US 2014O193391A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0193391 A1 Pernodet et al. (43) Pub. Date: Jul. 10, 2014

(54) METHOD AND COMPOSITIONS FOR Publication Classification IMPROVING SELECTIVE CATABOLYSIS AND VIABILITY IN CELLS OF KERATIN (51) Int. Cl. SURFACES A68/66 (2006.01) (71) Applicant: ELC Management LLC, Melville, NY A61O 19/00 (2006.01) (US) (52) U.S. Cl. CPC. A61K 8/66 (2013.01); A61O 19/00 (2013.01) (72) Inventors: Nadine A. Pernodet, Huntington USPC ...... 424/94.61 Station, NY (US); Donald F. Collins, Plainview, NY (US); Dawn Layman, Ridge, NY (US); Daniel B. Yarosh, Merrick, NY (US) (57) ABSTRACT (21) Appl. No.: 14/142,212 A composition for treating keratin Surfaces to stimulate selec (22) Filed: Dec. 27, 2013 tive catabolysis and improve cellular viability comprising at Related U.S. Application Data least one autophagy activator and at least one DNA repair (60) Provisional application No. 61/749,633, filed on Jan. enzyme, and a method for improving selective catabolysis 7, 2013. and cellular viability by treating with the composition. US 2014/O 193391 A1 Jul. 10, 2014

METHOD AND COMPOSITIONS FOR stimulate detoxification processes where the breakdown of IMPROVING SELECTIVE CATABOLYSIS the cellular debris and toxins results in amino acids or other AND VIABILITY IN CELLS OF KERATIN biological molecules that can be recycled by the cell. SURFACES 0008 Thus, there is a need to maximize cellular health and longevity by Stimulating selective catabolysis in cells so that CROSS-REFERENCE TO RELATED cellular debris and toxins are removed and by products of APPLICATIONS such degradation may be recycled. More preferably, the 0001. The present application claims priority from U.S. selective catabolysis is due to enhancing autophagy activity Provisional Application No. 61/749,633, filed Jan. 7, 2013. and promoting DNA repair using DNA repair enzymes. 0009. It has been discovered that compositions containing TECHNICAL FIELD at least one autophagy activator and at least one DNA repair enzyme in selective cellular catabolysis, that is, cleansing 0002 The invention is in the field of compositions for cells of toxic waste products by breaking down the waste application to skin which enhance selective catabolysis in products into molecules that may be recycled and used by the skin cells. cell in normal metabolic functions.

BACKGROUND OF THE INVENTION SUMMARY OF THE INVENTION 0003. It is well known that stress and environmental 0010. The invention is directed to a composition for treat aggressors such as UV light, pollution, and cigarette Smoke ment of keratin Surfaces to stimulate selective catabolysis can be very detrimental to skin and accelerate the appearance comprising at least one autophagy activator and at least one of aging. Exposure to stress and environmental aggressors DNA repair enzyme. often causes damage to cellular DNA, mitochondria, and cellular proteins, lipids, and tissue. Damaged cellular mate 0011. The invention is further directed to a method for rial found within the cell, for example, cytoplasmic or stimulating selective catabolysis in cells of keratin Surfaces organelle debris can exert a toxic effect on cells by impeding by applying to Such surfaces a composition comprising at their normal metabolic processes. least one autophagy activator and at least one DNA repair 0004 Healthy cells have a normal cleansing process that enzyme. eliminates damaged cellular material and debris. Such detoxification often occurs through a phagocytic process DETAILED DESCRIPTION referred to as autophagy, where the cellular debris is engulfed within a vacuole and degraded with cellular enzymes Such as I. Definitions lysozymes. Autophagy and the mechanism of autophagy acti 0012 All percentages mentioned herein are percentages vation in skin cells is described in U.S. Patent Publication No. by weight unless otherwise indicated. 2011/0243983 A1, hereby incorporated by reference in its 0013 All documents mentioned herein are incorporated entirety. There is much interest informulating skin treatment by reference in their entirety. compositions to contain ingredients that stimulate cellular 0014 Autophagy’ means the process by which cells autophagy because the ability of cells to cleanse and detoxify cleanse themselves of toxins and debris by forming a mem themselves of debris that otherwise impedes healthy meta brane around the debris, segregating it from the rest of the bolic function is improved. The cleansing through autophagy cell, and adjoining the formed vacuole with cellular lysos creates new Sources of energy for cellular functions because omes, which are cellular organelles that contain acid hydro the degradation products release building blocks such as lase enzymes that break down the cellular debris and waste amino acids that can be recycled by the cell. Improved cellu found in the vacuole. lar metabolic function in turn means improved cellular health and longevity and greater resistance to undesirable side 00.15 Autophagy Activator” means an ingredient that effects of aging Such as lines, wrinkles, mottled skin, hyper stimulates the normal cellular autophagy processes. pigmentation, laxity and so on. 0016 “CLOCK gene activator” means an ingredient that 0005) DNA repair enzymes are known to repair DNA in activates one or more CLOCK genes present in keratinocytes. various ways. Such enzymes are generally categorized 0017. The term “DNA repair enzyme” means an enzyme according to the type of DNA base mutagenic damage that is that is operable to repair DNA base mutagenic damage. Such repaired. enzymes are often categorized by the type of DNA damage 0006. It has been discovered that the combination of DNA they repair, for example BER (base excision repair) enzymes, repair enzymes and autophagy activators most unexpectedly nucleotide excision repair (NER) enzymes; mismatch repair will beneficially affect the normal cellular cleansing pro (MMR) enzymes; DNA helicases; DNA polymerases, and so cesses, promote cellular health and longevity, and minimize on. For example, mutations such as 8-oxo-7,8-dihydro-2'- the deleterious effects of environment, UV light, pollution, deoxyguanosine may be repaired by OGG1 (8-oxoGuanine and other environmental insults on skin. glycosylase); T-T dimers which may be repaired by (Nucle 0007 Accordingly it is of interest to maximize the cellular otide excision repair (NER) Photolyase); 6-4 photoproducts health and longevity of cells, particularly skin cells such as (which may be repaired by NER); and 06-methyl guanine keratinocytes or fibroblasts, by treating them with ingredients (which may be repaired by 06-alkyl guanine transferase that stimulate natural cellular repair processes by, for (AGT)). example, eliminating cellular debris and toxins, and in addi 0018. The term "keratin surfaces” means skin, hair, and tion, to maximize the effectiveness of such cellular detoxifi nails. cation by ensuring that the maximum number of detoxifica 0019. “PER1 gene activator” means an ingredient that tion mechanisms are operable. It is also of interest to activates one or more PER1 genes found in keratinocytes. US 2014/O 193391 A1 Jul. 10, 2014

