WO2023107448A1 - Compositions for diminishing the signs of aging - Google Patents

Abstract

Disclosed are compositions containing cannabinoid, cannabidiol, cannabidiol isomer, or cannabidiol analog and combinations thereof for treating oxidative stress and diminishing the signs of aging. In one aspect, a composition comprising about 10 % (w/w) to about 40 % (w/w) isolated cannabidiol or isolated cannabidiol, about 0.01 % (w/w) to about 5 % (w/w) bioenhancer, and about 0.01 % (w/w) to about 5 % (w/w) phospholipid is disclosed. Further disclosed are methods of using the disclosed compositions.

Description

COMPOSITIONS FOR DIMINISHING THE SIGNS OF AGING

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of U.S. Provisional Application Serial No. 63/286,437, filed December 6, 2021, entitled “Compositions for Diminishing the Signs of Aging,” the contents of which are incorporated herein it it’s entirety for all purposes.

BACKGROUND

[0002] While the field of aging is heavily studied, there remains a need for improved methods and compositions for addressing an increasing aging population. The disclosed compositions and methods seek to address one or more of the aforementioned needs in the art.

SUMMARY

[0003] Disclosed are compositions containing cannabinoid, cannabidiol, cannabidiol isomer, or cannabidiol analog and combinations thereof for treating oxidative stress and diminishing the signs of aging. Further disclosed are methods of using same.

DETAILED DESCRIPTION

[0004] Various aspects now will be described more fully hereinafter. Such aspects may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey its scope to those skilled in the art.

[0005] Where a range of values is provided, it is intended that each intervening value between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. For example, if a range of 1 ml to 8 ml is stated, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, and 7 ml are also intended to be explicitly disclosed, as well as the range of values greater than or equal to 1 ml and the range of values less than or equal to 8 ml.

[0006] The methods may comprise, consist of, or consist essentially of the elements of the compositions and/or methods as described herein, as well as any additional or optional element described herein or otherwise useful in the disclosed methods and/or compositions

[0007] All percentages, parts and ratios are based upon the total weight of the topical compositions and all measurements made are at about 25 °C, unless otherwise specified. [0008] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a “polymer” includes a single polymer as well as two or more of the same or different polymers; reference to an “excipient” includes a single excipient as well as two or more of the same or different excipients, and the like.

[0009] 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. For example, in a list of numerical values such as “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. Furthermore, 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.

[0010] The terms “administer,” “administering” or “administration” as used herein refer 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.

[0011] The term “carrier” as used herein encompasses carriers, excipients, and diluents, meaning a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material involved in carrying or transporting a pharmaceutical, cosmetic or other agent across a tissue layer such as the stratum comeum or stratum spinosum. In one aspect, the combination of CBD, quercetin, and phospholipid comprise the vehicle.

[0012] The transitional term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. By contrast, 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 invention. In aspects or claims where the term comprising is used as the transition phrase, such aspects can also be envisioned with replacement of the term “comprising” with the terms “consisting of’ or “consisting essentially of.”

[0013] The term “disorder” is used in this disclosure to mean, and is used interchangeably with the terms disease, condition, symptom, or illness, unless otherwise indicated. [0014] The terms “effective amount” and “therapeutically effective amount” are used interchangeably in this disclosure and refer to an amount of a compound that, when administered to a subject, is capable of reducing a symptom of a disorder in a subject or enhance the texture, appearance, color, sensation, or hydration of the intended tissue treatment area. The actual amount which comprises the “effective amount” or “therapeutically effective amount” will vary depending on a number of conditions including, but not limited to, the severity of the disorder, the size and health of the patient, and the route of administration. A skilled medical practitioner can readily determine the appropriate amount using methods known in the medical arts.

[0015] The phrase “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. In some aspects, 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.

[0016] The term “salts” as used herein embraces pharmaceutically acceptable salts commonly used to form alkali metal salts of free acids and to form addition salts of free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. The term “salts” also includes solvates of addition salts, such as hydrates, as well as polymorphs of addition salts. Suitable pharmaceutically acceptable acid addition salts can be prepared from an inorganic acid or from an organic acid. Non-limiting examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric, and phosphoric acid. Appropriate organic acids can be selected from aliphatic, cycloaliphatic, aromatic, aryl aliphatic, and heterocyclyl containing carboxylic acids and sulfonic acids, for example formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, stearic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, cyclohexylaminosulfonic, algenic, 3-hydroxybutyric, galactaric and galacturonic acid.

[0017] The term “patient” and “subject” are interchangeable and may be taken to mean any living organism which may be treated with compounds of the present invention. As such, the terms “patient” and “subject” may include, but is not limited to, any non-human mammal, primate or human. In some aspects, the “patient” or “subject” is a mammal, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, or humans. In some aspects, the patient or subject is an adult, child or infant. In some aspects, the patient or subject is a human.

[0018] The term “treating” is used herein, for instance, in reference 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.

[0019] The term “herb” is used herein, for instance, in reference to plants that in certain aspects and delivered by appropriate methods have a therapeutic or medicinal purpose, such as, but not limited to river mint, eucalyptus, wattle, cocoa, plants of the family cannabaceae, plants containing cannabinoids, and plants containing cannabinoid precursors and analogs.

[0020] By hereby reserving the right to proviso out or exclude any individual members of any such group, including any sub-ranges or combinations of sub-ranges within the group, that can be claimed according to a range or in any similar manner, less than the full measure of this disclosure can be claimed for any reason. Further, by hereby reserving the right to proviso out or exclude any individual substituents, analogs, compounds, ligands, structures, or groups thereof, or any members of a claimed group, less than the full measure of this disclosure can be claimed for any reason. Throughout this disclosure, various patents, patent applications and publications are referenced. The disclosures of these patents, patent applications and publications in their entireties are incorporated into this disclosure by reference in order to more fully describe the state of the art as known to those skilled therein as of the date of this disclosure. This disclosure will govern in the instance that there is any inconsistency between the patents, patent applications and publications cited and this disclosure.

