USOO8481 015B2

(12) United States Patent (10) Patent No.: US 8.481,015 B2 Oblong et al. (45) Date of Patent: Jul. 9, 2013

(54) REGULATION OF MAMMALIAN HAIR 6,495,149 B1 12/2002 Scavone et al. GROWTH 6,716,441 B1 4/2004 Osborne 7,235,249 B2 * 6/2007 Bissett ...... 424/401 2003/0.139711 A1* 7/2003 Roe et al...... 604,367 (75) Inventors: John Erich Oblong, oveland, OH 2003/0165447 A1 9, 2003 Scavone et al. (US); Sara Johnson McPhail, West 2003. O190337 A1 10, 2003 Bissett Chester, OH (US); Shannon Christine 2006/0127431 A1 6/2006 Oblong McArthur, Indian Springs, OH (US); 2008. O1885.05 A1 8/2008 Oblong sh E. ision, OH FOREIGN PATENT DOCUMENTS ; Uavid Josepn LIcKno, Fl. JP 632O3608 8, 1988 Mitchell, KY (US); John McMillan JP 11-035425 2, 1999 McIver, Cincinnati, OH (US) JP 11-322548 11, 1999 JP 2000-302659 10, 2000 (73) Assignee: The Procter & Gamble Company, JP 2000-319154 11, 2000 Cincinnati, OH (US) JP 2002-24.9414 9, 2002 s RO 86639 A * 4f1985 (*) Notice: Subject to any disclaimer, the term of this W. W. 99.69; A. 23: patent is extended or adjusted under 35 WO WO-99/37277 7, 1999 U.S.C. 154(b) by 614 days. WO WOO1/43717 A1 6, 2001 WO O3O13245 A1 2, 2003 (21) Appl. No.: 12/056,377 WO WOO3,O13245 A1 2/2003 9 WO O3O92268 11, 2003 (22) Filed: Mar 27, 2008 WO WO 03/092668 A1 11, 2003 e Aff 9 OTHER PUBLICATIONS (65) Prior Publication Data Lewis Sr., Richard J. Editor, Hawley's Condensed Chemical Dictio US 2008/O188505 A1 Aug. 7, 2008 nary, Fourteenth Edition, 2002, Wiley, John & Sons, Inc. Publisher, 3 pageS. Related U.S. Application Data Farady, C.J. and Craik, C. S. Protease Inhibitors: Mechanism, Wiley (62) Division of application No. 10/783,151, filed on Feb. Encyclopedia of Chemical Biology, 2008, Wiley, John & Sons, Inc. 19, 2004, now abandoned. Publisher, pp. 1-12. US 5,674.447, 10/1997, Ahluwalia (withdrawn) (60) Provisional application No. 60/451,910, filed on Mar. 4, 2003. * cited by examiner (51) Int. Cl. Primary Examiner — Lakshmi Channavaljala A6 IK 8/19 (2006.01) (74) Attorney, Agent, or Firm — John G. Powell; Melody A. (52) U.S. Cl. Jones; Angela K. Haughey USPC ...... 424/73; 424/65; 424/70.1; 424/401 (58) Field of Classification Search (57) ABSTRACT CPC ...... A61Q 7/02: A61Q 9/02: A61Q 9/04 USPC ...... 424/70.1 The present invention relates to a topical skin care composi See application file for complete search history. tion containing a safe and effective amount of a skin care active comprising agmatine, and its salt; a safe and effective (56) References Cited amount of a first additional skin care active selected from the group consisting of BHT or BHA, hexamidine, cetyl pyri U.S. PATENT DOCUMENTS dinium chloride, green tea catechins, phytosterols, ursolic 4,505,924. A * 3/1985 Taylor et al...... 514,399 acid, compounds derived from plant extracts, their salts and 4,507,321 A 3, 1985 Raisfeld derivatives; and a dermatologically acceptable carrier for the 5,004,734. A * 4/1991 Philippe et al...... 514, 29 agmatine composition. 5,204,093 A * 4, 1993 Victor ...... 424f73 5,554,608 A * 9/1996 Ahluwalia et al...... 514, 20.7 The present invention also relates to methods of using Such 5,674.477 A 10, 1997 Ahluwalia agmatine compositions to regulate hair growth and the con 5,709,847 A 1/1998 Bissett dition of mammalian skin. Said methods generally comprise 5,776.442 A 7, 1998 Ahluwalia the step of topically applying the composition to the skin of a 6,060,471 A 5/2000 Styczynski 6,075,052 A 6, 2000 Suzuki et al. mammal needing Such treatment, a safe and effective amount 6,149,896 A 11, 2000 Riklis of such compositions.

6,207,596 B1* 3/2001 Rourke et al...... 442/123 6,375,948 B1 * 4/2002 Tsuji et al...... 424/94.65 19 Claims, No Drawings US 8,481,015 B2 1. 2 REGULATION OF MAMMALIAN HAIR hirsutism, can have unpleasant physical side effects as well as GROWTH possible birth defect implications. Since in non-hirsutistic females, the role of androgens is not required for normal hair CROSS REFERENCE TO RELATED growth, there is a need for technologies that do not function APPLICATION(S) via androgen mediated pathways due to the birth defect impli cations. Depilatory devices can be painful to use and are not This application is a divisional of U.S. patent application well-suited for many areas of the body including underarms Ser. No. 10/783,151 filed Feb. 19, 2004 now abandoned, and face. Finally, depilatory creams, although effective, are which claims the benefit of U.S. Provisional Application Ser. messy to apply and typically are not recommended for fre No. 60/451,910, filed Mar. 4, 2003, all of which are incorpo 10 quent use due to their high irritancy potential. rated by reference herein. Therefore, a need exists for a safe, effective way to not only regulate the condition of mammalian keratinous tissue, but TECHNICAL FIELD also to retard, inhibit, and/or stop unwanted mammalian hair The present invention relates to topical compositions con 15 growth on designated areas of the body. taining a combination of skin care actives, particularly agna Surprisingly, it has now been discovered that compositions tine and its salts, in combination with other skin care actives containing agmatine and its Sulfate salt, in combination with such as butylated hydroxytoluene (BHT) and butylated other selected skin care actives, are useful for regulating hydroxyanisole (BHA), cetyl pyridinium chloride, hexami mammalian hair growth, including retarding, inhibiting, or dine, phytosterols, compounds derived from plant extracts, eliminating hair growth. Without being limited by theory, it is green tea catechin compounds, ursolic acid, and free fatty believed that agmatine is able to modulate hair growth by acids. Such compositions are useful for regulating the condi inhibiting protease activity in and Surrounding the hair folli tion of keratinous tissue, including, but not limited to, regu cular unit in mammalian skin. Proteases are key components lating mammalian hair growth, preferably inhibiting and/or in restructuring of the extracellular matrix during follicular retarding hair growth and/or reducing shaving frequency. 25 progression through the dermis of skin in early anagen. Addi tionally, proteases play a role in angiogenesis, a key process BACKGROUND OF INVENTION for vascularization of the hair follicle during early anagen as well as maintenance of the vasculature bed during all of As is well-known in the art, normal hair growth occurs by anagen. Additionally, it is believed that agmatine can modu a cycle of activity which involves alternating periods of 30 late hair growth by upregulating antizyme, a protein that growth and rest. This cycle is often divided into three main regulates and degrades ornithine decarboxylase (ODC). Orni stages which are known as anagen, catagen, and telogen. thine decarboxylase is a critical enzyme for cell viability. Anagen is the growth phase of the cycle and may be charac Agmatine can therefore inhibit ODC activity indirectly by terized by penetration of the hair follicle deep into the dermis upregulating antizyme. Thus, agnatine plays a role in block with rapid proliferation of cells which are differentiating to 35 ing structural remodeling of the hair follicular unit as well as form hair. The next phase is catagen, which is a transitional inhibiting the vascularization of the follicular unit and hair stage marked by the cessation of cell division, and during follicle cellular proliferation via ODC, thereby altering mam which the hair follicle regresses through the dermis and hair malian hair growth properties. growth is ceased. The next phase, telogen, is often character Surprisingly, it has also been discovered that select skin ized as the resting stage during which the regressed follicle 40 care compositions such as BHT or BHA, cetyl pyridinium contains a germ with tightly packed dermal papilla cells. At chloride, hexamidine, and ursolic acid can be used alone for telogen, the initiation of a new anagen phase is caused by regulating mammalian hair growth, including retarding, rapid cell proliferation in the germ, expansion of the dermal inhibiting, or eliminating hair growth. papilla, and elaboration of basement membrane components. None of the existing art provides all the advantages and This cycle is repeated throughout hair growth. Wherein hair 45 benefits of the present invention. growth ceases, most of the hair follicles reside intelogen and anagen is not engaged, thus causing the onset of full or partial SUMMARY baldness. A main function of mammalian hair growth is to provide The present invention also relates to methods of using Such environmental protection. However, that function has been 50 cetyl pyridinium chloride compositions to regulate hair lost inhumans, in whom, hair is kept or removed from various growth and the condition of mammalian skin. Said methods parts of the body, essentially for cosmetic reasons. For generally comprise the step of topically applying the compo example, for women in the United States, it is generally sition to the skin of a mammal needing Such treatment, a safe preferred to have hair on the scalp, but not on the legs, under and effective amount of such compositions. arms, or certain areas of the face. 55 The present invention also relates to methods of regulating Various procedures and personal care products have been hair growth using a safe and effective amount of hexamidine, developed to remove unwanted hair, including shaving, elec cetyl pyridinium chloride, ursolic acid or BHT, their salts and trolysis, depilatory creams or lotions, depilatory devices, derivatives; and a dermatologically acceptable carrier for any waxing, plucking, therapeutic androgens, and laser hair of the compounds. removal. However, such conventional procedures frequently 60 The present invention also relates to methods of regulating have drawbacks associated with them. Shaving, for instance, hair growth using a safe and effective amount of BHT or may cause nicks, cuts, rash and irritation and often leaves an BHA; a safe and effective amount of an additional skin care undesirable stubble. Electrolysis and laser hair removal can active selected from the group consisting of hexamidine, cetyl keep a treated area free of hair for prolonged periods of time, pyridinium chloride, phytosterol, green tea catechins, and but can be either expensive, painful, and/or sometimes leave 65 ursolic acid, their salts and derivatives, and mixtures thereof, scarring. Waxing and plucking are painful and are poor and a dermatologically acceptable carrier for the BHT com options for shorter hair. Anti-androgens, used to treat female pound. US 8,481,015 B2 3 4 The present invention also relates to methods of regulating regulation may also stem from hair growth patterns induced hair growth using a safe and effective amount of hexamidine; or caused by factors internal and/or external to the body. a safe and effective amount of an additional skin care active Examples include, environmental damage, radiation expo selected from the group consisting of cetyl pyridinium chlo Sure (including ultraviolet radiation and radiation therapy), ride, phytosterol, green tea catechins, and ursolic acid, their heredity, chronological aging, menopausal status (e.g., post salts and derivatives, and mixtures thereof, and a dermato menopausal changes in hair growth), stress, diseases, chemo logically acceptable carrier for the hexamidine compound. therapy, etc. The present invention also relates to methods of regulating "Regulatinghair growth, namely mammalian hair growth, hair growth using a safe and effective amount of cetyl pyri includes reducing, modulating, inhibiting, attenuating, dinium chloride; a safe and effective amount of an additional 10 retarding, promoting, enhancing, and/or the diminuation of skin care active selected from the group consisting of phy hair growth, and/or reducing shaving frequency. tosterol, green tea catechins, and ursolic acid, their salts and “Reduction/Inhibition of hair growth, as referenced derivatives, and mixtures thereof, and a dermatologically herein, is demonstrated when the frequency of hair removal is acceptable carrier for the cetyl pyridinium chloride com reduced, or the tactile and visual feel of mammalian hair is pound. 