0020) “Proteasome” means a protein complex typically During the autophagocytic process cellular debris Such as located in the nucleus or cytoplasm of cells that is operable to oxidized proteins and peroxidized lipids are degraded. Such degrade damaged cellular proteins by proteolysis into Smaller cellular debris often affects normal metabolic function. Subunits which may then be further digested into singleamino Screening of ingredients to determine efficacy by ability to acids. These recycled amino acids may be used by the cell in stimulate or inhibit cellular, preferably keratinocyte, genes the synthesis of new proteins. and/or proteins mentioned above may be done according to 0021 “Proteasome activator” means an active ingredient methods as set forth in US Patent Publication No. 2011/ that stimulates the activity of proteasomes in cells of keratin 0243983 or other methods known in the art. Surfaces such as keratinocytes, fibroblasts, etc. 0029. For example, one general process for identifying 0022 “Recycle” means, with respect to the degradation of ingredients that may be autophagy activators is by first induc cellular debris and toxins, that the debris and toxins may be ing nutritive stress in cultured cells such as keratinocytes. For broken down into molecules such as proteins, lipids, amino example, the cells are first cultured in complete culture acids, or other biological materials that are usable by the cell medium with growth factors, for about 24 hours. The culture in its normal healthy metabolic processes. medium is then removed and replaced with a non-nutritive 0023 “Repair’ means, with respect to skin cells, that the culture medium, for example one that does not contain growth damaged portions of cells, such as DNA, mitochondria, pro factors. The cells are cultured for about 30 minutes to about teins, lipids, or other cellular materials are reduced or elimi 25 hours in a state of nutritive stress. Then, the non-nutritive nated. culture medium is removed and replaced with complete cul 0024) “Selective catabolysis” means, with respect to the ture medium to promote cellular recovery. Thereafter, the cells of keratin surfaces, that the cells are able to cleanse cells are evaluated for autophagocytic activity by measuring themselves of debris, waste, and toxins selectively without the expression of one or more of MAP-LC3; ATGS-12; phos compromising healthy cellular constituents, and preferably phorylated mTOR: phosphorylated p53: DRAM; orphospho by one or more of mechanisms such as activating cellular rylated AMPK in those cells. Measurement of such expres autophagy or activating cellular proteasome processes. sion can take place by immunofluorescence measurements. In addition, the expression can be ascertained by Western Blot II. Autophagy Activator analysis of phosphorylated proteins associated with the 0025. The composition of the invention contains at least expressed genes. one ingredient that is operable to activate normal cellular 0030 Examples of ingredients that are known to exert autophagic processes. The autophagy activator is present in either the stimulatory or inhibitory effects on the above men amounts ranging from about 0.00001 to 20%, preferably tioned genes which, in turn, stimulate autophagy, are yeast 0.0001-15%, more preferably from about 0.001 to 10%. In extracts including but not limited to those from the genuses general, the cellular autophagy process comprises four gen Such as Lithothamnium, Melilot, Citrus, Candida, Lens, eral steps. Step 1 is the initiation of vacuole formation; Step 2 Urtica, Carambola, Momordica, Yarrowia, Plumbago, etc. the formation of the initial vacuole or autophagosome which Further specific examples include Lithothamniumn calca sequesters the cytoplasmic material to be degraded. Step 3 is neum, Melilotus officinalis, Citrus limonum, Candida sai the maturation of the autophagosome into a degradative vacu toana, Lens culinaria, Urtica dioica, Averrhoa carambola, ole. Step 4 is the actual degradation of the sequestered mate Momordica charantia, Yarrowia lipolytica, Plumbago zey rial. lanica and so on. 0026 Ingredients with autophagy activation activity can 0031. Also suitable are ingredients such as amiodarone be identified by their ability to either stimulate or inhibit hydrochloride, GF 109203X which is also referred to as (3- various cellular metabolic pathways. For example, ingredi (N-Dimethylaminopropyl-3-indolyl)-4-(3-indolyl)male ents that stimulate the expression of MAP-LC3, ATG5-12, imide 3-1-3-(Dimethylamino)propyl1H-indol-3-yl)-4-(1 protein p53, AMPK, or DRAM are suitable autophagy acti Hindol-3-yl)1H-pyrrole-2.5dione Bisindolylmaleimide I: vators. Ingredients that inhibit the expression of mTOR are N-Hexanoyl-D-sphingosine; Niclosamide: Rapamycin from also Suitable autophagy activators. Streptomyces hygroscopicus; Rottlerin which is also referred 0027. The gene MAP-LC3 codes for microtubule-associ to as (1-6-(3-Acetyl-2,4,6-trihydroxy-5-methylphenyl)me ated protein 1 light chain 3, a protein that initiates formation thyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-8-yl)- of autophagosomes. ATG5-12 also stimulates formation of 3-phenyl-2-propen-1-one, Mallotoxin); STF-62247, also autophagosomes. mTOR, also known as mammalian target of known as 5-Pyridin-4-yl-thiazol-2-yl-m-tolyl-amine; rapamycin, is also known as the mechanistic target of rapa Tamoxifen: Temsirolimus which is also known as 42-3-Hy mycin or FK506 binding protein 12-rapamycin associated droxy-2-methylpropanoate, CCI-779, Rapamycin; ATG1 protein 1 (FRAP1). FRAP1 is encoded by the FRAP gene. autophagy related 1 homolog: ATG1, Serine/threonine-pro Any ingredient that inhibits the expression of mTOR, tein kinase ULK1, UNC-51-like kinase; or Z36 which is also involved in autophagosome creation, will have autophagy referred to as ((Z)-5-Fluoro-1-(3'-dimethylamino)propyl-3- activating properties. Also suitable as autophagy activators (5'-methoxyindol-3-ylidene)methyl-indolin-2-one; or 1-3- are ingredients that stimulate expression of protein p53, (dimethylamino)propyl-5-fluoro-1,3-dihydro-3-(5-meth AMPK, and/or DRAM (damage remedy autophagy modula oxy-1H-indol-3-yl)methylene-2H-Indol-2-one); Bufalin, tor protein) in keratinocytes. Protein p53, also known as a also referred to as 3.f3, 14-Dihydroxy-5B.20(22)-bufadieno tumor suppressor protein, is encoded by the p53 gene. AMPK lide, 5 B.20(22)-Bufadienolide-3?,14-diol. Such ingredients means AMP activated protein kinase and DRAM, damage may be purchased from Sigma-Aldrich Chemical Company. related autophagy modulator. Both are known to stimulate autophagy activation in keratinocytes. III. DNA Repair Enzyme 0028. Thus any ingredient that has the above mentioned 0032. The composition contains one or more DNA repair effects on the genes may be Suitable autophagy activators. enzymes. Suggested ranges are from about 0.00001 to about US 2014/O 193391 A1 Jul. 10, 2014

35%, preferably from about 0.00005 to about 30%, more (XRCC1); DNA 5'-kinase/3'-phosphatase (PNKP); ADP-ri preferably from about 0.0001 to about 25% of one or more bosyltransferase (PARP1 or 2). DNA repair enzymes. 0039. Another category of DNA repair enzymes includes 0033 DNA repair enzymes as disclosed in U.S. Pat. Nos. those that are believed to directly reverse damage such as 5,077,211; 5,190,762: 5,272,079; and 5,296,231, all of which O' MeC alkyl transferase (MGMT): 1-meA dioxygenase are hereby incorporated by reference in their entirety, are (ALKBH2 or ALKBH3). suitable for use in the compositions and method of the inven 0040. Yet another category of enzymes operable to repair tion. One example of such a DNA repair enzyme may be DNA/protein crosslinks includes Tyr-DNA phosphodi purchased from AGI/Dermatics under the trade name Roxi esterase (TDP1). somes.(R), and has the INCI name Arabidopsis Thaliana 0041. Also suitable are MMR (mismatch exision repair) extract. It may be present alone or in admixture with lecithin DNA repair enzymes such as MutS protein homolog and water. This DNA repair enzyme is known to be effective (MSH2); mismatch repair protein (MSH3); mutS homolog 4 in repairing 8-oxo-Guanine base damage. (MSH4); MutS homolog5 (MSH5); or G/T mismatch-bind ing protein (MSH6); DNA mismatch repair protein (PMS1, 0034. Another type of DNA repair enzyme that may be PMS2, MLH1, MLH3); Postmeiotic segregation increased used is one that is known to be effective in repairing 06-me 2-like protein (PMS2L3); or postmeiotic segregation thylguanine base damage. It is sold by AGI/Dermatics under increased 2-like 4 pseudogene (PMS2L4). the tradename Adasomes(R), and has the INCI name Lactoba 0042. Also suitable are DNA repair enzymes are those cillus ferment, which may be added to the composition of the known as nucleotide excision repair (NER) enzymes and invention by itself or in admixture with lecithin and water. include those such as Xeroderma pigmentosum group 0035 Another type of DNA repair enzyme that may be C-complementing protein (XPC); RAD23 (S. cerevisiae) used is one that is known to be effective in repairing TT homolog (RAD23B); caltractin isoform (CETN2); RFA Pro dimers. The enzymes are present in mixtures of biological or tein 1, 2, of 3 (RPA1, 2, or 3); 3' to 5' DNA helicase (ERCC3): botanical materials. Examples of such ingredients are sold by 5' to 3' DNA helicase (ERCC2); basic transcription factor AGI/Dermatics under the tradenames Ultrasomes(R or Pho (GTF2H1, GTF2H2, GTF2H3, GTF2H4, GTF2H5); CDK tosomes.(R). Ultrasomes(R) comprises a mixture of Micrococ activating kinase (CDK7, CCNH); cyclin G1-interacting pro cus lysate (an end product of the controlled lysis of various tein (MNAT1); DNA excision repair protein ERCC-51; exci species of micrococcus), lecithin, and water. Photosomes.(R) sion repair cross-complementing 1 (ERCC1); DNA ligase 1 comprise a mixture of plankton extract (which is the extract of (LIG1); ATP-dependent helicase (ERCC6); and the like. marine biomass which includes one or more of the following 0043. Also suitable may be DNA repair enzymes in the organisms: thalassoplankton, green micro-algae, diatoms, category that facilitate homologous recombination and greenish-blue and nitrogen-fixing seaweed), water, and leci include, but are not limited to DNA repair protein RAD51 thin. homolog (RAD51, RAD51L1, RAD51B etc.); DNA repair 0036) Another type of DNA repair enzyme may be a com protein XRCC2: DNA repair protein XRCC3; DNA repair ponent of various inactivated bacterial lysates such as Bifida protein RAD52: ATPase (RAD50): 3' exonuclease lysate or Bifida ferment lysate, the latter a lysate from Bifido (MRE 11 A); and so on. bacteria which contains the metabolic products and cytoplas 0044) DNA repair enzymes that are DNA polymerases are mic fractions when Bifido bacteria are cultured, inactivated also suitable and include DNA polymerase beta subunit and then disintegrated. This material has the INCI name (POLB); DNA polymerase gamma (POLG); DNA poly Bifida Ferment Lysate. merase subunit delta (POLD1); DNA polymerase II subunit A 0037 Other suitable DNA repair enzymes include Endo (POLE); DNA polymerase delta auxiliary protein (PCNA); nuclease V, which may be produced by the denV gene of the DNA polymerase Zeta (POLZ); MAD2 homolog (REV7): bacteriophage T4. Also suitable are T4 endonuclease; O-me DNA polymerase eta (POLH): DNA polymerase kappa thylguanine-DNA methyltransferases; photolyases such as (POLK): and the like. uracil- and hypoxanthine-DNA glycosylases; apyrimidinic/ 0045 Various types of DNA repair enzymes that are often apurinic endonucleases; DNA exonucleases, damaged-bases referred to as "editing and processing nucleases include glycosylases (e.g., 3-methyladenine-DNA glycosylase); cor 3'-nuclease; 3'-exonuclease, 5'-exonuclease; endonuclease; rendonucleases either alone or in complexes (e.g., E. coli and the like. uvrA/uvrB/uvrC endonuclease complex); APEX nuclease, 0046. Other examples of DNA repair enzymes include which is a multi-functional DNA repair enzyme often DNA helicases including such as ATP DNA helicase and so referred to as “APE'; dihydrofolate reductase; terminal trans O. ferase: topoisomerase: O' benzyl guanine; DNA glycosy 0047. The DNA repair enzymes may be present as com lases. ponents of botanical extracts, bacterial lysates, biological materials, and the like. For example, botanical extracts may 0038. Other types of suitable DNA repair enzymes may be contain DNA repair enzymes. categorized by the type of repair facilitated and include BER (base excision repair) or BER factor enzymes such as uracil 0048. The compositions of the invention may contain one DNA glycosylase (UNG); single strand selective monofunc or more DNA repair enzymes. tional uracil DNA glycosylase (SMUG1): 3.N(4)-ethenocy tosine glycosylase (MBD4); thymine DNA-glycosylase IV. Other Ingredients (TDG); A/G-specific adenine DNA glycosylase (MUTYH): 0049. A. Proteasome Activator 8-oxoguanine DNA glycosylase (OGG1); endonuclease III 0050. The composition may contain one more proteasome like (NTHL1): 3-methyladenine DNA glycosidase (MPG): activators in amounts ranging from about 0.0001 to 65%, DNA glycosylase/AP lyase (NEIL1 or 2); AP endonuclease preferably from about 0.0005 to 50%, more preferably from (APEX 1 and 2), DNA ligase (LIG3), ligase accessory factor about 0.001 to 40%. US 2014/O 193391 A1 Jul. 10, 2014