[0021] For convenience, certain terms employed in the specification, examples and claims are collected here. Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0022] Numerous diseases and health conditions are linked to oxidative stress, including, for example, neurodegenerative disease, inflammation, metabolic disorders, aging, cancer, and atherosclerosis. Oxidative stress refers to an imbalance between the reactive oxygen species present within a cell and the cell’s ability to neutralize the reactive oxygen species. Reactive oxygen species are characterized by a superoxide radical that can damage cellular nucleic acids, proteins, and lipids. Damage to nucleic acids such as deoxyribose nucleic acid (DNA) can include damage to bases and double stranded breaks. Damage to proteins can cause disruption to cell signaling and function, and reactive oxygen species-mediated damage to lipids can lead to disturbances in the cellular membrane.

[0023] The cell has defenses to prevent and mitigate damage by reactive oxygen species. These defenses include various enzymes and other molecules that neutralize reactive oxygen species and repair damage caused by reactive oxygen species. Examples of reactive oxygen species-neutralizing enzymes include superoxide dismutase, glutathione transferases and glutathione peroxidases. Repair enzymes destroy free-radical-damaged proteins, DNA, and oxidized fatty acids. Non-enzyme antioxidant molecules can include tocopherol, reduced glutathione, vitamin C, carotenoids, and urate. Oxidative stress can result when such defenses are inadequate relative to an amount of reactive oxygen species in a cell.

[0024] Disclosed herein are methods and pharmaceutical compositions for treating aging. Such pharmaceutical compositions may include an isolated cannabinoid, a bioenhancer, and one or more phospholipids that, without intending to be limited by theory, when administered, may reduce the presence of reactive oxygen species in various cells and tissues of the patient and activate immune cells and tissues. The combined effect may diminish the impact of oxidative stress on the patient, reducing inflammation, while stimulating cellular and tissue repair mechanisms, thereby reducing and in some cases, reversing the signs of aging. In some aspects, sublingual administration of the compositions may enhance these effects by increasing absorption of the composition and enhancing bioavailability.

[0025] In one aspect, the disclosed compositions may include an isolated cannabinoid. Cannabinoids include any of a broad class of compounds that are known to interact with cannabinoid receptors, and encompass endocannabinoids (produced naturally in the body by animals), the phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (manufactured artificially). Example cannabinoids include, but are not limited to, tetrahydropyran analogs, such as, A⁹-tetrahydrocannabinol, A⁸-tetrahydrocannabinol, 6,6,9- trimythel-3-pentyl-6H-dibenzo[b,d]pyran-l-ol, 3-(l,l-dimethylheptyl)-6,6a7,8,10,10a- hexahydro-l-lhydroxy-6,6-dimythel-9H-dibezo[b,d]pyran-9-ol, (-)-(3S,4S)-7-hydroxy-delta-6- tetrahydrocannabinol- 1 , 1 -dimethylheptyl, (+)-(3S ,4S)-7-hydroxy- A-6-tetrahydrocannabinol, and A⁸-tetrahydrocannabinol-l l-oic acid, piperidine analogs, such as, (-)-(6S,6aR,9R,10aR)- 5,6,6a,7,8,9,10,10a-octahydro-6-methyl-l-3-[(R)-l-methyl-4-phenylbutoxy]-l,9 phenanthridinediol 1-acetate), aminoalkylindole analogs, such as, (R)-(+)-[2,3-dihydro-5-methyl- 3-(4-morpholinylm-ethyl)-pyrrolo[l,2,3,-de]-l,4-benzoxazin-6-yl]-l-naphthelenyl-methanone, open pyran-ring analogs, such as, 2-[3-methyl-6-(l-methylethenyl-2-cyclohexen-l-yl]-5-pentyl- 1,3-benzendi-ol, and 4-(l,l-dimethylheptyl)-2,3'-dihydroxy-6'-a-(3-hydroxypropyl)-l ',- 2',3',4',5',6'-hexahydrobiphenyl, lipophilic alkylamides, such as, dodeca-2E,4E,8Z,10E/Z- tetraenoic-acid-isobutylamide, cannabinoid mimetics, salts, solvates, metabolites, and metabolic precursors of these compounds and combinations thereof. The compositions of various aspects can include any number of isolated cannabinoids in various concentrations; however, in certain aspects, the composition may include a single, isolated cannabinoid, such as, cannabidiol (2-(6- isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol, CBD) or cannabigerol (2- [(2E)-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene-l,3-diol, CBG). Cannabidiol and cannabigerol each have 7 double bonds and 30 stereoisomers. Aspects include compositions containing each stereoisomer individually and compositions containing a combination of these stereoisomers.

[0026] In certain aspects, the isolated cannabinoid may be cannabidiolic acid (“CBDA”). Without intending to be bound by theory, CBDA may exhibit improved hydrophilicity over other isomers of cannabidiol, which may allow for improved solubility and delivery of CBDA to the skin. The CBDA may be modified, partially digested, or otherwise acted upon by enzymes in the skin to produce for example cannabidiol (CBD) or cannabigerol (CBG), which may be the active form cannabidiol in the composition. Thus, in some aspects, CBDA may act as a prodrug. Other cannabidiol analogs or isomers may produce a similar effect and are encompassed by prodrug aspects of the invention.

