Patent Publication Number: US-2010120871-A1

Title: Hair care compositions, methods, and articles of commerce that can increase the appearance of thicker and fuller hair

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of U.S. Provisional Application No. 61/112,916 filed Nov. 10, 2008. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to hair care compositions, methods, and articles of commerce that can increase the appearance of thicker and/or fuller hair. The present invention also relates to methods of marketing such compositions. 
     BACKGROUND OF THE INVENTION 
     Many attributes contribute to the appearance of hair considered to be attractive. For instance, hair with a full and thick appearance is very desirable, whether it be on the scalp, beard, or moustache regions. In contrast, hair with a thin appearance is not as attractive, and can even lead to a perception that the thin-haired individual is older than his chronological age. Furthermore, thin hair can be more difficult to style, and typically cannot be styled into as many hairstyles, leaving the individual frustrated and with an unkempt appearance. Because of the foregoing problems associated with thin hair, many thin-haired individuals expend great effort and time on grooming, yet still do not attain their desired hairstyle and appearance. This can lead to frustration and/or lack of confidence in his or her appearance. These problems can be experienced by both female and male consumers. 
     Accordingly, there is a need to provide consumers with a way to increase the fullness and thickness of hair appearance, thus resulting in younger-looking, more attractive hair appearance. 
     SUMMARY OF THE INVENTION 
     The present invention relates to hair care compositions, methods, and articles of commerce that can help increase the appearance of fuller and/or thicker of hair, thus resulting in younger-looking hair, by increasing the diameter of hair shafts and follicles. The invention also relates to methods of marketing. 
     In one aspect, the hair care composition comprises a synergistic mixture of an indole compound, a vitamin B3 compound, and a panthenol compound. In a particular embodiment, the synergistic mixture comprises indole-3-acetic acid, niacinamide, and panthenol. In one embodiment, the composition comprises from about 0.01% to about 10% of an indole compound (e.g., indole-3-acetic acid), in another embodiment from about 0.05% to about 5% of an indole compound, and in yet another embodiment from about 0.1% to about 2% of an indole compound. In some embodiments, the composition comprises from about 0.1% to about 25% of a vitamin B3 compound (e.g., niacinamide), in another embodiment from about 0.25% to about 15% of a vitamin B3 compound, and in yet another embodiment from about 1% to about 10% of a vitamin B3 compound. In some embodiments, the composition comprises from about 0.01% to about 3% of a panthenol compound (e.g., panthenol), in another embodiment from about 0.02% to about 2% of a panthenol compound, and in yet another embodiment from about 0.1% to about 1% of a panthenol compound. The composition can optionally comprise any other suitable ingredients as desired. In one embodiment, the composition also comprises a thickener that helps to hold the active agents on the scalp, providing substantivity to the composition, such that it does not drip undesirably onto unintended areas of the body, clothing, or home furnishings. 
     A wide variety of other additional components can be formulated into the present compositions. These include: hair growth agents such as minoxidil; anti-dandruff agents such as zinc pyrithione and selenium sulfide; conditioning agents such as hydrolysed collagen, vitamins, hydrolysed keratins, proteins, plant extracts, xanthines (e.g., caffeine), and nutrients. 
     These and other features, aspects, and advantages of the present invention will become evident to those skilled in the art from a reading of the present disclosure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a graphical representation of Table 1A data from Example 13. This figure demonstrates the synergistic effect that an indole-3-acetic acid (“IAA”), niacinamide, and panthenol combination has on dermal papilla (“DP”) cell survival. 
         FIG. 1B  is a graphical representation of Table 1B data from Example 13. This figure demonstrates the synergistic effect that an indole-3-acetic acid (“IAA”), niacinamide, and panthenol combination has on dermal papilla (“DP”) cell survival. 
         FIG. 2A  is a graphical representation of Table 2A data from Example 13. This figure demonstrates the synergistic effect that an indole-3-Carbinol (“I3C”), niacinamide, and panthenol combination has on dermal papilla (“DP”) cell survival. 
         FIG. 2B  is a graphical representation of Table 2B data from Example 13. This figure demonstrates the synergistic effect that an indole-3-Carbinol (“I3C”), niacinamide, and panthenol combination has on dermal papilla (“DP”) cell survival. 
         FIG. 3  is a graphical representation of Table 3 data from Example 13. This figure demonstrates the synergistic effect that a tryptophol (“HI”), niacinamide, and panthenol combination has on dermal papilla (“DP”) cell survival. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     While the specification concludes with the claims particularly pointing out and distinctly claiming the invention, it is believed that the present invention will be better understood from the following description. 
     Although not wishing to be limited by theory, it is believed by applicants that topical application of the inventive synergistic composition stimulates aquaporin 3 (“AQP3”) up-regulators, which in turn results in thicker hair shafts and follicles. This increase in the diameter of the hair shafts and follicles leads to the appearance of hair that is thicker and fuller, thus resulting in the appearance of fuller and/or thicker hair. Furthermore, it leads to the appearance of younger looking hair, since hair diameter is known to decrease with one&#39;s chronological age. (Olsen, E. A. et al., Evaluation and treatment of male and female pattern hair loss. J. Am. Acad. Dermatol. Vol. 52, Number 2, Feb. 2005, pg. 305.); (Birch, M. P. et al., Hair density, hair diameter and the prevalence of female pattern loss. British Journal of Dermatology 2001; 144: 297-304.); (Courtois, M. et al. Ageing and hair cycles. British Journal of Dermatology 1995; 132:86-93.); (Lacarrubba, F. et. al., Videodermatoscopy enhances diagnostic capability in some forms of hair loss. Am. J. Clin. Dermatol. 2004; 5 (3): 205-208); (De Lacharrière, O. et al., Hair Diameter Diversity. Arch. Dematol. 2001; 137:641-646); (Hoffman, R., Trichoscan: combining epiluminescence microscopy with digital image analysis for the measurement of hair growth in vivo. Eur. J. Drmatol. 2001; 11:362-8.) 
     Aquaporins (“AQP”) are a family of water-channel proteins found in the plasma membrane. Currently, 13 AQP have been identified in humans, and they are classified into two groups: aquaporins and aquaglyceroporins. Most of the identified aquaporins belong to the aquaporin group that is selective primarily for the passage of water. AQP 3, 7, 9, and 10 belong to the aquaglyceroporin group that facilitates the movement of water, glycerol, and various other solutes. 
     Through immunocytochemistry, applicants have found that AQP3 is strongly expressed in the proliferating keratinocytes of the hair follicles. In addition, applicants have also found that AQP3 immunostaining can be detected in the hair shaft. It is believed by applicants that AQP3 up-regulators increase the thickness of hair fibers and follicles by stimulating AQP3 expression, which allows more water and water-binding molecules to be transported into the cells, thus improving cellular metabolism and increasing cellular size. This leads to increased hydration of the hair&#39;s cuticle layer, which expands the cuticle, making it thicker. As a result, the diameter of the hair fiber and of the hair follicle increase, resulting in the appearance of thicker, fuller hair. 
     Because consumers are not familiar with the use of the synergistic composition described herein for the purpose of increasing the appearance of thicker and fuller hair, the present invention also provides methods of marketing that can be advantageously used to help potential consumers appreciate the benefits that they can derive from such a product and/or its method of use. Furthermore, a method of marketing a first composition by comparing it to a second composition is also provided. This method helps consumers to identify products that can potentially give similar benefits. 
     All percentages, parts and ratios are based upon the total weight of the hair care compositions of the present invention and all measurements made are at 25° C., unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include carriers or by-products that may be included in commercially available materials, unless otherwise specified. 
     As used herein, the term “hair care compositions” are compositions that are applied to the hair and/or the skin underneath the hair, including compositions used to treat or care for the hair. Products contemplated by the phrase “hair care composition” include, but are not limited to liquids, creams, wipes, hair conditioners (rinse-off and leave-on), hair tonics, shampoos, hair colorants, mousses, propellant lotions, emulsions, shave gels, after-shave tonics and lotions, temporary beard hair dyes, and the like. 
     “Increase the appearance of fuller and thicker hair” means the diameters of hair follicles and/or shafts in the subject region of hair (e.g., scalp, beard) are increased by a statistically significant amount, when an effective amount of a composition of the present invention is topically applied to the desired region over a result-effective period of time. 
     “Mammalian hair,” as referenced herein, includes hair on any part of the body of a mammal, and can include but is not limited to facial, cranial, or body hair. For instance, it can include hair on the scalp, head, neck, beard, moustache, eyebrows and sideburns hair. 
     The term “topical application,” as used herein, means to apply or spread the compositions of the present invention onto the surface of the keratinous tissue from which the hair to be affected grows. 
     The term “dermatologically-acceptable,” as used herein, means that the compositions or components thereof so described are suitable for use in contact with mammalian keratinous tissue without undue toxicity, incompatibility, instability, allergic response, and the like. 
     The term “effective amount,” as used herein, means an amount of a compound or composition sufficient to increase the diameter of the shafts in the subject region of hair by a statistically significant amount. 
     The term “result-effective period of time,” as used herein, means a period of time sufficient to increase the diameter of the hair shafts in the subject region of hair by a statistically significant amount. 
     The term “safe and effective amount,” as used herein, means an amount of a compound or composition sufficient to increase the diameter of the hair shafts in the subject region of hair by a statistically significant amount, when used for a result-effective period of time, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan. 
     The term “same color,” as used herein, means a HunterLab color space Delta E (Delta L+Delta a+Delta b) of 1 or less. The Hunter L, a, b Color Scale is well accepted in the art, and is described in the Applications Note “Insight on Color,” Vol. 8, No. 9, by HunterLab, Hunter Associates Laboratory, Inc., Reston, Va., U.S.A. (2008). 
     Unless otherwise specified, in all embodiments of the present invention, all percentages are by weight of the total composition, unless specifically stated otherwise. All ratios are weight ratios, unless specifically stated otherwise. All ranges are inclusive and combinable. The number of significant digits conveys neither limitations on the indicated amounts nor on the accuracy of the measurements. All numerical amounts are understood to be modified by the word “about” unless otherwise specifically indicated. All measurements are understood to be made at 25° C. and at ambient conditions, where “ambient conditions” means conditions under about one atmosphere of pressure and at about 50% relative humidity. 
     A. Hair Care Compositions 
     In one aspect, the present invention provides hair care compositions that can be used to increase the appearance of thicker and fuller hair. In one embodiment, the hair care composition comprises a synergistic composition comprising an indole compound, a vitamin B3 compound, and a panthenol compound. Preferably, the indole compound, vitamin B3 compound, and panthenol compound are present in a safe and effective amount. Optionally, the hair care compositions can comprise a dermatologically-acceptable carrier and/or any desired suitable optional ingredients. 
     Particular materials are described in more detail below. 
     1. Indole Compounds 
     The compositions of the present invention can include an indole compound. As used herein, “indole compound” means one or more indoles, derivatives thereof, mixtures thereof, or salts thereof Indole compounds are represented by the structure: 
     