0051 Suitable proteasome activators are any compounds, (0072 Cysteine (C) molecules, or active ingredients that stimulate proteasome (0073. Glutamic Acid (E) activity in the cells of keratin surfaces. (0074) Glutamine (Q) 0052 Examples of suitable proteasome activators include, 0075) Glycine (G) but are not limited to, algin, alginates, hydrolyzed algin, (0076. Histidine (H) molasses extract, Trametes extracts, including extracts from (0077. Isoleucine (I) Trametes versicolor, olea hydroxol. (0078 Leucine (L) 0053. The composition of the invention may be in the form (0079 Lysine (K) of an emulsion, aqueous Solution or dispersion, gel, or anhy 0080 Methionine (M) drous composition. If in the form of an emulsion, it may be a I0081 Phenylalanine (F) water in oil or oil in water emulsion. If in the form of an I0082 Proline (P) emulsion, the composition may contain from about 1-99%, preferably from about 5-90%, more preferably from about I0083 Serine (S) 10-85% water and from about 1-99%, preferably from about I0084. Threonine (T) 5-90%, more preferably from about 5-75% of oil. If in the I0085. Tryptophan (W) form of an aqueous Suspension or dispersion, the composition I0086 Tyrosine (Y) may generally contain from about 1-99.9%, preferably from I0087 Valine (V) about 5-95%, more preferably from about 10-90% water, I0088 More preferred are peptides of the above formula as with the remaining ingredients being the active ingredients or follows: other formula ingredients. 0054 The composition may additionally contain other ingredients including but not limited to those set forth herein. S-T-P-NH2 0055 B. CLOCK, PER1 Gene Activator Ser-Thr-Pro-NH2 0056. The composition of the invention may contain a CLOCK or PER1 cellular gene activator. Suggested ranges are from about 0.000001 to about 40%, preferably from about 0.000005 to 35%, more preferably from about 0.00001 to Tyr-Val-Ser-Thr-Pro-Tyr-Asn-NH, 25%. Suitable CLOCK or PER1 activators may be present in (SEQ ID NO. 3) the form of botanical extracts, polypeptides, peptides, amino N acids, and the like. 0057 1. Peptide CLOCK or PER1 Gene Activator 2-Val-Ser-Thr-Pro-Glu-NH2 0058. A particularly preferred CLOCK and/or PER1 gene (SEQ ID No. 4) activator comprises a peptide of the formula (I): N 2-Leu-His-Ser-Thr-Pro-Pro-NH2 (0059. Where (AA)-X-S-T-P-X-(AA), is (SEQ ID No. 1) and: (SEQ ID No. 5) 0060 X represents a threonine, a serine, or is equal to Zero, -NH-Arg-His-Ser-Thr-Pro-Glu-NH 0061 X represents an isoleucine, leucine, proline, Valine, alanine, glycine, or is equal to Zero, (SEQ ID No. 6) 0062 AA represents any amino acid or derivative thereof, and nandpare whole numbers between 0 and 4, CH-NH-His-Ser-Thr-Pro-Glu-CH-NH 0063 R represents the primary amine function of the I0089 More preferred is the S-T-P-NH. peptide, SEQID N-terminal amino acid, either free or substituted by a No. 4, or mixtures thereof. protective grouping that may be chosen from either an (0090 Most preferred is a peptide manufactured by ISP acetyl group, a benzoyl group, a tosyl group, or a ben Vinscience under the trademark ChronoluxRhaving the INCI Zyloxycarbonyl group, name Tripeptide-32 or ChronogenR) having the INCI name 0064 R represents the hydroxyl group of the car Tetrapeptide-26, which has an amino acid sequence of: boxyl function of the C-terminal amino acid, substi tuted by a protective grouping that may be chosen from either a C to Co alkyl chain oran NH, NHY, (SEO ID No. 7) or NYY group with Y representing a C to C alkyl S-P-L-Q-NH chain, 0065 wherein the sequence of general formula (I) com Ser-Pro-Leu-Gln-NH, prises from about 3 to 13 amino acid residues, 0091 2. Botanical Extracts 0.066 said sequence of general formula (I) possibly 0092. Also suitable as the CLOCK or PER1 gene activator containing Substitutions of amino acids X and X with is cichoric acid or isomers or derivatives thereof. Cichoric other chemically equivalent amino acids; acid may be synthetic or naturally derived. Synthetic cichoric 0067 wherein the amino acids are: acid may be purchased from a number of commercial manu 0068 Alanine (A) facturers including Sigma Aldrich. Cichoric acid may also be 0069 Arginine (R) extracted from botanical sources that are known to contain (0070 Asparagine (N) cichoric acid Such as Echinacea, Cichorium, Taraxacum, (0071 Aspartic Acid (D) Ocimum, Melissa, or from algae or sea grasses. More specifi US 2014/O 193391 A1 Jul. 10, 2014

cally, botanical extracts such as Echinacea purpurea, Cicho 4,4'-diisopropylbenzoylmethane, 2-methyl-5-isopropyl-4- rium intybus, Taraxacum officinale, Ocimum basilicum, or methoxydibenzoymethane, 2-methyl-5-tert-butyl-4'-meth Melissa officinalis. The term “cichoric acid when used oxydibenzoylmethane, and so on. Particularly preferred is herein also includes any isomers thereof that are operable to 4-tert-butyl-4'-methoxydibenzoylmethane, also referred to as increase PER1 gene expression in skin cells. Avobenzone. Avobenzone is commercially available from 0093. A specific example includes a botanical extract from Givaudan-Roure under the trademark ParsolR 1789, and Echinacea purpurea sold by Symrise under the brand name Merck & Co. under the tradename EusoleXCR 9020. Symfinity TM 1298 which is an extract of Echinacea purpurea which is standardized during the extraction process to contain 0100 Other types of UVA sunscreens includedicamphor about 3% by weight of the total extract composition of Sulfonic acid derivatives, such as ecamsule, a Sunscreen sold cichoric acid. Echinacea extracts from different sources will under the trade name Mexoryl(R), which is terephthalylidene vary in cichoric acid content, and as Such will yield variable dicamphor Sulfonic acid, having the formula: results in induction of PER1 gene expression. For example, we have observed that another component commonly found in extracts of Echinacea, specifically caftaric acid, does not O increase PER1 gene expression in skin cells. Moreover, each Hos/ species of Echinacea will differ in content of phenolic and cichoric acids. Ethanolic extract of the roots of Echinacea purpura will provide more cichoric acid than ethanolic extracts of Echineacea angustifolia or Echinacea pallida. The content of active ingredients in any extract is also very dependent on the method of extraction. For example, it is known that in many cases enzymatic browning during the extraction process will reduce the phenolic acid content of the resulting extract. / NoH 0094. C. Sunscreens 0095. It may also be desirable to include one or more Sunscreens in the compositions of the invention. Such Sun 0101 The composition may contain from about 0.001 screens include chemical UVA or UVB sunscreens or physi 20%, preferably 0.005-5%, more preferably about 0.005-3% cal Sunscreens in the particulate form. Inclusion of sunscreens by weight of the composition of UVA sunscreen. In the pre in the compositions containing the whitening active ingredi ferred embodiment of the invention the UVA sunscreen is ent will provide additional protection to skin during daylight Avobenzone, and it is present at not greater than about 3% by hours and promote the effectiveness of the whitening active weight of the total composition. ingredient on the skin. If present, the Sunscreens may range from about 0.1 to 50%, preferably from about 0.5 to 40%, 0102 2. UVB Chemical Sunscreens more preferably from about 1 to 35%. 0103) The term “UVB sunscreen” means a compound that 0096 1. UVA Chemical Sunscreens blocks UV radiation in the wavelength range of from about 0097. If desired, the composition may comprise one or 290 to 320 nm. A variety of UVB chemical sunscreens exist more UVA sunscreens. The term “UVA sunscreen” means a including alpha-cyano-beta,beta-diphenyl acrylic acid esters chemical compound that blocks UV radiation in the wave as set forth in U.S. Pat. No. 3.215,724, which is hereby length range of about 320 to 400 nm. Preferred UVA sun incorporated by reference in its entirety. One particular screens are dibenzoylmethane compounds of the formula: example of an alpha-cyano-beta.beta-diphenyl acrylic acid ester is Octocrylene, which is 2-ethylhexyl 2-cyano-3,3- diphenylacrylate. In certain cases the composition may con R2 tain no more than about 10% by weight of the total compo O O sition of octocrylene. Suitable amounts range from about | 0.001-10% by weight Octocrylene may be purchased from BASF under the tradename Uvinul RN-539. R R3 0104. Other suitable sunscreens include benzylidene cam phor derivatives as set forth in U.S. Pat. No. 3,781,417, which wherein R is H, OR and NRR wherein each R is indepen is hereby incorporated by reference in its entirety. Such ben dently H, Co straight or branched chain alkyl; R is H or Zylidene camphor derivatives have the general formula: OH; and R is H. Co straight or branched chain alkyl. 0.098 Preferred is where R is OR where R is a C straight or branched alkyl, preferably methyl; R is H; and R. is a Co straight or branched chain alkyl, more preferably, butyl. CH-R 0099 Examples of suitable UVA sunscreen compounds of this general formula include 4-methyldibenzoylmethane, 2-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, wherein R is p-tolyl or styryl, preferably styryl. Particularly 4-tert-butyldibenzoylmethane, 2,4-dimethyldibenzoyl preferred is 4-methylbenzylidene camphor, which is a lipid methane, 2,5-dimethyldibenzoylmethane, 4.4" diisopropyl soluble UVB sunscreen compound sold under the tradename benzoylmethane, 4-tert-butyl-4'-methoxydibenzoylmethane, Eusolex 6300 by Merck. US 2014/O 193391 A1 Jul. 10, 2014