15 improved wherein the subject perceives less hair on the The present invention also relates to methods of regulating treated site (i.e., hair is perceived to be softer, finer, less hair growth using a safe and effective amount of phytosterol; noticeable), or quantitatively, when the weight of the hair a safe and effective amount of an additional skin care active removed by shaving (i.e., hair mass) is reduced thereby selected from the group consisting of green tea catechins and improving the ease, frequency, and effectiveness of shaving ursolic acid, their salts and derivatives, and mixtures thereof, of a mammal. and a dermatologically acceptable carrier for the BHT com "Mammalian hair as referenced herein, includes hair on pound. any part of the body of a mammal and may include facial, The present invention also relates to methods of regulating cranial, or body hair. Male facial hair commonly refers to the hair growth using a safe and effective amount of green tea beard, moustache, eyebrows and sideburns hair, but may catechins and a safe and effective amount of ursolic acid, their 25 include any area of the face and/or neck. Female facial hair salts and derivatives, and mixtures thereof, and a dermato (predominantly Vellus but can include terminal hair) com logically acceptable carrier for the green tea catechin com monly refers to eyebrows, upper lip, chin, and cheeks area, pound. but may also include any area of the face and/or neck. Other These and other features, aspects, and advantages of the areas of hair growth typically desired to be regulated include present invention will become evident to those skilled in the 30 underarms, bikini area, legs, arms, back, and chest. The desire art from a reading of the present disclosure. for hair loss reduction is frequently associated with cranial hair, especially cranial hair in chemotherapy and/or radiation DETAILED DESCRIPTION therapy patients. The compositions of the present invention are particularly Suitable for reducing the growth of unwanted While the specification concludes with the claims particu 35 hair in women Suffering from hirsutism or other conditions. larly pointing and distinctly claiming the invention, it is The composition is particularly suitable for the treatment believed that the present invention will be better understood of hirsutism. In humans, the composition should be applied from the following description. once or twice a day, or even more frequently, for at least three The compositions of the present invention can include, months to achieve a perceived reduction in hair growth. consist essentially of, or consist of the components of the 40 The term “improving the tactile and visual feel as used present invention as well as other ingredients described herein, refers to the more noticeable improvement in the herein. As used herein, "consisting essentially of means that appearance of the hair on the skin Such that it is perceived to the composition or component may include additional ingre be softer, finer, less noticeable. Additionally, the ease, fre dients, but only if the additional ingredients do not materially quency, and effectiveness of shaving will be perceived by the alter the basic and novel characteristics of the claimed com 45 mammal. Reduction of hair growth is demonstrated when the positions or methods. frequency of hair removal is reduced, or the Subject perceives All percentages, parts and ratios are based upon the total less hair on the treated site, or quantitatively, when the weight weight of the topical compositions of the present invention of hair removed by shaving (i.e., hair mass) is reduced. and all measurements made are at 25°C., unless otherwise The term "keratinous tissue,” as used herein, refers to kera specified. All Such weights as they pertain to listed ingredi 50 tin-containing layers disposed as the outermost protective ents are based on the active level and, therefore, do not covering of mammals (e.g., humans, dogs, cats, etc.) which include carriers or by-products that may be included in com includes, but is not limited to, skin, hair, etc. mercially available materials, unless otherwise specified. The term “topical application', as used herein, means to All publications cited herein are hereby incorporated by apply or spread the compositions of the present invention reference in their entirety. 55 onto the Surface of the keratinous tissue. As used herein, the “beauty care products are those used The term “dermatologically-acceptable as used herein, to treat or care for, or somehow moisturize, improve, or clean means that the compositions or components thereof So the skin and/or hair. Products contemplated by the phrase described are Suitable for use in contact with mammalian “beauty care products include, but are not limited to mois keratinous tissue without undue toxicity, incompatibility, turizers, personal cleansing products, occlusive drug delivery 60 instability, allergic response, and the like. patches, powders, wipes, hair conditioners, hair tonics, sham The term "safe and effective amount as used herein means poos, hair colorants, skin treatment emulsions, shaving an amount of a compound or composition Sufficient to sig creams, antiperspirants, deodorants, and the like. nificantly induce a positive benefit, preferably a hair growth The compositions of the present invention are useful for regulating benefit, or positive hair appearance or feel benefit, regulating the growth of mammalian hair. Hair growth regu 65 including independently or in combinations the benefits dis lation is often desired in certain parts of the body due to closed herein, but low enough to avoid serious side effects, hygiene or Societal pressures. The desire for hair growth i.e., to provide a reasonable benefit to risk ratio, within the US 8,481,015 B2 5 6 Scope of Sound judgment of the skilled artisan. The term B. Skin Care Actives “ambient conditions' as used herein refers to surrounding The topical composition of the present invention includes a conditions under about one atmosphere of pressure, at about first additional skin care active selected from the group con 50% relative humidity, and at about 25°C. unless otherwise sisting of BHT or BHA, hexamidine, cetyl pyridinium chlo specified. The compositions of the present invention provide ride, green tea catechins, phytosterols, ursolic acid, and their additional benefits, including stability, absence of significant salts and derivatives. (consumer-unacceptable) skin irritation and good aesthetics. The topical composition of the present invention also The compositions of the present invention are stable. The includes a second additional skin care active selected from the ingredients used herein, including the agmatine, are compat group consisting of BHT or BHA, hexamidine, cetyl pyri ible with each other and with the other skin care actives such 10 dinium chloride, green tea catechins, phytosterols, ursolic as terpene alcohols, retinoids, peptides, tocopherol Sorbate, acid, and their salts and derivatives, and mixtures thereof, and vitamin B compounds. Therefore, the compositions con wherein the second additional skin care active is different taining the combination of agmatine in conjunction with an from the first skin care active. additional skin care active, Such as hexamidine, cetyl pyri 1. Butylated hydroxytoluene (BHT) and butylated dinium chloride, phytosterols, BHT, BHA, compounds 15 hydroxyanisole (BHA) derived from plant extracts, green tea catechin compounds, The topical compositions of the present invention comprise ursolic acid, and free fatty acids, are capable of providing a safe and effective amount of BHT or BHA. The BHT useful additive and/or synergistic skin benefits. Additionally, the herein can be described by the general structure: resulting skin care composition has good product stability and a reasonably long shelf-life. The resulting compositions containing agmatine in com X bination with other selected skin care actives have good aes thetics. Examples of good aesthetics include compositions, R R3 Such as luxurious creams and lotions, that (i) are light and nongreasy, (ii) have a smooth, silky feel upon the skin, (iii) 25 spread easily, and/or (iv) absorb quickly. Other examples of R R4 good aesthetics include compositions that have a consumer Y acceptable appearance (i.e. no unpleasant odor or discolora tion present), and provide good skin feel. The compositions 30 X=OH, SH herein may include a wide variety of other optional ingredi Y-H, OH, ORs, COORs, alkyl, cycloalkyl, heteroalkyl, het entS. erocycloalkyl, aromatic, heteroaromatic, carboxamido, The compositions of the present invention, including the Sulfonamido, carbamate, urea, trialkylsilyl essential and optional components thereof, are described in R. R. R. R. alkyl, cycloalkyl, heteroalkyl, heterocy detail hereinafter. 35 cloalkyl, aromatic, heteroaromatic, ORs, carboxamido, I. Materials Sulfonamido, formyl, acyl, carboxyl, carboxylate, carbam A. Agmatine ate, urea, trialkylsilyl, hydroxyl, hydrogen The topical composition of the present invention comprises Rs alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aro a safe and effective amount of agmatine. The agmatine useful matic, heteroaromatic, trialkylsilyl, acyl, hydrogen. 40 In the composition of the present invention, BHT or BHA herein can be described by the general structure: preferably comprises from about 0.0001% to about 99.99% by weight of the composition, more preferably from about R R 0.001% to about 10%, more preferably from about 0.01% to N1 3 R1 7 about 5%, and most preferably from about 0.1% to about 45 O.5%. 2. Hexamidine *s-s-s-s-s-s The topical composition of the present invention comprises k l a safe and effective amount of hexamidine, its salt, and deriva tives. More preferably, the hexamidine is hexamidine 50 isethionate. As used herein, "hexamidine' includes any iso R. R. R. R. R. R. R. R. R. alkyl, cycloalkyl, het mers and tautomers of Such and is commercially available as eroalkyl, heterocycloalkyl, aromatic, heteroaromatic, car hexamidine isethionate under the tradename Elastab(R) boxamido, Sulfonamido, carboxyl, carboxylate, carbam HP100 from Laboratoires Serobiologiques (Pulnoy, France). ate, urea, Sulfate, phosphate, silyl, acyl, amino acid, In the composition of the present invention, hexamidine polypeptide, imino, hydrogen, nitro, nitrogen, oxygen, Sul 55 preferably comprises from about 0.0001% to about 99.99% fur, phosphorus, nil. by weight of the composition, more preferably from about A, D carbon, nitrogen, aromatic, heteroaromatic, hydrogen, 0.001% to about 10%, more preferably from about 0.01% to nil. about 5%, and most preferably from about 0.1% to about B, C nitrogen, oxygen, Sulfur, phosphorus, hydrogen, nil. 2.0%. 60 3. Cetyl Pyridinium Chloride n=0 to 20. The topical composition of the present invention comprises In the composition of the present invention, agmatine pref a safe and effective amount of cetyl pyridinium chloride. erably comprises from about 0.0001% to about 99.99% by Alternate forms of cetyl pyridinium chloride include those in weight of the composition, more preferably from about which one or two of the Substitutes on the quaternary nitrogen 0.001% to about 10%, more preferably from about 0.01% to 65 has a carbon chain length (typically alkyl group) from about about 5%, and most preferably from about 0.1% to about 8 to about 20, typically from about 10 to about 18 carbon 2.5%. atoms while the remaining Substitutes (typically alkyl or ben US 8,481,015 B2 7 8 Zyl group) have a lower number of carbonatoms, such as from 0.1% to about 20%, still more preferably from about 0.2% to about 1 to about 7 carbon atoms, typically methyl or ethyl about 10%, and most preferably from about 0.5% to about groups. Dodecyl trimethyl ammonium bromide, tetrade 10%. cylpyridinium chloride, domiphenbromide, N-tetradecyl-4- 6. Ursolic Acid ethyl pyridinium chloride, dodecyl dimethyl (2-phenoxy The topical composition of the present invention comprises ethyl) ammonium bromide, benzyl dimethylstearyl a safe and effective amount of ursolic acid. In the composition ammonium chloride, cetyl pyridinium chloride, quaternized of the present invention, the ursolic acid preferably comprises 5-amino-1,3-bis(2-ethyl-hexyl)-5-methyl hexahydropyrimi from about 0.0001% to about 99.99% by weight of the com dine, benzalkonium chloride, benzethonium chloride and position, more preferably from about 0.001% to about 10%, methylbenzethonium chloride are exemplary of typical qua 10 ternary ammonium agents. Other compounds are bis)4-(R- more preferably from about 0.01% to about 5%, and most amino)-1-pyridinium alkanes as disclosed in U.S. Pat. No. preferably from about 0.05% to about 5%. 4.206,215, Jun. 3, 1980 to Bailey which is incorporated 7. Compounds Derived from Plant Extracts herein by reference. The pyridinium compounds are the pre The topical compositions of the present invention comprise ferred quaternary ammonium compounds for use in the 15 a safe and effective amount of compounds derived from plant present invention, the most preferred being cetyl pyridinium extracts selected from the group consisting of leguminosae, chloride. Solanaceae, gramineae, cucurbitaceae. Preferably, the com In the composition of the present invention, cetyl pyri pound derived from plant extracts is a protease inhibitor and dinium chloride preferably comprises from about 0.0001% to one or more isoflavone. In the composition of the present about 99.99% by weight of the composition, more preferably invention, compounds derived from plant extracts preferably from about 0.001% to about 5%, more preferably from about comprises from about 0.0001% to about 99.99% by weight of 0.01% to about 2%, and most preferably from about 0.05% to the composition, more preferably from about 0.001% to about 1.0%. about 10%, more preferably from about 0.01% to about 5%, 4. Green Tea Catechins and most preferably from about 0.05% to about 5%. The topical composition of the present invention comprises 25 C. Dermatologically Acceptable Carrier a safe and effective amount of one or more catechin com The topical compositions of the present invention also pounds selected from the group consisting of catechin, epi comprise a dermatologically acceptable carrier for the cat catechin, epigallocatechin, epicatechin gallate, epigallocat echin composition. The phrase "dermatologically acceptable echin gallate, gallocatechin, and mixtures thereof. More carrier, as used herein, means that the carrier is suitable for preferably, the catechin is free of caffeine and is extracted and 30 topical application to the keratinous tissue, has good aesthetic enriched for from a green tea plant source. Most preferably, properties, is compatible with the actives of the present inven the catechin is epigallocatechin gallate. tion and any other components, and will not cause any safety In the composition of the present invention, the catechin or toxicity concerns. A safe and effective amount of carrier is mixture preferably comprises from about 0.0001% to about from about 50% to about 99.99%, preferably from about 60% 99.99%, by weight of the composition, more preferably from 35 to about 99.9%, more preferably from about 70% to about about 0.001% to about 10%, more preferably from about 98%, and most preferably from about 80% to about 95% of 0.01% to about 5%, and most preferably from about 0.1% to the composition. about 2.5%, by weight of the composition. The carrier can be in a wide variety of forms. For example, 5. Phytosterols emulsion carriers, including, but not limited to, oil-in-water, The topical composition of the present invention comprises 40 water-in-oil, water-in-oil-in-water, and oil-in-water-in-sili a safe and effective amount of one or more phytosterols cone emulsions, are useful herein. selected from the group consisting of B-sitosterol, campes Preferred carriers comprise an emulsion Such as oil-in terol, brassicasterol, A5-avennasterol, lupenol, C.