AU3323499A - Depilatory compositions comprising chelating agents - Google Patents

Description

WO 99/53892 PCT/AU99/00296 -1 DEPILATORY COMPOSITIONS COMPRISING CHELATING AGENTS 5 FIELD OF THE INVENTION The present invention relates to the field of hair removal from mammalian skin. More particularly, the present invention relates to compositions and methods for reducing or retarding hair growth, or for eliminating unwanted hair from mammalian skin. 10 BACKGROUND OF THE INVENTION For both medical and cosmetic reasons, considerable attention has been focused on developing methods for removing unwanted facial and body hair. Conventional methods for removing 15 unwanted hair focus on mechanical and chemical methods of depilation once the hair is above the surface of the skin. Other methods involve the prevention or retardation of hair growth by an alteration in the rate and character of growth. Mechanical depilation methods commonly include tweezing, plucking, waxing, electrolysis and 20 shaving. Tweezing and plucking are of limited application because individual hairs or at most only a few hairs at one time can be removed. For large areas of hair removal such methods are not efficacious. Waxing is painful and has a tendency to cause irritation, swelling and even burns to the skin. Also, the method of application is tedious and messy. Electrolysis techniques are also painful and involve the use of expensive equipment whilst shaving results 25 in almost immediate regrowth of coarse hair leaving a rough surface feel to the skin. Chemical depilatory compositions are effective in removing unwanted hair from larger areas of skin. Most products currently available for topical use are based on thioglycollates as the active ingredient. Thioglycollates function in this role as reducing agents at high pH, reducing 30 disulphide bonds in the hair following penetration into the follicular canal. The hair is WO 99/53892 PCT/AU99/00296 -2 weakened in the region above the keratinizing zone causing the hair shaft to break offjust below the skin surface leaving a soft smooth surface feel to the skin. Hair regrowth does not however cease and since the hair is broken near the surface, regrowth occurs within a relatively short time and the cosmetic advantage is rapidly lost. Retreatment with the thioglycollate product is 5 then necessary if the skin is to be maintained in a hairless state. Furthermore, because most chemical depilatory compositions are strongly alkaline, dermal irritation is often encountered, particularly on sensitive facial skin. Of the methods employed to alter the rate and character of hair growth, most involve the 10 application of anti-androgens to control dermatological conditions associated with androgen dependent disorders, such as, female hirudism. However, these methods have undesirable side effects such as systemic anti-androgen effects, teratogenicity and pituitary dysfunction and are consequently of limited use. 15 For the foregoing reasons there is a need to develop a method of hair removal which is efficacious, free of unpleasant or harmful side effects, simple and economical to produce and use and can eliminate unwanted hair growth or at least retard or reduce hair growth to provide long lasting results. 20 It is therefore an object of the present invention to provide methods of hair removal which solve or substantially ameliorate many of the problems associated with prior art methods of hair removal. It is a further object of the present invention to provide topical compositions for reducing, retarding or eliminating hair growth from mammalian skin. It is also an object of the present invention to provide methods for reducing, retarding or eliminating hair growth from 25 mammalian skin. Other objections of the present invention will become apparent from the following description thereof. 