TOPICAL COMPOSITIONS AND METHODS OF USING SAME AGAINST MITOCHONDRIAL FRAGMENTATION

Abstract

Topical personal care compositions for improving cellular energy efficiency by protecting skin from mitochondrial fragmentation that takes place in an aging individual in need thereof. Use of a topical personal care composition comprising niacinamide and S-adenosyl-L-methionine. Use of niacinamide and S-adenosyl-L-methionine in the manufacture of a topical personal care composition for decreasing or preventing mitochondrial fragmentation in skin cells and for increasing skin cellular energy.

Claims

1. A topical personal care composition for improving energy efficiency of skin cells, comprising: (a) from 0.001 to 10% by weight, of niacinamide; and (b) from 0.001 to 10% by weight, of S-adenosyl-L-methionine compound of Structural Formula 1: ##STR00006## (c) an optional additional skin benefit agent; and (d) a cosmetically acceptable carrier.

2. The topical personal care composition according to claim 1.sub.1 wherein said composition is a skin cosmetic composition.

3. A method for preventing mitochondrial fragmentation in the skin of an individual in need thereof by topically applying to the skin the composition according to claim 1.

4. The method according to claim 3 which improves cellular energy efficiency by protecting the skin of an aging individual in need thereof from mitochondrial fragmentation.

5. (canceled)

6. (canceled)

7. The topical personal care composition according to claim 1, wherein said composition comprises from 0.01 to 6% by weight of niacinamide.

8. The topical personal care composition according to claim 1, wherein said composition comprises from 0.05 to 3.5% by weight of niacinamide.

9. The topical personal care composition according to claim 1, wherein said composition comprises from 0.01 to 6% by weight of S-adenosyl-L-methionine compound of Structural Formula 1.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0036] The present invention is directed to topical personal care compositions comprising: niacinamide (B3) in combination with SAMe in a cosmetically acceptable vehicle. Also provided are methods for preventing mitochondrial fragmentation in the skin of an individual in need thereof by topically applying to the skin the inventive personal care compositions; use of the inventive compositions for preventing or reducing mitochondrial fragmentation; and use of B3 with SAMe in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

[0037] The present invention is based on discovery of active ingredients for incorporation in topical compositions, which can deliver consumer skin benefits by protecting mitochondria and/or lowering mitochondrial fragmentation in skin cells. These compounds are associated with efficient use of energy, control of glucose and lipid metabolism, increase of cellular repair/rejuvenation and increase of anti-oxidant benefit. The personal care benefits of applying the inventive cosmetic compositions include, without limitation, anti-ageing and anti-stress (including UV and oxidative stresses).

[0038] In a first aspect, the present invention is topical personal care composition comprising: from 0.001 to 10% niacinamide (B3) compound and from 0.001 to 10%, preferably from 0.01 to 6%, of SAMe in a cosmetically acceptable vehicle.

[0039] SAMe is a compound of Structural Formula 1:

##STR00002##

[0040] in the combination with niacinamide of Structural Formula 2:

##STR00003##

[0041] In a second aspect, the present invention is a method for prevention of mitochondrial fragmentation in the skin of an individual in need thereof by topically applying to the skin the personal care composition comprising: B3 with SAMe in a cosmetically acceptable vehicle. Preferably, the inventive method improves cellular energy efficiency by protecting the skin of an aging individual in need thereof from mitochondrial fragmentation.

[0042] In a third aspect, the present invention is the use of the inventive compositions comprising B3 with SAMe for reducing mitochondrial fragmentation.

[0043] In a fourth aspect, the present invention is the use of B3 with SAMe in the manufacture of a topical personal care composition for preventing mitochondrial fragmentation in skin cells.

S-Adenosyl-L-methionine (“SAMe”)

[0044] According to the present invention, S-adenosyl-L-methionine compounds (Structural Formula 1 shown below) are used in combination with Niacinamide.

##STR00004##

[0045] Typically, the amount of S-adenosyl-L-methionine (SAMe) used in the compositions of this invention is from 0.001 to 10%, and preferably, from 0.01 to 6%, and most preferably, from 0.05 to 3.5%, based on total weight of the composition and including all ranges subsumed therein.