-spinasterol, water emulsions and water-in-oil emulsions, e.g., silicone-in Stigmasterol, their derivatives, and combinations thereof. water or water-in-silicone emulsions. As will be understood More preferably, the phytosterol is selected from the group 45 by the skilled artisan, a given component will distribute pri consisting of B-sitosterol, campesterol, brassicasterol, Stig marily into either the water or oil phase, depending on the masterol, their derivatives, and combinations thereof. Even water solubility/dispensability of the component in the com more preferably, the phytosterol is selected from the group position. The catechin compound distributes primarily into consisting of B-sitosterol, campesterol, brassicasterol, Stig the oil phase. Oil-in-water emulsions are especially preferred. masterol, and combinations thereof. Most preferably, the 50 Emulsions according to the present invention generally phytosterol is stigmasterol. contain a solution as described above and a lipid or oil. Lipids Phytosterols of the present invention can be synthetic or and oils may be derived from animals, plants, or petroleum natural in origin and can be used as essentially pure com and may be natural or synthetic (i.e., man-made). Preferred pounds or mixtures of compounds (e.g., extracts from natural emulsions also contain a humectant, such as glycerin. Emul Sources). Phytosterols are generally found in the unsaponifi 55 sions will preferably further contain from about 1% to about able portion of vegetable oils andfats and are available as free 10%, more preferably from about 2% to about 5%, of an sterols, acetylated derivatives, sterol esters, ethoxylated or emulsifier, based on the weight of the composition. Emulsi glycosidic derivatives. More preferably, the phytosterols are fiers may be nonionic, anionic or cationic. Suitable emulsifi free sterols. As used herein, “phytosterol includes isomers, ers are disclosed in, for example, U.S. Pat. No. 3,755,560, tautomers, and derivatives (e.g., esters) of Such and are com 60 issued Aug. 28, 1973, Dickert et al.; U.S. Pat. No. 4,421,769, mercially available from Aldrich Chemical Company (Mil issued Dec. 20, 1983, Dixon et al.; and McCutcheon's Deter waukee, Wis.), Sigma Chemical Company (St. Louis, Mo.), gents and Emulsifiers, North American Edition, pages 317 Cognis, and Karlshamns (Karlshamns, Sweden). 324 (1986). In the compositions of the present invention, the phy The emulsion may also contain an anti-foaming agent to tosterol preferably comprises from about 0.01% to about 65 minimize foaming upon application to the keratinous tissue. 99.99%, by weight of the composition, more preferably from Anti-foaming agents include high molecular weight silicones about 0.01% to about 50%, even more preferably from about and other materials well known in the art for such use. US 8,481,015 B2 9 10 Suitable emulsions may have a wide range of Viscosities, available polyalkylsiloxanes include the polydimethylsilox depending on the desired product form. Exemplary low vis anes, which are also known as dimethicones, examples of cosity emulsions, which are preferred, have a viscosity of which include the Vicasil.R series sold by General Electric about 50 centistokes or less, more preferably about 10 cen Company and the Dow Corning.R. 200 series sold by Dow tistokes or less, most preferably about 5 centistokes or less. 5 Corning Corporation. Specific examples of suitable polydim Preferred water-in-silicone and oil-in-water emulsions are ethylsiloxanes include Dow Corning.R. 200 fluid having a described in greater detail below. viscosity of 0.65 centistokes and a boiling point of 100° C. 1) Water-in-Silicone Emulsion Dow Corning.R. 225 fluid having a viscosity of 10 centistokes Water-in-silicone emulsions contain a continuous silicone and a boiling point greater than 200°C., and Dow Corning R phase and a dispersed aqueous phase. 10 200 fluids having viscosities of 50, 350, and 12,500 centis (a) Continuous Silicone Phase tokes, respectively, and boiling points greater than 200° C. Preferred water-in-silicone emulsions of the present inven Suitable dimethicones include those represented by the tion comprise from about 1% to about 60%, preferably from chemical formula (CH4)SiO(CH4)2SiO), ICHRSiO, Si about 5% to about 40%, more preferably from about 10% to (CH) wherein R is straight or branched chain alkyl having about 20%, by weight of a continuous silicone phase. The 15 from two to about 30 carbon atoms and X and y are each continuous silicone phase exists as an external phase that integers of 1 or greater selected to achieve the desired molecu contains or Surrounds the discontinuous aqueous phase lar weight which can range to over about 10,000,000. described hereinafter. Examples of these alkyl-substituted dimethicones include The continuous silicone phase contains a polyorganosilox cetyl dimethicone and lauryl dimethicone. ane oil. A preferred water-in-silicone emulsion system is Cyclic polyalkylsiloxanes Suitable for use in the composi formulated to provide an oxidatively stable vehicle for an tion include those represented by the chemical formula optional retinoid. The continuous silicone phase of these pre SiR OL, wherein R is an alkyl group (preferably R is ferred emulsions comprises between about 50% and about methyl or ethyl, more preferably methyl) and n is an integer 99.9% by weight of organopolysiloxane oil and less than from about 3 to about 8, more preferably n is an integer from about 50% by weight of a non-silicone oil. In a preferred 25 about 3 to about 7, and most preferably n is an integer from embodiment, the continuous silicone phase comprises at least about 4 to about 6. When R is methyl, these materials are about 50%, preferably from about 60% to about 99.9%, more typically referred to as cyclomethicones. Commercially preferably from about 70% to about 99.9%, and even more available cyclomethicones include Dow Corning.R. 244 fluid preferably from about 80% to about 99.9%, polyorganosilox having a viscosity of 2.5 centistokes, and a boiling point of ane oil by weight of the continuous silicone phase, and up to 30 172° C., which primarily contains the cyclomethicone tet about 50% non-silicone oils, preferably less about 40%, more ramer (i.e. n=4), Dow Corning.R. 344 fluid having a viscosity preferably less than about 30%, even more preferably less of 2.5 centistokes and a boiling point of 178° C., which than about 10%, and most preferably less than about 2%, by primarily contains the cyclomethicone pentamer (i.e. n=5), weight of the continuous silicone phase. These preferred Dow Corning R245 fluid having a viscosity of 4.2 centistokes emulsion systems provide more oxidative stability to a retin 35 and a boiling point of 205° C., which primarily contains a oid over extended periods of time than comparable water-in mixture of the cyclomethicone tetramer and pentamer (i.e. oil emulsions containing lower concentrations of the polyor n=4 and 5), and Dow Corning R345 fluid having a viscosity ganosiloxane oil. Concentrations of non-silicone oils in the of 4.5 centistokes and a boiling point of 217, which primarily continuous silicone phase are minimized or avoided alto contains a mixture of the cyclomethicone tetramer, pentamer, gether so as to further enhance oxidative stability of the 40 and hexamer (i.e. n=4, 5, and 6). selected retinoid in the compositions. Water-in-silicone Also useful are materials such as trimethylsiloxysilicate, emulsions of this type are described in copending U.S. patent which is a polymeric material corresponding to the general application Ser. No. 08/570,275, filed Dec. 11, 1995, in the chemical formula (CH2)SiO2), SiO, wherein X is an names of Joseph Michael Zukowski, Brent William Mason, integer from about 1 to about 500 and y is an integer from Larry Richard Robinson and Greg George Hillebrand. 45 about 1 to about 500. A commercially available trimethylsi The organopolysiloxane oil for use in the composition may loxysilicate is sold as a mixture with dimethicone as Dow be volatile, non-volatile, or a mixture of volatile and non Corning R 593 fluid. volatile silicones. The term “nonvolatile' as used in this con Dimethiconols are also suitable for use in the composition. text refers to those silicones that are liquid under ambient These compounds can be represented by the chemical formu conditions and have a flash point (under one atmospheric of 50 las RSiORSiOSiROH and HORSiORSiOSiROH pressure) of or greater than about 100°C. The term “volatile' wherein R is an alkyl group (preferably R is methyl or ethyl, as used in this context refers to all other silicone oils. Suitable more preferably methyl) and x is an integer from 0 to about organopolysiloxanes can be selected from a wide variety of 500, chosen to achieve the desired molecular weight. Com silicones spanning a broad range of Volatilities and Viscosi mercially available dimethiconols are typically sold as mix ties. Examples of Suitable organopolysiloxane oils include 55 tures with dimethicone or cyclomethicone (e.g. Dow Corn polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalky ing(R) 1401, 1402, and 1403 fluids). larylsiloxanes. Polyalkylaryl siloxanes are also suitable for use in the Polyalkylsiloxanes useful in the composition herein composition. Polymethylphenyl siloxanes having viscosities include polyalkylsiloxanes with viscosities of from about 0.5 from about 15 to about 65 centistokes at 25°C. are especially to about 1,000,000 centistokes at 25°C. Such polyalkylsilox 60 useful. anes can be represented by the general chemical formula Preferred for use herein are organopolysiloxanes selected RSiORSiOSiR wherein R is an alkyl group having from from the group consisting of polyalkylsiloxanes, alkyl Sub one to about 30 carbonatoms (preferably R is methyl or ethyl, stituted dimethicones, cyclomethicones, trimethylsiloxysili more preferably methyl; also mixed alkyl groups can be used cates, dimethiconols, polyalkylaryl siloxanes, and mixtures in the same molecule), and X is an integer from 0 to about 65 thereof. More preferred for use herein are polyalkylsiloxanes 10,000, chosen to achieve the desired molecular weight and cyclomethicones. Preferred among the polyalkylsilox which can range to over about 10,000,000. Commercially anes are dimethicones. US 8,481,015 B2 11 12 As Stated above, the continuous silicone phase may contain chains, polypropylene oxide chains, mixtures of these chains, one or more non-silicone oils. Concentrations of non-silicone and polyether chains containing moieties derived from both oils in the continuous silicone phase are preferably mini ethylene oxide and propylene oxide. Other examples include mized or avoided altogether so as to further enhance oxidative alkyl-modified dimethicone copolyols, i.e., compounds that stability of any retinoids in the compositions. Suitable non contain C2-C30 pendant side chains. Still other useful dime silicone oils have a melting point of about 25°C. or less under thicone copolyols include materials having various cationic, about one atmosphere of pressure. Examples of non-silicone anionic, amphoteric, and Zwitterionic pendant moieties. oils suitable for use in the continuous silicone phase are those The dimethicone copolyol emulsifiers useful herein can be well known in the chemical arts in topical personal care described by the following general structure: products in the form of water-in-oil emulsions, e.g., mineral 10 oil, vegetable oils, synthetic oils, semisynthetic oils, etc. (b) Dispersed Aqueous Phase The topical compositions of the present invention comprise from about 30% to about 90%, more preferably from about st |f| | | | | | | | It 50% to about 85%, and most preferably from about 70% to 15 cit-i-o —o –o i-o -ch about 80% of a dispersed aqueous phase. In emulsion tech CH CH R LR CH nology, the term “dispersed phase' is a term well-known to one skilled in the art which means that the phase exists as Small particles or droplets that are suspended in and Sur wherein R is C1-C30 straight, branched, or cyclic alkyl and rounded by a continuous phase. The dispersed phase is also R is selected from the group consisting of: known as the internal or discontinuous phase. The dispersed —(CH), O (CHCHR), H, aqueous phase is a dispersion of Small aqueous particles or and droplets Suspended in and Surrounded by the continuous sili —(CH), O (CHCHRO), (CHCHRO), H, cone phase described hereinbefore. wherein n is an integer from 3 to about 10; R and R are The aqueous phase can be water, or a combination of water 25 selected from the group consisting of Hand C1-C6 straight or and one or more water soluble or dispersible ingredients. branched chain alkyl such that R and R are not simulta Nonlimiting examples of Such optional ingredients include neously the same; and m, o, X, and y are selected Such that the thickeners, acids, bases, salts, chelants, gums, water-soluble molecule has an overall molecular weight from about 200 to or dispersible alcohols and polyols, buffers, preservatives, about 10,000,000, with m, o, X, and y being independently Sunscreening agents, colorings, and the like. 30 selected from integers of Zero or greater Such that mando are The topical compositions of the present invention will typi not both simultaneously Zero, and Z being independently cally comprise from about 25% to about 90%, preferably selected from integers of 1 or greater. It is recognized that from about 40% to about 80%, more preferably from about positional isomers of these copolyols can be achieved. The 60% to about 80%, water in the dispersed aqueous phase by chemical representations depicted above for the R moieties weight of the composition. 