       
         
         
             
             
         
       
     
     Indole compounds that can be useful herein include, but are not limited to, indole-3-acetic acid and indole-3-carbinol. In particular embodiments, the indole compound comprises an indole derivative at 3 and/or 5 position of the indole ring. In some embodiments, the indole compound comprises one or more of Indole-3-acetic acid (CAS#87-51-4), Indole-3-carbinol (CAS#700-06-1), 3-Methoxymethylindole (CAS#78440-76-3), 5-Methoxytryptophol (CAS#712-09-4), 5-Hydroxytryptophol (CAS#154-02-9), Tryptophol (CAS#526-55-6), 5-methoxy-1H-Indole-3-methanol (CAS#77419-78-4), 5-methyl-1H-Indole-3-methanol (CAS#215997-77-6), 5-fluoro-1H-Indole-3-methanol (CAS#773869-43-5), 5-Hydroxyindol-3-ylacetic acid (CAS#54-16-0), and 5-hydroxy-1H-Indole-3-propanoic acid (CAS#103986-23-8). 
     In one embodiment, the composition comprises from about 0.01% to about 10% of an indole compound, in another embodiment from about 0.05% to about 5% of an indole compound, and in yet another embodiment from about 0.1% to about 2% of an indole compound. 
     2. Vitamin B 3  Compounds 
     The compositions of the present invention can include a vitamin B3 compound. Vitamin B3 compounds are particularly useful for regulating skin conditions, as described in U.S. Pat. No. 5,939,082. In some embodiments, the composition comprises from about 0.1% to about 25% of a vitamin B3 compound, in another embodiment from about 0.25% to about 15% of a vitamin B3 compound, and in yet another embodiment from about 1% to about 10% of a vitamin B3 compound. 
     As used herein, “vitamin B3 compound” means one or more compounds having the formula: 
     
