Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/37—Esters of carboxylic acids
  • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/55—Phosphorus compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
  • A61K8/602—Glycosides, e.g. rutin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
  • A61K2800/52—Stabilizers
  • A61K2800/522—Antioxidants; Radical scavengers

Definitions

• Embodiments disclosed herein are directed to antioxidant compositions comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyfphenyl)prop-2- enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7- dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of treating skin or hair damaged by reactive oxygen species in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4- dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L- rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of preventing skin or hair damage in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4- dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2- (3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D- glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of treating aged skin in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2- enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7- dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Figure 1 Representation of antioxidants tested and pathways in which individual components are known to function.
• Figure 2 Light absorbance of 2% of antioxidant compositions Ex1-Ex8 in pentylene glycol from 250nm to 500nm under the Ocean Optics UV is Spectrometer.
• Figure 3 Overall ranking of experimental antioxidant compositions Ex1- Ex8 based on comprehensive analysis of assays designed to tests multiple targets.
• Figure 4 Interaction plots for phototoxicity assay.
• Figure 5 Interaction plots for light absorbance assay at 250-500 nm.
• FIG. 6 Interaction plots for reactive oxygen species (ROS) fluorescence assay.
• ROS reactive oxygen species
• Figure 7 Interaction plots for IC50 assay.
• Figure 8 Optimization plot in order to minimize IC50, maximize fibroblastmetabolic activity, minimize intracellular ROS, and maximize absorbance at 250-500 nm.
• Figure 9 Spectral data for MCAP, rosmarinic acid and rutin each individually and blend of three components.
• ROS reactive oxygen species
• a topical agent capable of scavenging ROS generated by external factors may aid in decreasing ROS propagation and, therefore, minimize skin damage.
• Antioxidants have demonstrated the ability to mitigate skin damage caused by ROS when topically applied. Many mechanisms exist for antioxidants, and antioxidants vary in function and efficacy.
• creation of an antioxidant composition targeting multiple pathways may more effectively function to slow the development of skin damage caused by ROS-mediated pathways and to contribute to overall environmental protection compared with targeting a single pathway alone.
• Kyoto molecule formally known as Nahlsgen with chemical name methyl carboxymethylphenylaminocarboxy propylphosphonate (“MCAP”), is an inhibitor of gamma-glutamyltranspeptidase (GGT) and functions to control cell redox status.
• GTT gamma-glutamyltranspeptidase
• Rosmarinic acid a phenolic acid, structurally functions to trap free radicals and inhibit lipid oxidation.
• Rutin is a flavonoid that functions to chelate metal ions and scavenges free radicals.
• this novel blend of antioxidants targets multiple pathways, including inhibition of gamma-glutamyltranspeptidase (GGT) to control cell redox status, structural trapping of free radicals, inhibition of lipid oxidation, chelation of metal ions, and scavenging of free radicals.
• GTT gamma-glutamyltranspeptidase
• Embodiments described herein are directed to an antioxidant composition of MCAP, rosmarinic acid, and rutin that act synergistically to effectively treat and/or prevent the skin damage caused by exposure to external aggressors, such as UV radiation.
• the word“about” when immediately preceding a numerical value means a range of plus or minus 10% of that value, e.g,“about 50” means 45 to 55,“about 25,000” means 22,500 to 27,500, etc, unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation.
• “about 49, about 50, about 55,“about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g, more than 49.5 to less than 52.5.
• the phrases“less than about” a value or“greater than about” a value should be understood in view of the definition of the term“about” provided herein.
• administer refers to either directly administering a compound (also referred to as an agent of interest) or pharmaceutically acceptable salt of the compound (agent of interest) or a composition to a subject.
• transitional term “comprising,” which is synonymous with “including,”“containing,” or“characterized by,” is inclusive or open-ended and does not exclude additional, un-recited elements or method steps.
• the transitional phrase “consisting of” excludes any element, step, or ingredient not specified in the claim.