35 containing the RandR'groups are not meant to be limiting (c) Emulsifier for Dispersing the Aqueous Phase but are shown as such for convenience. The water-in-silicone emulsions of the present invention Also useful herein, although not strictly classified as dime preferably comprise an emulsifier. In a preferred embodi thicone copolyols, are silicone surfactants as depicted in the ment, the composition contains from about 0.1% to about structures in the previous paragraph wherein R is: 10% emulsifier, more preferably from about 0.5% to about 40 —(CH), O-R. 7.5%, most preferably from about 1% to about 5%, emulsifier wherein R is a cationic, anionic, amphoteric, or Zwitterionic by weight of the composition. The emulsifier helps disperse moiety. and Suspend the aqueous phase within the continuous silicone Dimethicone copolyol emulsifiers useful herein are phase. described, for example, in U.S. Pat. No. 4,960.764, to A wide variety of emulsifying agents can be employed 45 Figueroa, Jr. et al., issued Oct. 2, 1990; European Patent No. herein to form the preferred water-in-silicone emulsion. EP 330,369, to Sanogueira, published Aug. 30, 1989; G. H. Known or conventional emulsifying agents can be used in the Dahms, et al., “New Formulation Possibilities Offered by composition, provided that the selected emulsifying agent is Silicone Copolyols.” Cosmetics & Toiletries, vol. 110, pp. chemically and physically compatible with essential compo 91-100, March 1995; M. E. Carlotti et al., “Optimization of nents of the composition, and provides the desired dispersion 50 W/O SEmulsions And Study Of The Quantitative Relation characteristics. Suitable emulsifiers include silicone emulsi ships Between Ester Structure And Emulsion Properties. J. fiers, non-silicon-containing emulsifiers, and mixtures Dispersion Science And Technology, 13(3), 315-336 (1992); thereof, known by those skilled in the art for use in topical P. Hameyer, “Comparative Technological Investigations of personal care products. Preferably these emulsifiers have an Organic and Organosilicone Emulsifiers in Cosmetic Water HLB value of or less than about 14, more preferably from 55 in-Oil Emulsion Preparations.” HAPPI 28(4), pp. 88-128 about 2 to about 14, and most preferably from about 4 to about (1991); J. Smid-Korbar et al., “Efficiency and usability of 14. Emulsifiers having an HLB value outside of these ranges silicone surfactants in emulsions. Provisional Communica can be used in combination with other emulsifiers to achieve tion, International Journal of Cosmetic Science, 12, 135-139 an effective weighted average HLB for the combination that (1990); and D. G. Krzysik et al., “A New Silicone Emulsifier falls within these ranges. 60 For Water-in-Oil Systems. Drug and Cosmetic Industry, vol. Silicone emulsifiers are preferred. A wide variety of sili 146(4), pp. 28-81 (April 1990). cone emulsifiers are useful herein. These silicone emulsifiers Among the non-silicone-containing emulsifiers useful are typically organically modified organopolysiloxanes, also herein are various non-ionic and anionic emulsifying agents knownto those skilled in the art as silicone surfactants. Useful Such as Sugar esters and polyesters, alkoxylated Sugar esters silicone emulsifiers include dimethicone copolyols. These 65 and polyesters, C1-C30 fatty acid esters of C1-C30 fatty materials are polydimethylsiloxanes that have been modified alcohols, alkoxylated derivatives of C1-C30 fatty acid esters to include polyether side chains such as polyethylene oxide of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty US 8,481,015 B2 13 14 alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 The exact surfactant chosen will depend upon the pH of the esters of polyols, C1-C30 ethers of polyols, alkylphosphates, composition and the other components present. polyoxyalkylene fatty ether phosphates, fatty acid amides, Preferred are cationic Surfactants, especially dialkyl qua acyl lactylates, Soaps, and mixtures thereof. Other Suitable ternary ammonium compounds, examples of which are emulsifiers are described, for example, in McCutcheons, 5 described in U.S. Pat. Nos. 5,151,209; 5,151,210; 5,120,532: Detergents and Emulsifiers, North American Edition (1986), 4,387,090; 3,155,591; 3,929,678; 3,959,461. McCutcheon's, published by Allured Publishing Corporation; U.S. Pat. No. Detergents & Emulsifiers, (North American edition 1979) M. 5,011,681 to Ciotti et al., issued Apr. 30, 1991; U.S. Pat. No. C. Publishing Co.; and Schwartz, et al., Surface Active 4,421,769 to Dixon et al., issued Dec. 20, 1983; and U.S. Pat. Agents, Their Chemistry and Technology, New York: Inter No. 3,755,560 to Dickert et al., issued Aug. 28, 1973. 10 science Publishers, 1949; which descriptions are incorpo 2) Oil-in-Water Emulsions rated herein by reference. Other preferred topical carriers include oil-in-water emul A wide variety of anionic Surfactants are also useful herein. sions, having a continuous aqueous phase and a hydrophobic, See, e.g., U.S. Pat. No. 3,929.678, to Laughlin et al., issued water-insoluble phase (“oil phase') dispersed therein. Dec. 30, 1975, which is incorporated herein by reference in its Examples of Suitable carriers comprising oil-in-water emul- 15 entirety. Nonlimiting examples of anionic Surfactants include sions are described in U.S. Pat. No. 5,073,371, to Turner, D. the alkoylisethionates, and the alkyl and alkyl ether sulfates. J. et al., issued Dec. 17, 1991, and U.S. Pat. No. 5,073,372, to The alkoyl isethionates typically have the formula RCO - Turner, D. J. et al., issued Dec. 17, 1991. An especially pre OCHCHSOM wherein R is alkyl or alkenyl of from about ferred oil-in-water emulsion, containing a structuring agent, 10 to about 30 carbonatoms, and M is a water-soluble cation hydrophilic surfactant and water, is described in detail here- 20 Such as ammonium, sodium, potassium and triethanolamine. inafter. Nonlimiting examples of these isethionates include those (a) Structuring Agent alkoyl isethionates selected from the group consisting of A preferred oil-in-water emulsion comprises a structuring ammonium cocoyl isethionate, Sodium cocoyl isethionate, agent to assist in the formation of a liquid crystalline gel Sodium lauroylisethionate, Sodium Stearoylisethionate, and network structure. Without being limited by theory, it is 25 mixtures thereof. believed that the structuring agent assists in providing rheo The alkyl and alkyl ether sulfates typically have the respec logical characteristics to the composition that contribute to tive formulae ROSOM and RO(CHO), SOM, wherein R the stability of the composition. The structuring agent may is alkyl or alkenyl of from about 10 to about 30 carbonatoms, also function as an emulsifier or surfactant. Preferred com X is from about 1 to about 10, and M is a water-soluble cation positions of this invention comprise from about 0.5% to about 30 Such as ammonium, sodium, potassium and triethanolamine. 20%, more preferably from about 1% to about 10%, most Another Suitable class of anionic Surfactants is the water preferably from about 1% to about 5%, by weight of the soluble salts of the organic, sulfuric acid reaction products of composition, of a structuring agent. the general formula: The preferred structuring agents of the present invention are selected from the group consisting of stearic acid, palmitic 35 acid, Stearyl alcohol, cetyl alcohol, behenyl alcohol, Stearic wherein R is chosen from the group consisting of a straight or acid, palmitic acid, the polyethylene glycol ether of Stearyl branched chain, Saturated aliphatic hydrocarbon radical hav alcohol having an average of about 1 to about 21 ethylene ing from about 8 to about 24, preferably about 10 to about 16, oxide units, the polyethylene glycol ether of cetyl alcohol carbon atoms; and M is a cation. Still other anionic synthetic having an average of about 1 to about 5 ethylene oxide units, 40 Surfactants include the class designated as Succinamates, ole and mixtures thereof. More preferred structuring agents of the fin Sulfonates having about 12 to about 24 carbonatoms, and present invention are selected from the group consisting of B-alkyloxy alkane Sulfonates. Examples of these materials stearyl alcohol, cetyl alcohol, behenyl alcohol, the polyeth are sodium lauryl Sulfate and ammonium lauryl Sulfate. ylene glycol ether of Stearyl alcohol having an average of Other anionic materials useful herein are soaps (i.e. alkali about 2 ethylene oxide units (steareth-2), the polyethylene 45 metal salts, e.g., Sodium or potassium salts) of fatty acids, glycol ether of Stearyl alcohol having an average of about 21 typically having from about 8 to about 24 carbon atoms, ethylene oxide units (steareth-21), the polyethylene glycol preferably from about 10 to about 20 carbon atoms. The fatty ether of cetyl alcohol having an average of about 2 ethylene acids used in making the soaps can be obtained from natural oxide units, and mixtures thereof. Even more preferred struc Sources such as, for instance, plant or animal-derived glycer turing agents are selected from the group consisting of Stearic 50 ides (e.g., palm oil, coconut oil, soybean oil, castor oil, tallow, acid, palmitic acid, Stearyl alcohol, cetyl alcohol, behenyl lard, etc.) The fatty acids can also be synthetically prepared. alcohol, steareth-2, steareth-21, and mixtures thereof Soaps are described in more detail in U.S. Pat. No. 4,557,853. (b) Hydrophilic Surfactant Amphoteric and Zwitterionic Surfactants are also useful The preferred oil-in-water emulsions comprise from about herein. Examples of amphoteric and Zwitterionic Surfactants 0.05% to about 10%, preferably from about 1% to about 6%, 55 which can be used in the compositions of the present inven and more preferably from about 1% to about 3% of at least tion are those which are broadly described as derivatives of one hydrophilic Surfactant which can disperse the hydropho aliphatic secondary and tertiary amines in which the aliphatic bic materials in the water phase (percentages by weight of the radical can be straight or branched chain and wherein one of composition). The Surfactant, at a minimum, must be hydro the aliphatic substituents contains from about 8 to about 22 philic enough to disperse in water. 60 carbon atoms (preferably Cs-Cs) and one contains an Suitable surfactants include any of a wide variety of known anionic water solubilizing group, e.g., carboxy, Sulfonate, cationic, anionic, Zwitterionic, and amphoteric Surfactants. Sulfate, phosphate, orphosphonate. Examples are alkylimino See, McCutcheon's, Detergents and Emulsifiers, North acetates, and iminodialkanoates and aminoalkanoates of the American Edition (1986), published by Allured Publishing formulas RNICH2)COM and RNH(CH2)COM Corporation; U.S. Pat. Nos. 5,011,681; 4,421,769; and 3,755, 65 wherein m is from 1 to 4, R is a C-C alkyl or alkenyl, and 560; these references are incorporated herein by reference in M is H. alkali metal, alkaline earth metal ammonium, or their entirety. alkanolammonium. Also included are imidazolinium and US 8,481,015 B2 15 16 ammonium derivatives. Other examples of useful amphoter The physical form of the cleansing compositions is not ics include phosphates, such as coamidopropyl PG-dimo critical. The compositions can be, for example, formulated as nium chloride phosphate (commercially available as toilet bars, liquids, shampoos, bath gels, hair conditioners, Monaquat PTC, from Mona Corp.). hair tonics, pastes, or mousses. Toilet bars are most preferred Also useful herein as amphoteric or Zwitterionic Surfac since this is the form of cleansing agent most commonly used tants are the betaines, Sultaines and hydroxysultaines such as to wash the skin. Rinse-off cleansing compositions. Such as cocamidopropyl hydroxysultaine (available as Mirataine shampoos, require a delivery system adequate to deposit Suf CBS from Rhone-Poulenc), and the alkanoyl sarcosinates ficient levels of actives on the skin and scalp. A preferred corresponding to the formula RCON(CH)CHCHCOM delivery system involves the use of insoluble complexes. For wherein R is alkyl or alkenyl of about 10 to about 20 carbon 10 a more complete disclosure of such delivery systems, see U.S. atoms, and M is a water-soluble cation Such as ammonium, Pat. No. 4,835,148, Barford et al., issued May 30, 1989. Sodium, potassium and trialkanolamine (e.g., triethanola The compositions of the present invention may also be in mine), a preferred example of which is sodium lauroyl sarco the form of cosmetics. Suitable cosmetic forms include, but sinate. are not limited to, foundations, lipsticks, rouges, mascaras, (c) Water 15 and the like. Such cosmetic products may include conven The preferred oil-in-water emulsion comprises from about tional ingredients such as oils, colorants, pigments, emol 25% to about 98%, preferably from about 65% to about 95%, lients, fragrances, waxes, stabilizers, and the like. Exemplary more preferably from about 70% to about 90% water by carriers and Such other ingredients which are suitable for use weight of the topical carrier. herein are described, for example, in copending patent appli The hydrophobic phase is dispersed in the continuous cation Ser. No. 08/.430,961, filed on Apr. 28, 1995 in the aqueous phase. The hydrophobic phase may contain water names of Marcia L. Canter, Brain D. Barford, and Brian D. insoluble or partially soluble materials such as are known in Hofrichter. the art, including but not limited to the silicones described D. Optional Components herein in reference to silicone-in-water emulsions, and other The compositions of the present invention may contain a oils and lipids such as described above in reference to emul 25 variety of other ingredients that are conventionally used in sions. given product types provided that they do not unacceptably (d) Composition Forms alter the benefits of the invention. The topical compositions of the Subject invention, includ The optional components, when incorporated into the ing but not limited to lotions and creams, may comprise a composition, should be suitable for use in contact with human dermatologically acceptable emollient. Such compositions 30 keratinous tissue without undue toxicity, incompatibility, preferably contain from about 2% to about 50% of the emol instability, allergic response, and the like within the scope of lient. As used herein, "emollient” refers to a material useful sound judgment. The