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US 20170042791A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0042791 A1 Ghalili et al. (43) Pub. Date: Feb. 16, 2017

(54) TOPICAL COMPOSITIONS COMPRISING A6IR 8/73 (2006.01) HYDROXY ACIDS AND A6IR 8/92 (2006.01) FOR SKIN CARE A6IR 9/00 (2006.01) A6II 45/06 (2006.01) (71) Applicant: Kannannovations LLC, New York, A636/85 (2006.01) NY (US) A6II 3/19 (2006.01) A6II 3/94 (2006.01) (72) Inventors: Babek Ghalili, New York, NY (US); A63L/92 (2006.01) Kevin McGovern, Palm Beach, FL A63L/366 (2006.01) (US) A61O 19/00 (2006.01) (52) U.S. Cl. (73) Assignee: Kannannovations LLC, New York, CPC ...... A61K 8/97 (2013.01); A61O 19/00 NY (US) (2013.01); A61O 19/08 (2013.01); A61K 8/365 (2013.01); A61K 8/498 (2013.01); A61K 8/345 (21) Appl. No.: 15/233,251 (2013.01); A61K 8/731 (2013.01); A61K 8/922 (22) Filed: Aug. 10, 2016 (2013.01); A61K 9/0014 (2013.01); A61 K 45/06 (2013.01); A61K 36/185 (2013.01); Related U.S. Application Data A61K 31/19 (2013.01); A61K 31/194 (2013.01); A61K 31/192 (2013.01); A61 K (60) Provisional application No. 62/203,698, filed on Aug. 3 1/366 (2013.01) 11, 2015. Publication Classification (57) ABSTRACT (51) Int. Cl. The present invention relates to compositions and methods A 6LX 8/97 (2006.01) for the prevention and treatment of skin disorders and for the A61O 19/08 (2006.01) rejuvenation of the skin. In particular, the application A6 IK 8/365 (2006.01) describes topical compositions and methods of treatments A6I SA9 (2006.01) comprising the combined use of one or more cannabinoids A6 IK 8/34 (2006.01) and one or more hydroxy acids in a suitable carrier. Patent Application Publication Feb. 16, 2017. Sheet 1 of 5 US 2017/0042791 A1

FIGURE 1

Tetrahydrocannabinol (THC)

Tetrahydrocannabinol Carboxylic Acid (THCA)

Cannabidiol (CBD)

Cannabidiol Carboxylic Acid (CBDA) Patent Application Publication Feb. 16, 2017. Sheet 2 of 5 US 2017/0042791 A1

FIGURE 1 (continued) (CBG)

HO (CBC)

Cannabinol (CBN)

Tetrahydrocannabivarin (THCV) Patent Application Publication Feb. 16, 2017 Sheet 3 of 5 US 2017/0042791 A1

FIGURE 2

Baseline Day 28 Patent Application Publication Feb. 16, 2017. Sheet 4 of 5 US 2017/0042791 A1

