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