Nicotinamide

[0046] Nicotinamide, also known as Niacinamide or a form of Vitamin 83, has the following Structural Formula 2:

##STR00005##

[0047] Typically, the amount of nicotinamide used in the compositions of this invention is from 0.001 to 10%, and preferably, from 0.01 to 6%, and most preferably, from 0.05 to 3.5%, based on total weight of the composition and including all ranges subsumed therein.

[0048] Advantageously and unexpectedly, the combinations of SAMe+B3 demonstrate the ability to lower mitochondrial fragmentation in skin cells.

Salt Forms

[0049] Compounds of the present invention (SAMe and nicotinamide) are capable of forming a salt with a variety of physiologically suitable counterions, including, without limitation, chloride, bromide, iodide, hydroxide, sulfate, sulfonate, nitrate, phosphate, formate, tartrate, lactate, oxalate, fumarate, maleate, succinate, malonate, citrate or R.sub.5CO.sub.2 where R.sub.5 is a C.sub.1-C.sub.22 alkyl group, which may be linear, branched or cyclic, saturated or unsaturated, and substituted with one or more heteroatoms selected from O, S.

Carrier

[0050] The compositions of this invention can have as cosmetically acceptable carriers non-polar liquids like oils. Alternatively, such non-polar liquids can be used as the oil phase when the composition is an emulsion.

[0051] When the compositions of the present invention are emulsions, they will typically include cosmetically acceptable carrier components iaddition to non-polar liquid. Water is the most preferred additional carrier. Amounts of water may range from 1 to 99%, and preferably, from 5 to 90%, and most preferably, from 35 to 80%, and optimally, from 40 to 75% by weight, based on total weight of the composition and including all ranges subsumed therein. Ordinarily the compositions of this invention will be water and oil emulsions, most preferably, of the oil-in-water variety. Water-in-oil emulsions, and especially, those generally classified as water-in-oil and high internal phase emulsions are, however, an option. Illustrative examples of the high internal phase emulsions suitable to as carrier for this invention are described in commonly owned U.S. Patent Application Publication No. 2008/0311058 and U.S. Pat. No. 8,425,882, the disclosures of which are incorporated herein by reference.

[0052] Other cosmetically acceptable carriers suitable for use (with or without water) in this invention may include mineral oils, silicone oils, esters, and alcohols. Amounts of these materials may collectively range from 0.1 to 99%, and preferably, from 0.1 to 45%, and most preferably, from 1 to 20% by weight of the composition of this invention, including all ranges subsumed therein.

[0053] Silicone oils may be divided into the volatile and non-volatile variety. The term “volatile” as used herein refers to those materials which have a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably chosen from cyclic or linear polydimethylsiloxanes containing from 3 to 9, and preferably, from 4 to 5 silicon atoms.

[0054] Linear volatile silicone materials generally have viscosities of less than 5 centistokes at 25° C. while cyclic materials typically have viscosities of less than about 10 centistokes.

[0055] Nonvolatile silicone oils useful as carrier material include polyalkyl siloxanes, polyalkylaryl siloxanes and polyether siloxane copolymers. The essentially non-volatile polyalkyl siloxanes useful herein include, for example, polydimethylsiloxanes (like dimethicone) with viscosities of from 5 to 100,000 centistokes at 25° C.

[0056] A preferred silicone source is a cyclopentasiloxane and dimethiconol solution.

[0057] Among suitable esters are: [0058] (1) Alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms like isopropyl palmitate, isopropyl isostearate, isononyl isonanonoate, oleyl myristate, isopropyl myristate, oleyl stearate, and oleyl oleate; [0059] (2) Ether-esters such as fatty acid esters of ethoxylated fatty alcohols; [0060] (3) Polyhydric alcohol esters such as ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 mono stearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol poly-fatty esters, ethoxylated glyceryl mono-stearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxy-ethylene sorbitan fatty acid esters; [0061] (4) Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate; and [0062] (5) Sterol esters, of which soya sterol and cholesterol fatty acid esters are examples thereof.

[0063] Often, oils such as caprylic capric triglyceride are preferred as carriers.