30 WO 99/53892 PCT/AU99/00296 -3 SUMMARY OF THE INVENTION According to one embodiment of the present invention there is provided a mammalian hair growth reducing, retarding or eliminating topical composition comprising: a) an effective 5 amount of one or more chelating agents and/or cosmetically and/or pharmaceutically acceptable salts thereof; and b) one or more cosmetically and/or pharmaceutically acceptable topical carriers. According to a further embodiment of the present invention there is provided a method for 10 reducing, retarding or eliminating mammalian hair growth which comprises topically applying to the skin of a mammal in need of treatment to reduce, retard or eliminate hair growth a composition according to the present invention. According to a still further embodiment of the present invention there is provided a method for 15 softening and lightening terminal hair in mammalian skin which comprises topically applying to the skin of a mammal in need of treatment to soften and lighten mammalian terminal hair a composition according to the present invention. DETAILED DESCRIPTION OF THE INVENTION 20 It has been unexpectedly found that compositions containing chelating agents exhibit the ability to reduce or retard hair growth or eliminate hair growth altogether from parts of the mammalian body where unwanted hair exists, especially vellus hair, without undesirable side effects such as skin irritation and odour commonly associated with known depilatory formulations. 25 It is well established that in most mammals, including man, hair does not grow continuously but undergoes a cycle of activity involving alternate periods of growth and rest. The metabolism of the hair follicle during growth is not well understood. While not limited to any particular mode of action, it is believed that chelating agents eliminate or at least retard or reduce the 30 growth of hair by complexing out metals in the hair follicle essential for normal hair growth WO 99/53892 PCT/AU99/00296 -4 following penetration of the chelating agent into the follicular canal. As used herein, "chelating agent" means a polydentate ligand that is able to bond to a central metal atom through more than one donor atom simultaneously. However, in the present invention "chelating agent" may also include monodentate ligands. Furthermore, "vellus hair" as used 5 herein means a fine short hair of less than one centimetre in length, containing little or no pigmentation as opposed to "terminal hair" which is coarse, pigmented, medullated hair which is longer than vellus hair. It is envisaged that the compositions of the present invention are employed in one of several 10 treatments for eliminating unwanted hair from the body surface or at least in reducing its rate of growth, such as: i) a two step treatment in which hair is first removed by a conventional method and the regrowth prevented, or retarded by subsequent application of the compositions; or 15 ii) a one step treatment in which the rate of hair growth is reduced by application of the substance without necessarily being accompanied by hair loss. In the present invention, any chelating agent maybe employed which does not cause undue 20 toxicity, incompatibility, irritation, allergic response and the like upon application to the skin. Preferred chelating agents are those capable of complexing out zinc and/or other metals such as calcium from the immediate environment of the hair follicle. Examples of preferred chelating agents include OH, NH 3 , xanthates, carboxylates, nitrates, ethylenediamene (en), 2,2' bipyridine (bipy), 1, 10-phenanthroline (phen), terpyridine (terpy), diethylenetriamine (dien), 25 glyme, P-diketonates, triethylenetetramine (trien), ethylenediaminetetraacetic acid (EDTA), triethylenetriaminepentaacetic acid (DPTA), ethyleneglycol-bis(P-aminoethylether)-N,N,N',N' tetracetic acid (EGTA), phthalocyanine, porphyrin, acetylacetonate (acac), carbonate, glycine (gly), tetraazacyclotetradecane (cyclam), oxalate (ox) and nitrilotriacetate (nta). Particularly preferred is EDTA. 30 WO 99/53892 PCT/AU99/00296 -5 The amount of chelating agent employed in the compositions according to the present invention is an effective amount which is sufficient to significantly induce a positive modification which can be determined by a person skilled in the art. The amount of the chelating agent will vary depending upon the particular condition being treated, the age and physical condition of the 5 subject being treated, the duration of treatment, the