       
         
         
             
             
         
       
     
     wherein R is —CONH 2  (i.e., niacinamide), —COOH (i.e., nicotinic acid) or —CH2OH (i.e., nicotinyl alcohol); derivatives thereof; mixtures thereof; and salts of any of the foregoing. 
     Exemplary derivatives of the foregoing vitamin B3 compounds include nicotinic acid esters, including non-vasodilating esters of nicotinic acid (e.g., tocopherol nicotinate, myristyl nicotinate), nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide. 
     Suitable esters of nicotinic acid include nicotinic acid esters of C 1 -C 22 , preferably C 1 -C 16 , more preferably C 1 -C 6  alcohols. The alcohols are suitably straight-chain or branched chain, cyclic or acyclic, saturated or unsaturated (including aromatic), and substituted or unsubstituted. The esters are preferably non-vasodilating. As used herein, “non-vasodilating” means that the ester does not commonly yield a visible flushing response after application to the skin in the subject compositions (the majority of the general population would not experience a visible flushing response, although such compounds may cause vasodilation not visible to the naked eye, i.e., the ester is non-rubifacient). Non-vasodilating esters of nicotinic acid include tocopherol nicotinate and inositol hexanicotinate; tocopherol nicotinate is preferred. 
     Other derivatives of the vitamin B 3  compound are derivatives of niacinamide resulting from substitution of one or more of the amide group hydrogens. Nonlimiting examples of derivatives of niacinamide useful herein include nicotinyl amino acids, derived, for example, from the reaction of an activated nicotinic acid compound (e.g., nicotinic acid azide or nicotinyl chloride) with an amino acid, and nicotinyl alcohol esters of organic carboxylic acids (e.g., C1-C18). Specific examples of such derivatives include nicotinuric acid (C8H8N2O3) and nicotinyl hydroxamic acid (C6H6N2O2), which have the following chemical structures: nicotinuric acid: 
     
       
         
         
             
             
         
       
     
     nicotinyl hydroxamic acid: 
     
       
         
         
             
             
         
       
     