CTEA Cosmetic Ingredient Handbook, for the prevention or relief of dryness, as well as for the Second Edition (1992) describes a wide variety of nonlimit protection of the skin. A wide variety of suitable emollients ing cosmetic and pharmaceutical ingredients commonly used are known and may be used herein. Sagarin, Cosmetics Sci 35 in the skin care industry, which are suitable for use in the ence and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), compositions of the present invention. incorporated herein by reference, contains numerous In any embodiment of the present invention, however, the examples of materials suitable as an emollient. A preferred actives useful herein can be categorized by the benefit they emollient is glycerin. Glycerin is preferably used in an provide or by their postulated mode of action. However, it is amount of from about 0.001% to about 20%, more preferably 40 to be understood that the actives useful herein can in some from about 0.01% to about 10%, and most preferably from instances provide more than one benefit or operate via more about 0.1% to about 7%, e.g., 5%. than one mode of action. Therefore, classifications herein are Lotions and creams according to the present invention made for the sake of convenience and are not intended to limit generally comprise a solution carrier system and one or more the active to that particular application or applications listed. emollients. Lotions typically comprise from about 1% to 45 1.) Hair Growth Inhibiting Compounds about 20%, preferably from about 5% to about 10%, of emol The compositions of the present invention may also com lient; from about 50% to about 90%, preferably from about prise other hair growth inhibiting compounds. These com 60% to about 80%, water; and the catechin in the above pounds are known in the art as inhibiting hair growth and described amounts. A cream typically comprises from about consist of the following: 1,10-phenanthroline; 5'-p-fluorosul 5% to about 50%, preferably from about 10% to about 20%, 50 phonyl benzoyl adenosine; 5-keto-D-fructose; 5-keto-D- of emollient; from about 45% to about 85%, preferably from fructose-1,6-bisphosphate: 6-amino-6-deoxy-glucose; agaric about 50% to about 75%, water; and the catechin in the above acid; Br-cAMP; cysteine sulphinic acid; D-mannosamine: described amounts. diethylaminomalonate, doxycycline; ethacrynic acid; ethox Ointments of the present invention may comprise a simple ycuin, eupacunin, euparotin acetate; fluvastatin; guanidino carrier base of animal or vegetable oils or semi-solid hydro 55 Succinic acid; inhibitor of a cysteine pathway enzyme; meth carbons (oleaginous); absorption ointment bases which acycline; mevastatin: mevinolin; minocycline; N-alpha-(p- absorb water to form emulsions; or water soluble carriers, tosyl)-L-lysine chloromethyl ketone; N-acetyl-beta-D-man e.g., a water Soluble solution carrier. Ointments may further nosamine; oxaloacetic acid; phosphoglycerate; pravastatin: comprise a thickening agent, such as described in Sagarin, protocatechuic aldehyde; quinaldic acid; rivastatin; simvas Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 60 tatin: squalestatin; taxodione; taxodone; tetracycline; Vemol 72-73 (1972), incorporated herein by reference, and/or an epin; 1,10-phenanthroline; 1,8-diaminooctane, 2-methyl-6- emollient. heptyne-2,5-diamine: 3-carboxypropyl disulphide; saw Compositions of this invention useful for cleansing palmetto extract, willow herb extract, pumpkin seed extract, ("cleansers') are formulated with a Suitable carrier, e.g., as 5-(N-benzyloxycarbonyl)-1-phenylalanamidomethyl)-3- described above, and preferably contain, in addition to the 65 bromo-4,5-dihydroisoxazole; 5'-deoxy-5'-(N-methyl-N-(2- catechin in the above described amounts and from about 1% aminooxy-ethyl)-aminoadenosine (MAOEA); 5'-deoxy-5'- to about 90% of a dermatologically acceptable surfactant. methyl-thioadenosine; 6-heptyne-2,4-diamine; actinonin; US 8,481,015 B2 17 18 alpha-methyl-DL-methionine; alpha-ethyl-ornithine; apige ing hormone releasing hormone (LHRH) analogs; tetrahy nin; arginase inhibitor; batimistat; Br-cAMP; caffeic acid; droisoquinoline derivatives; tetrahydroisoquinoline deriva captopril; chlorotaurine; cholesterol pathway enzyme inhibi tives; 3-(anilinomethylene) oxindole derivatives; benzo-f- tor, cyclooxygenase inhibitor; cysteamine; cysteine Sulphinic quinolin-3-one derivative; ((S-(-)-N-(alpha-ethylbenzyl)-3- acid; cysteinyl-glycine; D-cysteine; D-penicillamine; difluo hydroxy-2-phenylduinoline-4-carboxamide); 24-ethyl romethylomithine (DFMO); diethyl aminomalonate; diethyl (Delta)4.22-cholestadien-3-one; extracts from Hydrangea glyoxal bis(quanylhydraZone); diethyldithiocarbamic acid; macrophylla, Hydrangea serrata; Iridaceae Belamcanda dimethyl cysteamine, doxycycline; eicosapentaenoic acid; Adans; Iridaceae Iris L.; Moraceae Humulus; CDK binding estramustine; ethacrynic acid; etoposide; guanidino Succinic proteins; chimeric polypeptide with cyclin-dependent kinase acid; H-homoarginine; inhibitor of a cholesterol pathway 10 (CDK) binding motif. E6AP-binding polypeptides; 2-mer enzyme; inhibitor of the formation of glycoproteins, pro captoethanol; 2-mercaptopropionic acid; cysteine; dieth teoglycans or glycosaminoglycans; inhibitor of the hypusine yldithiocarbamic acid; dithiothreitol, glutathione; homocys biosynthetic pathway; L-alanosine: L-argininamide: L-aspar teine; lipoic acid; mercaptopropionic acid; N-acetyl-L- aginamide: L-cysteine methyl ester, lipoic acid; lovastatin: cysteine; thiodiglycol; thiodiglycolic acid; thioglycerol; marimistat; matlyStatin-B; meso-dimercaptosuccinic acid; 15 thioglycolic acid; thiolactic acid; thiomalic acid; thiopropi methacycline; methylglyoxal bis(guanylhydraZone); onic acid; thiosalicylic acid; thioxanthine; benzoic acid lac minocycline; N(G)-methyl-L-arginine; N-NI((R)-1- tone ether, 1-halomethyl-5alpha-androstanes and delta-an phosphonopropyl)-(S)-leucyl-(S)-phenylalanine-N-methy drosteness; hedgehog antagonists; patched antagonists; lamide: N-acetylcysteine; N-phosphonalkyl dipeptides: copper; iron; Zinc, 1 dehydromelengestrol acetate: 1-dehy N-phosphonoacetyl-aspartic acid; nalidixic acid; N-alpha dromegestrol acetate; chlormadinone acetate, cyproterone acetyl-L-arginine, N-alpha-benzoyl-L-argininamide, N-al acetate; medroxyprogesterone acetate; megestrol acetate; pha-benzoyl-L-arginine; N-alpha-benzoyl-L-arginine melengestrol acetate; nomegestrol acetate; non-elastomeric methyl ester; NG-L-arginine benzyl ester; NG-nitro-L-argi polyolefin resin; partially fluorinated polyolefin resin; nine; NG-nitro-L-arginine methyl ester, nordihydrogua nucleic acid molecule; trypsin analogs; bacteriostatic or hae ianetic acid (NDGA); extract from creosote:oxaloacetic acid; 25 mostyptic agent, especially Stannous fluoride; alpha- or pantothenic acid; pantothenic acid analogues; phosphocys gamma-linolenic acid; EGF; lipoxygenases; extract of teamine; propyl gallate; protein kinase C inhibitor, protocat Reguloplant (Abelmoschus moschatus); extract of Wolo plant echuic aldehyde; protocatechuic aldehyde; quercetin: S-car (Borassus flabellifer); androstenedione analogues; activin A bamyl-L-cysteine; S-trityl-L-cysteine; SulphaSalazine; (polypeptide); hydrindanes; butyric acid derivatives; phy Suppressor of angiogenesis; tetracycline; thiosalicylic acid; 30 toestrogen; Tetrahydroisoquinolines; tetrahydronaphtha tyramine: 2-difluoromethyl-, 2,5-diamino pentanoic acid; lenes; 3-amino-2,3-dihydro benzoic acid: 6-fluoro-2,5-di herbimycin; HNMPA (AM)3; inhibitor of alkaline phos amino hexanoic acid: (S)-2-amino-4-amino oxy-butyric acid; phatase; lavendustin A; methyl caffeate; protein-tyrosine extracts of fruits and other plant parts from Serenoa repens; kinase inhibitors; Tryphostin A47; O-p-nitrohydroxylamine, carrot oil; clove oil; diazo compounds; essential oil; honey; alpha.-fluoromethylhistidine, mycophenolic acid, bromoc 35 juniper oil; lavender oil; lemonjuice; palmarosa oil; rosemary ryptine, cromoglycate, quinoline-3-carboxamide, 16 alpha oil; Sugar, Sugary Substance; thuia oil; triarylmethane com or beta-substituted 4-aza-5 alpha-androst-1-en-3-ones; pounds; Perfluoro-substituted aniline derivatives; 17alpha 2-aryl-indole derivatives; 2-phenyl-3-aminoalkyl-indole propyltestosterone: 4-androstene-3-one 17beta-carboxylic derivatives; 3-oxo-4-aza-5 alpha-androstane derivs. 5alpha acid; (4R)-5,10-seco-19-norpregna 4,5-diene-3,10.20-trione: androstan-3-ones; 5-(aminocarbonylalkyl)-3-(heterobicy 40 chlormadinone acetate; cyproterone acetate; progesterone; clyl-alkylaminoalkyl)-2-phenylindole derivatives: 6-azain spironolactone; melatonin; Bowman Birk inhibitor (soy dole derivatives; 7-azaindole derivatives: aryl-imidazo derived); 2-substd. 6-tetrahydronaphthyl or indanyl naphtha pyridines; finasteride; GnRH inhibitors, aloe; lene derives; aqueous alcoholic extract from genus Centi carboxyalkylamine derivatives; clove; Echinacea angustifo peda; antagonist of the hedgehog signal transduction path lia, Echinacea purpurea; elasatin decomposition enzyme 45 way; epidermal growth factor (EGF); finasteride; inhibitor, extracts from ginger; hydrolyzing almond; Lithos spironolactone; fatty acids; 2-phenyl-benzothiophene perumum; peptides; extract of Rosaceae; extract of San derivs. 2-arylimino-oxaza or thiaza heterocyclic com guisorba officinalis, Tropaeolum maius; extract of white pounds; glutathione synthesis stimulators; indole derivatives; birch and rubiaceae plant groups; extract of Juniperus genus Cinnamomum verum, Curcurbita pepo, Epilobium roseum, and/or malt extract; malonamide derivatives; elastase inhibi 50 Salvia officinalis, Serenoa repens, Cassia obtusifoila Linne; tor, papain, trypsin, chymotrypsin, pepsin, bromelain, ficin or polynucleotide; dormant cell extracts: N-substituted. benzyl pancreatin; plant fruit enzyme extracts; compounds from or thienylmethyl-4-pyridone cpds; (1H)-benzo(c)(quinolizin Pleione sp., Curcuma longa L. or Diopyros kaki, 2-indole 3-one derivatives; 5-alpha-reductase inhibitors; adenylsucci carboxylic acid derivatives; alpha-TNF antagonist; amino nate synthetase inhibitor, aspartate transcarbamylase inhibi propanes; bacterium ribosomes; non-steroidal anti-inflam 55 tor; gammaglutamyl transpeptidase inhibitor, Ornithine matory drugs (NSAIDS); diethylenediamines; histamine decarboxylase inhibitors; citric acid; Dead Sea salt; visab antagonist; interleukin-1 antagonist, lipoxygenase inhibitors orol; ant eggs; androgen receptor blockers; previtamin D; and stimulants; phenothiazines; Sulfotransferase inhibitors; provitamin D; vitamin D; vitamin K: Cucurbitaceae; extract tetrazolyl-benzofuran carboxamides; tetrazolyl-ben of Ikurinin; phosphodiesterase; Phlondrin: phloretin: 5 alpha Zothiophene carboxamides; cyanoguanidine derivatives; 60 androstene-3 alpha, 17 beta-diol; cyproterone; Hedera helex: 17alpha-hydroxy-4,9011)-pregnadiene-320-dione deriva Lithospermum root; medoroxyprogesterone; mestanolone; tives...; anti-angiogenic steroids; pyrimidine-cyanoguanidine norethisterone: Scutellaria root; tomato; extract of Commi derivs. Substd. amidine or guanidine. benzothiophene deriva phora myrrha, Cymbopogon nardus, Lagerstroemia spe tives: (-)cis 6(S)-phenyl-5(R)-4-(2-pyrrolidin-1-ylethox ciosa, phyllanthus nuriri, Smilax zeylanica, Woodfordia fru yphenyl-5,6,7,8-tetrahydronaphthelen-2-ol D-tartrate (I); 65 ticosa; chelating agents; chlorophenol; o-phenylphenol; tetrahydronaphthalene derivatives; estrogen agonists or phenol; Niphtolide; peach oil; sorbic acid; Cistanche salsa; antagonists; tetrahydroisoquinolines; Heptapeptide luteiniz Plantago asiatica L.; Stachys sieboldii, 2-amino-5-substd. US 8,481,015 B2 19 20 benzophenone; Aniline derives; bur marigold infusion; cam 5.) Anti-Wrinkle Actives/Anti-Atrophy Actives phor oil; citric acid; conifer extract; daisy infusion; honey; The compositions of the present invention may further sea-buckthorn oil; tannin solution; capsicum, capsicum comprise a safe and effective amount of one or more anti extract (Solanaceae family); conjugate comprising active wrinkle actives or anti-atrophy actives. Exemplary anti agent Substituted with amino acid, peptide or trisamine car wrinklefanti-atrophy actives suitable for use in the composi rying fatty acid ester and dithioalkanoyl groups; recombinant tions of the present invention include Sulfur-containing Dand DNA encoding EGF; recombinant DNA encoding TGFalpha; Lamino acids and their derivatives and salts, particularly the 11-beta-aryl-17-spiro-pyrrolin-2-ylidene N-oxide steroid N-acetyl derivatives, a preferred example of which is progestins and antiprogestins; phenylimidazolidines; ammo N-acetyl-L-cysteine; thiols, e.g. ethane thiol: hydroxy acids nium salt of weak acids; essential oils; vitamin F. Coumarin 10 derivatives; leuteinizing hormone-releasing hormone; leu (e.g., Salicylic acid, glycolic acid), keto acids (e.g., pyruvic teinizing hormone-releasing hormone analogs; Hydroxamic acid), ascorbic acid (vitamin C), phytic acid, lipoic acid; acid derivatives; borneol; cineole: linalol; methylheptenone; lysophosphatidic acid, skin peel agents (e.g., phenol and the oil of ginger; shogaol; Zingerone; Zingiberol; Zingiberone; like), flavonoids (e.g., flavanones, chalcones, isoflavones, fla glutathione S-transferase modulator; aminoacid(s); lipoxy 15 Vones, etc.), Stilbenes, cinnamates, resveratrol, kinetin, dase; inhibitor of glutamine metabolism; thiomolybdate Zeatin, dimethylaminoethanol, peptides from natural sources compound; Hairless protein inhibitor, aromatase inhibitor, (e.g., soy peptides), salts of Sugar acids (e.g., Mn gluconate), trifluoroanilide derivatives; EGF: EGF analogues; and extract terpene alcohols (e.g., farnesol), peptides, vitamin B com of seeds of Coix lachrymaiobi. pounds and retinoids which enhance the keratinous tissue 2.) Depilatories appearance benefits of the present invention, especially in Certain embodiments of the present invention may option regulating keratinous tissue condition, e.g., skin condition, ally contain a depilatory. As used herein, “depilatory' means