[0064] Emulsifiers may be present in the compositions of the present invention. Total concentration of the emulsifier may range from about 0.1 to 40%, and preferably, from 1 to 20%, and most preferably, from 1 to 5% by weight of the composition, including all ranges subsumed therein. The emulsifier may be selected from the group consisting of anionic, nonionic, cationic and amphoteric actives. Particularly preferred nonionic actives are those with a C.sub.10-C.sub.20 fatty alcohol or acid hydrophobe condensed with from about 2 to about 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe; C.sub.2-C.sub.10 alkyl phenols condensed with from 2 to 20 moles of alkylene oxide; mono- and di-fatty acid esters of ethylene glycol; fatty acid monoglyceride; sorbitan, mono- and di-C.sub.8-020 fatty acids; and polyoxyethylene sorbitan as well as combinations thereof. Alkyl polyglycosides and saccharide fatty amides (e.g. methyl gluconamides) are also suitable nonionic emulsifiers.

[0065] Preferred anionic emulsifiers include alkyl ether sulfate and sulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates, alkyl and dialkyl sulfosuccinates, C.sub.8-C.sub.20acyl isethionates, C.sub.8-C.sub.20 alkyl ether phosphates, alkyl ether carboxylates and combinations thereof.

[0066] Cationic emulsifiers that may be used include, for example, almitamidopropyltrimonium chloride, distearyldimonium chloride and mixtures thereof. Useful amphoteric emulsifiers include cocoamidopropyl betaine, C.sub.12-C.sub.20 trialkyl betaines, sodium lauroamphoacetate, and sodium laurodiamphoacetate or a mixture thereof.

[0067] Other generally preferred emulsifiers include glyceryl stearate, glycol stearate, stearamide AMP, PEG-100 stearate, cetyl alcohol as well as emulsifying/thickening additives like hydroxyethylacrylate/sodium acryloyldimethyl taurates copolymer/squalane and mixtures thereof.

Composition

[0068] Preservatives can desirably be incorporated into the compositions of this invention to protect against the growth of potentially harmful microorganisms. Suitable traditional preservatives for compositions of this invention are alkyl esters of para-hydroxybenzoic acid. Other preservatives which have more recently come into use include hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. Cosmetic chemists are familiar with appropriate preservatives and routinely choose them to satisfy the preservative challenge test and to provide product stability.

[0069] Particularly preferred preservatives are iodopropynyl butyl carbamate, phenoxyethanol, 1,2-octanediol, ethylhexylglycerine, hexylene glycol, methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol. The preservatives should be selected having regard for the use of the composition and possible incompatibilities between the preservatives and other ingredients in the emulsion.

[0070] Preservatives are preferably employed in amounts ranging from 0.01% to 2% by weight of the composition, including all ranges subsumed therein. Combinations of 1,2-octanediol and phenoxyethanol, or iodopropynyl butyl carbamate and phenoxyethaol are preferred, with phenoxyethanol making up from 35 to 65% by weight of the total weight of the preservative combination with the phenoxyethanol.

[0071] Thickening agents may optionally be included in compositions of the present invention. Particularly useful are the polysaccharides. Examples include starches, natural/synthetic gums and cellulosics. Representative of the starches are chemically modified starches such as sodium hydroxypropyl starch phosphate and aluminum starch octenylsuccinate. Tapioca starch is often preferred. Suitable gums include xanthan, sclerotium, pectin, karaya, arabic, agar, guar, carrageenan, alginate and combinations thereof. Suitable cellulosics include hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethylcellulose and sodium carboxy methylcellulose. Synthetic polymers are yet another class of effective thickening agent. This category includes crosslinked polyacrylates such as the Carbomers, polyacrylamides such as Sepigel 305 and taurate copolymers such as Simulgel EG and Arlstoflex AVC, the copolymers being identified by respective INCI nomenclature as Sodium Acrylate/Sodium Acryloyldimethyl Taurate and Acryloyl Dimethyltaurate/Vinyl Pyrrolidone Copolymer. Another preferred synthetic polymer suitable for thickening is an acrylate-based polymer made commercially available by Seppic and sold under the name Simulgel INS100.

[0072] Amounts of the thickener, when used, may range from 0.001 to 5%, and preferably, from 0.1 to 2%, and most preferably, from 0.2 to 0.5% by weight of the composition and including all ranges subsumed therein.