0105. Also suitable are cinnamate derivatives having the hydroxyl or NH, the compound having the name homom general formula: ethyl salicylate (also known as Homosalate) or menthyl anthranilate. Homosalate is available commercially from Merck under the trademark Eusolex(R) HMS and menthyl OR anthranilate is commercially available from Haarmann & Reimer under the trademark Heliopan R. If present, the Homosalate should be found at no more than about 15% by weight of the total composition. 0.109 Various amino benzoic acid derivatives are suitable UVB absorbers including those having the general formula: CH=CH-C-R COOR wherein R and R are each independently a Co straight or branched chain alkyl. Preferred is where R is methyl and R is a branched chain Co. preferably Cs alkyl. The preferred compound is ethylhexyl methoxycinnamate, also referred to as Octoxinate or octyl methoxycinnamate. The compound may be purchased from Givaudan Corporation under the tradename Parsol(R) MCX, or BASF under the tradename Uvinul R. MC 80. wherein R, R2, and R are each independently H. Co 0106. Also suitable are mono-, di-, and triethanolamine straight or branched chain alkyl which may be substituted derivatives of Such methoxy cinnamates including diethano with one or more hydroxy groups. Particularly preferred is lamine methoxycinnamate. Cinoxate, the aromatic ether wherein R is Hor Cs straight or branched alkyl, and R and derivative of the above compound is also acceptable. If Rs are H, or Cs straight or branched chain alkyl. Particularly present, the Cinoxate should be found at no more than about preferred are PABA, ethylhexyl dimethyl PABA (Padimate 3% by weight of the total composition. O), ethyldihydroxypropyl PABA, and the like. If present 0107 Also suitable as UVB screening agents are various Padimate O should be found at no more than about 8% by benzophenone derivatives having the general formula: weight of the total composition. 0110 Salicylate derivatives are also acceptable UVB absorbers. Such compounds have the general formula: R R Rs R6 wherein R is a straight or branched chain alkyl, including O derivatives of the above compound formed from mono-, di-, or triethanolamines. Particular preferred are octyl salicylate, R C R7 TEA-salicylate, DEA-salicylate, and mixtures thereof. Generally, the amount of the UVB chemical sunscreen present may range from about 0.001-45%, preferably 0.005 40%, more preferably about 0.01-35% by weight of the total composition. wherein R throughRs are each independently H, OH, NaOS, 0111. If desired, the compositions of the invention may be SOH, SONa, C1, R", OR" where R" is Co straight or formulated to have certain SPF (sun protective factor) values branched chain alkyl Examples of Such compounds include ranging from about 1-50, preferably about 2-45, most prefer Benzophenone 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. Particu ably about 5-30. Calculation of SPF values is well known in larly preferred is where the benzophenone derivative is Ben the art. Zophenone 3 (also referred to as Oxybenzone), BenZophe none 4 (also referred to as Sulisobenzone), Benzophenone 5 0112 D. Surfactants (Sulisobenzone Sodium), and the like. Most preferred is Ben 0113. It may be desirable for the composition to contain Zophenone 3. one more surfactants, especially if in the emulsion form. However, Such surfactants may be used if the compositions 0108. Also suitable are certain menthyl salicylate deriva are solutions, Suspensions, or anhydrous also, and will assist tives having the general formula: in dispersing ingredients that have polarity, for example pig ments. Such surfactants may be silicone or organic based. The R4 R surfactants will also aid in the formation of stable emulsions of either the water-in-oil or oil-in-water form. If present, the O R surfactant may range from about 0.001 to 30%, preferably C from about 0.005 to 25%, more preferably from about 0.1 to 20% by weight of the total composition. 0114 1. Organic Nonionic Surfactants 0115 The composition may comprise one or more non ionic organic Surfactants. Suitable nonionic Surfactants wherein R. R. R. and Ra are each independently H, OH, include alkoxylated alcohols or ethers, formed by the reaction NH, or Co straight or branched chain alkyl. Particularly of an alcohol with an alkylene oxide, usually ethylene or preferred is where R, R2, and Rs are methyl and R is propylene oxide. Suitable alcohols include mono-, di-, or US 2014/O 193391 A1 Jul. 10, 2014 polyhydric short chain (C1-6) alcohols; aromatic oraliphatic Vegetables, and so on, including yeastferment extract, Padina saturated or unsaturated fatty (C12-40) alcohols, of choles Pavonica extract, Thermus Thermophilis ferment extract, terol; and so on. Camelina Sativa seed oil, Boswellia Serrata extract, olive 0116. In one embodiment the alcohol is cholesterol, or an extract, Acacia Dealbata extract, Acer Saccharinum (Sugar aromatic or aliphatic Saturated or unsaturated fatty alcohol maple), Acidopholus, Acorus, Aesculus, Agaricus, Agave, which may have from 6 to 40, preferably from about 10 to 30, Agrimonia, algae, aloe, citrus, Brassica, cinnamon, orange, more preferably from about 12 to 22 carbonatoms. Examples apple, blueberry, cranberry, peach, pear, lemon, lime, pea, include oleyl alcohol, cetearyl alcohol, cetyl alcohol, Stearyl seaweed, caffeine, green tea, chamomile, willowbark, mul alcohol, isostearyl alcohol, behenyl alcohol, and the like. berry, poppy, and those set forth on pages 1646 through 1660 Examples of such ingredients include Oleth 2-100; Steareth of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, 2-100; Beheneth 5-30; Ceteareth 2-100; Ceteth 2-100: Volume 2. Further specific examples include, but are not Choleth 2-100 wherein the number range means the number limited to, Glycyrrhiza Glabra, Salix Nigra, Macrocycstis of repeating ethylene oxide units, e.g. Ceteth 2-100 means Pyrifera, Pyrus Malus, Saxifraga Sarmentosa, Vitis Vinifera, Ceteth where the number of repeating ethylene oxide units Morus Nigra, Scutellaria Baicalensis, Anthemis Nobilis, ranges from 2 to 100. Derivatives of alkoxylated alcohols are Salvia Sclarea, Rosmarinus Officianalis, Citrus Medica also Suitable. Such as phosphoric acid esters thereof. Limonum, Panax Ginseng, Siegesbeckia Orientalis, Fructus 0117 Some preferred organic nonionic surfactants Mume, Ascophyllum Nodosum, Glycine Soia extract, Beta include Oleth-3, Oleth-5, Oleth-3 phosphate, Choleth-24: Vulgaris, Haberlea Rhodopensis, Polygonum Cuspidatum, Ceteth-24; and so on. Citrus Aurantium Dulcis, Vitis Vinifera, Selaginella Tama 0118. Also suitable are alkoxylated alcohols formed with riscina, Humulus Lupulus, Citrus Reticulata Peel, Punica mono-, di-, or polyhydric short chain alcohols, for example Granatum, Asparagopsis, Curcuma Longa, Menyanthes Tri those having from about 1 to 6 carbon atoms. Examples foliata, Helianthus Annuus, Hordeum Vulgare, Cucumis Sati include glucose, glycerin, or alkylated derivatives thereof. vus, Evernia Prunastri, Evernia Furfitracea, Kola Acumi Examples include glycereth 2-100; gluceth 2-100; methyl nata, and mixtures thereof. If desired Such botanical extracts gluceth 2-100 and so on. More preferred are methylgluceth may be fermented to increase potency or activity. Fermenta 20; glycereth-26 and the like. tion may be accomplished by standard fermentation tech 0119) Other types of alkoxylated alcohols are suitable sur niques using bacteria or yeast. factants, including ethylene oxide polymers having varying (O127 G. Biological Materials numbers of repeating EO groups, generally referred to as I0128. Also suitable are various types of biological mate PEG 12 to 200. More preferred are PEG-75, which is may be rials such as those derived from cells, fermented materials, purchased from Dow Chemical under the trade name Carbo and so on. If present such materials may range from about wax PEG-3350. 