and other vitamin B compounds (e.g., thiamine (vitamin B1). an agent capable of removanghair from the skin by cleaving pantothenic acid (vitamin B5), camitine (vitamin Bt), ribo the disulfide flavin (vitamin B2), cobalamine (vitamin B12), pangamic bonds in hair keratin, thereby causing the hair fiber to disin 25 acid or diisopropylamine dichloroacetate (vitamin B15 s), tegrate. Preferred depilatories useful in the subject invention and their derivatives and salts (e.g., HCl salts or calcium include ammonium thioglycolate, barium sulfate, calcium salts)). thioglycolate, ethanolamine thioglycolate, potassium (a) Vitamin B Compounds thioglycolate, Sodium thioglycolate, thioglycolic acid and The compositions of the present invention may comprise a thioacetic acid. When present in the composition, the com 30 safe and effective amount of a vitamin B compound. Vitamin position contains from about 0.0001 % to about 99.9 %, B compounds are particularly useful for regulating skin con preferably from about 0.001% to about 10%, and more pref dition as described in co-pending U.S. application Ser. No. erably from about 0.01% to about 5%, by weight of the 08/834,010, filed Apr. 11, 1997 (corresponding to interna composition, of the depilatory. Examples of Suitable depila tional publication WO 97/39733 A1, published Oct. 30, tories are described in further detail in U.S. Pat. No. 5,897, 35 1997). When vitamin B compounds are present in the com 857. positions of the instant invention, the compositions prefer 3.) Desquamation Actives ably comprise from about 0.01% to about 50%, more prefer A safe and effective amount of a descquamation active may ably from about 0.1% to about 10%, even more preferably be added to the compositions of the present invention, more from about 0.5% to about 10%, and still more preferably from preferably from about 0.01% to about 10%, even more pref 40 about 1% to about 5%, most preferably from about 2% to erably from about 0.5% to about 5%, also preferably from about 5%, by weight of the composition, of the vitamin B about 0.1% to about 2%, by weight of the composition. compound. Desquamation actives enhance the skin appearance benefits (b) Retinoids of the present invention. For example, the descquamation The compositions of the present invention may also com actives tend to improve the texture of the skin (e.g., Smooth 45 prise a retinoid. As used herein, “retinoid includes all natural ness). One descquamation system that is suitable for use herein and/or synthetic analogs of Vitamin A or retinol-like com comprises Sulfhydryl compounds and Zwitterionic Surfac pounds which possess the biological activity of Vitamin A in tants and is described in U.S. Pat. No. 5,681,852, issued on the skinas well as the geometric isomers and stereoisomers of Oct. 28, 1997, in the name of Donald L. Bissett, correspond these compounds. The retinoid is preferably retinol, retinol ing to WO 96/01101, published on Jan. 18, 1996. Another 50 esters (e.g., C-C alkyl esters (Saturated or unsaturated alkyl descuamation system that is suitable for use herein comprises chains) of retinol, including retinyl palmitate, retinyl acetate, salicylic acid and Zwitterionic Surfactants and is described in retinyl propionate), retinal, and/or retinoic acid (including U.S. Pat. No. 5,652,228, issued on Jul. 29, 1997, as a con all-trans retinoic acid and/or 13-cis-retinoic acid), more pref tinuation of Ser. No. 08/209,041, filed on Mar. 9, 1994, now erably retinoids other than retinoic acid. These compounds abandoned, in the name of Bissett, corresponding to WO95/ 55 are well known in the art and are commercially available from 13048, published on May 18, 1995. Zwitterionic surfactants a number of Sources, e.g., Sigma Chemical Company (St. Such as described in these applications are also useful as Louis, Mo.), and Boerhinger Mannheim (Indianapolis, Ind.). descuamatory agents herein, with cetyl betaine being particu Preferred retinoids are retinol, retinyl palmitate, retinyl larly preferred. acetate, retinyl propionate, retinal and combinations thereof 4.) Anti-Acne 60 (c) Anti-Oxidants/Radical Scavengers The compositions of the present invention may comprise a The compositions of the present invention may include a safe and effective amount of one or more anti-acne actives. safe and effective amount of an anti-oxidant/radical scaven Examples of useful anti-acne actives include resorcinol, Sul ger. The anti-oxidant/radical scavenger is especially useful fur, Salicylic acid, erythromycin, Zinc, etc. Further examples for providing protection against UV radiation that can cause of suitable anti-acne actives are described in further detail in 65 increased scaling or texture changes in the stratum corneum U.S. Pat. No. 5,607,980, issued to McAtee et al., on Mar. 4, and against other environmental agents, which can cause skin 1997. damage. US 8,481,015 B2 21 22 A safe and effective amount of an anti-oxidant/radical will depend on the particular anti-inflammatory agent utilized Scavenger may be added to the compositions of the Subject since Such agents vary widely in potency. Anti-inflammato invention, preferably from about 0.1% to about 10%, more ries can selected from several classes. One is comprised of preferably from about 1% to about 5%, of the composition. steroidal anti-inflammatory agents, including but not limited Anti-oxidants/radical scavengers such as ascorbic acid (vi to, corticosteroids. The preferred steroidal anti-inflammatory tamin C) and its salts, ascorbyl esters of fatty acids, ascorbic for use is hydrocortisone. acid derivatives (e.g., magnesium ascorbyl phosphate), toco A second class of anti-inflammatory agents, which is use pherol (vitamin E), tocopherol Sorbate, tocopherol acetate, ful in the compositions, includes the nonsteroidal anti-in other esters of tocopherol, butylated hydroxybenzoic acids flammatory agents. Such compounds are known in the art as and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2- 10 carboxylic acid (commercially available under the tradename non-steroidal anti-inflammatory agents (“NSAIDS) and are TroloX(R), gallic acid and its alkyl esters, especially propyl described in detail, along with methods for manufacture in the gallate, uric acid and its salts and alkyl esters, Sorbic acid and following U.S. Pat. Nos. 5,280,045; 4,708,966; 5,189,066: its salts, lipoic acid, amines (e.g., N,N-diethylhydroxy 5,510,361; 5,189,066; 5,476,876; and 5,684,204, all of which lamine, amino-guanidine), Sulfhydryl compounds (e.g., glu 15 are incorporated herein by reference. tathione), dihydroxy fumaric acid and its salts, lycine pidol Mixtures of these non-steroidal anti-inflammatory agents ate, arginine pilolate, nordihydroguaiaretic acid, may also be employed, as well as the dermatologically bioflavonoids, lysine, methionine, proline, Superoxide dis acceptable salts and esters of these agents. mutase, silymarin, tea extracts, grape skin/seed extracts, Finally, so-called “natural anti-inflammatory agents are melanin, and rosemary extracts may be used. Preferred anti useful in methods of the present invention. Such agents may oxidants/radical scavengers are selected from tocopherol Sor suitably be obtained as an extract by suitable physical and/or bate and other esters of tocopherol, more preferably toco chemical isolation from natural Sources (e.g., plants, fungi, pherol sorbate. For example, the use of tocopherol sorbate in by-products of microorganisms). For example, candelilla topical compositions and applicable to the present invention wax, alpha-bisabolol, aloe Vera, Manjistha (extracted from is described in U.S. Pat. No. 4,847,071, issued on Jul. 11, 25 plants in the genus Rubia, particularly Rubia Cordifolia), and 1989 to Donald L. Bissett, Rodney D. Bush and Ranjit Chat Guggal (extracted from plants in the genus Commiphora, terjee. particularly Commiphora Mukul), kola extract, chamomile, (d) Chelators red clover extract, and sea whip extract, may be used. The compositions of the present invention may also com Additional anti-inflammatory agents useful herein include prise a safe and effective amount of a chelator or chelating 30 allantoin and compounds of the Licorice (the plant genus/ agent. As used herein, “chelator” or “chelating agent’ means species Glycyrrhiza glabra) family, including glycyrrhetic an active agent capable of removing a metalion from a system acid, glycyrrhizic acid, and derivatives (e.g., salts and esters). by forming a complex so that the metal ion cannot readily Specific examples of the foregoing include oil soluble licorice participate in or catalyze chemical reactions. The inclusion of extract, the glycyrrhizic and glycyrrhetic acids themselves, a chelating agent is especially useful for providing protection 35 monoammonium glycyrrhizinate, monopotassium glycyr against UV radiation that can contribute to excessive scaling rhizinate, dipotassium glycyrrhizinate, 1-beta-glycyrrhetic or skin texture changes and against other environmental acid, Stearylglycyrrhetinate, and 3-stearyloxy-glycyrrhetinic agents, which can cause skin damage. acid, and disodium 3-succinyloxy-beta-glycyrrhetinate. A safe and effective amount of a chelating agent may be Stearyl glycyrrhetinate is preferred. added to the compositions of the subject invention, preferably 40 The active component of these anti-inflammatory agents from about 0.1% to about 10%, more preferably from about (e.g., biabolol, glycyrrhetinate esters) may also be obtained 1% to about 5%, of the composition. Exemplary chelators that via extraction from natural sources or prepared synthetically. are useful herein are disclosed in U.S. Pat. No. 5,487,884, (g) Anti-Cellulite Agents issued Jan. 30, 1996 to Bissett et al.; International Publication The compositions of the present invention may also com No. 91/16035, Bush et al., published Oct. 31, 1995; and 45 prise a safe and effective amount of an anti-cellulite agent. International Publication No. 91/16034, Bush et al., pub Suitable agents may include, but are not limited to, Xanthine lished Oct. 31, 1995. Preferred chelators useful in composi compounds (e.g., caffeine, theophylline, theobromine, and tions of the subject inventionarefurildioxime and derivatives. aminophylline). (e) Flavonoids (h) Topical Anesthetics The compositions of the present invention may optionally 50 The compositions of the present invention may also com comprise a flavonoid compound. Flavonoids are broadly dis prise a safe and effective amount of a topical anesthetic. closed in U.S. Pat. Nos. 5,686,082 and 5,686,367, both of Examples of topical anesthetic drugs include benzocaine, which are herein incorporated by reference. lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, The herein described flavonoid compounds are preferably mepivacaine, tetracaine, dyclonine, hexyl-caine, procaine, present in the instant invention at concentrations of from 55 cocaine, ketamine, pramoxine, phenol, and pharmaceutically about 0.01% to about 20%, more preferably from about 0.1% acceptable salts thereof. to about 10%, and most preferably from about 0.5% to about (i) Tanning Actives 5%. The compositions of the present invention may comprise a (f) Anti-Inflammatory Agents tanning active. When present, it is preferable that the compo A safe and effective amount of an anti-inflammatory agent 60 sitions comprise from about 0.1% to about 20%, more pref may be added to the compositions of the present invention, erably from about 2% to about 7%, and most preferably from preferably from about 0.1% to about 10%, more preferably about 3% to about 6%, by weight of the composition, of from about 0.5% to about 5%, of the composition. The anti dihydroxyacetone as an artificial tanning active. inflammatory agent enhances the skin appearance benefits of Dihydroxyacetone is also known to be more stable at acidic the present invention, e.g., such agents contribute to a more 65 pH values. See The Merck Index, Tenth Edition, entry 31.67, p. uniform and acceptable skin tone or color. The exact amount 463 (1983), and “Dihydroxyacetone for Cosmetics’. E. of anti-inflammatory agent to be used in the compositions Merck Technical Bulletin, 03-304 110, 319 897, 180588. US 8,481,015 B2 23 24 () Skin Lightening Agents lamine; and mixtures thereof. Also useful herein are the pro The compositions of the present invention may comprise a poxylated glycerols described in U.S. Pat. No. 4,976,953, to skin lightening agent. When used, the compositions prefer Orr et al., issued Dec. 11, 1990. ably comprise from about 0.1% to about 10%, more prefer Also useful are various C-C monoesters and polyesters ably from about 0.2% to about 5%, also preferably from about of Sugars and related materials. These esters are derived from 0.5% to about 2%, by weight of the composition, of a skin a Sugar or polyol moiety and one or more carboxylic acid lightening agent. Suitable skin lightening agents include moieties. Such ester materials are further described in, U.S. those known in the art, including kojic acid, arbutin, tranex Pat. No. 2,831,854, U.S. Pat. No. 4,005,196, to Jandacek, amic acid, ascorbic acid and derivatives, e.g., magnesium issued Jan. 25, 1977; U.S. Pat. No. 4,005, 195, to Jandacek, ascorbyl phosphate or sodium ascorbyl phosphate or other 10 issued Jan. 25, 1977, U.S. Pat. No. 5,306,516, to Letton et al., salts of ascorbyl phosphate. Skin lightening agents Suitable issued Apr. 26, 1994; U.S. Pat. No. 5,306,515, to Letton et al., for use herein also include those described in copending issued Apr. 26, 1994; U.S. Pat. No. 5,305.514, to Letton et al., patent application Ser. No. 08/479,935, filed on Jun. 7, 1995 issued Apr. 26, 1994: U.S. Pat. No. 4,797,300, to Jandaceket in the name of Hillebrand, corresponding to PCT Application al., issued Jan. 10, 1989; U.S. Pat. No. 3,963,699, to RiZZi et No. U.S. 95/07432, filed Jun. 12, 1995; and copending patent 15 al., issued Jun. 15, 1976; U.S. Pat. No. 4,518,772, to Volpen application Ser. No. 08/390,152, filed on Feb. 24, 1995 in the hein, issued May 21, 1985; and U.S. Pat. No. 4,517,360, to names of Kalla L. Kvalnes, Mitchell A. DeLong, Barton J. Volpenhein, issued May 21, 1985. Bradbury, Curtis B. Motley, and John D. Carter, correspond Preferably, the conditioning agent is selected from the ing to PCT Application No. U.S. 95/02809, filed Mar. 1, 1995, group consisting of glycerol, urea, guanidine. Sucrose poly published Sep. 8, 1995. ester, and combinations thereof. (k) Antimicrobial and Antifungal Actives (n) Thickening Agent (Including Thickeners and Gelling The compositions of the present invention may comprise Agents) an antimicrobial orantifungalactive. Such actives are capable The compositions of the present invention can comprise of destroying microbes, preventing the development of one or more thickening agents, preferably from about 0.1% to microbes or preventing the pathogenic action of microbes. A 25 about 5%, more preferably from about 0.1% to about 3%, and safe and effective amount of an antimicrobial or antifungal most preferably from about 0.25% to about 2%, by weight of active may be added to the present compositions, preferably, the composition. from about 0.001% to about 10%, more preferably from Nonlimiting classes of thickening agents include those about 0.01% to about 5%, and most preferably from about selected from the group consisting of: 0.05% to about 2%. 