[0027] In some aspects, the isolated cannabinoid in the composition may be cannabidiol analogs. The term “cannabidiol analogs” refers to synthetically produced compounds that are structurally similar, but not structurally identical, to cannabidiol. Various cannabidiol analogs are known in the art and aspects encompass such cannabidiol analogs. For example, PCT Publication WO2017/132526 and U.S. Patent No. 6,630,507, which are each hereby incorporated by reference in their entirety, describes various analogs of cannabidiol. In some aspects, the analogs of cannabidiol may be of general Formula I:

where R¹ is hydrogen, methyl, linear or branched C2-C10 alkyl, linear or branched C2-C10 alkenyl, linear or branched C2-C10 substituted alkyl, linear or branched C2-C10 substituted alkenyl, R² and R³ are each, individually, hydrogen, methyl, linear or branched C2-C10 alkyl, linear or branched C2-C10 substituted alkyl, linear or branched C2-C10 alkenyl, linear or branched C2-C10 substituted alkenyl, linear or branched C2-C10 acyl, linear or branched C2-C10 substituted acyl, an amine or amino acid, amino acid ester, R⁴ is hydrogen, substituted or unsubstituted alkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino, and n may an integer of 2 to 10 and the like and salts and solvates thereof. In some aspects, R² and R³ may, independently, be a linear or branched, substituted or unsubstituted C2-C10 acyl having a carboxylic acid terminus thereby producing a dicarboxylic acid, and salts thereof. Like cannabidiol, cannabidiol analogs can have various isomers. Aspects include all isomers of such cannabidiol analogs. In some aspects, cannabidiol analogs, such as those described above may be combined with cannabidiol, to produce a mixture of cannabidiol and cannabidiol analogs. Thus, as used herein the term “cannabidiol” encompasses cannabidiol, cannabidiol analogs, and the various isomers of cannabidiol and cannabidiol analogs.

[0028] The compositions of various aspects can include up to about 50% (w/w) isolated cannabidiol, isolated cannabidiol analogs, isolated isomers of cannabidiol, or isolated cannabidiol analogs (collectively, “cannabidiol”). In some aspects, the compositions may include from about 50% (w/w) to about 0.5% (w/w), about 30% (w/w) to about 1% (w/w), about 20% (w/w) to about 1% (w/w), about 20% (w/w) to about 5% (w/w) cannabidiol, or any range of or individual concentration encompassed by these example ranges. In particular aspects, the composition may include about 15% (w/w) to about 10% (w/w) cannabidiol.

[0029] The cannabinoids of aspects are “isolated” meaning that the cannabinoid component of the composition contains a single cannabinoid species or a combination of cannabinoids in which a single cannabinoid is the majority cannabinoid species and any additional cannabinoid species are present in de minimis amounts and do not contribute to the biological effect of the compositions as a whole. “Isolated” cannabinoids do not include extracts. In some aspects, the cannabinoid may contain trace amounts of other non-cannabinoid compounds such as tetrahydrocannabinol (THC). Generally, compositions that include THC will include less than 0.3% THC.

[0030] In certain aspects, the cannabinoid may be cannabidiol. The cannabidiol in the compositions of aspects may be 100% cannabidiol, or oils, solvents, and emulsions containing 100% cannabidiol. In some aspects, the compositions of the invention may include cannabidiol derived from hempseed oil. Hempseed oil is generally manufactured from varieties of Cannabis sativa that do not contain significant amounts of tetrahydrocannabinol (THC). The manufacturing process typically includes cleaning the seed to 99.99% before pressing the oil. Hempseed oil generally also contains omega-6 and omega-3 fatty acids. For example, about 30-35% of the weight of hempseed oil are essential fatty acids (EFAs),

linoleic acid, omega-6 (LA, 55%), a- linolenic acid, omega-3 (ALA, 22%), y-linolenic acid, omega-6 (GLA, 1-4%), and stearidonic acid, omega-3 (SDA, 0-2%). Thus, the compositions of some aspects may contain fatty acids such as omega-6 and omega-3 fatty acids. However, in various aspects, the cannabidiol containing component of the compositions will contain less than about 1% (w/v) other cannabinoid species, and in some aspects, the cannabidiol containing component may contain less than about 0.5% (w/v) cannabinoid, less than about 0.25% (w/v) cannabinoid, or less than about 0.1% (w/v) cannabidiol. In one aspect the cannabinoid is CBD from hemp isolate.

[0031] In various aspects, the compositions may include a bioenhancer. Bioenhancers are compounds that improve the bioavailability and/or efficacy of compounds or drugs with which they are combined. The bioenhancers of various aspects are not limited and can include any compound capable of producing these effects. In certain aspects, the bioenhancer may include, but are not limited to, ketoconazole, troleandomycin, guestden, flavones such as quercetin and naringenin, erythromycin, ethinyl estradiol, prednisolone, and the like and combinations thereof. In particular aspects, the bioenhancer may be a flavone. Flavones are a class of flavonoids based on the backbone of 2-phenylchromen-4-one an include various compounds found in foods and spices including, for example, apigenin (4',5,7-trihydroxyflavone), luteolin (3', 4', 5,7- tetrahydroxy flavone), tangeritin (4',5,6,7,8-pentamethoxyflavone), chrysin (5,7- dihydroxy flavone), and 6-hydroxyflavone. In some aspects, the bioenhancer may be quercetin (3,3',4',5,7-pentahydroxyflavone). In one aspect, the bioenhancer may be provided in a dose, said dose being from about 1 to about 1000 ug, or from about 10 to about 900 ug, or from about 20 to about 800 ug, or from about 30 to about 700 ug, or from about 40 to about 600 ug, or from about 50 to about 500 ug, or about 100 to about 400 ug, or about 300 or 330 ug.

[0032] The amount of bioenhancer is not limited and includes any therapeutically effective amount. For example, in some aspects, the amount of bioenhancer may be about 0.01 % (w/w) to about 5 % (w/w), relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w), relative to the total amount of the formulation, or any range or individual concentration encompassed by these example ranges.