specific chelating agents employed, the particular cosmetically and/or pharmaceutically acceptable carriers utilized, and like factors. Preferably, the compositions contain 0.1 to 50.0% (w/v), more particularly 0.5 to 5.0% (w/v) of chelating agent. It has been found, however, that surprisingly small amounts of chelating agent in the present invention are sufficient. A particularly preferred amount is 1.0 to 2.0% 10 (w/v). Cosmetically and/or pharmaceutically acceptable salts of the chelating agents may also be employed. Such salts include, but are not limited to alkali metal salts, eg, sodium, lithium, rubidium and potassium salts; alkaline metal earth salts, eg, magnesium, calcium and strontium 15 salts; non-toxic heavy metals, eg, aluminium salts and zinc salts; boron salts; silicon salts and ammonium salts. Most preferred salts are sodium salts. The compositions according to the present invention also comprise one or more solid, semi solid or liquid cosmetically and/or pharmaceutically acceptance topical carriers to act as a 20 diluent, dispersant or vehicle to facilitate delivery of the chelating agent to the immediate environment of the hair follicle at an appropriate concentration. As the present invention can be embodied in several commercial forms, such as creams, lotions, solution gels, aerosols, sticks or pastes or the like, the selection of a carrier depends on the required product form of the composition. The topical carrier itself can be inert or it can possess physiological or 25 pharmaceutical benefits of its own. The carrier in the present invention is present in an amount of 50.0 to 99.9% (w/v), preferably 90.0 to 99.9% (w/v) and more particularly 94.0 to 96.0%(w/v). 30 Generally, the carrier is either aqueous or organic in nature or an aqueous emulsion which is WO 99/53892 PCT/AU99/00296 -6 capable of having the chelating agent dispersed or dissolved therein. Carriers other than water may be selected from the group which includes liquid or solid emollients, solvents, skin penetration enhancers, thickening agents, emulsifiers and preservatives. 5 As used herein "emollients" refer to materials used for the prevention or relief of dryness, as well as for the protection of the skin. A wide variety of suitable solid and liquid emollients are known and may be used in the compositions of the present invention in amounts of 0.1 to 50.0% (w/v), preferably 0.1 to 20.0% (w/v) and more particularly 0.5 to 1.0% (w/v). Examples of suitable emollients are glycerine, sorboline, lanolin (wool fat), paraffin, petrolatum, mineral oils 10 and waxes, fatty alcohols and silicone oils. Particularly preferred is glycerine. The topical carrier is preferably one which can aid and/or enhance penetration of the chelating agent into the skin to reach the immediate environment of the hair follicle. Carriers useful in topical compositions according to the present invention may include penetration enhancers such 15 as liposomes, latex lattices, microspheres and cyclodextrans. A preferred amount of penetration enhancing agent is from 0.1 to 5.0% (w/v). Topical compositions of the present invention maybe formulated as a cream. Preferably, the creams of the present invention comprise an effective amount of a chelating agent, preferably 20 0.1 to 50.0% (w/v), more preferably 0.1 to 1.0% (w/v), preferably 0.1 to 25.0% (w/v) of an emollient, and from 25.0 to 95.0% water. Optionally, the cream may contain a suitable emulsifier present in an amount from 0.1 to 50.0% (w/v), more preferably 0.5 to 20.0% (w/v). Emulsifiers useful in the present invention may be non-ionic, anionic or cationic or mixtures thereof. Particularly preferred emulsifiers are anionic surfactants such as fatty alcohol sulfates 25 and/or alkyl aryl sulfates and non-ionic surfactants such as condensation products of aliphatic

(C

8 -Cl 8 ) primary or secondary linear or branched chain alcohols. A particularly convenient form of the composition according to the present invention is as an emulsion in which an oil or other materials having the properties of an oil are employed together 30 with an emulsifier to provide either an oil-in-water emulsion or a water-in-oil-emulsion.