• the transitional phrase“consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed subject matter.
• composition means an agent utilized, and/or intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, altering the appearance of the skin or any combination thereof.
• phrases“pharmaceutically acceptable” or“cosmetically acceptable” is employed herein to refer to those agents of interest/compounds, salts, compositions, dosage forms, etc, which are within the scope of sound medical judgment suitable for use in contact with the tissues of human beings and/or other mammals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
• pharmaceutically acceptable means approved by a regulatory agency of the federal or a state government, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals (e.g, animals), and more particularly, in humans.
• the terms“patient” and“subject” are interchangeable and may be taken to mean any living organism which may be treated with compounds or compositions provided for herein.
• the terms“patient” and“subject” may comprise, but is not limited to, any non-human mammal, primate or human.
• the patient or subject is an adult, child, or infant.
• the patient or subject is a human.
• composition refers to a combination or a mixture of two or more different ingredients, components, or substances; e.g., a combination of antioxidants.
• inhibitor or“enzyme inhibitor” as used herein refers to a molecule that binds to an enzyme and decreases its activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors
• GTT gamma-glutamyltranspeptidase
• ROS reactive oxygen species
• examples of ROS comprise peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
• topically and“topical” as used herein refer to application of the compositions to the surface of the skin, mucosal cells, keratins and tissues. Examples of keratins are nails and hair.
• treating refers to methods of treating a skin disorder or a systemic condition, and generally includes the administration of a compound or composition which reduces the frequency of, or delays the onset of, symptoms of a medical condition or enhance the texture, appearance, color, sensation, or hydration of the intended tissue treatment area of the tissue surface in a subject relative to a subject not receiving the compound or composition. This can include reversing, reducing, or arresting the symptoms, clinical signs, and underlying pathology of a condition in a manner to improve or stabilize a subject’s condition.
• Embodiments disclosed herein are directed to antioxidant compositions comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2- enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7- dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2- enoyl]oxy ⁇ propanoic acid also known
• the antioxidant composition demonstrates a synergistic effect compared with the MCAP, the rosmarinic acid, or the rutin alone, or a combination of two of such compounds.
• the amount of MCAP in the antioxidant composition is present in an amount of about 1.0 wt. % to about 5.0 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of less than about 1.0 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 1.0 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.003 wt. % to about 1.0 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.03 wt.
• the amount of MCAP in the antioxidant composition is present in an amount of about 0.000003 wt. % to about 0.0003 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.00003 wt. % to about 0.003 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 0.03 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.003 wt. % to about 0.3 wt. %.
• the amount of MCAP in the antioxidant composition is present in an amount of about 0.001 wt. % to about 0.002 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000003 wt. % to about 0.003 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000003 wt. % to about 0.0003 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000003 wt. % to about 0.00003 wt. %.
• the amount of MCAP in the antioxidant composition is present in an amount of about 0.000001 wt. % to about 1.0 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000001 wt. % to about 0.1 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000001 wt. % to about 0.01 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000001 wt. % to about 0.001 wt. %. In some embodiments, the amount of MCAP in the antioxidant composition is present in an amount of about 0.000001 wt. % to about 0.0001 wt. %.
• the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 1.0 wt. % to about 5.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of less than about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.003 wt. % to about 1.0 wt. %.
• the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.03 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 0.03 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.003 wt. % to about 0.03 wt. %. In some embodiments, the amount of rosmarininc acid in the antioxidant composition is present in an amount of about 0.001 wt. % to about 0.002 wt. %.
• the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 0.003 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.01 wt. % to about 1.0 wt. %.
• the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.1 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.1 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.01 wt. %. In some embodiments, the amount of rosmarinic acid in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.001 wt. %.
• the amount of rutin in the antioxidant composition is present in an amount of about 1.0 wt. % to about 5.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of less than about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.003 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.03 wt.