[0033] The compositions of various aspects may further include a phospholipid. In some aspects, the phospholipid may be polyoxyethylene, sorbitan monolaurate, sorbitan monooleate, polyethylene glycol-hydrogenated castor oil (e.g. cremophor and cremophor RH), egg phospholipid, a soy phospholipid and lecithin of various grades and purities, and combinations thereof. In certain aspects, the phospholipid may be lecithin, and in some aspects, the phospholipid may be sunflower lecithin.

[0034] The amount of phospholipid is not limited and includes any therapeutically effective amount. For example, in some aspects, the amount of phospholipid may be about 0.01 % (w/w) to about 5 % (w/w), relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w), relative to the total amount of the formulation, or any range or individual concentration encompassed by these example ranges.

[0035] The compositions of various aspects may reduce the presence of reactive oxygen species in the cells and tissues of a patient to whom the composition is administered. “Reactive oxygen species” (“ROS”) is a collective term that includes oxygen radicals and non-radical derivatives of oxygen. ROS are byproducts of the normal metabolism of oxygen. ROS are intrinsic to cellular functioning and are present at low and stationary levels in normal cells. However, ROS can cause irreversible damage to DNA as they oxidize and modify some cellular components and prevent them from performing their original functions. During times of environmental stress (e.g. UV or heat exposure), ROS levels can increase dramatically, which may result in significant damage to cell structures, and can be generated by exogenous sources such as ionizing radiation. This is known as oxidative stress, and oxidative stress can generate irreversible effects in the development of tissues.

[0036] ROS can be formed when a covalent bond is broken if one electron from each of the pair shared remains with each atom. The oxygen radicals or free radicals include superoxide anion (02*'), hydroxyl (HO*), peroxy (ROO*), alkoxy (RO*), and hydroperoxy (HOO*) radicals. Non-radical derivatives include hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen (¹O2). The compositions of aspects may reduce the presence of oxygen radicals and ROS reducing oxidative stress and diminishing the irreversible effects associated with these compounds. In some aspects, oxidative stress may be associated with reactive nitrogen species, such as, nitric oxide (NO*) and superoxide (02*'). In some aspects, this reduction in oxidative stress reduces the signs of aging such as fine lines and wrinkles in the skin, crow's feet, dullness of skin, uneven skin tone, dry skin, blotchiness and age spots, rough skin texture, visible pores, and the like and combinations thereof.

[0037] In some aspects, the compositions may activate immune cells and/or repair tissue damage associated with oxidative stress. In such aspects, the composition may activate CB2 receptors expressed in immune tissues. CB2 receptors can modulate immune cell functions and reduce inflammation. By activating these receptors, the compositions may stimulate cellular and tissue repair mechanisms connected to immune cells, reduce inflammation allowing repair of inflamed cells and tissues, or both stimulate immune cells and reduce inflammation. In certain aspects, the cells and tissue may be associated with skin diminishing the signs of aging associated with oxidative stress.

[0038] In some aspects, the compositions may further include a brassinosteroid or combinations of brassinosteroids. Brassinosteroids are a group of compounds related to brassinolide, a C28 steroid with a lactone B-ring structure. Brassinosteroids include, but are not limited to, 24(S) ethylbrassinone analogs, (22R,23R,24S)-2alpha, 3 alpha, 5 alpha, 22,23- pentahydroxy-stigmastan-6-one, (22R,23R,24S)-3beta-bromo-5alpha,22,23- trihydroxystigmastan-6-one, (22S,23S,24S)-2alpha,3alpha,22,23-tetrahydroxy- 5alpha,stigmastan-6-one, (22R,23R,24S)-3beta-acetoxy-22,23-dihydroxy-5alpha-cholestan-6- one, (22S ,23 S ,24S )-3beta-bromo-22,23 -dihydroxy-5alpha-cholestan-6-one, (22S ,23 S ,24S )- 3beta-bromo-5alpha,22,23-trihydroxy-stigmastan-6-one, and (22S,23S)-3P-bromo-5a, 22,23- trihydroxystigmastan-6-one.

[0039] The amount of brassinosteroid in the topical formulation is not limited, so long as it is a therapeutically effective amount. In some aspects, the brassinosteroid may have a concentration of about 0.01 % (w/w) to about 5 % (w/w) , relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w) , relative to the total amount of the composition, or any range or individual value encompassed by these example ranges.