WO 99/53892 PCT/AU99/00296 -7 Examples of suitable oils include mineral oil, vegetable oil and silicone oils. For the purposes of forming an emulsion, the oil or oily material will normally be present in an amount up to 90.0% (w/v), preferably from 10.0 to 80.0% (w/v). The amount of emulsifier or mixtures thereof to be incorporated in the composition of the present invention is from 0.1 to 50.0% 5 (w/v), preferably 0.5 to 20.0% (w/v) and more preferably from 1.0 to 2.0% (w/v). Topical compositions of the present invention may also be formulated as a lotion. Preferably, the lotions of the present invention comprise an effective amount of a chelating agent, preferably 0.1 to 50.0% (w/v), more preferably 0.5 to 1.0% (w/v), preferably 0.5 to 15.0% (w/v) 10 of an emollient and 50.0 to 95.0% (w/v) of water. Optionally, the lotion may comprise a suitable emulsifier comprising 0.1 to 50.0% (w/v), preferably from 0.5 to 20.0% (w/v) of the composition. Preferably, a solution form of the present invention comprises an effective amount of a 15 chelating agent, water and suitable organic solvent. Suitable organic solvents are, for example, glycerin, propylene glycol, ethanol, isopropanol, acetone, polypropylene glycol and butanediol. Water may function as the sole cosmetically acceptable carrier. Gel compositions of the present invention may be formulated by simply mixing a suitable 20 thickening agent to a solution form of the present invention. Thickeners include both natural and synthetic such as clays, starch, gums, fatty and polyvinyl alcohols modified starches and sugars and methyl or hydroxyethyl cellulose. Gel compositions preferably comprise an effective amount of a chelating agent, preferably 0.1 to 50.0% (w/v), preferably 0.1 to 2.0% (w/v), more preferably 0.5 to 1.0% (w/v), preferably 0.5 to 50.0% (w/v) of an organic solvent as previously 25 described for solutions; and from 0.1 to 20.0% (w/v), preferably from 0.5 to 10.0% (w/v) of a thickening agent. Compositions of solid forms of the present invention here use as stick-type compositions. Such compositions preferably comprise an effective amount of chelating agent, and from about 50% 30 to 98%, preferably from about 60% to 90% of the previously described emollients. Such WO 99/53892 PCT/AU99/00296 -8 compositions can further comprise from about 1% to about 20%, preferably from about 5% to about 15% of a suitable thickening agent, and optionally emulsifiers and water. When in the form of an aerosol, the compositions in the form of a solution comprise one or 5 more propellants such as propane, butane, isobutane, dimethyl ether, carbon dioxide and nitrous oxide preferably in an amount of 0.1 to 20.0% (w/v). The preferred compositions of the present invention may also comprise a preservative so that the compositions enjoy an extended shelf life following manufacture and prior to sale and use. 10 It is apparent that chelating agents are prone to attack by bacteria, fungi, moulds and other types microorganisms which cause spoilage. Preferred preservatives are, for example, urea, methyl paraben, propyl paraben, ethyl paraben, ethanol, and sorbic acid. Particularly preferred is urea. Preservatives are employed in the present invention in an amount of 0.1 to 50.0% (w/v), preferably 0.1 to 5.0% (w/v) and more preferably 0.5 to 2.0% (w/v). 15 The compositions of this invention may also include other actives capable of functioning in different ways to enhance the benefits of the compositions, such as, depilatories/hair growth suppressants, sunscreens, hair lightening agents, antiperspirants, fragrants and colouring agents. 20 It will be appreciated that following topical application of the composition to remove unwanted hair regrowth of hair will generally occur in some individuals unless the composition is reapplied repeatedly to prevent regrowth. If the hair is very dark in colour it may be advantageous to incorporate in the compositions a hair lightening agent to ensure that regrowth is light in colour and therefore less noticeable. A preferred hair lightening agent is kojic acid 25 preferably present in an amount of 0.1 to 20% by weight of the composition. However, it has also been unexpectedly found that following application of the subject compositions to mammalian skin, hair regrowth is softer in texture and lighter in colour. Individual hair strands are of decreased diameter. Thus, the present invention also provides a 30 method for softening and lightening terminal mammalian hair.