     Exemplary nicotinyl alcohol esters include nicotinyl alcohol esters of the carboxylic acids salicylic acid, acetic acid, glycolic acid, palmitic acid and the like. Other non-limiting examples of vitamin B3 compounds useful herein are 2-chloronicotinamide, 6-aminonicotinamide, 6-methylnicotinamide, n-methyl-nicotinamide, n,n-diethylnicotinamide, n-(hydroxymethyl)-nicotinamide, quinolinic acid imide, nicotinanilide, n-benzylnicotinamide, n-ethylnicotinamide, nifenazone, nicotinaldehyde, isonicotinic acid, methyl isonicotinic acid, thionicotinamide, nialamide, 1-(3-pyridylmethyl)urea, 2-mercaptonicotinic acid, nicomol, and niaprazine. 
     Examples of the above vitamin B3 compounds are well known in the art and are commercially available from a number of sources, e.g., the Sigma Chemical Company (St. Louis, Mo.); ICN Biomedicals, Inc. (Irvin, Calif.) and Aldrich Chemical Company (Milwaukee, Wis.). 
     One or more vitamin B3 compounds may be used herein. Preferred vitamin B3 compounds are niacinamide and tocopherol nicotinate. Niacinamide is more preferred. 
     When used, salts, derivatives, and salt derivatives of niacinamide are preferably those having substantially the same efficacy as niacinamide. Salts of the vitamin B3 compound are also useful herein. Nonlimiting examples of salts of the vitamin B3 compound useful herein include organic or inorganic salts, such as inorganic salts with anionic inorganic species (e.g., chloride, bromide, iodide, carbonate, preferably chloride), and organic carboxylic acid salts (including mono-, di- and tri-C1-C18 carboxylic acid salts, e.g., acetate, salicylate, glycolate, lactate, malate, citrate, preferably monocarboxylic acid salts such as acetate). These and other salts of the vitamin B3 compound can be readily prepared by the skilled artisan, for example, as described by W. Wenner, “The Reaction of L-Ascorbic and D-Iosascorbic Acid with Nicotinic Acid and Its Amide”, J. Organic Chemistry, Vol. 14, 22-26 (1949). Wenner describes the synthesis of the ascorbic acid salt of niacinamide. 
     In a preferred embodiment, the ring nitrogen of the vitamin B3 compound is substantially chemically free (e.g., unbound and/or unhindered), or after delivery to the skin becomes substantially chemically free (“chemically free” is hereinafter alternatively referred to as “uncomplexed”). More preferably, the vitamin B3 compound is essentially uncomplexed. Therefore, if the composition contains the vitamin B3 compound in a salt or otherwise complexed form, such complex is preferably substantially reversible, more preferably essentially reversible, upon delivery of the composition to the skin. For example, such complex should be substantially reversible at a pH of from about 5.0 to about 6.0. Such reversibility can be readily determined by one having ordinary skill in the art. 
     More preferably the vitamin B3 compound is substantially uncomplexed in the composition prior to delivery to the keratinous tissue. Exemplary approaches to minimizing or preventing the formation of undesirable complexes include omission of materials which form substantially irreversible or other complexes with the vitamin B3 compound, pH adjustment, ionic strength adjustment, the use of surfactants, and formulating wherein the vitamin B3 compound and materials which complex therewith are in different phases. Such approaches are well within the level of ordinary skill in the art. 
     Thus, in a preferred embodiment, the vitamin B3 compound contains a limited amount of the salt form and is more preferably substantially free of salts of a vitamin B3 compound. Preferably the vitamin B3 compound contains less than about 50% of such salt, and is more preferably essentially free of the salt form. The vitamin B3 compound in the compositions hereof having a pH of from about 4 to about 7 typically contain less than about 50% of the salt form. 
     The vitamin B3 compound may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources. The vitamin B3 compound is preferably substantially pure, more preferably essentially pure. 
     3. Panthenol Compounds 
     The compositions of the present invention may comprise a panthenol compound. As used herein, the term “panthenol compound” is broad enough to include panthenol, one or more pantothenic acid derivatives, salts thereof, and mixtures thereof. Panthenol and its derivatives can include D-panthenol ([R]-2,4-dihydroxy-N-[3-hydroxypropyl)]-3,3-dimethylbutamide), DL-panthenol, pantothenic acids and their salts, preferably the calcium salt, panthenyl triacetate, royal jelly, panthetine, pantotheine, panthenyl ethyl ether, pangamic acid, pantoyl lactose, Vitamin B complex, or mixtures thereof 
     In one embodiment, the composition comprises from about 0.01% to about 3% panthenol compound, in another embodiment from about 0.02% to about 2%, and in yet another embodiment from about 0.1% to about 1%. 
     Compositions comprising pantothenic acid derivatives that remain more stable than panthenol and other similar materials in acidic compositions or in compositions containing acid-producing materials such as aluminum-containing actives, can also be suitable for use herein. The selected pantothenic acid derivatives are most typically in liquid form and dispersed throughout or otherwise solubilized within the liquid carrier component of the composition. 
     The term “pantothenic acid derivative” as used herein refers to those materials that conform to the formula: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  are hydrogen, C2-C20 hydrocarbons, C2-C20 carboxylic acid esters, or combinations thereof, provided that not more than two of R1, R2 and R3 are hydrogen. In one embodiment, R 1 , R 2  and R 3  are independently selected from hydrogen, C2-C8 hydrocarbons, C2-C8 carboxylic acid esters, or combinations thereof; in another embodiment, R 1  and R 2  are hydrogen, and R 3  is a C2-C8 hydrocarbon, C2-C8 carboxylic acid ester, or combinations thereof; in yet another embodiment, R 1  and R 2  are hydrogen and R 3  is ethyl. The selected pantothenic acid derivatives may be derived or otherwise obtained from any known source, which may include pantothenic acid or materials other than pantothenic acid, so long as the resulting material has the above defined chemical formula. 
     Specific non-limiting examples of selected pantothenic acid derivatives for use herein include ethyl panthenol, panthenyl triacetate, and combinations thereof In a particular embodiment, a pantothenic acid derivative comprises the d-isomeric form(s) of such derivative form(s), such as d-ethyl panthenol. 
     4. Optional Ingredients 
     The compositions of the present invention can also additionally comprise any suitable optional ingredients as desired. For example, the composition can optionally include other active or inactive ingredients. 
     A wide variety of additional components can be formulated into the present compositions. These include: hair growth agents such as minoxidil; anti-dandruff agents such as zinc pyrithione and selenium sulfide; conditioning agents such as hydrolysed collagen, vitamins, hydrolysed keratins, proteins, plant extracts, xanthines (e.g., caffeine), and nutrients . 
     For instance, the present invention may include additional skin care actives selected from the group consisting of sugar amines, retinoids, peptides, dialkanoyl hydroxyproline, hexamidine, salicylic acid, phytosterol, sunscreen actives, water soluble vitamins, oil-soluble vitamins, their derivatives, their precursors, and combinations thereof. Furthermore, the composition may include suitable ingredients that are conventionally used in given product types. The CTFA Cosmetic Ingredient Handbook, Tenth Edition (published by the Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, D.C.) (2004) (hereinafter “CTFA”), describes a wide variety of nonlimiting materials that can be added to the composition herein. Examples of these ingredient classes include, but are not limited to: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, etc. (e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti-caking agents, antifoaming agents, antimicrobial agents (e.g., iodopropyl butylcarbamate), antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or materials, e.g., polymers, for aiding the film-forming properties and substantivity of the composition (e.g., copolymer of eicosene and vinyl pyrrolidone), opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin bleaching and lightening agents, (e.g. hydroquinone, kojic acid, ascorbic acid, magnesiuim ascorbyl phosphate, ascorbyl glucoside, pyridoxine), skin-conditioning agents (e.g. humectants and occlusive agents), skin treating agents (e.g. vitamin D compounds, mono-,di-, and tri-terpenoids, beta-ionol, cedrol), thickeners, hair conditioning agents, and surfactants. 
     In one embodiment, the composition comprises a thickener to increase the substantivity of the composition, such that it does not drip undesirably onto other areas of the body, onto clothing, or onto home furnishings. Any suitable thickener can be used, for example, a cellulose-based thickener such as hydroxypropylmethylcellulose. In some embodiments, the composition comprises alcohol and/or water. In a particular embodiment, the composition comprises from 10-90% alcohol, alternatively from 15-75% alcohol, or alternatively from 25-50% alcohol. Any suitable alcohol, such as ethanol, can be used. 
     In one embodiment, the composition can comprise at least one nitrone derivative. Nitrones are capable of irreversibly capturing electrons and/or free radicals, thereby reducing the relative amount of oxidative potential in a microenvironment. Thus, these materials have been referred to as “spin traps” since the ability to detect a free radical via spectroscopic means involves monitoring the spin resonance of free radicals. By irreversibly binding the free radical, the spectroscopic signal becomes reduced due to the free radical becoming trapped by a nitrone such as a-phenyl butyl nitrone (“PBN”). These can include α-phenyl butyl nitrone, PBN doxylcyclohexane radicals, 5,5-dimethyl pyrroline N-oxide (“DMPO”), α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (“POBN”), 2,2,6,6-tetramethylpiperidine 1-oxide, 4-hydroxytetramethylpiperidine 1-oxide, and the salts of N-(1-oxido-2,2,6,6-tetramethyl-4-piperidyl)-N,N-dimethyl-N-hydroxyethylammonium, 3,5-dibromo-4-nitrosobenzenesulfonic acid, 2-methyl-2-nitrosopropane, nitrosodisulfonic acid, α-(4-pyridyl-1-oxide)-N-t-butylnitrone, 3,3,5,5-tetramethylpyrroline N-oxide, and 2,4,6-tri-t-butylnitrosobenzene, or spin-trapping derivatives thereof, and mixtures thereof In a particular embodiment, the spin trap is PBN. 
     C. Method for Increasing the Appearance of Thicker and Fuller Hair 
     The present invention also provides a method for increasing the diameter of the hair shaft and follicle, leading to an appearance of thicker and/or fuller hair. In one aspect, the method comprises applying a hair care composition comprising the synergistic composition of the present invention to a skin surface from which a region of styled hair grows. For instance, the hair care composition can be applied to the scalp and/or face (e.g., beard or moustache area). In another embodiment, the method comprises topically applying a hair care composition comprising an effective amount of the synergistic composition to a region of skin of a mammal seeking to increase the appearance of thicker and/or fuller hair. 
     The region of hair can be located on any part of the body. For instance, it can grow from a skin surface located on at least a portion of the scalp or the face. 
     In still another embodiment, the method comprises applying the composition according to a regimen, wherein said regimen comprises: 
     (a) cleansing the scalp and/or face to form a cleansed scalp and/or face; 
     (b) topically applying the composition to said cleansed scalp and/or cleansed face. 
     D. Article of Commerce and Method of Marketing 
     In another aspect, the present invention provides articles of commerce and methods of marketing hair care compositions that can be used to increase the appearance of thicker and fuller hair. In one embodiment, the article of commerce comprises: 
     (1) a container; 
     (2) a hair care composition contained within said container, wherein said hair care composition comprises an indole compound, a vitamin B3 compound, and a panthenol compound; and 
     (3) a communication, wherein said communication communicates that use of said hair care composition can increase the appearance of thicker and fuller hair. 
     In another aspect, the present invention provides methods of marketing hair care compositions that can be used to increase the appearance of thicker and fuller hair. In one embodiment, the method comprises: 
     (a) offering for sale a hair care composition comprising an indole compound, a vitamin B3 compound, and a panthenol compound; 
     (b) communicating that said composition can be used to increase the appearance of thicker and fuller hair. 
     In another aspect, the invention provides a marketing method that utilizes a comparison of a first hair care composition to a second hair care composition, in order to market the first hair care composition. In one embodiment, the method comprises offering for sale a first article of commerce, wherein said first article of commerce comprises: 
     (a) a first hair care composition; and 
     (b) a communication, wherein said communication compares said first hair care composition to a second hair care composition, wherein said second hair care composition is comprised in a second article of commerce, wherein said second article of commerce comprises:
         (1) said second hair care composition comprising an indole compound, a vitamin B3 compound, and a panthenol compound; and   (2) a second communication, wherein said second communication communicates that said second hair care composition can be used to increase the appearance of thicker and fuller hair.       