30 (i) Carboxylic Acid Polymers (1) Sunscreen Actives These polymers are crosslinked compounds containing Generally, the sunscreens can comprise from about 0.5% to one or more monomers derived from acrylic acid, substituted about 20% of the compositions useful herein. Exact amounts acrylic acids, and salts and esters of these acrylic acids and the will vary depending upon the Sunscreen chosen and the Substituted acrylic acids, wherein the crosslinking agent con desired Sun Protection Factor (SPF). SPF is a commonly used 35 tains two or more carbon-carbon double bonds and is derived measure of photoprotection of a Sunscreen against erythema. from a polyhydric alcohol. Polymers useful in the present See Federal Register, Vol. 43, No. 166, pp. 38206-38269, invention are more fully described in U.S. Pat. No. 5,087,445, Aug. 25, 1978. to Haffey et al., issued Feb. 11, 1992; U.S. Pat. No. 4,509,949, Also particularly useful in the compositions are Sunscreen to Huang et al., issued Apr. 5, 1985; U.S. Pat. No. 2,798,053, actives such as those disclosed in U.S. Pat. No. 4,937,370 40 to Brown, issued Jul. 2, 1957; and in CTFA International issued to Sabatelli on Jun. 26, 1990, and U.S. Pat. No. 4,999, Cosmetic Ingredient Dictionary, Fourth Edition, 1991, pp. 12 186 issued to Sabatelli & Spirnak on Mar. 12, 1991. The and 80. Sunscreening agents disclosed therein have, in a single mol Examples of commercially available carboxylic acid poly ecule, two distinct chromophore moieties, which exhibit dif mers useful herein include the carbomers, which are ferent ultra-violet radiation absorption spectra. One of the 45 homopolymers of acrylic acid crosslinked with allyl ethers of chromophore moieties absorbs predominantly in the UVB sucrose or pentaerytritol. The carbomers are available as the radiation range and the other absorbs strongly in the UVA Carbopol(R) 900 series from B.F. Goodrich (e.g., CarbopolR) radiation range. 954). In addition, other suitable carboxylic acid polymeric (m) Conditioning Agents agents include copolymers of Coso alkyl acrylates with one The compositions of the present invention may comprise a 50 or more monomers of acrylic acid, methacrylic acid, or one of conditioning agent selected from the group consisting of their short chain (i.e., C alcohol) esters, wherein the humectants, moisturizers, or skin conditioners. A variety of crosslinking agent is an allyl ether of Sucrose or pentaerytri these materials can be employed and each can be present at a tol. These copolymers are known as acrylates/Coso alkyl level of from about 0.01% to about 20%, more preferably acrylate crosspolymers and are commercially available as from about 0.1% to about 10%, and most preferably from 55 Carbopol.R. 1342, Carbopol.R. 1382, Pemulen TR-1, and about 0.5% to about 7% by weight of the composition. These Pemulen TR-2, from B.F. Goodrich. In other words, examples materials include, but are not limited to, guanidine; urea; of carboxylic acid polymer thickeners useful herein are those glycolic acid and glycolate salts (e.g. ammonium and quater selected from the group consisting of carbomers, acrylates/ nary alkyl ammonium); salicylic acid; lactic acid and lactate Co-Co alkyl acrylate crosspolymers, and mixtures thereof. salts (e.g., ammonium and quaternary alkyl ammonium); aloe 60 (ii) Crosslinked Polyacrylate Polymers Vera in any of its variety of forms (e.g., aloe Vera gel); poly The compositions of the present invention can optionally hydroxy compounds such as Sorbitol, mannitol, glycerol, comprise crosslinked polyacrylate polymers useful as thick hexanetriol, butanetriol, propylene glycol, butylene glycol, eners or gelling agents including both cationic and nonionic hexylene glycol and the like; polyethylene glycols; Sugars polymers, with the cationics being generally preferred. (e.g., melibiose) and starches; Sugar and starch derivatives 65 Examples of useful crosslinked nonionic polyacrylate poly (e.g., alkoxylated glucose, fructose, Sucrose, etc.); hyaluronic mers and crosslinked cationic polyacrylate polymers are acid; lactamide monoethanolamine; acetamide monoethano those described in U.S. Pat. No. 5,100,660, to Hawe et al., US 8,481,015 B2 25 26 issued Mar. 31, 1992; U.S. Pat. No. 4,849,484, to Heard, amount of from about 0.001% to about 10%, by weight of the issued Jul.18, 1989; U.S. Pat. No. 4,835,206, to Farrar et al., composition, preferably from about 0.01% to about 7%, and issued May 30, 1989; U.S. Pat. No. 4,628,078 to Gloveretal. most preferably from about 0.025% to about 5%. issued Dec. 9, 1986; U.S. Pat. No. 4,599,379 to Flesher et al. Composition Preparation issued Jul. 8, 1986; and EP228,868, to Farraret al., published The compositions of the present invention are generally Jul. 15, 1987. prepared by conventional methods such as are known in the (iii) Polyacrylamide Polymers art of making topical compositions. Such methods typically The compositions of the present invention can optionally involve mixing of the ingredients in one or more steps to a comprise polyacrylamide polymers, especially nonionic relatively uniform state, with or without heating, cooling, polyacrylamide polymers including Substituted branched or 10 application of vacuum, and the like. The compositions are unbranched polymers. Most preferred among these polyacry preferably prepared such as to optimize stability (physical lamide polymers is the nonionic polymer given the CTFA stability, chemical stability, photostability) and/or delivery of designation polyacrylamide and isoparaffin and laureth-7. the active materials (e.g., agmatine, BHT or BHA, and an available under the Tradename Sepigel 305 from Seppic Cor additional skin care active selected from the group consisting poration (Fairfield, N.J.). 15 of hexamidines, cetyl pyridinium chlorides, phytosterols, Other polyacrylamide polymers useful herein include ursolic acids, and green tea catechins.). This optimization multi-block copolymers of acrylamides and Substituted acry may include appropriate pH (e.g., less than 7), exclusion of lamides with acrylic acids and Substituted acrylic acids. Com materials that can complex with the active agent and thus mercially available examples of these multi-block copoly negatively impact stability or delivery (e.g., exclusion of con mers include Hypan SR 150H, SS500V, SS500W, taminating iron), use of approaches to prevent complex for SSSA100H, from Lipo Chemicals, Inc., (Patterson, N.J.). mation (e.g., appropriate dispersing agents or dual compart (iv) Polysaccharides ment packaging), use of appropriate photostability A wide variety of polysaccharides are useful herein. approaches (e.g., incorporation of sunscreen/sunblock, use of “Polysaccharides' refer to gelling agents that contain a back opaque packaging), etc. bone of repeating Sugar (i.e., carbohydrate) units. Nonlimit 25 In a preferred embodiment, the composition is chronically ing examples of polysaccharide gelling agents include those applied to the skin. By "chronic topical application' is meant selected from the group consisting of cellulose, carboxym continued topical application of the composition over an ethyl hydroxyethylcellulose, cellulose acetate propionate extended period during the subjects lifetime, preferably for a carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcel period of at least about one week, more preferably for a period lulose, hydroxypropylcellulose, hydroxypropyl methylcellu 30 of at least about one month, even more preferably for at least lose, methyl hydroxyethylcellulose, microcrystalline cellu about three months, even more preferably for at least about lose, sodium cellulose sulfate, and mixtures thereof. Also six months, and more preferably still for at least about one useful herein are the alkyl-substituted celluloses. In these year. While benefits are obtainable after various maximum polymers, the hydroxy groups of the cellulose polymer is periods of use (e.g., five, ten or twenty years), it is preferred hydroxyalkylated (preferably hydroxyethylated or hydrox 35 that chronic applications continue throughout the Subjects ypropylated) to form a hydroxyalkylated cellulose which is lifetime. Typically applications would be on the order of then further modified with a Co-Co straight chain or about once per day over Such extended periods, however branched chain alkyl group through an ether linkage. Typi application rates can vary from about once per week up to cally these polymers are ethers of Co-Co straight or about three times per day or more. branched chain alcohols with hydroxyalkylcelluloses. 40 A wide range of quantities of the compositions of the Other useful polysaccharides include Scleroglucans com present invention can be employed to provide a skin appear prising a linear chain of (1-3) linked glucose units with a (1-6) ance and/or feel benefit. Quantities of the present composi linked glucose every three units, a commercially available tions, which are typically applied per application, are, in mg example of which is ClearogeITM CS11 from Michel Mercier composition/cm skin, from about 0.1 mg/cm to about 20 Products Inc. (Mountainside, N.J.). 45 mg/cm. Aparticularly useful application amount is about 0.5 (v) Gums mg/cm to about 10 mg/cm. Other thickening and gelling agents useful herein include Methods for Regulating Skin Condition materials that are primarily derived from natural Sources. The compositions of the present invention are useful for Nonlimiting examples of these gelling agent gums include regulating keratinous tissue, particularly hair growth and materials selected from the group consisting of acacia, agar, 50 mammalian skin condition. Such regulation of keratinous algin, alginic acid, ammonium alginate, amylopectin, cal tissue conditions can include prophylactic and therapeutic cium alginate, calcium carrageenan, camitine, carrageenan, regulation. It may also include providing a more noticeable dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyl improvement, both tactile and visual, in the appearance and trimonium chloride, hectorite, hyaluroinic acid, hydrated feel of the hair on the kin of a mammal. For example, such silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya 55 regulating methods are directed to making the hair appear gum, kelp, locust bean gum, natto gum, potassium alginate, softer, finer, and/or less noticeable. Also, Such methods pro potassium carrageenan, propylene glycol alginate, Sclero vide ease, frequency, and effectiveness of shaving on a mam tium gum, Sodium carboyXmethyl dextran, Sodium carrag mal. Examples of regulating skin conditions include, but are eenan, tragacanth gum, Xanthan gum, and mixtures thereof. not limited to thickening keratinous tissue (i.e., building the Preferred compositions of the present invention include a 60 epidermis and/or dermis layers of the skin and where appli thickening agent selected from the group consisting of car cable the keratinous layers of the nail and hair shaft) and boxylic acid polymers, crosslinked polyacrylate polymers, preventing and/or retarding atrophy of mammalian skin, pre polyacrylamide polymers, and mixtures thereof, more pref venting and/or retarding the appearance of spider vessels erably selected from the group consisting of carboxylic acid and/or red blotchiness on mammalian skin, treating (i.e. pre polymers, polyacrylamide polymers, and mixtures thereof. 