WO 99/53892 PCT/AU99/00296 -9 The composition according to the invention can also optionally comprise a conventional hair removal ingredient such as thioglycollate in an amount sufficient to remove unwanted hair already present to obtain best results. Alternatively, a two step procedure can be employed in which unwanted hair is first removed by a conventional method, and then a composition 5 according the present invention, with or without a further thioglycollate, is applied to the skin to eliminate hair regrowth. In a preferred embodiment, the hair is first removed by a method, such as, shaving or waxing which breaks the surface layer of the skin facilitating penetration of the composition into the follicular canal. 10 The compositions according the present invention can also comprise one or more conventional antiperspirant active substances which can be of particular value if the composition is to be used on the underarm. Such compositions can thus be used on a daily basis to prevent unwanted hair growth and eliminate or reduce perspiration and body malodour. Examples of conventional antiperspirant activities include astringent metallic salts such as aluminium chloride. 15 The compositions may also be formulated as a shaving product such as a shaving mousse. The compositions of the present invention are preferably formulated to have a pH of 7. The pH values of these compositions most preferably range from about 6 to 8, even more preferably 20 from about 6.5 to 7.5. Compositions having a pH within the range of about 6.5 to 7.5 tend to exhibit less skin irritation and odour and have greater shelf stability than compositions having a pH of greater than about 8.5. The pH of the compositions of the present invention may be adjusted by the addition of a base such as sodium hydroxide. 25 The compositions of the present invention are generally prepared by conventional methods such as are known in the art of making topical compositions. Such methods typically involve mixing an effective amount of one or more chelating agents with one ore more cosmetically and/or pharmaceutically acceptable topical carriers. 30 The present invention accordingly provides for the use of one or more chelating agents, as WO 99/53892 PCT/AU99/00296 - 10 herein defined, for topical application to mammalian skin for reducing or retarding hair growth, or for eliminating unwanted hair from the skin surface. A preferred method of applying the subject compositions involves multiple topical application to areas where unwanted hair grows. Once applied, the composition is left on and is not removed. The subject compositions are 5 administered to the skin in an amount and frequency which can vary widely depending on the area in question, the desired effect and/or personal needs. It is suggested, for example, that topical application occurs five times daily to once every other day, preferably three times daily to once daily and most preferably two times daily (morning and night). Preferably, the compositions are applied to the skin after the skins surface has been broken, for example, by 10 waxing or shaving so as to facilitate penetration of the composition into the follicular canal. The compositions will preferably contain 0.001 to 50.0 mg of the chelating agent per cm 2 skin, more preferably from 0.01 to 30 mg/cm 2 skin, more preferably still from 2.0 to 10.0 mg/cm 2 skin. The period of topical application should be as is needed by the individual. Thus, the compositions may be used prophylactically over a mammals life for continued regulation of hair 15 regrowth. In certain individuals, application of the compositions may result in elimination of hair regrowth altogether. The present invention is now illustrated by the following non-limiting examples. 20 Example I A topical composition is prepared by combining the following components utilizing conventional mixing techniques and the pH is adjusted to 6.8 by adding NaOH. 25 %w/v EDTA 2.0 Glycerin 1.0 Urea 1.0 Water 96.0 30 WO 99/53892 PCT/AU99/00296 -11 A dark haired 24 year old female topically applied the above composition in the form of a lotion to the skin of her leg. Before application, terminal hair was first removed by waxing. The composition was applied topically morning and night for the next five days. Vellus hair regrowth (mm) was measured weekly using calipers. After three weeks when the vellus hair had 5 grown to a noticeable 4.8 mm, the hair was removed by a second waxing and the composition re-applied topically morning and night for the next five days. This time it took six weeks for the vellus hair to grow to a length of 5.1 mm. The hair was then removed by a third waxing and the composition topically reapplied morning and night for the next five days. By the eighth week, the hair had only grown to a length of 3.7 mm. The hair was removed by a fourth waxing 10 and the composition topically reapplied morning and night for the next five days. By the eighth week the hair had only grown to a length of 2.3 mm. The results of the experiment are shown in Table 1. Waxing Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 15 No: 1 0.4 1.9 4.8 2 0.2 1.0 1.6 2.2 4.2 5.1 3 0 0.3 0.7 1.2 1.9 2.5 3.2 3.7 4 0 0 0.4 0.6 0.9 1.4 1.9 2.3 20 Table 1 Regrowth of vellus hair (mm) per week. By comparing the results for week 3 after waxing No. 1 and week 3 after waxing No. 4 it can be seen that there is a 92% reduction in vellus hair regrowth. Furthermore, the rate of vellus 25 hair re-growth is significantly reduced. Moreover, the hair which regrew was much lighter and finer in texture. Example 2 30 The experiment described in Example 1 was performed on a 28 year old female with blond hair.