[0040] In some aspects, the compositions may further include an anti-inflammatory compound such as hyaluronic acid, curcumin, glutathione, methotrexate, tofacitinib, 6- mercaptopurine, azathioprine sulfasalazine, mesalazine, olsalazine chloroquine/hydroxychloroquine, penicillamine, aurothiomalate (intramuscular and oral), azathioprine, colchicine, corticosteroids (oral, inhaled, and local injection), a beta-2 adrenoreceptor agonist (salbutamol, terbutaline, salmeterol), a xanthine (theophylline, aminophylline), cromoglycate, nedocromil, ketotifen, ipratropium and oxitropium, cyclosporin, FK506, rapamycin, mycophenolate mofetil, leflunomide, an NSAID (e.g. ibuprofen), a corticosteroid (e. g. prednisolone), a phosphodiesterase inhibitor, an adenosine agonist, an antithrombotic agent, a complement inhibitor, an adrenergic agent, an agent that interferes with signalling by proinflammatory cytokines such as TNF or IL-1 (e.g., a NIK, IKK, p38 or MAP kinase inhibitor), an IL-1 converting enzyme inhibitor, a T-cell signalling inhibitor (e.g. a kinase inhibitor), a metalloproteinase inhibitor, sulfasalazine, a 6-mercaptopurine, an angiotensin converting enzyme inhibitor, a soluble cytokine receptor (e.g. soluble p55 or p75 TNF receptors and the derivatives p75TNFRigG (etanercept) and p55TNFRigG (Lenercept), siL-lRI, siL-lRII, siL-6R), an antiinflammatory cytokine (e.g. IL-4, IL-1 0, IL-11, IL-13 and TGF), celecoxib, folic acid, hydroxychloroquine sulfate, rofecoxib, etanercept, infliximab, adalimumab, certolizumab, tocilizumab, abatacept, naproxen, valdecoxib, sulfasalazine, methylprednisolone, meloxicam, methylprednisolone acetate, gold sodium thiomalate, aspirin, triamcinolone acetonide, propoxyphene napsylate/apap, folate, nabumetone, diclofenac, piroxicam, etodolac, diclofenac sodium, oxaprozin, oxycodone HC1, hydrocodone bitartrate/apap, diclofenac sodium/misoprostol, fentanyl, anakinra, tramadol HC1, salsalate, sulindac, cyanocobalamin/fa/pyridoxine, acetaminophen, alendronate sodium, prednisolone, cortisone, betamethasone, morphine sulfate, lidocaine hydrochloride, indomethacin, glucosamine sulf/chondroitin, amitriptyline HC1, sulfadiazine, oxycodone HCV acetaminophen, olopatadine HC1 misoprostol, naproxen sodium, omeprazole, cyclophosphamide, rituximab, IL-1 TRAP, MRA, CTLA4-IG, IL- 18 BP, anti-IL-12, Anti-ILIS, BIRB-796, SCIO-469, VX-702, AMG-548, VX-740, Roflumilast, IC-485, CDC-801, S1PI agonists (such as FTY720), a PKC family inhibitor (e.g. Ruboxistaurin or AEB-071) or Mesopram, budesonide; epidermal growth factor; a corticosteroid; cyclosporin, sulfasalazine; an aminosalicylate; 6-mercaptopurine; azathioprine; metronidazole; a lipoxygenase inhibitor; mesalamine; olsalazine; balsalazide; an antioxidant; a thromboxane inhibitor; an IL-1 receptor antagonist; an anti-IL-1 monoclonal antibody; an anti-IL-6 monoclonal antibody; a growth factor; an elastase inhibitor; a pyridinyl-imidazole compound; an antibody to or antagonist of other human cytokines or growth factors (e.g. TNF, LT, IL-1, IL-2, IL-6, IL-7, IL-8, IL-12, IL-15, IL-16, IL- 23, EMAP-II, GM-CSF, FGF, and PDGF); a cell surface molecule (e.g. CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, or CD90 or their ligands); methotrexate; cyclosporine; FK506; rapamycin; mycophenolate mofetil; leflunomide; an NSAID (e.g. ibuprofen); a corticosteroid (e.g. prednisolone); a phosphodiesterase inhibitor; an adenosine agonist; an antithrombotic agent; a complement inhibitor; an adrenergic agent; an agent that interferes with signalling by proinflammatory cytokines such as TNF 5 or IL-1 (e.g. a NIK, IKK, or MAP kinase inhibitor); an IL-1 converting enzyme inhibitor; a TNF converting enzyme inhibitor; a T-cell signalling inhibitor such as kinase inhibitors; a metalloproteinase inhibitor; sulfasalazine; azathioprine; a 6-mercaptopurine; an angiotensin converting enzyme inhibitor; a soluble cytokine receptor (e.g. soluble p55 or p75 TNF receptors, siL-lRI, siL-lRII, siL-6R), an antiinflammatory cytokine (e.g. IL-4, IL-1 0, IL-11, IL-13 or TGF), therapeutic agents that target an intrinsic checkpoint blockade, such as, for example, the gene encoding Cytokine-inducible SFE-containing protein (CISH), antibody BGB-A317, Nivolumab, or Pembrolizumab, atezolizumab, avelumab, durvalumab, ipilimumab, and the like and combinations thereof. In one aspect, the antiinflammatory compound is provided in a dose, said dose being from about 2 to about 20 mg, or from about 3 to about 15 mg, or from about 4 to about 10 mg, or from about 5 to about 9 mg, or about 8 mg.

[0041] The amount of anti-inflammatory agent is not limited and includes any therapeutically effective amount. For example, in some aspects, the amount of anti-inflammatory agent may be about 0.01 % (w/w) to about 5 % (w/w) , relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w) , relative to the total amount of the formulation, or any range or individual concentration encompassed by these example ranges.

[0042] In some aspects, the compositions may further include an antibiotic. The type of antibiotic is not limited, and can be, for example, subtilosin, ampicillin, bacampicillin, carbenicillin indanyl, mezlocillin, piperacillin, ticarcillin, amoxicillin-clavulanic acid, ampicillinsulbactam, benzylpenicillin, cioxacillin, dicloxacillin, methicillin, oxacillin, penicillin G, penicillin V, piperacillin tazobactam, ticarcillin clavulanic acid, nafcillin, procaine penicillin, cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cephradine, cefaclor, cefamandol, cefonicid, cefotetan, cefoxitin, cefprozil, cefmetazole, cefuroxime, loracarbef cefdinir, ceftibuten, cefoperazone, cefixime, cefotaxime, cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone, cefepime, azithromycin, clarithromycin, clindamycin, dirithromycin, erythromycin, lincomycin, troleandomycin, cinoxacin, ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, oxolinic acid, gemifloxacin, perfloxacin, imipenem-cilastatin, meropenem, and aztreonam.

[0043] The amount of the antibiotic in the compositions is not limited, and includes any therapeutically effective amount. For example, the antibiotic may have a concentration of about 0.01 % (w/w) to about 5 % (w/w) , relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w) , relative to the total amount of the composition, or any range or individual concentration encompassed by these example ranges.

[0044] In some aspects, the compositions may further contain a mineral, mineral salt, or combinations thereof. Such minerals are not limited, and can include selenium, such as selenomethionine, sulfur, zinc, such as zinc citrate, iron, chlorine, cobalt, copper, manganese, molybdenum, and iodine. In one aspect, the mineral, such as zinc citrate, may be provided in a dose, said dose being from about 0.1 to about 10 mg, or from about 0.5 to about 5 mg, or from about 0.7 to about 3 mg, or from about 0.8 to about 2 mg, or from about 0.9 mg to about 1 mg.

