about 20 cm. After wrapping, the total wrap thickness should not be so thick as to impair evaporative cooling. When an elastic cotton crepe bandage is used, 20-60% overlap per revolution is suitable. For treatment of inflammation, an overlap of about 50% is preferred.

When a wetted fabric wrap is used, the initial wetting can be done before or after the wrap is placed on the body. A convenient and effective technique is to dip a cotton elastic crepe bandage into the solution, gently wring excess solution from the bandage, and then wrap the bandage onto the portion of the body to be treated. Preferably, the bandage contains enough solution to feel wet, but not enough to result in dripping. As the solution evaporates during a skin cooling treatment, additional solution can be applied to the fabric by any convenient means, as necessary to maintain an optimal moisture content. During the skin cooling treatment, the person being treated can stand, sit or lie down, according to personal preference and comfort .

A "skin cooling treatment" is a single instance of contacting the solution with a region of the skin of the subject and maintaining the solution in contact with the region for 10 to 60 minutes, thereby cooling the skin. Typically, multiple skin cooling treatments are applied at effective time intervals.

A "thermal cycle" is a single instance of contacting the solution with a region of the skin, maintaining the solution in contact with the region of 10 to 60 minutes, removing the cooling solution from contact with the skin, and allowing the skin to rewarm to its pre-treatment temperature. The length of time required for the skin to rewarm to its pre-treatment temperature can vary. When allowed to rewarm naturally, the skin is expected to return to its pre-treatment temperature in 60 to 90 minutes. Rewarming time following a skin temperature decrease of 6°C is typically about 75 minutes (Fig. 1) , provided the surrounding environment is at normal room temperature (20°C) before, during, and after the skin cooling treatment. Rewarming time following a skin temperature decrease of 7-8°C is typically about 90 minutes (Fig. 2) .

When skin cooling treatments are used to reduce body fat, preferably rewarming is allowed to occur naturally, e.g., over a period of about 75 minutes, (Fig. 1) . When the skin cooling treatments are used to reduction inflammation, rewarming may be assisted, and thus hastened. Assisted rewarming is preferably by a gentle means, e.g., a heating pad, and can be relatively rapid, e.g., about 5 minutes. Preferably the methods and compositions of the invention are used in a series of skin cooling treatments. The intervals between treatments can vary. The optimal interval depends on whether the skin cooling treatments are being used to promote fat loss or to reduce inflammation.

For promoting fat loss, the interval between treatments is preferably between one week and 12 hours. More preferably, the interval is from 24 to 48 hours. For reduction of inflammation, the interval between treatments can be as short as the time necessary for rewarming to complete a thermal cycle.

In order that the invention may be more fully understood, the following examples are provided. It should be understood that these examples are for illustrative purposes only, and are not to be construed as limiting the invention in any way.

Examples Example 1 Skin cooling treatments are performed on 40 female subjects, twice per week, for 12 weeks. The subjects are between 25 and 50 years of age.

Baseline data are collected at the beginning of the study, and after 4, 8 and 12 weeks of treatment. Measurements at these time points included body weight, circumference of each thigh at about 25 cm above the knee. Experimental data from each patient are compared to the patient's own baseline measurements. Means and standard deviations are calculated for the entire group, with the data broken down by part of the body. Body circumference at breast-level serves as a negative control, with breasts not being subjected to treatment. Data are analyzed by paired Student-t-test , using SYSTAT 7 software . In each skin cooling treatment, portions of the subject's body are wrapped in elastic bandages soaked with an aqueous alcohol solution consisting of (by weight) about 8% ethanol, 7% isopropanol, about 84% water; about 0.9% cetiol; about 0.13% menthol; and about 0.13% camphor. The breasts are not wrapped, so they are not subjected to the skin cooling treatment. During each skin cooling treatment, the patients remain in a supine position for 25 minutes. Evaporation of the cooling solution from the wet bandages lowers the skin temperature to approximately 24-25°C.