0.001 to 30%, preferably from about 0.005 to 25%, more 0120. Other suitable nonionic surfactants include alkoxy preferably from about 0.01 to 20%. Examples include frag lated sorbitan and alkoxylated sorbitan derivatives. For ments of cellular RNA or DNA, probiotic microorganisms, or example, alkoxylation, in particular ethoxylation of Sorbitan ferments of microorganisms and organic materials from provides polyalkoxylated sorbitan derivatives. Esterification plants such as leaves, seeds, extracts, flowers, etc. Particularly of polyalkoxylated Sorbitan provides Sorbitan esters such as preferred are RNA fragments. the polysorbates. For example, the polyalkyoxylated sorbitan I0129. H. Aqueous Phase Structuring Agent can be esterified with C6-30, preferably C12-22 fatty acids. 0.130. In the case where the compositions are in the form of Examples of such ingredients include Polysorbates 20-85, aqueous solutions, dispersions or emulsions, in addition to Sorbitan oleate, Sorbitan sesquioleate, Sorbitan palmitate, Sor water the aqueous phase may contain one or more aqueous bitan sesquiisoStearate, Sorbitan Stearate, and so on. phase structuring agents, that is, an agent that increases the 0121 2. Silicone or Silane Surfactants Viscosity or, or thickens, the aqueous phase of the composi 0122. Also suitable are various types of silicone or silane tion. This is particularly desirable when the composition is in based Surfactants. Examples include organosiloxanes Substi the form of a serum or gel. Suitable ranges of aqueous phase tuted with ethylene oxide or propylene oxide groups such as structuring agent, if present, are from about 0.01 to 30%, PEG dimethicones which are dimethicones substituted with preferably from about 0.1 to 20%, more preferably from polyethylene glycols including those having the INCI names about 0.5 to 15% by weight of the total composition. PEG-1 dimethicone; PEG-4 dimethicone; PEG-8 dimethi Examples of such agents include various acrylate based thick cone; PEG-12 dimethicone; PEG-20 dimethicone; and so on. ening agents, natural or synthetic gums, polysaccharides, and 0123. Also suitable are silanes substituted with ethoxy the like, including but not limited to those set forth below. groups or propoxy groups or both, such as various types of I0131 1. Polysaccharides PEG methyl ether silanes such as bis-PEG-18 methyl ether I0132 Polysaccharides may be suitable aqueous phase dimethylsilane; and so on. thickening agents. Examples of such polysaccharides include 0.124. Further examples of silicone based surfactants naturally derived materials such as agar, agarose, alicalligenes include those having the generic names dimethicone polysaccharides, algin, alginic acid, acacia gum, amylopec copolyol; cetyl dimethicone copolyol; and so on. tin, chitin, dextran, Cassia gum, cellulose gum, gelatin, gellan 0.125 F. Botanical Extracts gum, hyaluronic acid, hydroxyethyl cellulose, methyl cellu 0126. It may be desirable to incorporate one more addi lose, ethyl cellulose, pectin, Sclerotium gum, Xanthan gum, tional botanical extracts into the composition. If present Sug pectin, trehelose, gelatin, and so on. gested ranges are from about 0.0001 to 20%, preferably from (0.133 2. Acrylate Polymers about 0.0005 to 15%, more preferably from about 0.001 to I0134. Also suitable are different types of synthetic poly 10%. Suitable botanical extracts include extracts from plants meric thickeners. One type includes acrylic polymeric thick (herbs, roots, flowers, fruits, seeds) such as flowers, fruits, eners comprised of monomers A and B wherein A is selected US 2014/O 193391 A1 Jul. 10, 2014 from the group consisting of acrylic acid, methacrylic acid, One commercial example of Such polymers are crosslinked and mixtures thereof, and B is selected from the group con terpolymers of methacrylic acid, of ethyl acrylate, of poly sisting of a C-22 alkyl acrylate, a C-22 alky methacrylate, and ethylene glycol (having 10 EO units) ether of stearyl alcohol mixtures thereof are suitable. In one embodiment the A or steareth-10, in particular those sold by the company Allied monomer comprises one or more of acrylic acid or meth Colloids under the names SALCARE SC80 and SALCARE acrylic acid, and the B monomer is selected from the group SC90, which are aqueous emulsions containing 30% of a consisting of a Co., most preferably C. alkyl acrylate, a crosslinked terpolymer of methacrylic acid, of ethyl acrylate Co., most preferably C alkyl methacrylate, and mixtures and of steareth-10 allyl ether (40/50/10). thereof. Most preferably the B monomer is one or more of 0.137 Also suitable are acrylate copolymers such as Poly methyl or ethyl acrylate or methacrylate. The acrylic copoly acrylate-3 which is a copolymer of methacrylic acid, meth mer may be supplied in an aqueous solution having a solids ylmethacrylate, methylstyrene isopropylisocyanate, and content ranging from about 10-60%, preferably 20-50%, PEG-40 behenate monomers: Polyacrylate-10 which is a more preferably 25-45% by weight of the polymer, with the copolymer of Sodium acryloyldimethyltaurate, sodium acry remainder water. The composition of the acrylic copolymer late, acrylamide and vinyl pyrrolidone monomers; or Poly may contain from about 0.1-99 parts of the A monomer, and acrylate-11, which is a copolymer of Sodium acryloyldim about 0.1-99 parts of the B monomer. Acrylic polymer solu ethylacryloyldimethyl taurate, Sodium acrylate, tions include those sold by Seppic, Inc., under the tradename hydroxyethyl acrylate, lauryl acrylate, butyl acrylate, and Capigel. acrylamide monomers. 0135 Also suitable are acrylic polymeric thickeners that 0.138. Also suitable are crosslinked acrylate based poly are copolymers of A, B, and C monomers wherein A and Bare mers where one or more of the acrylic groups may have as defined above, and C has the general formula: substituted long chain alkyl (such as 6-40, 10-30, and the like) groups, for example acrylates/Co-so alkyl acrylate crosspoly mer which is a copolymer of C10-30 alkyl acrylate and one or CH2=CH more monomers of acrylic acid, methacrylic acid, or one of their simple esters crosslinked with the allyl ether of sucrose or the allyl ether of pentaerythritol. Such polymers are com monly sold under the Carbopol or Pemulen tradenames and wherein Z is —(CH), wherein mis 1-10, n is 2-3, o is 2-200, have the CTFA name carbomer. and Risa Co-so straight or branched chain alkyl. Examples of I0139 Also suitable are acrylate based polymeric thicken the secondary thickening agent above, are copolymers where ers sold by Clariant under the Aristoflex trademark such as A and B are defined as above, and C is CO, and wherein n, o, Aristoflex AVC, which is ammonium acryloyldimethyltau and R are as above defined. Examples of Such secondary rate/VP copolymer; Aristoflex AVL which is the same poly thickening agents include acrylates/steareth-20 methacrylate mer has found in AVC dispersed in mixture containing copolymer, which is sold by Rohm & Haas under the trade caprylic/capric triglyceride, trilaureth-4, and polyglyceryl-2 name Acrysol ICS-1. sesquiisostearate; or Aristoflex HMB which is ammonium 0136. Also suitable are acrylate based anionic amphiphilic acryloyldimethyltaurate/beheneth-25 methacrylate cross polymers containing at least one hydrophilic unit and at least polymer, and the like. one allyl ether unit containing a fatty chain. Preferred are 0140. 