[0073] Fragrances, fixatives and abrasives may optionally be included in compositions of the present invention. Each of these substances may range from about 0.05 to about 5%, preferably between 0.1 and 3% by weight.

[0074] To enhance skin moisturization, cationic ammonium compounds may optionally be used in the compositions of this invention to enhance moisturization. Such compounds include salts of hydroxypropyltri (C.sub.1-C.sub.3alkyl) ammonium mono-substituted-saccharide, salts of hydroxypropyltri (C.sub.1- C.sub.3 alkyl) ammonium mono-substituted polyols, dihydroxypropyltri (C.sub.1- C.sub.3 alkyl) ammonium salts, dihydroxypropyldi (C.sub.1—C.sub.3 alkyl) mono(hydroxyethyl) ammonium salts, guar hydroxypropyl trimonium salts, 2,3-dihydroxypropyl tri (C.sub.1—C.sub.3 alkyl or hydroxalkyl) ammonium salts or mixtures thereof. In a most preferred embodiment and when desired, the cationic ammonium compound employed in this invention is the quaternary ammonium compound 1,2-dihydroxypropyltrimonium chloride. If used, such compounds typically make up from 0.01 to 30%, and preferably, from 0.1 to 15% by weight of the composition.

[0075] When cationic ammonium compounds are used, additional preferred additives for use with the same are moisturizing agents such as substituted ureas like hydroxymethyl urea, hydroxyethyl urea, hydroxypropyl urea; bis(hydroxymethyl) urea; bis(hydroxyethyl)urea; bis(hydroxypropyl)urea; N, N′-dihydroxymethyl urea; N, N′-di-hydroxyethyl urea; N, N′-dihydroxypropyl urea; N, N, N′-tri-hydroxyethyl urea; tetra (hydroxymethyl)urea; tetra(hydroxyethyl)urea; tetra (hydroxypropyl)urea; N-methyl-N′-hydroxyethyl urea; N-ethyl-N, N—N′-hydroxyethyl urea; N-hydroxypropyl-N′-hydroxyethyl urea and N, N′-dimethyl-N-hydroxyethyl urea or mixtures thereof. Where the term hydroxypropyl appears, the meaning is generic for either 3-hydroxy-n-propyl, 2-hydroxy-n-propyl, 3-hydroxy-i-propyl or 2-hydroxy-i-propyl radicals. Most preferred is hydroxyethyl urea. The latter is available as a 50% aqueous liquid from the National Starch & Chemical Division of ICI under the trademark Hydrovance.

[0076] Amounts of substituted urea, when used, in the composition of this invention range from 0.01 to 20%, and preferably, from 0.5 to 15%, and most preferably, from 2 to 10% based on total weight of the composition and including all ranges subsumed therein.

[0077] Conventional humectants may be employed in the present invention as skin benefit agent and in addition to the bioenergetic combinations hereof. These are generally polyhydric alcohol type materials. Typical polyhydric alcohols include glycerol (i.e., glycerine or glycerin), propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. Most preferred is glycerin, propylene glycol or a mixture thereof. The amount of humectant employed may range anywhere from 0.5 to 20%, preferably between 1 and 15% by weight of the composition.

[0078] When cationic ammonium compound and substituted urea are used, in a most especially preferred embodiment at least from 1 to 15% glycerin is used, based on total weight of the composition and including all ranges subsumed therein.

[0079] Compositions of the present invention may optionally and additionally include vitamins, along with the actives, skin benefit agents, and/or derivatives thereof according to the present invention. Illustrative vitamins are retinol (Vitamin A), Vitamin B2, Vitamin B6, Vitamin C, Vitamin E, Folic Acid and Biotin. Derivatives of the vitamins may also be employed. For instance, Vitamin C derivatives include ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate and ascorbyl glycoside. Derivatives of Vitamin E include tocopheryl acetate, tocopheryl palmitate and tocopheryl linoleate. DL-panthenol and derivatives may also be employed and Vitamin D and K are also options. Total amount of optional vitamins when present in compositions according to the present invention may range from 0.0 to 10%, preferably from 0.001 to 1%, optimally from 0.01 to 0.5% by weight of the composition.