• the amount of rutin in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 0.03 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.003 wt. % to about 0.03 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.001 wt. % to about 0.002 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.0003 wt. % to about 0.003 wt. %.
• the amount of rutin in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.01 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.1 wt. % to about 1.0 wt. %.
• the amount of rutin in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.1 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.01 wt. %. In some embodiments, the amount of rutin in the antioxidant composition is present in an amount of about 0.0001 wt. % to about 0.001 wt. %.
• the ratio of the MCAP: the rutin in the antioxidant composition is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid in the antioxidant composition is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the rosmarinic acid: the rutin in the antioxidant composition is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid: the rutin in the antioxidant composition is in a range of about 1:100:100 to about 1:1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid: the rutin in the antioxidant composition is 1:1:1.
• the antioxidant composition is a pharmaceutically acceptable excipient.
• the pharmaceutically acceptable excipient is a topical formulation.
• the topical formulation further comprises a solvent.
• the solvent is selected from the group consisting of pentylene glycol, butylene glycol, water, glycols, propylene glycol, isopropylene glycol, Coco-caprylate/caprate, 1,2-hexanediol, ethanol, and combinations thereof.
• the antioxidant composition is formulated into a topical formulation. In some embodiments, the antioxidant composition is present in the topical formulation at about 0.000001 wt. % to about 5.0 wt. %. In some embodiments, the antioxidant composition is present in a topical formulation at about 0.1 wt. % to about 5.0 wt. %. In some embodiments, the antioxidant composition is present in a topical formulation at about 0.01% to about 1.0%.
• the amount of MCAP present in the topical formulation is in an amount of about 0.000001 wt. % to about 5.0 wt. %. In some embodiments, the amount of MCAP present in the topical formulation is in an amount of about 0.001 wt. % to about 1.0 wt. %. In some embodiments, the amount of MCAP present in the topical formulation is in an amount of about 0.01 wt. % to about 0.1 wt. %. In some embodiments, the amount of MCAP present in the topical formulation is in an amount of about 0.0001 wt. % to about 0.01 wt.
• the amount of MCAP present in the topical formulation is in an amount of less than about 0.01 wt. %. In some embodiments, the amount of MCAP present in the topical formulation is in an amount of less than about 0.1 wt. %. In some embodiments, the amount of MCAP present in the topical formulation is in an amount of less than about 1.0 wt. %.
• the amount of rosmarinic acid present in the topical formulation is in an amount of about 0.0001 wt. % to about 5.0 wt. %. In some embodiments, the amount of rosmarinic acid present in the topical formulation is in an amount of about 0.001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rosmarinic acid present in the topical formulation is in an amount of about 0.01 wt. % to about 0.1 wt. %.In some embodiments, the amount of rosmarinic acid present in the topical formulation is in an amount of less thanabout 0.01 wt. %.
• the amount of rosmarinic acid present in the topical formulation is in an amount of less than about 0.1 wt. %. %. In some embodiments, the amount of rosmarinic acid present in the topical formulation is in an amount of less than about 1.0 wt. %.
• the amount of rutin present in the topical formulation is in an amount of about 0.0001 wt. % to about 5.0 wt. %. In some embodiments, the amount of rutin present in the topical formulation is in an amount of about 0.001 wt. % to about 1.0 wt. %. In some embodiments, the amount of rutin present in the topical formulation is in an amount of about 0.01 wt. % to about 0.1 wt. %.In some embodiments, the amount of rutin present in the topical formulation is in an amount of less than about 0.01 wt. %.
• the amount of rutin present in the topical formulation is in an amount of less than about 0.1 wt. %. In some embodiments, the amount of rutin present in the topical formulation is in an amount of less than about 1.0 wt. %.
• the ratio of the MCAP: the rutin in the topical formulation is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid in the topical formulation is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the rosmarinic acid: the rutin in the topical formulation is in a range of about 1:100 to about 1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid: the rutin in the topical formulation is in a range of about 1:100:100 to about 1:1:1. In some embodiments, the ratio of the MCAP: the rosmarinic acid: the rutin in the topical formulation is 1:1:1.