     In another aspect, the invention provides a marketing method that utilizes at least one visual cue to communicate that a first hair care composition is similar to or the same as a second hair care composition, in order to market the first hair care composition. In one embodiment, the visual cue comprises a message. In particular embodiments, the message can comprise words such as “compare,” “compare to”, “like”, “similar”, “try instead of,” or the like. In another embodiment, the visual cue can comprise the same or similar graphics as those included on or near the packaging of the second hair care composition. A visual cue can be located at or on any suitable location. For instance, a visual cue can be located on or near product packaging, or on or near a store shelf. 
     In a particular embodiment, the first hair care composition is marketed in a container having at least two of the same colors as the container in which the second hair care composition is marketed. In one embodiment, the method comprises a method of marketing a first hair care composition, wherein said method comprises: 
     (a) offering for sale a first article of commerce, wherein said first article of commerce comprises:
         (1) a first container;   (2) a first hair care composition contained within said container;   (3) a first set of graphics disposed upon said first container, wherein said first set of graphics comprises at least two colors;       

     (b) locating said first article of commerce within visual sight of a second article of commerce, wherein said second article of commerce comprises:
         (1) a second container;   (2) a second hair care composition contained within said second container,   (3) a second set of graphics disposed upon said second container, wherein said second set of graphics comprises:
           (i) at least two of the same colors as those colors included in said first set of graphics; and   (ii) a communication, wherein said communication communicates that said second hair care composition can be used to increase the appearance of thicker and fuller hair.   
               

     As used herein, the term “consumer” or “potential consumer” means an actual or potential purchaser and/or an actual or potential user of the article of commerce and/or hair care composition. 
     Any container from which the hair care composition can be stored and/or contained can be used herein. Suitable containers can include, but are not limited to, bottles, tottles (i.e. a bottle that rests on its dispensing end), tubes, pouches, boxes, tubs, and cans. Furthermore, containers can include primary containers, which contain the hair care composition itself, or secondary containers, which contain at least one primary container that contains the composition. 
     As used herein, “set of graphics” or “graphics” refers to the text and/or pictorial images that are disposed on a container. As used herein, “disposed on” means integral with and/or located on the container and can include, but is not limited to, disposed directly thereon (e.g., printed directly on the container), disposed indirectly thereon (e.g., printed on a sticker that is affixed to the outer portion of the container), and/or applied to the container by any other suitable means (e.g., sprayed, bonded, drawn, painted, printed, or molded). 
     As used herein, “communication” means a message, and can include but is not limited to a printed (e.g., printed material attached directly or indirectly to the container), electronic, or broadcast message. 
     Optionally, said first article of commerce and said second article of commerce can be located within visual sight of one another. In a particular embodiment, said first article of commerce and said second article of commerce can be located adjacent to one another on a retail shelf or other retail display. 
     As used herein, “located within visual sight” of one another” means that the first article of commerce and the second article of commerce are located in proximity to one another such that a human (e.g., a potential consumer) with unassisted 20/20 vision can see both the first article of commerce and the second article of commerce at the same time. In a particular embodiment, said first article of commerce and said second article of commerce are located within 2 meters of each other. In another embodiment, said first article of commerce and said second article of commerce are located within 1 meter of each other. In a specific embodiment, said first article of commerce and said second article of commerce are located within 0.5 meter of each other. 
     As used herein, “similar” means providing one or more of the same consumer benefits (e.g., thicker hair) or comprising one or more of the same ingredients. 
     Examples 
     The following are non-limiting examples of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention, which would be recognized by one of ordinary skill in the art. 
     In the examples, all concentrations are listed as weight percent, unless otherwise specified, and the stated concentrations exclude materials such as diluents, filler, and so forth. The listed formulations, therefore, comprise the listed components at the stated concentrations, and exclude any minor materials associated with such components. As is apparent to one of ordinary skill in the art, the selection of these minors will vary depending on the physical and chemical characteristics of the particular ingredients selected to make the present invention as described herein. 
     