3. Alkylene Glycols those where the hydrophilic unit contains an ethylenically 0.141. Also Suitable as the aqueous phase thickening unsaturated anionic monomer, more specifically a vinyl car agents are various polyethylene glycols (PEG) derivatives boxylic acid such as acrylic acid, methacrylic acid or mix where the degree of polymerization ranges from 1,000 to tures thereof, and where the allyl ether unit containing a fatty 200,000. Such ingredients are indicated by the designation chain corresponds to the monomer of formula: “PEG” followed by the degree of polymerization in thou sands, such as PEG-45M, which means PEG having 45,000 CH=CR'CHOBR repeating ethylene oxide units. Examples of suitable PEG in which R" denotes H or CH, B denotes the ethylenoxy derivatives include PEG 2M, 5M, 7M, 9M, 14M, 20M, 23M, radical, n is Zero or an integer ranging from 1 to 100, R 25M, 45M, 65M, 90M, 115M, 16OM, 18OM, and the like. denotes a hydrocarbon radical selected from alkyl, arylalkyl, 0142. Also suitable are polyglycerins which are repeating aryl, alkylaryland cycloalkyl radicals which contain from 8 to glycerin moieties where the number of repeating moieties 30 carbon atoms, preferably from 10 to 24, and even more ranges from 15 to 200, preferably from about 20-100. particularly from 12 to 18 carbon atoms. More preferred in Examples of Suitable polyglycerins include those having the this case is where R' denotes H. n is equal to 10 and R denotes CFTA names polyglycerin-20, polyglycerin-40, and the like. a stearyl (C18) radical. Anionic amphiphilic polymers of this 0.143 I. Humectants type are described and prepared in U.S. Pat. Nos. 4,677,152 0144. The composition may contain one or more humec and 4,702,844, both of which are hereby incorporated by tants. If present, they may range from about 0.01 to 75%, reference in their entirety. Among these anionic amphiphilic preferably from about 0.5 to 70%, more preferably from polymers, polymers formed of 20 to 60% by weight acrylic about 0.5 to 40%. Examples of suitable humectants include acid and/or methacrylic acid, of 5 to 60% by weight lower glycols, Sugars, and the like. Suitable glycols are in mono alkyl methacrylates, of 2 to 50% by weight allyl ether con meric or polymeric form and include polyethylene and taining a fatty chain as mentioned above, and of 0 to 1% by polypropylene glycols such as PEG 4-10, which are polyeth weight of a crosslinking agent which is a well-known copo ylene glycols having from 4 to 10 repeating ethylene oxide lymerizable polyethylenic unsaturated monomer, for instance units; as well as C. alkylene glycols such as propylene diallyl phthalate, allyl(meth)acrylate, divinylbenzene, (poly) glycol, butylene glycol, pentylene glycol, and the like. Suit ethylene glycol dimethacrylate and methylenebisacrylamide. able Sugars, some of which are also polyhydric alcohols, are US 2014/O 193391 A1 Jul. 10, 2014 also suitable humectants. Examples of Such Sugars include Methyl trimethicone may be purchased from Shin-Etsu Sili glucose, fructose, honey, hydrogenated honey, inositol, mal cones under the tradename TMF-1.5, having a viscosity of 1.5 tose, mannitol, maltitol, Sorbitol. Sucrose, Xylitol. Xylose, and centistokes at 25°C. so on. Also suitable is urea. Preferably, the humectants used in 0154 (b). Volatile Paraffinic Hydrocarbons the composition of the invention are C, preferably Ca 0155 Also suitable as the volatile oils are various straight alkylene glycols, most particularly butylene glycol. or branched chain paraffinic hydrocarbons having 5,6,7,8,9, (0145 J. Oils 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbonatoms, more 0146 In the event the compositions of the invention are in preferably 8 to 16 carbon atoms. Suitable hydrocarbons emulsion form, the composition will comprise an oil phase. include pentane, hexane, heptane, decane, dodecane, tetrade Oily ingredients are desirable for the skin moisturizing and cane, tridecane, and Cso isoparaffins as disclosed in U.S. protective properties. Suitable oils include silicones, esters, Pat. Nos. 3,439,088 and 3,818,105, both of which are hereby Vegetable oils, synthetic oils, including but not limited to incorporated by reference. Preferred volatile paraffinic those set forth herein. The oils may be volatile or nonvolatile, hydrocarbons have a molecular weight of 70-225, preferably and are preferably in the form of a pourable liquid at room 160 to 190 and a boiling point range of 30 to 320, preferably temperature. The term “volatile” means that the oil has a 60 to 260°C., and a viscosity of less than about 10 cst. at 25° measurable vapor pressure, or a vapor pressure of at least C. Such paraffinic hydrocarbons are available from EXXON about 2 mm. of mercury at 20° C. The term “nonvolatile' under the ISOPARS trademark, and from the Permethyl Cor means that the oil has a vapor pressure of less than about 2 poration. Suitable C isoparaffins are manufactured by Per mm. of mercury at 20°C. If present, such oils may range from methyl Corporation under the tradename Permethyl 99A. about 0.01 to 85%, preferably from about 0.05 to 80%, more Various C isoparaffins commercially available, such as iso preferably from about 0.1 to 50%. hexadecane (having the tradename Permethyl R), are also 0147 1. Volatile Oils suitable. 0148 Suitable volatile oils generally have a viscosity 0156 2. Non-Volatile Oils ranging from about 0.5 to 5 centistokes 25° C. and include 0157. A variety of nonvolatile oils are also suitable for use linear silicones, cyclic silicones, paraffinic hydrocarbons, or in the compositions of the invention. The nonvolatile oils mixtures thereof generally have a viscosity of greater than about 5 to 10 cen 0149 (a). Volatile Silicones tistokes at 25° C., and may range in Viscosity up to about 0150 Cyclic silicones are one type of volatile silicone that 1,000,000 centipoise at 25° C. Examples of nonvolatile oils may be used in the composition. Such silicones have the include, but are not limited to: general formula: 0158 (a). Esters 0159 Suitable esters are mono-, di-, and triesters. The composition may comprise one or more esters selected from CH3 the group, or mixtures thereof. o (i). Monoesters CH pi 0160 Monoesters are defined as esters formed by the reac tion of a monocarboxylic acid having the formula R—COOH, wherein R is a straight or branched chain satu where n=3-6, preferably 4, 5, or 6. rated or unsaturated alkyl having 2 to 45 carbon atoms, or 0151. Also suitable are linear volatile silicones, for phenyl; and an alcohol having the formula R-OH wherein R example, those having the general formula: is a straight or branched chain Saturated or unsaturated alkyl having 2-30 carbonatoms, orphenyl. Both the alcohol and the where n=0, 1, 2, 3, 4, or 5, preferably 0, 1, 2, 3, or 4. acid may be substituted with one or more hydroxyl groups. 0152 Cyclic and linear volatile silicones are available Either one or both of the acid or alcohol may be a “fatty' acid from various commercial sources including Dow Corning or alcohol, and may have from about 6 to 30 carbon atoms, Corporation and General Electric. The Dow Corning linear more preferably 12, 14, 16, 18, or 22 carbonatoms in straight volatile silicones are sold under the tradenames Dow Corning or branched chain, Saturated or unsaturated form. Examples 244, 245, 344, and 200 fluids. These fluids include hexam of monoester oils that may be used in the compositions of the ethyldisiloxane (viscosity 0.65 centistokes (abbreviated cst)). invention include hexyl laurate, butyl isostearate, hexadecyl octamethyltrisiloxane (1.0 cst), decamethyltetrasiloxane (1.5 isostearate, cetyl palmitate, isostearyl neopentanoate, Stearyl cst), dodecamethyl-pentasiloxane (2 cSt) and mixtures heptanoate, isostearyl isononanoate, Steary lactate, Stearyl thereof, with all viscosity measurements being at 25°C. octanoate, Stearyl Stearate, isononyl isononanoate, and so on. 0153 Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone having the general (ii). Diesters formula: 0.161 Suitable diesters are the reaction product of a dicar boxylic acid and an aliphatic or aromatic alcohol or an ali phatic or aromatic alcohol having at least two Substituted CH hydroxyl groups and a monocarboxylic acid. The dicarboxy lic acid may contain from 2 to 30 carbon atoms, and may be (CH)SiO-SiO-Si(CH) in the straight or branched chain, Saturated or unsaturated form. The dicarboxylic acid may be substituted with one or more hydroxyl groups. The aliphatic or aromatic alcohol may also contain 2 to 30 carbon atoms, and may be in the straight US 2014/O 193391 A1 Jul. 10, 2014