Optional Skin Benefit Agents

[0080] The compositions of the present invention can comprise in addition to niacinamide, skin benefit agents, and/or derivatives thereof, additional optional skin benefit agents (SBAs). It is preferred that to niacinamide, skin benefit agents, and/or derivatives thereof make up at least 25% by weight, and preferably, at least 40 to 95% by weight, and most preferably,100% by weight of the skin benefit agents. Optional skin benefit agents or additives may, if desired, be provided to make up the portion of the skin benefit agent that is not niacinamide or cooperative skin benefit agent and/or a derivative thereof.

[0081] Also optionally suitable for use include materials like chelators (e.g., EDTA), opacifiers (like TiO.sub.2, particle size from 50 to 1200 nm, and preferably, 50 to 350 nm), C.sub.8-22 fatty acid substituted saccharides, lipoic acid, retinoxytrimethylsilane (available from Clariant Corp. under the SilCare IM-75 trademark), dehydroepiandrosterone (DHEA) and combinations thereof. Ceramides (including Ceramide I, Ceramide 3, Ceramide 36 and Ceramide 6) as well as pseudoceramides may also be useful. Amounts of these materials may range from 0.000001 to 10%, preferably from 0.0001 to 1% by weight of the composition of this invention.

[0082] Sunscreen actives may also be included in compositions of the present invention. Particularly preferred are such materials as ethylhexyl p-methoxycinnamate, available as Parsol MCX, Avobenzene, available as Parsol 1789 and benzophenone-3, also known as Oxybenzone. Inorganic sunscreen actives may be employed such as microfine titanium dioxide, octocrylene zinc oxide, polyethylene and various other polymers.

[0083] Amounts of the sunscreen agents when present may generally range from 0.1 to 30%, preferably from 0.5 to 20%, optimally from 0.75 to 10% by weight.

[0084] Conventional buffers/pH modifiers may be used. These include commonly employed additives like sodium hydroxide, potassium hydroxide, hydrochloric acid, citric acid and citrate/citric acid buffers. In an especially preferred embodiment, the pH of the composition of this invention is from 4 to 8, and preferably, from 4.25 to 7.75, and most preferably, from 6 to 7.5, including all ranges subsumed therein.

[0085] The composition of the present invention preferably is a leave-on skin lotion, cream, shampoo, conditioner, shower gel, antiperspirant, deodorant, depilatory, shave cream or toilet bar.

Packaging

[0086] A wide variety of packaging can be employed to store and deliver the compositions of this invention. Packaging is often dependent upon the type of personal care end-use. For instance, leave-on skin lotions and creams, shampoos, conditioners and shower gels generally employ plastic containers with an opening at a dispensing end covered by a closure. Typical closures are screw-caps, nonaerosol pumps and flip-top hinged lids. Packaging for antiperspirants, deodorants and depilatories may involve a container with a roll-on ball on a dispensing end. Alternatively, these types of personal care products may be delivered in a stick composition formulation in a container with propel repel mechanism where the stick moves on a platform towards a dispensing orifice. Metallic cans pressurized by a propellant and having a spray nozzle serve as packaging for antiperspirants, shave creams and other personal care products. Toilette bars may have packaging constituted by a cellulosic or plastic wrapper or within a cardboard box or even encompassed by a shrink wrap plastic film.

[0087] The following examples are provided to facilitate an understanding of the present invention. The examples are not intended to limit the scope of the claims.

Examples

Experimental Methods

Materials and Cell Treatment

[0088] Test compounds (B3 and SAMe) were purchased from Sigma (St. Loius, MO). Cell culture growth media (Epilife media with calcium (Cat#MEPI500CA) and Epilife media supplement HKGS 100X (Cat#S-001-5)) was purchased from Thermofisher (Waltham, Mass.). Cryopreserved human keratinocytes cells (˜1×10.sup.6 cells) were plated on 12-well glass bottom plates at a confluence of ˜15%. The cells were suspended in primary keratinocyte growth media (Epilife media with calcium) and incubated @ 37° C. for 1d (Day 0). At Day 1, cells began treatment with supplemented primary keratinocyte growth media (Epilife media with calcium supplemented with HKGS 100X; 25m1 total) without test compound (Control sample) or containing test compounds B3 (10 mM), SAMe (500 μM) or B3 (10 mM)+SAMe (500 uM). Cell treatment (25m1 media with or without test compounds as above) continued daily for 2 additional days (Days 2 and 3). On Day 4, cells were subjected to UV treatment by replacing media with PBS, exposing cells to UV light (4 J/cm.sup.2 of UVA+UVB) for 14 min and feeding cells with media with or without corresponding test compounds as defined above. UV treatments continued daily for 3 additional days (Days 5, 6 and 7). Image acquisition and analysis on all wells to assess mitochondrial fragmentation was conducted on Day 1, 3, 5 and 8.