       
         
           
               
            
               
                   
               
               
                 Examples 1-4: Shampoo examples 
               
            
           
           
               
               
               
               
               
            
               
                   
                 1 
                 2 
                 3 
                 4 
               
               
                 Component 
                 (wt %) 
                 (wt %) 
                 (wt %) 
                 (wt %) 
               
               
                   
               
               
                 Water 
                 Q.S. 
                 Q.S. 
                 Q.S. 
                 Q.S. 
               
               
                 Rheology modifying system, anionic 
                 0.05 
                 0.05 
                 — 
                 — 
               
               
                 polymer MVE/MA crosslinked copolymer 
               
               
                 (Stabileze 06) 
               
               
                 Rheology modifying system, clay Hydrous 
                 0.05 
                 0.05 
                 0.05 
                 — 
               
               
                 Na, Mg silicate (Laponite XLS) 
               
               
                 Hydroxypropyl methylcellulose (PrimaFlo) 
                 — 
                 — 
                 0.10 
                 — 
               
               
                 Polyquaternium 10 (Ucare Polymer LR-400) 
                 0.50 
                 0.50 
                 0.50 
                 0.50 
               
               
                 Coconut monoethanolamide (Monamid CMA) 
                 1.09 
                 1.03 
                 1.03 
                 1.50 
               
               
                 Disodium EDTA (Disslovine Na 2 S) 
                 0.14 
                 0.14 
                 0.14 
                 0.10 
               
               
                 Sodium Benzoate (Purox S Grains) 
                 0.25 
                 0.25 
                 0.25 
                 0.25 
               
               
                 Sodium Citrate Dihydrate 
                 0.45 
                 0.45 
                 0.45 
                 0.45 
               
               
                 Sodium Laureth-3-Sulfate (SLE3S) 
                 2.18 
                 — 
                 — 
                 — 
               
               
                 Cocamidopropyl Betaine (Tegobetaine F-B) 
                 2.18 
                 — 
                 — 
                 — 
               
               
                 Sodium lauryl sulfate (SLS) 
                 6.55 
                 — 
                 — 
                 — 
               
               
                 Citric Acid 
                 0.08 
                 — 
                 — 
                 0.04 
               
               
                 BHT 
                 0.50 
                 0.50 
                 0.50 
                 0.50 
               
               
                 Sodium Chloride 
                 0.25 
                 0.75 
                 0.50 
                 0.01 
               
               
                 Sodium Hydroxide 
                 0.01 
                 — 
                 — 
                 — 
               
               
                 Dimethicone (Viscasil 3000,000) 
                 1.35 
                 1.35 
                 1.35 
                 1.35 
               
               
                 Ammonium Laureth-3-Sulfate (AE3S) 
                 0.07 
                 4.11 
                 6.00 
                 6.00 
               
               
                 Ethylene glycol distearate (EGDS) 
                 1.50 
                 1.50 
                 1.50 
                 1.50 
               
               
                 Ammonium Lauryl Sulfate (ALS) 
                 1.50 
                 6.88 
                 6.88 
                 10.00  
               
               
                 Indole-3-Acetic Acid 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                 Niacinamide 
                 2.00 
                 5.00 
                 2.00 
                 5.00 
               
               
                 Methylchloroisothiazolinone &amp; 
                  0.0005 
                  0.0005 
                  0.0005 
                  0.0005 
               
               
                 Methylisothiazolinone (Kathon CG) 
               
               
                 Fragrance 
                 0.70 
                 0.70 
                 0.70 
                 0.70 
               
               
                 PEG 7M (Polyox WSR-N-750) 
                 0.10 
                 — 
                 — 
                 0.10 
               
               
                 DL Panthenol 50% soln. (DL-Panthenol 50L) 
                 0.60 
                 0.60 
                 0.60 
                 0.60 
               
               
                 DL Panthenyl Ethyl Ether (Pantyl Ethyl Ether) 
                 0.03 
                 0.03 
                 0.03 
                 0.03 
               
               
                 Cetyl Alcohol 
                 — 
                 — 
                   
                 0.90 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 Example 5-7: Conditioner examples 
               
            
           
           
               
               
               
               
            
               
                   
                 5 
                 6 
                 7 
               
               
                 Component 
                 (wt %) 
                 (wt %) 
                 (wt %) 
               
               
                   
               
               
                 Dimethicone compound-1 *1 
                 — 
                 4.20 
                   
               
               
                 Dimethicone compound-2 *2 
                 — 
                 — 
                 2.00 
               
               
                 Silicone compound-2 *3 
                 3.50 
                 — 
               
               
                 Behenyl trimethyl 
                 2.25 
                 — 
                 3.38 
               
               
                 ammonium chloride *6 
               
               
                 Isopropyl alcohol 
                 0.60 
                 — 
                 0.90 
               
               
                 Stearamidopropyl 
                 — 
                 2.00 
                 — 
               
               
                 dimethylamine *7 
               
               
                 Glutamic acid *8 
                 — 
                 0.64 
                 — 
               
               
                 Cetyl alcohol *9 
                 1.90 
                 2.50 
                 2.30 
               
               
                 Stearyl alcohol *10 
                 4.60 
                 4.50 
                 4.20 
               
               
                 Polysorbate-20 *11 
                 — 
                 — 
                 — 
               
               
                 PPG-34 *12 
                 — 
                 — 
                 — 
               
               
                 Polyalphaolefm *13 
                 — 
                 — 
                 — 
               
               
                 BHT 
                 0.50 
                 0.50 
                 0.50 
               
               
                 Benzyl alcohol 
                 0.40 
                 0.40 
                 0.40 
               
               
                 Niacinamide 
                 2.00 
                 2.00 
                 5.00 
               
               
                 Methylchloroisothiazolinone/ 
                  0.0005 
                  0.0005 
                  0.0005 
               
               
                 Methylisothiazolinone *14 
               
               
                 Perfume 
                 0.35 
                 0.50 
                 0.35 
               
               
                 NaOH 
                  0.014 
                 — 
                  0.014 
               
               
                 Panthenol *15 
                 0.60 
                 0.60 
                 0.60 
               