or branched chain, saturated, or unsaturated form. Preferably, diglyceryl diiosostearate, polyglyceryl-3 isostearate, polyg one or more of the acid or alcohol is a fatty acid or alcohol, i.e. lyceryl-4 isostearate, polyglyceryl-6 ricinoleate, glyceryl contains 12-22 carbonatoms. The dicarboxylic acid may also dioleate, glyceryl diisotearate, glyceryl tetraisoStearate, glyc be an alpha hydroxy acid. The ester may be in the dimer or eryl trioctanoate, diglyceryl distearate, glyceryl linoleate, trimer form. Examples of diester oils that may be used in the glyceryl myristate, glyceryl isostearate, PEG castor oils, PEG compositions of the invention include diisotearyl malate, glyceryl oleates, PEG glyceryl Stearates, PEG glyceryl tallo neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl wates, and so on. dimer dilinoleate, dicetyl adipate, diisocetyl adipate, (0170 (d). Nonvolatile Silicones disononyl adipate, diisoStearyl dimer dilinoleate, diisos (0171 Nonvolatile silicone oils, both water soluble and tearyl fumarate, diisoStearyl malate, dioctyl malate, and so water insoluble, are also suitable for use in the composition. O. Such silicones preferably have a viscosity ranging from about greater than 5 to 800,000 cst, preferably 20 to 200,000 cstat (iii). Triesters 25° C. Suitable water insoluble silicones includeamine func 0162 Suitable triesters comprise the reaction product of a tional silicones Such as amodimethicone. tricarboxylic acid and an aliphatic or aromatic alcohol or 0172 For example, such nonvolatile silicones may have alternatively the reaction product of an aliphatic or aromatic the following general formula: alcohol having three or more substituted hydroxyl groups with a monocarboxylic acid. As with the mono- and diesters mentioned above, the acid and alcohol contain 2 to 30 carbon atoms, and may be saturated or unsaturated, straight or | | | | branched chain, and may be substituted with one or more A--o –0 i-o i hydroxyl groups. Preferably, one or more of the acid or alco R R LR. J. R. hol is a fatty acid or alcohol containing 12 to 22 carbonatoms. Examples of triesters include esters of arachidonic, citric, or behenic acids, Such as triarachidin, tributyl citrate, triisos wherein R and R' are each independently Cso straight or tearyl citrate, tri C-alkyl citrate, tricaprylin, tricaprylyl branched chain, Saturated or unsaturated alkyl, phenyl oraryl, citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl trialkylsiloxy, and X and y are each independently 1-1,000, behenate; or tridecyl cocoate, tridecyl isononanoate, and so 000; with the proviso that there is at least one of either X ory, O. and A is alkyl siloxy endcap unit. Preferred is where A is a 0163 Esters suitable for use in the composition are further methyl siloxy endcap unit; in particular trimethylsiloxy, and described in the C.T.F.A. Cosmetic Ingredient Dictionary and RandR' are each independently a Clso straight or branched Handbook, Eleventh Edition, 2006, under the classification of chain alkyl, phenyl, or trimethylsiloxy, more preferably a “Esters', the text of which is hereby incorporated by refer C. alkyl, phenyl, or trimethylsiloxy, most preferably ence in its entirety. methyl, phenyl, or trimethylsiloxy, and resulting silicone is (0164 (b). Hydrocarbon Oils dimethicone, phenyl dimethicone, diphenyl dimethicone, 0.165. It may be desirable to incorporate one or more non phenyl trimethicone, or trimethylsiloxyphenyl dimethicone. volatile hydrocarbon oils into the composition. Suitable non Other examples include alkyl dimethicones such as cetyl volatile hydrocarbon oils include paraffinic hydrocarbons and dimethicone, and the like wherein at least one R is a fatty alkyl olefins, preferably those having greater than about 20 carbon (C12, C14, C6, C1s, Co, or C22), and the other R is methyl, atoms. Examples of Such hydrocarbon oils include Cas and A is a trimethylsiloxy endcap unit, provided such alkyl olefins, Coas olefins, Coao isoparaffins, hydrogenated dimethicone is a pourable liquid at room temperature. Phenyl polyisobutene, polyisobutene, polydecene, hydrogenated trimethicone can be purchased from Dow Corning Corpora polydecene, mineral oil, pentahydrosqualene, squalene, tion under the tradename 556 Fluid. Trimethylsiloxyphenyl squalane, and mixtures thereof. In one preferred embodiment dimethicone can be purchased from Wacker-Chemie under Such hydrocarbons have a molecular weight ranging from the tradename PDM-1000. Cetyl dimethicone, also referred about 300 to 1000 Daltons. to as a liquid silicone wax, may be purchased from Dow 0166 (c). Glyceryl Esters of Fatty Acids Corning as Fluid 2502, or from DeGussa Care & Surface 0167 Synthetic or naturally occurring glyceryl esters of Specialties under the trade names Abil Wax 9801, or 9814. fatty acids, or triglycerides, are also suitable for use in the (0173 K. Vitamins and Antioxidants compositions. Both vegetable and animal sources may be 0.174. It may be desirable to incorporate one or more vita used. mins or antioxidants in the compositions. If present, Sug 0168 Examples of such oils include castor oil, lanolin oil, gested ranges are from about 0.001 to 20%, preferably from Cos triglycerides, caprylic/capric/triglycerides, Sweet about 0.005 to 15%, more preferably from about 0.010 to almond oil, apricot kernel oil, Sesame oil, camelina sativa oil, 10%. Preferably such vitamins, vitamin derivatives and/or tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed antioxidants are operable to Scavenge free radicals in the form oil, ink oil, olive oil, palm oil, illipe butter, rapeseed oil, of singlet oxygen. Such vitamins may include tocopherol or Soybean oil, grapeseed oil, Sunflower seed oil, walnut oil, and its derivatives Such as tocopherol acetate, tocopherol ferulate; the like. ascorbic acid or its derivatives such as ascorbyl palmitate, 0169. Also suitable are synthetic or semi-synthetic glyc magnesium ascorbyl phosphate; Vitamin A or its derivatives eryl esters, such as fatty acid mono-, di-, and triglycerides such as retinyl palmitate; or vitamins D, K., B, or derivatives which are natural fats or oils that have been modified, for thereof. example, mono-, di- or triesters of polyols such as glycerin. In (0175 L. Preferred Compositions an example, a fatty (C2) carboxylic acid is reacted with 0176 Preferred compositions are in the aqueous solution one or more repeating glyceryl groups. glyceryl Stearate, or emulsion form and contain at least one autophagy activator US 2014/O 193391 A1 Jul. 10, 2014 and at least one DNA repair enzyme. The composition may (a) Autophagy Activator. optionally contain at least one CLOCK or PER1 gene activa tor and/or at least one proteasome activator. 0185. 1%Yeast Extract: 300 ul of yeast extract was added 0177 More preferred is where within the composition the to 14.7 ml of Media Dulbecco's Modified Eagle Media autophagy activator is a yeast extract that may be fermented (DMEM) to create a 2% stock solution. Then 2.5 ml of this and the DNA repair enzyme is one or more of Arabidopsis stock solution was added to 2.5 ml of DMEM to create 1% by thaliana or ferment thereof. If present the proteasome activa weight solution. tor is algin, hydrolyzed algin, or alginate. If present, the nonionic organic Surfactant is an alkoxylated alcohol, the (b) DNA Repair Enzyme. chemical sunscreen is a UVB sunscreen, the CLOCK or PER1 keratinocyte gene activator is Tripeptide-32 or Tet 0186 Solution of 0.025% Arabidopsis thaliana extract: rapeptide-26, the DNA repair enzyme, if present, is a mixture 15 ul of Roxisomes(R) was combined with 14.985 ml of of Arabidopsis Thaliana extract, Micrococcus lysate, Bifida DMEM and filtered to create a 0.1% stock Solution. Then 2.5 Ferment lysate, Lactobacillus ferment, and Plankton extract, ml of this stock solution was diluted with 2.5 ml of DMEM to and the at least one oil is an organic ester or hydrocarbon. create a 0.05% solution. Then 2.5 ml of this 0.05% solution was diluted with 2.5 ml of DMEM to make a 0.025% solution 0178. The Method of the extract. 0179 The invention is also directed to a method for improving normal cellular detoxification processes by treat ing the cells with a composition that stimulates selective (c) Autophagy Activator+DNA Repair Enzyme. catabolysis by activating or enhancing cellular autophagy processes and/or repairing cellular DNA. In the case where a 0187 5 ml of the 2% yeast extract solution was mixed with CLOCK or PER1 gene activator may be present, it may 5 ml of the 0.05% solution of RoxisomesR to form a solution improve the synchronicity of the metabolic pathways of the containing 1% yeast extract and 0.025% Roxisomes(R). treated cells, which in turn will improve the efficiency of the 0188 Normal human dermal fibroblasts were seeded into autophagy and/or proteasome activation processes. a 96 well plate at a concentration of 150,000/well and incu 0180. In the method of the invention, the composition may bated at 37° C. in 5% CO, for 24 hours to enable cells to be applied to keratin Surfaces such as skin, Scalp, nails or hair acclimate. The next day each well was treated with 200 ul of one or more times per day. For example, the composition may mixture with each mixture being applied to 6 wells. The plate be applied to skin in the morning prior to beginning daily was incubated at 37° C. for 72 hours with 5% CO. activities and/or at night prior to retiring. The composition (0189 A 10% solution of Alamar Blue in 100 ul of DMEM may be applied as part of a regimen; that is, the skin is was prepared. 100 ul of a 10% solution of the Alamar Blue cleansed and treated with toner, after which the composition reagent was added to each well. The plate was incubated at of the invention is applied. The composition may be part of a 37°C., 5% CO for 2 hours. The fluorescence was read on a kit containing a cleanser, toner, and the composition of the plate reader. invention. (0190. Cells were then irradiated with 10 J/cm radiation 0181 Preferably the composition is applied to the face UV Radiation Chamber (Dr. Groebel, UV-Electronik, and/or neck and décolletage prior to retiring to repair or GmbH). The DPBS was aspirated and the treatment compo eliminate damaged cellular material and provide general sitions applied once again for 24 hours. The next morning the improvement of the skin. Combining the composition of the medium was aspirated and 100 ul of 10% Alamar Blue solu invention at night prior to retiring maximizes the cellular tion was added. The plate was incubated at 37°C. for 1.5 to 2 detoxification processes. In general, treatment of skin with hours. The fluorescence was measured at 530/590 nanom the composition of the invention promotes cellular viability, eters using a Spectra Max Gemini reader. The cell viability longevity, and health. was calculated and expressed as the percentage of Survival of 0182. The invention will be further described in connec cells treated with hydrogen peroxide. tion with the following examples which are set forth for the purposes of illustration only. 1% Yeast Extract + Example 1 1% Yeast O.025% O.025% Control Extract Roxisomes Roxisomes 0183 Normal human dermal fibroblasts were harvested Average Value 2167.787 2S64.93 1798.29 4393.74 and assayed for cellular viability when untreated, treated with Std Dew. 358.51 219.54 194.95 3O8.16 solutions containing 0.0025% of DNA repair enzyme Arabi Pvalue 1 O.OOO8O12 O.OO1132 460509EO8 dopsis thaliana extract, 1% autophagy activator in the form of % change O 18.32 -17.0449 102.68 yeast extract, and a solution containing a mixture of 0.025% *expressed as a percentage increase (or decrease, if a negative number) of the untreated Arabidopsis thaliana extract and 1% yeast extract autophagy control cells, activator. (0191 The above results demonstrate that when cells are 0184 The fibroblasts were placed in concentrations of treated with the combination of the autophagy activator and 150,000 cells per plate for the 48 hour test, and 300,000 cells DNA repair enzyme cellular viability is increased 102.68%. per plate for the 24 hour test on 96 well plates. The cells were Thus, the combination of the autophagy and DNA repair incubated at 37°C., 5% CO, and 95% humidity for 24 hours. enzyme dramatically improved cellular health and viability The test compositions were prepared as follows: both before and after irradiation with UV light. US 2014/O 193391 A1 Jul. 10, 2014