[0045] The amount of the mineral or mineral salts in the topical formulation is not limited, and includes any therapeutically effective amount. For example, the mineral or mineral salt may have a concentration of about 0.01 % (w/w) to about 5 % (w/w), relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w), relative to the total amount of the composition, or any range or individual concentration encompassed by these example ranges.

[0046] In some aspects, the compositions may further include a vitamin or a combination of vitamins. Vitamins are organic molecules that are essential nutrients that organisms need to sustain proper biological function and metabolism. The vitamins encompassed by the invention are not limited, and can be, for example, vitamin A, vitamin Bi, vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin Be, vitamin B7, vitamin Bs, vitamin B9, vitamin Bio, vitamin Bn, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K. In one aspect the vitamin C is ascorbyl palmitate, ascorbyl phosphatase, or combinations thereof. In one aspect, the vitamin or combination of vitamins is provided in a dose, said dose being from about 1 to about 20 mg, or from about 2 to about 15 mg, or from about 3 to about 10 mg, or from about 4 to about 8 mg, or about 4 mg.

[0047] The amount of the vitamin in the topical formulation is not limited and can be any therapeutically effective amount. For example, the vitamin may have a concentration of about 0.01 % (w/w) to about 5 % (w/w), relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w), relative to the total amount of the composition, or any range or individual concentration encompassed by these example ranges.

[0048] In some aspects, the compositions may further contain amino acids, peptides, or combinations thereof. Amino acids are organic compounds that combine through peptide bond formation to form peptides and proteins. Amino acids can chemically combine through peptide bond formation to form dipeptides, tripeptides, tetrapeptides, oligopeptides, polypeptides, peptides, and proteins. Amino acids are the building blocks for living organisms. The human body uses amino acids to break down food, grow, repair body tissue, and perform other necessary biological processes. The amino acid is not limited, and can be at least one member selected from the group consisting of L-arginine, D-arginine, L-histidine, D-histidine, L-lysine, D-lysine, L- aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, D-serine, L-serine, D-threonine, L-threonine, D-asparagine, L-asparagine, L-glutamine, D-glutamine, L-cystine, D-cysteine, L- selenocysteine, D-selenocysteine, L-glycine, D-glycine, L-proline, D-proline, L-alanine, D- alanine, L-valine, D-valine, L-isoleucine, D-isoleucine, L-leucine, D-leucine, L-methionine, D- methionine, L-phenylalanine, D-phenylalanine, L-tyrosine, D-tyrosine, L-tryptophan, D- tryptophan. In one aspect, the amino acid is provided in a dose, said dose being from about 2 to about 20 mg, or from about 3 to about 15 mg, or from about 4 to about 10 mg, or from about 5 to about 9 mg, or about 8 mg.

[0049] The amount of amino acids, peptides, or combinations thereof in the composition is not limited, and includes any therapeutically effective amount. For example, the amino acid, peptides, or combinations thereof may have a concentration of about 0.01 % (w/w) to about 5 % (w/w), relative to the total amount of the composition, about 0.1 % (w/w) to about 1 % (w/w), relative to the total amount of the composition, or any range or individual concentration encompassed by these example ranges.

[0050] In some aspects, the compositions may include one or more antioxidants such as, for example, ascorbic acid, ascorbic acid derivatives, glucosamine ascorbate, arginine ascorbate, lysine ascorbate, glutathione ascorbate, nicotinamide ascorbate, niacin ascorbate, allantoin ascorbate, creatine ascorbate, creatinine ascorbate, chondroitin ascorbate, chitosan ascorbate, DNA ascorbate, carnosine ascorbate, vitamin E, vitamin E derivatives, tocotrienol, rutin, hesperidin (citrus sinensis), diosmin (citrus sinensis), mangiferin (mangifera indica), mangostin (garcinia mangostana), cyanidin (vaccinium myrtillus), astaxanthin (haematococcus algae), lutein (tagetes patula), lycopene (lycopersicum esculentum), resveratrol (polygonum cuspidatum), tetrahydrocurcumin (curcuma longa), rosmarinic acid (rosmarinus officinalis), hypericin (hypericum perforatum), ellagic acid (punica granatum), chlorogenic acid (vaccinium vulgaris), oleuropein (olea europaea), a-lipoic acid, niacinamide lipoate, glutathione, andrographolide (andrographis paniculata), carnosine, niacinamide, potentilla erecta extract, polyphenols, grape seed extract, pycnogenol (pine bark extract), pyridoxine, magnolol, honokiol, paeonol, resacetophenone, quinacetophenone, arbutin, kojic acid, and the like and combinations thereof.

[0051] In some aspects, the compositions may include one or more essential oil. Essential oils refer to synthetic or natural oils derived from any source, but particularly from the flowers, seeds, fruits, roots, bark, sap, herbs, trees, and other plants. Such essential oils can generally be extracted by methods known in the art. Essential oils are generally aromatic and are typically named for the plant from which the oil is extracted. For example, rose oil or peppermint oil are derived from rose or peppermint plants, respectively. Examples of essential oils that can be used in the compositions of the invention include, but are not limited to, sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, sage oil, coriander oil, thyme oil, pimento berries oil, rose oil, almond oil, anise oil, balsam oil, bergamot oil, rosewood oil, camphor oil, cardamom oil, cedar oil, cedar leaf oil, chamomile oil, cinnamon oil, sage oil, clary sage oil, clove oil, clove leaf oil, cypress oil, eucalyptus oil, fennel oil, fistree oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, jojoba oil, juniper oil, lavender oil, lemon oil, lemongrass oil, lime oil, mandarin oil, marjoram oil, myrrh oil, menthol, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine seed oil, pine needle oil, rosehip oil, rose otto oil, rosemary oil, sandalwood oil, spearmint oil, spikenard oil, vetiver oil, walnut oil, whitepine oil, wintergreen oil, ylang ylang, and the like and combinations thereof. The amount of essential oil in such aspects may be about 0.01 % (w/w) to about 10 % (w/w), about 0.1 % (w/w) to about 5 % (w/w) based on the total weight of the composition, or any individual concentration or range encompassed by these ranges.