               
                 Panthenyl ethyl ether *16 
                 0.05 
                 — 
                 0.05 
               
               
                 Indole-3-Acetic Acid 
                 1.00 
                 1.00 
                 1.00 
               
               
                 Vitamin E *18 
                 — 
                 0.01 
                 — 
               
               
                 Octyl methoxycinnamate 
                 — 
                 0.09 
                 — 
               
               
                 Benzophenone-3 
                 — 
                 0.09 
                 — 
               
               
                 Disodium EDTA 
                 0.13 
                 0.13 
                 0.13 
               
               
                 Deionized water 
                 Qs 
                 Qs 
                 Qs 
               
               
                   
               
               
                 Definitions of Components 
               
               
                 *1 Dimethicone/Cyclomethicone: a blend dimethicone having a viscosity of 18,000,000 mPas and cyclopentasiloxane available from GE Toshiba 
               
               
                 *2 Dimethicone blend: a blend of dimethicone having a viscosity of 18,000,000 mPas and dimethicone having a viscosity of 200 mPas available from GE Toshiba 
               
               
                 *3 Available from GE having a viscosity 10,000 mPas, and having following formula (I): 
               
               
                 (R 1 ) a G 3-a -SiOSiG 2 ) n OSiG b (R 1 ) 2-b ) m —O—SiG 3-a (R 1 ) a  (I) 
               
               
                 wherein G is methyl; a is an integer of 1; b is 0, 1 or 2, preferably 1; n is a number from 400 to about 600; m is an integer of 0; R 1  is a monovalent radical conforming to the general formula CqH 2q L, wherein q is an integer of 3 and L is —N(CH 3 ) 2   
               
               
                 *6 Behenyl trimethyl ammonium chloride/Isopropyl alcohol: Genamin KDMP available from Clariant 
               
               
                 *7 Stearamidopropyl dimethylamine: Lexamine S-13 available from Inolex 
               
               
                 *8 Glutamic acid: available from Ajinomoto 
               
               
                 *9 Cetyl alcohol: Konol series available from Shin Nihon Rika. 
               
               
                 *10 Stearyl alcohol: Konol series available from Shin Nihon Rika. 
               
               
                 *11 Polysorbate-20: Glycosperse L-20K available from Lonza Inc. 
               
               
                 *12 PPG-34: New Pol PP-2000 available from Sanyo Kasei. 
               
               
                 *13 Polyalphaolefin: PureSyn 100 available from ExxonMobil Chemical Company 
               
               
                 *14 Methylchloroisothiazolinone/Methylisothiazolinone: Kathon CG available from Rohm &amp; Haas 
               
               
                 *15 Panthenol: Available from Roche. 
               
               
                 *16 Panthenyl ethyl ether: Available from Roche. 
               
               
                 *17 Hydrolyzed collagen: Peptein 2000 available from Hormel. 
               
               
                 *18 Vitamin E: Emix-d available from Eisai. 
               
               
                 *19 Decyl glucoside: Plantacare 2000UP available from Cognis Japan Ltd. 
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 Examples 8-10: Tonic examples 
               
            
           
           
               
               
               
               
            
               
                   
                 8 
                 9 
                 10 
               
               
                 Component 
                 (wt %) 
                 (wt %) 
                 (wt %) 
               
               
                   
               
               
                 Alcohol 100% DEB 100 (Ethanol) 
                 25.00  
                 25.00  
                 25.00  
               
               
                 Carbomer (Carbopol Ultrez 21) 
                 0.10 
                 0.10 
                 0.10 
               
               
                 Triethanolamine 
                 0.20 
                 0.20 
                 0.20 
               
               
                 Indole-3-acetic acid 
                 0.20 
                 — 
                 — 
               
               
                 Hydroxy Indole 
                 — 
                 0.20 
                 — 
               
               
                 Indole-3-carbinol 
                 — 
                 — 
                 0.20 
               
               
                 Niacinamide 
                 5.00 
                 5.00 
                 5.00 
               
               
                 Panthenol 
                 0.30 
                 0.30 
                 0.30 
               
               
                 Deionized water 
                 Qs 
                 Qs 
                 Qs 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 Example 11: Common base for dyeing example 
               
            
           
           
               
               
               
            
               
                   
                   
                 11 
               
               
                   
                 Component 
                 (wt %) 
               
               
                   
                   
               
               
                   
                 Propylene glycol 
                 9.50 
               
               
                   
                 Ammonium hydroxide 
                 5.00 
               
               
                   
                 Ethoxydiglycol 
                 4.00 
               
               
                   
                 Ethanolamine 
                 4.50 
               
               
                   
                 Oleic acid 
                 1.00 
               
               
                   
                 Hexylene glycol 
                 6.00 
               
               
                   
                 Niacinamide 
                 5.00 
               
               
                   
                 Panthenol 
                 0.30 
               
               
                   
                 Indole-3-Acetic Acid 
                 0.20 
               
               
                   
                 Cocamidopropyl betaine 
                 3.50 
               
               
                   
                 Oleth-10 
                 0.30 
               
               
                   
                 Oleth-2 
                 0.30 
               
               
                   
                 Dilinoleic acid 
                 1.50 
               
               
                   
                 C12-C15 Pareth-3 
                 0.50 
               
               
                   
                 Soytrimonium chloride 
                 7.00 
               
               
                   
                 Sodium metasilicate 
                 0.05 
               
               
                   
                 Erythorbic acid 
                 0.50 
               
               
                   
                 EDTA 
                 0.03 
               
               
                   
                 Sodium sulfite 
                 0.30 
               
               
                   
                 1-Phenyl-3-methyl-5-pyrazolone 
                 0.20 
               
               
                   
                 Deionized water 
                 Qs 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                 Examples 12-14: Common base for mousse 
               
            
           
           
               
               
               
               
            
               
                   
                 12 
                 13 
                 14 
               
               
                 Component 
                 (wt %) 
                 (wt %) 
                 (wt %) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Ethanol 
                 51.80 
                 51.80 
                 51.80 
               
               
                 Propylene glycol 
                 5.00 
                 5.00 
                 5.00 
               