Expected experimental results are summarized at the conclusion of the study. Waist circumference shows statistically significant reduction at 4 weeks. Waist circumference displays approximately a 10% mean decrease at 12 weeks. Body weight also shows statistically significant reduction at 8 weeks, i.e., 6-10% reduction. The results show a statistically significant reduction in circumference of all measured body locations except the breasts, which are not subjected to the skin cooling treatments . Where there is a difference between the circumferences of the right and left thighs at the beginning of the study, at 12 weeks both thighs show a statistically significant decrease in circumference, wherein the decrease in the larger thigh is statistically significantly greater than the decrease in the smaller thigh.

The data indicate a significant size reduction, which appears to result from loss of fat. Moreover, the data indicate a significant size reduction only in areas that were disproportionately large (relative to body symmetry) , and only in areas that received the therapy. Thus, the results indicate localized fat reduction, i.e., "spot reduction." Example 2

A second study, similar in design to that of Example 1, is conducted on 20 females and 10 males over a period of 10 weeks. The therapy is administered for 25 minutes, twice per week. During the treatments, skin temperature decreases approximately 6°C in areas of the body subjected to treatment. The waists of all subjects are treated. The thighs of 20 subjects are treated, the hips of 20 subjects are treated, and the arms of 17 subjects were treated. The difference in body areas subjected to treatment allow for evaluation of results in treated areas as compared to nontreated areas .

Ultrasonic imaging is performed at the beginning of the study, at 5 weeks, and at 10 weeks. Regions of the body imaged are hips, thighs, waist (below the umbilicus) , slightly below the xiphoid process, slightly below the distal end of the deltoid muscle, and the buttocks .

Waist circumference reductions among the subjects range from 3% to 10%. The reduction in waist circumference is statistically significant for all subjects. No statistically significant reduction in circumference of non-treated areas of the body are observed. Weight loss is statistically significant, with a mean loss of over 5.5%. Weight loss is greater in subjects that received treatment over a larger area of the body than in those from whom the treated area is relatively small . Ultrasound images reveal a progressive decrease in the subcutaneous fat layer in the treated areas of the body. Areas receiving no treatment show little or no decrease in the fat layer. The ultrasound images showed up to a 60% reduction of subcutaneous fat deposits in treated areas, over the 10 week period. Example 3

A skin cooling treatment is performed on a subject with localized inflammation resulting from an ankle sprain. The ankle is wrapped with a 5 cm elastic cotton crepe bandage soaked with a cooling solution consisting of about 12% ethanol, about 6% isopropanol, about 80.5% water, about 0.16% menthol, about 0.16% camphor, and about 1.1% PEG-7 glyceryl cocoate.

The wet bandage is securely wrapped from the base of the metatarsals of the foot to the midpoint between the medial malleolus and inferior most portion of the gastrocnemius . The bandage is wrapped with a 50% overlap. Thus, the entire area is covered by a double thickness of the bandage, except for portions of the first and last wraps. The ankle is elevated so the leg is substantially horizontal for a period of one hour. Thermocouples are placed under the bandage, against the skin, to monitor skin temperature over time.

Results include a decrease in skin temperature of approximately 7.5 Celsius degrees over a period of 10 minutes post application. The skin temperature then stabilizes until 90% or more of the aqueous solution evaporates from the bandages. This happens at approximately 60 minutes post application, at which point the bandage can be removed. The affected leg is maintained in the elevated position until approximately 150 minutes post application, at which time the skin temperature reaches the pre-application temperature.

The cooling of the skin coupled with the surface tension applied by the tensile properties of the bandage reduce swelling associated with the ankle inversion sprain. This reduction prevents cellular damage associated with localized inflammation, thus reducing injury recovery time. In addition, the analgesic effects of the menthol and the camphor in the concentrate, as well as that of the cooling effect caused by the evaporation of the liquid, reduce the pain resulting from the injury.

Other embodiments are within the following claims .

Claims

ClaimsWhat is claimed is :

1. A method for controlled lowering of skin temperature of a human subject, comprising: providing a cooling solution comprising (by weight) about 60-90% water, about 40-10% alcohol, about 0.02-2.0% menthol, and about 0.02-2.0% camphor; and contacting the cooling solution with a region of the skin of the subject for 10 to 60 minutes, thereby cooling the skin.