• the synergistic effect is an increase in absorbance of light at 250-400 nm. In some embodiments, the synergistic effect is a hyperchromic shift, a hypsochromic shift, or a bathochromic shift. In some embodiments, the total amount of the increased absorbance is significantly more than the absorbance of any of the MCAP, the rosmarinic acid, the rutin alone. In some embodiments, the increase is statistically significant.
• the topical formulation further comprises a pharmaceutical additive, a cosmetic additive, water, or combinations thereof.
• the pharmaceutical additive is selected from the group consisting of diluents, fillers, disintegrants, binders, lubricants, surfactants, hydrophobic vehicles, water soluble vehicles, emulsifiers, buffers, humectants, moisturizers, solubilizers, preservatives, colorants, plastizers, carriers, excipients, and combinations thereof.
• the cosmetic additive is selected from the group consisting of vitamins, cosmetic peptides, oil control agents, sensation modifying agents, skin lightening agents, hydrating formulations, a sunblock agent, a compound that absorbs or reflects UV photons, other skin care agent and combinations thereof.
• the topical formulation is formulated in a form selected from the group consisting of a solution, fluid, emulsion, suspension, solid, semi- solid, jelly, paste, gel, hydrogel, ointment, lotion, cream, foam, mousse, liquid, spray, suspension, dispersion, powder, aerosol, or transdermal patches formulated as a liquid, cream, ointment, gel, or aerosol.
• the antioxidant composition is part of an anti-aging regimen. In some embodiments, the antioxidant composition is part of regimen for after sun care. In some embodiments, the antioxidant composition is part of a photoprotective regimen. In some embodiments, the photoprotective regimen is a sunblock regimen or a sunscreen. In some embodiments, the antioxidant composition is part of regimen for skin lightening. In some embodiments, the antioxidant composition is part of regimen for skin brightening. In some embodiments, the antioxidant composition is part of regimen for acne treatment. In some embodiments, the antioxidant composition is part of regimen for inflammation treatment. In some embodiments, the antioxidant composition is part of a color cosmetic regimen. In some embodiments, the antioxidant composition is part of a hair treatment regimen. In some embodiments, the antioxidant composition is part of a scalp treatment regimen.
• compositions described herein may be prepared by combining the components of the formulation, as described herein, at a temperature and for a time sufficient to provide a pharmaceutically acceptable composition.
• MCAP, rosmarinic acid, and rutin are mixed with constant heating.
• MCAP, rosmarinic acid, and rutin are mixed with are blended and pre- mixed with the solvent and then added to the water phase with agitation and heated.
• the mixture of MCAP, rosmarinic acid, and rutin are heated to about 30oC to about 75oC, about 30oC to about 60oC, about 30oC to about 50oC, about 40o to about 75oC, about 50oC to about 75oC, about 60oC to about 75oC, or to about 40oC.
• Embodiments are directed to methods of treating skin damaged by reactive oxygen species in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4- dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L- rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of treating hair damaged by reactive oxygen species in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4- dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L- rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of preventing skin damage in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4- dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2- (3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D- glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of preventing hair damage in a subject in need thereof comprising topically administering to the hair of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4- dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2- (3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D- glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of treating aged skin in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4-dihydroxyphenyl)prop-2- enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2-(3,4-dihydroxyphenyl)-5,7- dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D-glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of improving the appearance of the skin in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4- dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2- (3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D- glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• Embodiments are directed to methods of improving the appearance of the hair in a subject in need thereof comprising topically administering to the skin of the subject an antioxidant composition comprising methyl carboxymethylphenylaminocarboxy propylphosphonate, also known as MCAP, (2R)-3-(3,4-dihydroxyphenyl)-2- ⁇ [(2E)-3-(3,4- dihydroxyphenyl)prop-2-enoyl]oxy ⁇ propanoic acid, also known as rosmarinic acid, and 2- (3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[a-L-rhamnopyranosyl-(1®6)-b-D- glucopyranosyloxy]-4H-chromen-4-one, also known as rutin.