Example 2 -continued

(0192 A skin treatment composition in accordance with Ingredient wfw % the invention was prepared as follows: Water bifida ferment lysate/hydrogenated lecithin 3.00 Butylene glycol wateri Cola Acuminata extract 3.00 Sodium ribonucleic acid O.O1 ngredient Wateributylene glycol/tripeptide-32* O.20 Lactobacilius ferment lecithin water O.OS Oleth-3 phosphate O45 Water/Arabidopsis Thaliana extract/lecithin *** O.OS O3S Phenoxyethanol O.O2 O.24 Sodium hyaluronate O.O1 O.2O FD&C Red No. 4 (1% aqueous solution with butylene O.04 OSO glycol) BHT O.10 FD&C Yellow No. 5 (1% aqueous solution with butylene O.09 hylhexyl methoxycinnamate O.10 glycol) eth-24f ceteth-24 O.10 Trie hanolamine O.11 D&C Green No. 5 (0.1% solution with butylene glycol) O.OO1 Yeast extract O.OO1 Retinyl palmitate?zea mays (corn) oil/BHT/BHA O.10 Buty lene glycol 1.1 Hydrolyzed Algin (Phyko A1, Codif Recherche & Nature) O.OO1 Chamomile O.O3 Water QS 100 Bisabolol O.10 *CLOCK or PER1 gene activator Water QS ** autophagy activator Methyl paraben O46 ***proteasome activator PEG-75 4.OO ****DNA repair enzyme Bis-PEG-18 methyl ether dimethylsilane 2.OO Glyc ereth-26 1.OO Methylgluceth-20 4.OO 0193 The composition was prepared by combining the Trisodium EDTA O.10 ingredients and mixing well to form a liquid. The composi Pantethine O.14 tion was stored in brown glass bottles. Caffeine O.OS 0194 While the invention has been described in connec Xan han gun 0.075 tion with the preferred embodiment, it is not intended to limit Carb Ole O.26 Trie hanolamine OSO the scope of the invention to the particular form set forth but, Phenoxyethanol O.70 on the contrary, it is intended to cover Such alternatives, Benzyl alcohol O.10 modifications, and equivalents as may be included within the Bif a ferment lysate 9.40 spirit and scope of the invention as defined by the appended claims.

SEQUENCE LISTING

<16 Os NUMBER OF SEO ID NOS: 7

<21 Os SEQ ID NO 1. &211s LENGTH: 13 212s. TYPE: PRT ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator 22 Os. FEATURE: <221s NAMEAKEY: misc feature &222s. LOCATION: (1) . . (4) <223> OTHER INFORMATION: Xaa can be any naturally occurring amino acid or no amino acid 22 Os. FEATURE: <221s NAMEAKEY: misc feature &222s. LOCATION: (5) <223> OTHER INFORMATION: Xaa can be threonine or serine or no amino acid 22 Os. FEATURE: <221s NAMEAKEY: misc feature &222s. LOCATION: (9) <223> OTHER INFORMATION: Xaa can be isoleucine, leucine, proline, valine, all anine, glycine or no amino acid 22 Os. FEATURE: <221s NAMEAKEY: misc feature &222s. LOCATION: (10) ... (13) <223> OTHER INFORMATION: Xaa can be any naturally occurring amino acid or no amino acid

<4 OOs SEQUENCE: 1.

Xaa Xala Xala Xala Xala Ser Thr Pro Xala Xaa Xala Xala Xala 1. 5

<21 Os SEQ ID NO 2 US 2014/O 193391 A1 Jul. 10, 2014 13

- Continued

&211s LENGTH: 7 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator <4 OOs, SEQUENCE: 2 Tyr Val Ser Thr Pro Tyr Asn 1. 5

<210s, SEQ ID NO 3 &211s LENGTH: 5 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator <4 OOs, SEQUENCE: 3

Wall Ser Thr Pro Glu 1. 5

<210s, SEQ ID NO 4 &211s LENGTH: 6 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator <4 OOs, SEQUENCE: 4

Lieu. His Ser Thr Pro Pro 1. 5

<210s, SEQ ID NO 5 &211s LENGTH: 6 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator <4 OOs, SEQUENCE: 5 Arg His Ser Thr Pro Glu 1. 5

<210s, SEQ ID NO 6 &211s LENGTH: 5 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator <4 OOs, SEQUENCE: 6

His Ser Thr Pro Glu. 1. 5

<210s, SEQ ID NO 7 &211s LENGTH: 4 212. TYPE: PRT <213> ORGANISM: Artificial Sequence 22 Os. FEATURE: <223> OTHER INFORMATION: CLOCK and/or PER1 gene activator

<4 OO > SEQUENCE: 7

Ser Pro Leul Glin 1. US 2014/O 193391 A1 Jul. 10, 2014

We claim: wherein said formula (I) sequence may contain Substi 1. A topical composition comprising at least one cellular tutions of amino acids X and X with other chemi autophagy activator and at least one DNA repair enzyme. cally equivalent amino acids; 2. The composition of claim 1 wherein the cells are kera (b) a peptide having the amino acid sequence Ser-Pro-Leu tinocytes or fibroblasts. Gln-NH: 3. The composition of claim 1 wherein autophagy activator comprises a yeast extract. (c) cichoric acid; and 4. The composition of claim 1 wherein the autophagy acti (d) mixtures thereof. vator comprises a yeast extract selected from the group con sisting of those from genuses Lithothamnium, Melilot, Citrus, 14. The composition of claim 13 wherein the CLOCK or Candida, Lens, Urtica, Carambola, Momordica, Yarrowia, PER1 gene activators are selected from the group consisting Plumbago, or mixtures thereof. of: 5. The composition of claim 1 wherein the autophagy acti vator is selected from the group consisting of Lithothamni S-T-P-NH2 umn calcaneum, Melilotus officinalis, Citrus limonum, Can dida Saitoana, Lens culinaria, Urtica dioica, Averrhoa Ser-Thr-Pro-NH carambola, Momordica charantia, Yarrowia lipolytica, (SEQ ID No. 2) Plumbago zeylanica. Y-V-S-T-P-Y-N-NH, 6. The composition of claim 1 wherein the autophagy acti vator is a stimulator of one or more of: (a) MAP-LC3; (b) Tyr-Val-Ser-Thr-Pro-Tyr-Asn-NH2 ATG5-12; (c) protein p53; (d)AMPK; or (e) DRAM. (SEQ ID No. 3) 7. The composition of claim 5 wherein the autophagy acti N vator is an inhibitor of mTOR. 8. The composition of claim 1 wherein the DNA repair 2-Val-Ser-Thr-Pro-Glu-NH2 enzyme is selected from the group consisting of base excision (SEQ ID No. 4) repair (BER) enzymes, nucleotide excision repair (NER) N enzymes, DNA polymerases, DNA helicases, Mismatch repair (MMR) enzymes, and mixtures thereof. N -Leu-His-Ser-Thr-Pro-Pro-NH, 9. The composition of claim 8 wherein the DNA repair (SEQ ID No. 5) enzyme is selected from the group consisting of Arabidopsis Thaliana extract either alone or inadmixture with lecithin and -NH-Arg-His-Ser-Thr-Pro-Glu-NH2 water, Lactobacillus ferment, Micrococcus lysate, Plankton extract, Bifida ferment lysate; and mixtures thereof. (SEQ ID No. 6) 10. The composition of claim 5 wherein the autophagy activator is yeast extract is from the genus Candida and the DNA repair enzyme comprises Arabidopsis thaliana extract CH-NH-His-Ser-Thr-Pro-Glu-CH-NH2 either alone or in admixture with lecithin and water. and mixtures thereof. 11. The composition of claim 1 additionally comprising at least one proteasome activator. 15. The composition of claim 13 wherein the CLOCK or 12. The composition of claim 11 wherein the proteasome PER1 gene activators are selected from: activator is algin, alginate, or hydrolyzed algin. 13. The composition of claim 1 additionally comprising a CLOCK or PER1 gene activator comprising: S-T-P-NH, (a) a peptide having from about 3 to 13 amino acid residues Ser-Thr-Pro-NH2 and of the formula (I) (SEQID No. 1): (SEQ ID No. 4) NH-L-H-S-T-P-P-NH2 X represents threonine, serine, or is equal to Zero, NH-Leu-His-Ser-Thr-Pro-Pro-NH, X represents an isoleucine, leucine, proline, valine, ala nine, glycine, or is equal to Zero, and mixtures thereof. AA represents any amino acid or derivative thereof, and 16. The composition of claim 1 additionally comprising a in and pare whole numbers between 0 and 4, CLOCK or PER1 gene activator selected from the group R represents the primary amine function of the N-ter consisting of Tripeptide-32, Tetrapeptide-26 or mixtures minal amino acid, either free or substituted by a pro thereof. tective grouping that may be chosen from either an acetyl group, a benzoyl group, a tosyl group, or a 17. A method for increasing cellular viability and selective benzyloxycarbonyl group, catabolysis in cells of keratin Surfaces in need of Such treat R represents the hydroxyl group of the carboxyl func ment comprising applying to the Surface a composition com tion of the C-terminal amino acid, which may be prising at least one autophagy activator and at least one DNA Substituted by a protective grouping that may be cho repair enzyme. Sen from either a C to Co alkyl chain or an NH2, 18. The method of claim 17 wherein the cellular viability NHY, or NYY group with Y representing a C to C and selective autophagy activation results in improved cellu alkyl chain, and lar detoxification. US 2014/O 193391 A1 Jul. 10, 2014 15

19. The method of claim 17 wherein the composition is applied at night prior to evening rest. 20. The method of claim 17 wherein the keratin surfaces are skin, hair, or nails. k k k k k