Image Acquisition

[0089] For two-photon excited fluorescence (TPEF) imaging, cell cultures were placed in microscope-compatible micro-incubator system, which maintained 37° C. within a humidified environment throughout the imaging session. HEPES buffering agent (Sigma) was added to cell cultures before imaging, which maintained the pH of cell cultures throughout the imaging session. Images were obtained using a Leica TCS SP8 confocal microscope equipped with a tunable (680-1300 nm) titanium-sapphire laser (InSight Deep See; Spectra Physics; Mountain View, Calif.). Images (1024×1024 pixels; 386×386 μm) were acquired using water-immersion 25x objective (NA 0.95; 2.4 mm working distance), with simultaneous collection by two non-descanned photomultiplier tube (PMT) detectors using a filter cube containing filters from Chroma (Bellows Falls, VT), including a 700 nm short pass filter (ET700SP-2P) and a 495 nm dichroic mirror (495DCXR). To isolate NADH fluorescence, a 460(±20) nm emission filter (Chroma, ET460/40M-2P), corresponding to the NADH emission peak, was placed before one of the non-descanned detectors. NADH fluorescence images were acquired from this 460 nm channel using 755 nm excitation. FAD fluorescence was isolated using a 525(±25) nm emission filter (Chroma, ET525/50M-2P) for the other non-descanned detector and 860 nm excitation. The two-photon action cross section of NADH decreases by several orders of magnitude between 755 nm and 860 nm excitation, enabling an efficient isolation of FAD at longer wavelengths. The fluorescence lifetime images (512×512 pixels; 386×386 μm) corresponding to NADH were acquired under the same excitation and emission settings, using SymPho software. PMT gain was adjusted for each image to maximize contrast while preventing a saturated pixel intensity value. The PMT gain and laser power were recorded for each image and used to normalize fluorescence intensity.

Mitochondrial Fragmentation Calculation

[0090] To assess mitochondrial fragmentation, a previously-established Fourier transform technique was used to obtain power spectral density (PSD) curves from each image. (M. Levitt et al., Diagnostic cellular organization features extracted from autofluorescence images. Opt Lett 32, 3305-3307 (2007); J. Xylas, K. P. Quinn, M. Hunter, I. Georgakoudi, Improved Fourier-based characterization of intracellular fractal features. Opt Express 20, 23442-23455 (2012). Briefly, the image intensity patterns within the cell cytoplasmic areas selected by the same binary mask used for the redox analysis were cloned and randomly positioned in the image background to create a new image without distinct cell borders and only cell mitochondrial patterns spanning the entire image (K. P. Quinn et al., Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Sci Rep 3, 3432 (2013). Upon Fourier transformation a power spectral density (PSD) curve was created for each image. An inverse power law behavior of the PSD curve at high spatial frequencies (>0.1 μm-1, corresponding to the size of mitochondria) was then identified. This portion between 0.1 μm-1 and the frequency at 98% of the entire PSD region was then fitted with an equation of the form R(k)- k-13 and the exponential power, 13, which represented the mitochondrial fragmentation throughout this study was determined.

Statistical Analyses

[0091] To compare means between treatments on each day, JMP and Tukey HSD was used for the statistical analyses. The significance level of the test (a, the probability of a type I error) was set to 0.05. P-values </= to 0.05 between two measurements are considered statistically significant.

EXAMPLE 1. Mitochondrial Fragmentation in keratinocytes-UV Study

[0092] The purpose of this experiment was to compare the extent of protection to skin delivered by different actives from mitochondrial fragmentation that takes place as a consequence of aging with or without UV exposure.