WO 99/53892 PCT/AU99/00296 -12 The results of the experiment are shown in Table 2. Waxing Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 No: 5 1 0.6 1.1 3.7 4.2 4.5 2 0.4 0.9 2.7 3.1 3.9 4.3 3 0.1 0.1 0.4 0.8 1.4 1.9 2.3 2.9 4 0 0 0 0.2 0.6 1.0 1.3 1.8 10 Table 2 Regrowth of vellus hair (mm) per week. It can be seen by comparing the results of week 5 after waxing No. 1 to week 5 after waxing No. 4 that there is a 87% reduction in hair re-growth. Similarly, the rate of hair-regrowth is significantly reduced and the hair which regrew was much finer in texture. 15 It should be understood that the present invention has been described by way of example only and that modifications and/or alterations thereto, which would be obvious to a person skilled in the art, based upon, the disclosure herein, are also considered to be included within the scope of the present invention as claimed in the appended claims. 20 Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising" will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Claims (15)

1. 2. The composition of claim 1, wherein said chelating agents are selected from the group comprising: OH, NH 3 , xanthates, carboxylates, nitrates, ethylenediamene (en), 2,2' 15 bipyridine (bipy), 1, 10-phenanthroline (phen), terpyridine (terpy), diethylenetriamine (dien), glyme, P-diketonates, triethylenetetramine (trien), ethylenediaminetetraacetic acid (EDTA), triethylenetriaminepentaacetic acid (DPTA), ethyleneglycol-bis(P aminoethylether)-N,N,N',N'-tetracetic acid (EGTA), phthalocyanine, porphyrin acetylacetonate (acac), carbonate, glycine (gly), tetraazacyclotetradecane (cyclam), 20 oxalate (ox) and nitrilotriacetate (nta).
2. 3. The composition of claim 2, wherein said chelating agent is EDTA.
3. 4. The composition according to anyone of claims 1 to 3, wherein said chelating agent is 25 a sodium salt.
4. 5. The composition according to anyone of claims 1 to 4, wherein the chelating agent is present in an amount between 0.1 to 50.0% (w/v). 30 WO 99/53892 PCT/AU99/00296 -14
5. 6. The composition according to claim 5, wherein said chelating agent is present in an amount between 0.5 to 5.0% (w/v).
6. 7. The composition according to claim 6, wherein said chelating agent is present in an 5 amount between 1.0 to 2.0% (w/v).
7. 8. The composition according to anyone of claims 1 to 7, wherein the composition has a pH between 6 and 8. 10 9. The composition according to claim 8, wherein the composition has a pH of 7.
8. 10. The composition according to anyone of claims 1 to 9 further comprising one or more of a hair lightening agent, a thioglycollate, an antiperspirant agent, a sunscreen agent, a fragrance or colouring agent. 15
9. 11. A method of reducing, retarding or eliminating mammalian hair growth which comprises topically applying to the skin of a mammal in need of treatment to reduce, retard or eliminate hair growth a composition according to anyone of claims 1 to 10. 20 12. The method according to claim 11, wherein the amount of chelating agent applied to the skin is from 0.001 to 50.0 mg per cm 2 skin.
10. 13. The method according to claim 12, wherein the amount of chelating agent applied to the skin is from 2.0 to 10.0 mg per cm 2 skin. 25
11. 14. The method according to anyone of claims 10-13, wherein the composition is applied from five times a day to once every other day.
12. 15. The method according to claim 14, wherein the composition is applied three times a day 30 to once a day. WO 99/53892 PCT/AU99/00296 - 15
13. 16. The method according to claim 15, wherein the composition is applied twice daily.
14. 17. The method according to anyone of claims 11-16, wherein terminal or vellus hair is first 5 removed by waxing or shaving prior to topical application of the composition.
15. 18. A method for softening and lightening terminal hair in mammalian skin which comprises topically applying to the skin of a mammal in need of treatment to soften and lighten mammalian terminal hair a composition according to anyone of claims 1 to 10. 10