[0052] In some aspects, the compositions may include one or more exfoliating agents. The exfoliating agents can be a chemical exfoliant or exfoliating particles of, for example, minerals, vegetables, organic particles, water- swellable pulverulent polymers (powder or beads), polyethylene particles (beads or powders), jojoba spheres, ground shells of fruit stones, pumice stone, glass beads, aluminium oxide, and the like and combinations or mixtures thereof. Exfoliating agents are present in variable amounts depending on the intended result. For example, the concentration of exfoliating agents may be about 2 % (w/w) to about 80 % (w/w) of the composition.

[0053] In some aspects, the compositions may include a carrier. Pharmaceutically acceptable carriers can include oils, waxes, petrolatum, or emulsifiers. In some aspects, the pharmaceutically acceptable carrier may be magnesium aluminum silicate, polyoxyethylene lauryl ether, polyoxyethylene monosteatate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, sorbitan monopalmitate, propylene glycol monostearate, sodium borate plus fatty acid, sodium lauryl sulfate, triethanolamine plus fatty acid, isopropyl myristate, cresol, propylparaben, methylparaben, sorbic acid, carbomer, cetyl alcohol, glyceryl monostearate, methylcerlulose, spermaceti, stearyl alcohol, petrolatum, and the like and combinations thereof. In one aspect, the composition may contain olive oil, for example extra virgin olive oil as a carrier. In one aspect, the oil carrier may comprise from about 0.1% to about 80% w/w of the total composition, from about 0.5% to about 70% w/w of the total composition, from about 1% to about 60% w/w of the total composition, from about 2% to about 50% w/w of the total composition, from about 3% to about 40% w/w of the total composition, from about 4% to about 30% w/w of the total composition, from about 5% to about 20% w/w of the total composition, of from about 10% to about 15% w/w of the total composition. Without intending to be limited by theory, it is believed that olive oil allows more efficient and/or longer absorption time for glutathione, where present, to take effect. [0054] Creams refer to semi-solid emulsions of oil and water in approximately equal proportions. They are divided into two types: oil-in-water (O/W) creams, composed of small droplets of oil dispersed in a continuous phase; and water-in-oil (W/O) creams, composed of small droplets of water dispersed in a continuous oily phase. Creams can provide a barrier to protect the skin. This may be a physical barrier or a chemical barrier as with UV-absorbing compounds. To aid in the retention of moisture (especially water-in-oil creams), creams are usually used for a variety of purposes including cleansing, emollient effects, and as a vehicle for drug substances such as local anesthetics, anti-inflammatories (NSAIDs or corticosteroids), hormones, antibiotics, antifungals or counterirritants.

[0055] Liniments or balms are topical formulations that are of a similar viscosity to lotions and less viscous than an ointment or cream. Liniments are generally applied with friction by rubbing the liniment into the skin. Liniments typically are formulated from alcohol, acetone, or similar quickly evaporating solvents and may contain counterirritant aromatic chemical compounds such as methyl salicylate, benzoin resin, or capsaicin.

[0056] Ointments are compositions in which oil and water are provided in a ratio of from 7:1 to 2:1, from 5:1 to 3:1, or 4:1. Ointments are generally formulated using oils, waxes, water, alcohols, petroleum products, water, and other agents to prepare formulations with various viscosities and solvent properties. Commonly used formulations include oleaginous base (White Ointment), absorption base, W/O emulsion base (Cold Cream type base), O/W emulsion base (Hydrophilic Ointment), water soluble base, in addition to others. These preparations are used to dissolve or suspend substances or products with medicinal or cosmetic value.

[0057] Lotions are low- to medium-viscosity topical preparation. Most lotions are oil-in- water emulsions containing an emulsifier such as cetyl alcohol to prevent separation of these two phases. Lotions can include fragrances, glycerol, petroleum jelly, dyes, preservatives, proteins and stabilizing agents.

[0058] In some aspects, the formulations can be in the form of a soap, which are formulations that comprise a salt of a fatty acid. Soaps are mainly used as surfactants for washing, bathing, and cleaning, but they are also used in textile spinning and are important components of lubricants. Soaps for cleansing can be obtained by treating vegetable or animal oils and fats with a strongly alkaline solution. Fats and oils are composed of triglycerides; three molecules of fatty acids are attached to a single molecule of glycerol. The alkaline solution, which is often called lye (although the term “lye soap” refers almost exclusively to soaps made with sodium hydroxide), is believed to promote a chemical reaction known as saponification. In saponification, fats are first hydrolyzed into free fatty acids, which then combine with the alkali to form crude soap. Glycerol (glycerine) is usually liberated and is either left in or washed out and recovered as a useful byproduct, depending on the process employed.

[0059] In some aspects, the composition can be in the form of a shampoo, which is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair. A goal may be to remove the unwanted build-up without stripping out so much sebum as to make hair unmanageable.

[0060] In some aspects, the composition can be in the form of a tincture. Tinctures are herbal extracts that provide a method for oral administration of an herbal component or components to a subject in need of treatment. Tinctures are prepared by mixing an herb or herbs or components and combinations thereof with a suitable solvent wherein a component or components of an herb or herbs or combinations thereof are extracted into a solvent in which the component or components of the herb are reasonably soluble. Suitable tincture solvents in the present invention include pharmacologically acceptable solvents such as organic solvents, water based solvents, alcohols, and other orally administrable solvents such as, but not limited to, water, purified water, preserved water, vegetable glycerin, propylene carbonate, 3-methoxy-3-methyl-l- butanol (MMB), polyethylene glycol, glycerol, rice bran oil, and combinations thereof.