[0093] The higher the Mitochondrial Fragmentation value, the less protection to the skin is delivered by the given active or combination of actives. Note, for biological systems such as mitochondria, which are microscale components of skin cells, the absolute values of mitochondrial fragmentation numbers are small, and small differences can be significant.

[0094] The effect of B3 and low levels of SAMe on mitochondrial fragmentation in keratinocytes 3 days before and 4 days after UV-exposure is shown in the Table below:

TABLE-US-00001 TABLE 1 Mitochondrial Fragmentation Test Sample (−) UV (3 days) (+) UV (4 days) Control (no treatment) 1.30 1.58 .sup.c B3 (10 mM) 1.18 1.34 .sup.d SAMe (500 uM) 1.30 1.58 .sup.c,e SAMe (500 uM) + B3 (10 mM) 1.22 1.16 .sup.a,b,d,f .sup.a Significantly better over Non UV-exposed control (P </= 0.05) .sup.b Significantly better over B3 alone (P </= 0.05) .sup.c Significantly worse over Non-UV exposed control (P </= 0.05) .sup.d Significantly better over UV-exposed control (P </= 0.05) .sup.e Significantly worse over B3 (P </= 0.05) .sup.f Significantly better over SAMe alone (P </= 0.05)

[0095] As can be seen from the data in Table 1 above, treatment of Non UV-exposed keratinocytes with high levels of B3 (10 mM), low levels of SAMe (500 uM) or a combination of low levels of SAMe (500 uM)+high levels of B3 (10 mM) does not significantly reduce mitochondrial fragmentation. UV exposure alone for four (4) days is effective at raising the control levels of mitochondrial fragmentation. While B3 alone at elevated doses (10 mM) is effective at reducing this UV-induced effect down to control levels, SAMe alone at much lower doses (500 uM) increases mitochondrial fragmentation beyond UV-exposed levels. However unexpectedly, the combination of B3 (10 mM) with small amounts (20-fold less) of SAMe (500 uM) effectively and synergistically lowers the mitochondrial fragmentation over either B3 or SAMe treatment alone and beyond Non UV-exposed control levels, hence, offering superior cooperative benefits.

EXAMPLE 2

[0096] Personal care formulations according to the present invention are illustrated in the Tables below. All numbers in Tables represent weight % in the composition.

TABLE-US-00002 TABLE 2A Oil-in-water formulations, lotions, and creams OW-1 OW-2 OW-3 OW-4 OW-5 Water To 100 To 100 To 100 To 100 To 100 Glycerine  0-40  1-40 1-5  1-10  1-40 Propylene glycol 0-5 0-5 Butylene glycol 0-5 0-5 0-5 Carbomer 0-2 0.03-1   Ammonium Acryloyl dimethyl taurate/VP 0-1 0.03-1   0.01-1   copolymer Styrene/Acrylates copolymer 0-1 0.01-1   Xanthan Gum 0-1 0.01-1   EDTA 0.01-0.01 0.01-0.01 0.01-1   0.01-1   0.01-1   Preservative 0.02-2   0.02-2   0.02-2   0.02-2   0.02-2   Titanium oxide  0-10 0.01-10   0.01-10   0.01-10   0.01-10   Colorant/Pigment 0-5 0-5 0-5 0-5 0-5 Triethanol amine/Sodium Hydroxide/ 0-3 0.01-3   0.01-3   0.01-3   0.01-3   potassium Hydroxide Stearic acid 0-5 0.01-5   0.01-5   0.01-5   0.01-5   Isopropyl Myristate  0-10 0.01-10   Capric/Caprylic Triglyceride  0-10 0.01-10   C12-C15 alkyl benzoate  0-10 0.01-10   Mineral oil  0-10 0.01-10   Glyceryl stearate 0-5 0.01-5   Steareth-2 0-5 0.01-5   0.01-5   Steareth-21 0-5 0.01-5   Peg 100 Stearate 0-5 0.01-2   0.01-5   Potassium Cetyl Phosphate 0-5 0.01-2   Tween20 0-5 0.01-5   Cetyl alcohol 0-4 0.01-4   0.01-4   Dicaprylyl carbonate 0-5 0.01-5   UVA and/or UVB Sunscreens 0-6 0.01-6   0.01-10   0.01-10   Silicones  0-15 0.01-10   0.01-15   B3 1-5 0.01-10   0.01-10   0.01-10   0.01-10   S-adenosylmethionine (SAMe) 0.01-10   0.01-2   0.01-5   0.01-5   0.01-7  