• MCAP methyl carboxymethylphenylaminocarboxy propylphosphonate
• the antioxidant composition demonstrates a synergistic effect compared with the MCAP, the rosmarinic acid, or the rutin alone.
• the antioxidant composition prevents the generation of reactive oxygen species in the skin or hair. In embodiments described herein, the antioxidant composition mitigates the generation of reactive oxygen species in the skin or hair.
• the reactive oxygen species is generated by UV radiation, pollution, heating, or combinations thereof.
• the skin damage is damage to lipids, proteins, DNA, or combinations thereof.
• the hair damage is damage to lipids, proteins, DNA, or combinations thereof.
• the treatment of the aged skin results in improvement in a characteristic of the skin.
• the characteristic of the skin is selected from the group consisting of firmness, elasticity, fine lines, wrinkles, skin texture, skin tone, appearance, and any combination thereof.
• improving the appearance of the skin results in smoother skin, firmer skin, softer skin, brighter complexion, improved texture of the skin, even-looking skin, improvement of discoloration, disappearance of blemishes, decreased redness, or younger-looking skin.
• improving the appearance of the skin results in an anti-inflammatory effect.
• improving the appearance of the skin results in an increase in elasticity of the skin, a decrease in the fine lines of the skin, a decrease in the wrinkles of the skin, a more consistent skin tone, and any combination thereof.
• the treatment of the hair results in improvement in a characteristic of the hair.
• the characteristic of the hair is selected from the group consisting of shine, texture, fullness, smoothness, density, and combinations thereof.
• improving the appearance of the hair results in smoother hair, softer hair, brighter hair, improved texture of the hair, shiner hair, fuller hair, or more vibrant hair.
• the subject is an infant, a child, an adolescent, or an adult.
• the antioxidant composition is formulated as a topical formulation for anti-aging, after sun care, skin lightening, skin brightening, acne treatment, inflammation treatment, hair treatment, or scalp treatment.
• the antioxidant composition is formulated as a sunblock. In some embodiments, the antioxidant composition is formulated as an anti-aging regimen. In some embodiments, the antioxidant composition is formulated as an after sun care product. In some embodiments, the antioxidant composition is formulated as a photoprotective regimen. In some embodiments, the photoprotective regimen is a sunblock regimen or a sunscreen. In some embodiments, the antioxidant composition is formulated as a skin lightening product. In some embodiments, the antioxidant composition is formulated as a skin brightening product. In some embodiments, the antioxidant composition is formulated as an acne treatment. In some embodiments, the antioxidant composition is formulated as an inflammation treatment. In some embodiments, the antioxidant composition is formulated as a color cosmetic regimen. In some embodiments, the antioxidant composition is formulated as a hair treatment regimen. In some embodiments, the antioxidant composition is formulated as a scalp treatment regimen.
• Example 1 Compositions of Ex1-Ex8.
• compositions for Ex1-Ex8 have been used as DOE test articles in order to determine possible synergistic effects.
• MCAP, rosmarinic acid, and rutin have been tested for their activity, using Test Method A (DPPH), Test Method C (DCFH), and Test Method B (PHTX). Table 2 provides results of these experiments.
• compositions of Ex1-Ex8 have been tested for inhibitory concentrations yielding 50% inhibition of free radical 2,2-diphenyl-1- picrylhydrazyl) as determined by the Test Method A and presented in Table 3. Additional data is also presented in Table 4. Table 3. IC50s of free radical 2,2-diphenyl-1- picrylhydrazyl for the composition of Ex1-Ex8.
• Ex4 demonstrates a synergy between MCAP and Rosmarinic Acid, with a lower IC50 of 1.9 compared to MCAP alone, which is inactive (Ex. 3), and rosmarinic acid alone with an IC50 of 8.9 (Ex.6).