2. The method of claim 1, wherein the amount of water is about 75% to about 90%, and the amount of alcohol is about 25% to about 10%.

3. The method of claim 2, wherein the amount of water is about 84% and the amount of alcohol is about

15%.

4. The method of claim 1, wherein the alcohol is ethanol, isopropanol, or a mixture thereof.

5. The method of claim 1, wherein the amount of menthol is about 0.02% to about 0.20%.

6. The method of claim 5 , wherein the amount of menthol is about 0.10% to about 0.15%.

7. The method of claim 6, wherein the amount of menthol is about 0.13%.

8. The method of claim 1, wherein the amount of camphor is about 0.02% to about 0.20%.

9. The method of claim 8 , wherein the amount of camphor is about 0.10% to about 0.15%.

10. The method of claim 9, wherein the amount of camphor is about 0.13%

11. The method of claim 1, wherein the solution further comprises a skin conditioning agent.

12. The method of claim 11, wherein the skin conditioning agent is an emollient.

13. The method of claim 12, wherein the emollient is PEG-7 glyceryl cocoate.

14. The method of claim 1, wherein the cooling solution is contacted with the skin for 10-40 minutes.

15. The method of claim 14, wherein the cooling solution is contacted with the skin for about 25 minutes.

16. The method of claim 1, wherein the cooling solution is contacted with the region of the skin by a woven or nonwoven fabric wrap.

17. The method of claim 16, wherein the fabric wrap is an elastic cotton crepe bandage.

18. The method of claim 17, wherein the bandage is about 5 cm to about 20 cm wide.

19. The method of claim 1, wherein the controlled reduction of skin temperature in the region of skin contacted with the cooling solution is a reduction of 3°C to 12°C.

20. The method of claim 19, wherein the controlled reduction of skin temperature in the region of skin contacted with the cooling solution is a reduction of 4°C to 8°C.

21. The method of claim 20, wherein the controlled reduction of skin temperature in the region of skin contacted with the cooling solution is a reduction of 5°C to 7°C.

22. The method of claim 21, wherein the controlled reduction of skin temperature in the region of skin contacted with the cooling solution is a reduction of about 6°C.

23. The method of claim 19, wherein the reduction of 3°C to 12 °C occurs over a period of 4 minutes to 10 minutes .

24. The method of claim 23, wherein the reduction of 3°C to 12°C occurs over a period of 5 minutes to 9 minutes .

25. The method of claim 24, wherein the reduction of 3°C to 12 °C occurs over a period of 6 minutes to 8 minutes.

26. The method of claim 25, wherein the reduction of 3°C to 12°C occurs over a period of about 7 minutes.

27. A composition comprising (by weight) : 85% to 95% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; 0.1% to 10% menthol; and 0.1% to 10% camphor.

28. The composition of claim 27, wherein the composition comprises (by weight) : about 60% ethanol; about 31% isopropanol; about 0.8% menthol; and about 0.8% camphor.

29. The composition of claim 27, further comprising a skin conditioning agent.

30. The composition of claim 29, wherein the skin conditioning agent is PEG-7 glyceryl cocoate.

31. The composition of claim 30, wherein the amount of PEG-7 glyceryl cocoate is from 4% to 7%.

32. The composition of claim 31, wherein the amount of PEG-7 glyceryl cocoate is about 5.5%.

33. A composition comprising (by weight) : about 15% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; about 84% water; about 0.13% menthol; and about 0.13% camphor.

34. The composition of claim 33, further comprising a about 0.9% PEG-7 glyceryl cocoate.

35. A composition comprising (by weight) : about 18% alcohol, wherein the alcohol is ethanol, isopropanol, or a mixture thereof; about 80.5% water; about 0.16% menthol; and about 0.16% camphor.

36. The composition of claim 35, further comprising a about 1.1% PEG-7 glyceryl cocoate.