65 venting and/or retarding the appearance of) dark circles under It is preferred that the composition of the present invention the eye of a mammal, preventing and/or retarding sallowness comprise an additional skin care active that is present in an of mammalian skin, regulating (i.e. preventing and/or retard US 8,481,015 B2 27 28 ing) sagging of mammalian skin, softening and/or Smoothing actives such as chemical initiators for exothermic reactions lips, hair and nails of a mammal, preventing and/or relieving such as those described in U.S. Pat. Nos. 5,821,250, 5,981, itch of mammalian skin, regulating skin texture (e.g. wrinkles 547, and 5,972,957 to Wu, et al. The patchis preferably left on and fine lines), regulating the appearance of shiny skin, treat the skin for a period of at least about 5 minutes, more prefer ing (i.e. preventing and/or retarding the appearance of) cel ably at least about 15 minutes, more preferably still at least lulite, increasing the rate of skin turnover, and improving skin about 30 minutes, even more preferably at least about 1 hour, color (e.g. redness, freckles). still more preferably at night as a form of night therapy. Regulating keratinous tissue condition involves topically applying to the keratinous tissue a safe and effective amount EXAMPLES of a composition of the present invention. The amount of the 10 composition which is applied, the frequency of application The following examples further describe and demonstrate and the period of use will vary widely depending upon the embodiments within the scope of the present invention. The level of skin care actives and/or other components of a given examples are given solely for the purpose of illustration and composition and the level of regulation desired, e.g., in light are not to be construed as limitations of the present invention, of the level of keratinous tissue damage present or expected to 15 as many variations thereof are possible without departing OCCU. In a preferred embodiment, the composition is chronically from the spirit and scope of the invention. applied to the skin. By "chronic topical application' is meant continued topical application of the composition over an Skin Cream extended period during the subject’s lifetime, preferably for a period of at least about one week, more preferably for a period Examples 1-5 of at least about one month, even more preferably for at least about three months, even more preferably for at least about A moisturizing skin creamflotion is prepared by conven six months, and more preferably still for at least about one tional methods from the following components. year. While benefits are obtainable after various maximum 25 periods of use (e.g., five, ten or twenty years), it is preferred that chronic application continue throughout the Subjects lifetime. Typically applications would be on the order of about once per day over Such extended periods, however Component 1 2 3 4 5 application rates can vary from about once per week up to 30 about three times per day or more. Phase A A wide range of quantities of the compositions of the Water qs Qs qs qS qs present invention can be employed to provide a skin appear Glycerol S.OOOO 7.OOOO 7.OOOO 10.OOOO S.OOOO ance and/or feel benefit. Quantities of the present composi phenylbenzimidazole O O O O 1.2SOO tions which are typically applied per application are, in mg 35 Sulfonic acid disodium EDTA O.1OOO O.1OOO O.1OOO. O.1OOO O.1OOO composition/cm skin, from about 0.1 mg/cm to about 10 Allantoin O.2OOO 0.2OOO O.2OOO O.2OOO O.2OOO mg/cm. A particularly useful application amount is about 1 Triethanolamine O O O O 0.7500 mg/cm to about 2 mg/cm. sodium metabisulfite O.1OOO 0.2OOO O.1OOO. O.1OOO O.1OOO Regulating keratinous tissue condition is preferably prac BHT OSO O.SO OSO O.SO O.SO itanium dioxide O.2SOO 0.4500 0.4SOO O.7SOO O.SSOO 40 ticed by applying a composition in the form of a skin lotion, Niacinamide O O 2.OOOO 3.SOOO 2.OOOO cream, gel, foam, ointment, paste, serum, Stick, emulsion, Dexpanthenol O.25 O.SOOO 1.OOOO 2.OOOO 1.OOOO spray, conditioner, tonic, cosmetic, lipstick, foundation, nail palmitoyl-pentapeptide' O O OOOO4 O O.OOO3 C12-C15 alkylbenzoate S.OO 2.SOOO 1 SOOO 2. SOOO O polish, after-shave, or the like which is preferably intended to caprylicicapric 1.O 1...SOOO 1 SOOO 1.5OOO 1.SOOO be left on the keratin structure for some esthetic, prophylactic, triglyceride therapeutic or other benefit (i.e., a “leave-on' composition). 45 Farnesol O O.SOOO S.OOOO 3.OOOO 3.OOOO After applying the composition to the skin, it is preferably left octyl salicylate O O O O S.OOOO Octocrylene O O O O 1.OOOO on the skin for a period of at least about 15 minutes, more butyl O O O O 2.OOOO preferably at least about 30 minutes, even more preferably at methoxy least about 1 hour, still more preferably for at least several dibenzoylmethane hours, e.g., up to about 12 hours. Any part of the external 50 cetyl alcohol OSOOO O.SOOO O.SOOO O.SOOO O.SOOO ocopherol acetate O O.SOOO OSOOO O.SOOO O.SOOO portion of the face, hair, and/or nails can be treated, e.g., face, ocopherol sorbate OSOOO O O O.SOOO O.2OOO lips, under-eye area, upper lip, eyelids, Scalp, neck, torso, sorbitan stearatef 1.OOOO 1.OOOO 1.OOOO 1.OOOO 1.OOOO arms, underarms, hands, legs, feet, fingernails, toenails, Scalp Sucrose cocoate hair, eyelashes, eyebrows, etc. The composition can be cetearyl glucoside OSOOO O.SOOO O.SOOO O.SOOO O.SOOO applied with the fingers or with an implement or device (e.g., 55 Stearyl alcohol O.7OOO O.7OOO O.7OOO O.7OOO O.7OOO behenyl alcohol O.6OOO O.6OOO O.6OOO O.6OOO O.6OOO pad, cotton ball, applicator pen, spray applicator, and the ethyl paraben O.2OOO 0.2OOO O.2OOO O.2OOO O.2OOO like). propyl paraben O.1OOO O.1OOO O.1OOO. O.1OOO O.1OOO Another approach to ensure a continuous exposure of the PEG-1OO Stearate O.1OOO O.1OOO O.1OOO. O.1OOO O.1OOO skin to at least a minimum level of the skin care active is to Polymethyl- O.2SOO O.SOOO 1.SOOO O.SOOO O.2SOO silsesquioxane apply the compound by use of a patch applied, e.g., to the 60 face. Such an approach is particularly useful for problem skin Phase C areas needing more intensive treatment (e.g., facial crows feet polyacrylamide/C13-14 2.OOO 2.2SOO 2. SOOO 2. SOOO 3.OOOO area, frown lines, under eye area, upper lip and the like). The isoparaffin/laureth-7 patch can be occlusive, semi-occlusive or non-occlusive and Phase D can be adhesive or non-adhesive. The composition can be 65 agmatine 2.SOOO 2. SOOO 2. SOOO 2. SOOO 2. SOOO contained within the patch or be applied to the skin prior to green tea extract 1.OOOO 1.OOOO 1.OOOO 1.OOOO O application of the patch. The patch can also include additional US 8,481,015 B2 29 30 -continued -continued Example Component 1 2 3 4 5 6 7 8 BHT OSO O.SO OSO O.SO OSO Component % Wiw % Wiw % wiw benzyl alcohol O.2SOO O.2SOO O.2SOO O.2SOO O.2SOO dimethicone? O.S 1.OOOO 2SOOO O.2SOO 2.OOOO Dimethicone (350 mm’s) O.S O.O O.6O dimethiconol Disodium EDTA O.10 O.10 O.10 Perfume O.2OOO 0.2OOO O.2OOO 0.2OOO O.2OOO 1.O 1.1 10 Nylon 12 1.5 "palmitoyl-pentapeptide : palmitoyl-lysine-threonine-threonine-lysine-serine available Titanium Dioxide (and) Mica 0.75 1.5 1.25 from Sederma. BHT OSO OSO OSO In a suitable vessel, the Phase A components are combined Petrolatum 1.00 4.OO 2.OO and mixed with a suitable mixer (e.g., Tekmar RW20DZM) Deionised water, fragrance, presevatives to 100% to 100% to 100% and heated with stirring to a temperature of about 70-80° C. 15 and this temperature is maintained. In a separate Suitable Orgasol (R) 2002 DNAT COS. vessel, the Phase B components are combined and mixed with 2A green interference pigment a suitable mixer and are heated with stirring to about 70-75° C. and this temperature is maintained. The Phase B mixture is then added to the Phase A mixture and mixed well so as to Antiperspirant/Deodorants emulsify the combination. The emulsion of Phase A and B components is then allowed to cool to about 60° C. and then Examples 9-12 the Phase C components are to the emulsion with continuous mixing. The emulsion of Phase A, B and C components is then allowed to further cool to about 40° C., and then the 25 An antiperspirant soft Solid/cream is prepared by conven Phase D components are added with mixing to the emulsion. tional methods from the following components. The resulting emulsion is then milled using a suitable mill (Tekmar T-25) for about 5 minutes or until the product is uniform. Example 30 Examples 6-8 Component 9 10 11 12 A moisturizing skin creamflotion for hand and body skin Al ZrTrichlorohydrex Glycinate 25.25 25.25 25.25 25.25 (solid) care is prepared by conventional methods from the following Dimethicone (10 cs) S.OO S.OO S.OO S.OO components. 35 Fully Hydrogenated High Erucic S.OO S.OO S.OO S.OO The following examples further describe and demonstrate Acid Rapeseed oil (HEAR oil) embodiments within the scope of the present invention. They agmatine 2.50 2.50 2.50 2.50 C-18-36 Acid Triglyceride 1.25 1.25 1.25 1.25 are given for the purpose of illustration and are not to be Syncrowax HGLC construed as limitations of the present invention. Where Perfume 0.75 0.75 0.75 0.75 applicable, ingredients are given in CTFA name. All of the 40 Calcium Pantothenate (solid) OSO O 3.SO O examples are oil-in-water emulsions prepared using conven BHT OSO OSO O.SO OSO tional formulating techniques. The coated titanium dioxide is Tocopherol Acetate OSO O O.SO O incorporated via the oil phase ingredients whereas the nylon Cyclopentasiloxane QS QS QS QS particles and interference pigment are added via the aqueous Total 1OOOO 1OOOO 10O.OO 100.00 phase. 45

Example 13 Example 6 7 8 50 A foundation compact of the present invention comprising Component % Wiw % Wiw % wiw cross-linked siloxane elastomer is prepared as follows: Niacinamide 2.0 4.0 6.0 Retinyl Propionate O.2 Panthenol 1.O 2.0 O.S Polyacrylamide & isoparaffin & laureth-7 2.0 2.25 2.25 55 Ingredient Glycerine S.O 3.0 7.0 Allantoin O.2 O.OS O.1 TiO2 silicone treated (SAT treated Tronox CR 837 5.25 Aloe veragel O.OS 0.075 O.OS Supplied US Cosmetics) Tocopheryl acetate 0.75 O.S O.S Pigment 1.23 Cetyl alcohol 2.0 1.O 1.25 Talc (silicone treated) (Hydrophobic Talc 9742 2.36 Stearyl alcohol 2.0 1.O 1.25 Supplied by Warner Jenkinson) Behenyl alcohol 1.O 1.O 1.25 60 Agmatine 2.50 Dimethicone & dimethiconol 0.75 O.S O.SO TiO2-MT100T (micronized TiO2 supplied by Tri O16 Steareth-21 O6 0.4 O.S K) Steareth-2 O.1 O.08 O.O3 DC245 (cyclomethicone) 29.26 PPG-15 stearyl ether 3.0 2.0 1.OO DC5225C (dimethicone copolyol-10% active in O.31 Isohexadecane O 7.0 S.O cyclomethicone) agmatine 2.50 2.50 2.50 65 GESFE 839 Cross-linked Siloxane Elastomer Gel' 48 Isononyl isononanoate S.O O O propylparaben (preservative) O.10 US 8,481,015 B2 32 -continued 8. The method of claim 7, wherein the composition com prises between about 0.01% and about 5% by weight of the Ingredient wt.% butylated hydroxytoluene. BHT OSO 9. The method of claim 7, wherein the composition com Glycerine 7.08 prises between about 0.1% and about 0.5% by weight of the Ozokerite Wax 3.25 butylated hydroxytoluene. Total: 1OOOO 10. The method of claim 1, wherein the unwanted mam 15% Dimethicone vinyl dimethicone cross-polymer in cyclomethicone malian hair is selected from the group consisting of female 10 facial hair, male facial hair, underarm hair, leg hair, and arm In a Suitable vessel equipped with a heating Source, the hair. pigments, TiO, (micronized and silicone treated), hydropho 11. The method of claim 1, wherein the composition is in a bic talc, GESFE 839, cyclomethicone (DC245) and dimethi form selected from the group consisting of a shaving cream, cone copolyol (DC5225C) are mixed until homogeneous and an antiperspirant, a deodorant, and a personal cleansing prod then milled using a Silverson L4RT mixer at 9000 rpms to the 15 uct. desired particle size. Next, the propylparaben and glycerine are added to the above mixture and mixed until homogenous. 12. The method of claim 1, wherein the unwanted mam The mixture is then heated to a temperature of between malian hair is female facial hair and the composition is in the 85-90° C., at which time the ozokerite wax is added (melted form of a cosmetic. into the mixture) with mixing until the mixture homogenous. 13. The method of claim 12, wherein the cosmetic is a The mixture is then poured into a mold and allowed to cool at foundation. room temperature. Once cooled, the mixture incorporated 14. The method of claim 1, wherein the unwanted mam into the appropriate package. malian hair is underarm hair and the composition is in the The foundation compact is applied to the face to provide form of an antiperspirant or a deodorant. color, moisturization and improved feel. 25 What is claimed is: 15. The method of claim 14, wherein the antiperspirant or 1. A method for reducing unwanted mammalian hair the deodorant comprises a water in oil emulsion. growth, comprising: 16. The method of claim 1, wherein the unwanted mam identifying a region of keratinous tissue on a keratinous malian hair is male facial hair and the composition is in the tissue surface comprising a plurality of unwanted mam 30 form of a shaving cream. malian hairs in need of hair growth reduction; 17. The method of claim 1, wherein the composition is topically applying a leave-on composition to the keratinous applied at least once a day for at least one month. tissue surface, wherein the composition comprises a der 18. The method of claim 1, wherein the composition is matologically acceptable carrier, a safe and effective applied at least once a day for at least 3 months. amount of an agent selected from the group consisting of 35 hexamidine and a salt of hexamidine; and a protease 19. A method for reducing unwanted mammalian hair inhibiting plant extract; and growth, comprising: wherein the composition is chronically applied to the kera identifying a region of keratinous tissue on a keratinous tinous tissue surface and permitted to remain on the tissue surface in need of hair growth reduction, the keratinous tissue Surface for at least 15 minutes Such that 40 region comprising a plurality of unwanted mammalian the composition reduces the growth of the plurality of hairs, wherein the hairs are selected from the group unwanted hairs. consisting of female facial hair, male facial hair, under 2. The method of claim 1, wherein the agent is hexamidine. arm hair, leg hair, and arm hair; 3. The method of claim 2, wherein the agent is hexamidine topically applying a leave-on composition to the keratinous isethionate. 45 tissue surface, wherein the composition comprises a der 4. The method of claim 2 wherein the composition com matologically acceptable carrier, a protease inhibiting prises between about 0.01% and about 5% by weight of the plant extract and hexamidine in a concentration between agent. about 0.1% and about 2% by weight of the composition; 5. The method of claim 2, wherein the composition com and prises between about 0.1% and about 2% by weight of the 50 agent. wherein the composition is chronically applied to the kera 6. The method of claim 1, wherein the protease inhibiting tinous tissue Surface and permitted to remain on the plant extract is selected from one of the leguminosae, Solan keratinous tissue Surface for at least 15 minutes such that aceae, gramineae, and cucurbitaceae families. the composition reduces the growth of the plurality of 7. The method of claim 1, wherein the composition further unwanted hairs. comprises butylated hydroxytoluene.