• Rutin has the largest effect as an individual component in this assay as shown in Ex.5.
• compositions of Ex1-Ex8 have been tested for the effects on cell viability pre- and post-UVA irradiation.
• the cell viability was measured by determining the cells metabolic activity with a MTT assay according to Test Method B, the results are presented in Table 5.
• An MTT assay is a colorimetric assay for assessing cell metabolic activity.
• the result of the antioxidant composition Ex1 indicate there is a synergy between rutin and rosmarinic acid in the UV-irradiation assay. Individually, rutin and rosmarinic acid have lower cell metabolism than solvent control, while Ex1 with rutin and rosmarinic acid results in 129% metabolic activity compared to solvent control. MCAP alone has the largest effect of an individual antioxidant in this assay as shown in Ex3. The tested materials were non phototoxic when tested up to 1 mg/ml, which is 10x higher than the normally tested highest concentration of 100 ⁇ g/ml.
• compositions of Ex1-Ex8 have been tested for reactive oxygen species quantification in UVA-irradiated human dermal fibroblasts.
• the quantification result is expressed as a percentage of the water control and determined by the Test Method C and presented in Table 6.
• ROS quantification data shows an unexpected finding that MCAP as shown in Ex3 is a pro-oxidant in this assay.
• MCAP pro-oxidant activity can be negated in the presence of rutin and rosmarinic acid as shown in Ex7. Therefore, the antioxidant composition unexpectedly mitigates the potentially negative side-effects of MCAP.
• Rosmarinic Acid has the largest effect of an individual antioxidant in this assay.
• Example 4 Laboratory testing methods:
• Example formulas were serially diluted and incubated with 100 ⁇ L of 2,2- diphenyl-1-picrylhydrazyl (DPPH) in triplicate. Reduction of absorbance at 520 nm was standardized to water control as an indication of DPPH-scavenging. Estimated IC50 values were extrapolated for the tread line equation of the graph (% inhibition) vs. ([test material]). Ascorbic acid was used as a positive control to validate the assay.
• DPPH 2,2- diphenyl-1-picrylhydrazyl
• DCF-originated fluorescence was taken before and after irradiation as, in the presence of free radicals, DCFH is oxidized to highly fluorescent DCF, which can be detected in living cells at ex/em 488/530nm.
• Total insoluble proteins were quantified to determine effect of test materials on cell number and to standardize ROS signal to cell number using the following equation:
• the antioxidant compositions were diluted to 2% in pentylene glycol. Absorbance was measured using a disposable 1.5mL cuvette with the Ocean Optic UVis Spectrometer (slit width 10L) to determine range of absorbance within UVB (290-320 nm), UVA (320-400 nm), blue light (400-490 nm), and near-vis (340-400 nm) ranges. The antioxidant compositions were blanked with pentylene glycol before measurement.
• antioxidant compositions could be incorporated in the binder phase of press-powders, as in the following table:
• Remaining ingredients of press powder may include: Mica, Kaolin, Synthetic Fluorphlogopite, Titanium Dioxide, Zinc Oxide, Silica, Barium sulfate, Nylon-12, Talc, Zinc stearate, Dimeticone, Tocopheryl acetate, Stearic acid, Boron Nitride, Dimethicone, Lauroyl Lysine, Methyl Methacrylate Crosspolymer, Stearic Acid, Plant Extracts, Preservative (e.g. Phenoxyethanol); Also may contain: Iron Oxides (Ci 77489, Ci 77491, Ci 77492, Ci 77499), Ultramarines (Ci 77007), Chromium Oxide Greens (Ci 77288). [0115] Example 6: Pickering emulsion formulation
• antioxidant compositions could be incorporated in Pickering emulsion, as in the following table:
• Phase B ingredient slowly to water phase with gentle agitation until it is fully incorporated and system is uniform.

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