TABLE-US-00003 TABLE 2B Water-in-oil topical lotions or creams WO-1 WO-2 WO-3 WO-4 Water To 100 To 100 To 100 To 100 Glycerine  0-70  1-70  1-70 Propylene glycol 0-5 0.01-5   Butylene glycol 0-5 0.01-5   0.01-5   Disteardimonium Hectorite 0.01-1   0.01-1   EDTA 0.01-.01  0.01-1   0.01-1   0.01-1   Preservative 0.02-2   0.02-2   0.02-2   0.02-2   TiO2  0-10 0.01-10   0.01-10   0.01-10   Colorant/pigment 0-5 0-5 0-5 0-5 TEA/Sodium Hydroxide/potassium Hydroxide 0-3 0.01-3   0.01-3   0.01-3   Stearic acid 0-5 0.01-5   Isopropyl Myristate  0-10 Capric/Caprylic Triglyceride  0-10 0.01-10   C12-C15 alkyl benzoate  0-10 0.01-10   Mineral oil  0-10 Glyceryl stearate 0-5 Dimethicone copolyol 0-5 0.01-5   0.01-5   Cetyl PEG/PPG-10/1 Dimethicone 0-5 0.01-5   Steareth-2 0-2 Sucrose Distearate 0-2 0.01-2   Cetyl alcohol 0-2 0.01-2   0.01-2   UVA and/or UVB Sunscreens 0-6 0.01-6   0.01-10   0.01-10   Dimethicone  0-10 0.01-10   0.01-10   Cyclomethicone  0-40 0.01-40   0.01-10   Caprylyl methicone  0-10 0.01-10   0.01-10   Dimethicone crosspolymer  0-90 0.01-90   0.01-90   C30-C45 alkyl cetearyl dimethicone crosspolymer 0.01-90   Glycolic acid  0-10 0.01-10   KCl 0-5 0.01-5   0.01-5   0.01-5   Nicotinamide (B3) 0.001-10   0.01-10   0.01-10   0.01-10   S-adenosylmethionine (SAMe) 0.01-2   0.01-2   0.01-1   0.01-5  

TABLE-US-00004 TABLE 2C Vanishing Creams VC1 VC2 VC3 VC4 Water To 100 To 100 To 100 To 100 Glycerine 0-5 0.01-5   0.01-5   EDTA 0.01-.01  0.01-.01  0.01-.01  0.01-.01  Preservative 0.02-2   0.02-2   0.02-2   0.02-2   TiO2 0.01-10   0.01-10   0.01-10   0.01-10   Colorant/pigment 0-5 0.01-5   0.01-5   EA/Sodium Hydroxide/potassium Hydroxide 0-3 0.01-3   0.01-3   0.01-3   Stearic acid  0-30 0.01-30   0.01-30   0.01-30   Isopropyl Myristate 0-5 0.01-10   0.01-10   C12-C15 alkyl benzoate 0-5 0.01-10   Brij 35 0-5 0.01-5   Tween40 0-5 0.01-5   Cetyl alcohol 0-2 0.01-2   0.01-2   Ethyl hexyl methoxycinnamate 0-6 0.01-6   0.01-6   Butyl Methoxydibenzoylmethane 0-3 0.01-3   0.01-3   0.01-3   Ensulizole 0-4 0.01-4   Octisalate 0-5 0.01-5   Octocrylene  0-10 0.01-10   0.01-10   Dimethicone 0-5 0.01-5   Cyclomethicone 0-5 0.01-5   Dimethicone crosspolymer 0-4 0.01-4   Hydroxystearic acid 0-5 0.01-5   0.01-5   0.01-5   Fragrance 0-2 0-2 0-2 0-2 Nicotinamide (B3) 0.01-3   0.01-3   0.01-3   0.01-3   S-adenosylmethionine (SAMe) 0.01-3   0.01-3   0.01-1   0.01-5