[0061] In some aspects, the composition can be in the form of a tonic. Tonics are extracts that provide a method for oral administration of an herbal component or components to a subject in need of treatment. Tonics are prepared by mixing an herb or herbs or components and combinations thereof with a suitable solvent wherein a component or components of an herb or herbs or combinations thereof are extracted into a solvent by aid of heating, often heat necessary such that the solvent reaches its boiling temperature, in which the component or components of the herb are reasonably soluble. Suitable tonic solvents in the present invention include pharmacologically acceptable solvents such as organic solvents, water based solvents, alcohols, and other orally administrable solvents such as, but not limited to, water, purified water, preserved water, vegetable glycerin, propylene carbonate, 3-methoxy-3-methyl-l-butanol (MMB), polyethylene glycol, glycerol, rice bran oil, and combinations thereof.

[0062] In certain aspects, the pharmaceutical composition may be a tincture containing about 10 % (w/w) to about 40 % (w/w) isolated cannabidiol or isolated cannabigerol, about 0.01 % (w/w) to about 5 % (w/w) bioenhancer, and about 0.01 % (w/w) to about 5 % (w/w) phospholipid. In some aspects, the pharmaceutical composition may be a tincture containing about 10 % (w/w) to about 40 % (w/w) isolated cannabidiol or isolated cannabigerol, about 0.01 % (w/w) to about 5 % (w/w) quercetin, and about 0.01 % (w/w) to about 5 % (w/w) lecithin or sunflower lecithin. Such compositions may be used for reducing oxidative stress and diminishing the signs or symptoms of aging. In one aspect, the isolated cannabidiol is provided in a dose, said dose being from about 1 to about 20 mg, or from about 2 to about 15 mg, or from about 3 to about 10 mg, or from about 4 to about 8 mg, or about 4 mg.

[0063] Various aspects include methods for reducing oxidative stress and diminishing the signs or symptoms of aging by administering any of the compositions described above including cannabinoids. Administering can be carried out topically, and in certain aspects, administering can be carried out by sublingual administration. Sublingual administration may include delivering about 1 drop to about 20 drops of a tincture as described above under the tongue of a patient in need of treatment. In some aspects, sublingual administration may include delivering about 50 pl to about 1.0 ml of a tincture as described above under the tongue of a patient in need of treatment. In other aspects, sublingual administration may include delivering about 50 pg to about 0.75 ml, about 50 pl to about 0.5 ml, about 50 pl to about 0.25 ml, about 50 pl to about 200 pl, about 50 pl to about 150 pl, or any range or individual value encompassed by these example ranges, of a tincture as described above under the tongue of a patient in need of treatment.

[0064] In various aspects, the methods described above may be repeated 1, 2, 3, or 4 times per day, resulting in a daily administration of about 50 pl to about 4.0 ml, or any range or individual value encompassed by this example range, per day. Single or multiple administration per day can be carried out each day or 2, 3, 4, or 5 times per week for 1 month or more, 2 months or more, 3 months or more, 6 months or more, 1 year or more, or throughout the lifetime of the patient. In certain aspects, the method may include administering the composition to the patient during periods of high oxidative stress, for example, when the patient is expecting to be outdoors for extended periods of time or when the patient is expected to be exposed to sources of ionizing radiation.

[0065] While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications may be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims

CLAIMS What is claimed:

1. A composition comprising about 10 % (w/w) to about 40 % (w/w) isolated cannabidiol or isolated cannabigerol, about 0.01 % (w/w) to about 5 % (w/w) bioenhancer, and about 0.01 % (w/w) to about 5 % (w/w) phospholipid.

2. The composition of claim 1, wherein the cannabinoid is selected from the group consisting of cannabidiol (2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol) or cannabigerol (2-[(2E)-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene- 1,3-diol), and stereoisomers and combinations thereof.

3. A composition comprising about 10 % (w/w) to about 40 % (w/w) isolated cannabidiol or isolated cannabigerol, about 0.01 % (w/w) to about 5 % (w/w) quercetin, and about 0.01 % (w/w) to about 5 % (w/w) lecithin or sunflower lecithin.

4. The composition of claim 1, wherein the cannabinoid is selected from the group consisting of cannabidiol (2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3- benzenediol) or cannabigerol (2-[(2E)-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene- 1,3-diol), and stereoisomers and combinations thereof.

5. The composition of any preceding claim, further comprising a bioenhancer, said bioenhancer being quercetin.

6. The composition of any preceding claim, further comprising an anti-inflammatory compound, said anti-inflammatory compound being glutathione.

7. The composition of any preceding claim, further comprising a mineral, said mineral being selected from zinc, zinc citrate, selenomethionine, and combinations thereof.

8. The composition of any preceding claim, further comprising a vitamin C, said vitamin C being selected from ascorbyl palmitate, ascorbyl phosphatase, and combinations thereof.

9. The composition of any preceding claim, further comprising an amino acid, said amino acid being L-lysine.

10. The composition of any preceding claim, said composition comprising a carrier, said carrier being an oil, preferably olive oil, more preferably extra virgin olive oil. The composition of any preceding claim, said composition being sterile. A method for treating oxidative stress comprising administering to a patient in need of treatment a composition comprising any of the compositions of claims 1 to 11. A method for diminishing the signs of aging comprising administering to a patient in need of treatment a composition comprising any of the compositions of claims 1 to 11. The method of claim 12 or 13, wherein said composition is administered sublingually. The method of any of claims 12 through 14 wherein said administration is twice daily. The method of any of claims 12 through 15 wherein said administration is carried out sufficient to enhance one or more of liver function, kidney function, metabolic function, immune function, and combinations thereof.