               
                 Propellant P75 
                 4.30 
                 4.30 
                 4.30 
               
               
                 Cetyl alcohol 
                 2.20 
                 2.20 
                 2.20 
               
               
                 Niacinamide 
                 5.00 
                 5.00 
                 5.00 
               
               
                 Stearyl alcohol 
                 1.00 
                 1.00 
                 1.00 
               
               
                 Polyoxyethylene lauryl alcohol 
                 1.00 
                 1.00 
                 1.00 
               
               
                 Indole-3-Acetic Acid 
                 0.20 
               
               
                 Hydroxy Indole 
                   
                 0.20 
               
               
                 Indole-3-carbinol 
                   
                   
                 0.20 
               
               
                 Polysorbate 60 
                 0.40 
                 0.40 
                 0.40 
               
               
                 Panthenol 
                 0.30 
                 0.30 
                 0.30 
               
               
                 Acetic acid 
                 Qs pH 6.0 
                 Qs pH 6.0 
                 Qs pH 6.0 
               
               
                 Deionized water 
                 Qs 
                 Qs 
                 Qs 
               
               
                   
               
            
           
         
       
     
     Example 11 
     Method of Marketing 
     The shampoo of Example 1 is packaged into a blue and white container and offered for sale to consumers at a retail store. A label on the container communicates that when this shampoo is used to wash hair, it will help to increase the appearance of thicker and fuller hair. 
     Example 12 
     Method of Marketing 
     A shampoo contained in a blue and white bottle (herein “Subject Shampoo”) is located on a shelf next to the shampoo of Example 11. A label is attached to the Subject Shampoo&#39;s bottle which directs the consumer to compare the Subject Shampoo to the shampoo of Example 11. 
     Example 13 
     Synergy Example 
     An in vitro model, consisting of primary human dermal papilla cells (“DP”) in culture, demonstrates a surprising synergistic increase in the survival of metabolically stressed dermal papilla cells. Primary human dermal papilla cells were metabolically stressed for 48 hours in reduced standard tissue culture media. During this period of stress the cells were treated with the mixtures below dosed from a DMSO vehicle. After 48 hours the metabolic activity of the cells was measured by the amount of ATP using the Cell Titer Glo™ kit (Promega). 
     While the individual components provided little or no benefit in increasing the survival of stressed dermal papilla cells, the mixture of the three components resulted in a synergistic effect that produced a statistically significant increase in DP cell survival, not only above the calculated average but also above the expected additive effect of the individual components. Thus, the investigators demonstrated that the combination provided a significantly greater increase in cell survival than one would expect, given the effects of the individual components alone or in addition to one another. The dermal papilla, in normal human hair, is the control center for hair diameter. Increasing survival of dermal papilla cells in situ leads to increased hair diameter. Accordingly, an increase in survival of dermal papilla cells correlates with an increase in hair diameter. 
     Tables 1A and 1B below, and their corresponding graphical representations,  FIG. 1A  and  FIG. 1B , demonstrate the synergy between indole-3-acetic acid (“IAA”), niacinamide, and panthenol. 
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 1A 
               
               
                   
                   
               
               
                   
                 Survival 
                 SE 
                 P 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Vehicle 
                 0 
                 0.07 
                   
               
               
                   
                 Niacinamide 
                 −0.02 
                 0.05 
               
               
                   
                 Panthenol 
                 −0.17 
                 0.05 
               
               
                   
                 IAA 
                 −0.17 
                 0.06 
               
               
                   
                 Calculated Total 
                 −0.36 
               
               
                   
                 Actual Response 
                 0.37 
                 0.11 
                 0.0069 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 1B 
               
               
                   
                   
               
               
                   
                 Survival 
                 SE 
                 P 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Vehicle 
                 0 
                 0.07 
                   
               
               
                   
                 Niacinamide 
                 −0.02 
                 0.05 
               
               
                   
                 Panthenol 
                 −0.17 
                 0.05 
               
               
                   
                 IAA 
                 −0.18 
                 0.02 
               
               
                   
                 Calculated Total 
                 −0.37 
               
               
                   
                 Actual Response 
                 0.39 
                 0.17 
                 0.014 
               
               
                   
                   
               
            
           
         
       
     
     Tables 2A and 2B below, and their corresponding graphical representations,  FIG. 2A  and  FIG. 2B , demonstrate the synergy between Indole-3-Carbinol (“I3C”), nicacinamide, and panthenol. 
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 2A 
               
               
                   
                   
               
               
                   
                 Survival 
                 SE 
                 P 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Vehicle 
                 0 
                 0.06 
                   
               
               
                   
                 Niacinamide 
                 −0.16 
                 0.09 
               
               
                   
                 Panthenol 
                 −0.01 
                 0.05 
               
               
                   
                 I3C 
                 −0.16 
                 0.06 
               
               
                   
                 Calculated Total 
                 −0.33 
               
               
                   
                 Actual Response 
                 0.2 
                 0.05 
                 0.0324 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 2B 
               
               
                   
                   
               
               
                   
                 Survival 
                 SE 
                 P 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Vehicle 
                 0 
                 0.05 
                   
               
               
                   
                 Niacinamide 
                 0.1 
                 0.05 
               
               
                   
                 Panthenol 
                 −0.13 
                 0.12 
               
               
                   
                 I3C 
                 0.08 
                 0.06 
               
               
                   
                 Calculated Total 
                 0.05 
               
               
                   
                 Actual Response 
                 0.73 
                 0.27 
                 0.0385 
               
               
                   
                   
               
            
           
         
       
     
     Table 3, and the corresponding graphical representation,  FIG. 3 , demonstrates the synergy between Tryptophol (“HI”), niacinamide, and panthenol. 
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 Survival 
                 SE 
                 P 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Vehicle 
                 0 
                 0.11 
                   
               
               
                   
                 N + P 
                 0.06 
                 0.06 
               
               
                   
                 HI 
                 1.72 
                 0.10 
               
               
                   
                 Calculated Total 
                 1.78 
                 0.08 
               
               
                   
                 Actual Response 
                 2.73 
                 0.31 
                 0.0119 
               
               
                   
                   
               
            
           
         
       
     
     The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm” 
     Every document cited herein, including any cross referenced or related patent or application, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern. 
     While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.