FIGURE 3

Patent Application Publication Feb. 16, 2017 Sheet 5 of 5 US 2017/0042791 A1

FIGURE 4

Baseline Day 28

US 2017/0042791 A1 Feb. 16, 2017

TOPCAL COMPOSITIONS COMPRISING 0006. Accordingly, there is a need in the art for improved HYDROXY ACDS AND CANNABINOIDS treatment options for improving skin condition, delaying FOR SKN CARE and reducing the effects of skin aging and treating or preventing skin disorders. CROSS-REFERENCE TO RELATED APPLICATIONS SUMMARY OF THE INVENTION 0007. It is, therefore, an object of the invention to provide 0001. This application claims the benefit of priority from Solutions to the aforementioned problems, among other U.S. Provisional Application No. 62/203,698, filed Aug. 11, objects. 2015, the content of which is incorporated by reference in its 0008. One embodiment of the invention is a topical entirety. composition for treating skin that comprises a therapeuti cally effective amount of at least one and a FIELD OF THE INVENTION therapeutically effective amount of a hydroxy acid in a topically acceptable carrier. The at least one cannabinoid and 0002 The present invention relates to the use of hydroxy at least one hydroxy acid may optionally be the only active acids and cannabinoids for skin care. ingredients of the composition. In one aspect of the inven tion, the cannabinoids are present in the topical composition BACKGROUND OF THE INVENTION in a concentration between 0.1 and 30% by weight of the composition. Preferably, the cannabinoids are one or more 0003. The skin is the largest organ of the body, with a of a natural phytocannabinoid, an organic cannabinoid, an Surface area of 18 Square feet. In the epidermis, the kera endocannabinoid, a cannabinoid analog, a cannabinoid tinocytes produce keratin, a protein that gives skin its derivative, a synthetic cannabinoid and a cannabinoid recep strength and flexibility and waterproofs the skin surface. tor agonist. The hydroxy acid is an alpha hydroxy acid, a Collagen and elastic fibers in the dermis give strength to the beta hydroxy acid or a combination thereof. In one aspect of skin. The skin is continuously exposed to changes in the the invention, the hydroxy acid is an alpha hydroxy acid, and external environment, including oxidative insults, heat, cold, the alpha hydroxy acid is , citric acid, glycolic UV radiation, injury, and mechanical stresses. The stratum acid, mandelic acid, benzylic acid, malic acid, tartaric acid, corneum, composed of terminally differentiated keratino gluconolactone, galactonolactone, glucuronolactone, galac cytes, constitutes the natural barrier that prevents loss of turonolactone, gulonolactone, ribonolactone, Saccharic acid water and penetration of infectious agents, such as bacteria lactone, pantoylactone, glucoheptonolactone, mannonolac and viruses, and foreign particles. Keratin intermediate tone, or galactoheptonolactone. In a different aspect of the filaments provide the cells with mechanical resilience and invention, the hydroxy acid is a beta hydroxy acid, and the protects them against physical stress. Disruption of the beta hydroxy acid is or lipohydroxy acid. keratin scaffold leads to tissue and cell fragility in the skin 0009. In one aspect of the invention, the cannabinoid is and its appendages (hair, nail, glands), oral mucosa, and hemp oil or human breast milk. cornea, and exposes the skin to pathological conditions and 0010. In a different aspect of the invention, the cannabi diseases. noid is one or more of (CBGA), can nabigerolic acid monomethylether (CBGAM), cannabigerol 0004 Dermatitis, also known as eczema, is an inflam (CBG), cannabigerol monomethylether (CBGM), cannab mation of the skin that is characterized by the presence of igerovarinic acid (CBGVA), cannabigerovarin (CBGV), itchy, erythematous, Vesicular, weeping, and crusting cannabichromenic acid (CBCA), cannabichromene (CBC), patches. Inflammatory agents include bacteria, fungi, cannabichromevarinic acid (CBCVA), viruses, and autoimmune, allergic, hormonal and malignant (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), inflammatory agents. The most common skin diseases or cannabidiol monomethylether (CBDM), cannabidiol-C disorders include eczema, psoriasis, dermatitis, itching der (CBD-C), cannabidivarinic acid (CBDVA), matosis, rosacea, perioral dermatitis, acne, non-melanoma (CBDV), cannabidiorcol (CBD-C), delta-9-tetrahydrocan skin cancer and melanoma. Although symptoms vary, recur nabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic rent dermatitis conditions include pruritus, dryness and skin acid B (THCA-B), delta-9-tetrahydrocannabinol (THC), rashes, which may be accompanied by redness, skin Swell delta-9-tetrahydrocannabinolic acid-C (THCA-C), delta ing, itching and dryness, crusting, flaking, blistering, crack 9-tetrahydrocannabinol-C (THC-C), delta-9-tetrahydro ing, oozing, or bleeding. Common forms of dermatitis cannabivarinic acid (THCVA), delta-9-tetrahydrocannabi include atopic dermatitis, an allergic disease characterized varin (THCV), delta-9-tetrahydrocannabiorcolic acid by the presence of itchy rashes, contact dermatitis, which (THCA-C), delta-9-tetrahydrocannabiorcol (THC-C), may be caused by an allergen or an irritant, Xerotic eczema, delta-7-cis-iso-, delta-8-tetrahydro which is caused by dry skin, and seborrheic dermatitis, cannabinolic acid (A-THCA), delta-8-tetrahydrocannabinol which is more common in infants. (A-THC), cannabicyclolic acid (CBLA), 0005 Sunlight is a major cause of skin aging. Symptoms (CBL), cannabicyclovarin (CBLV), cannnabielsoic acid A of skin aging are wrinkles, age spots and dryness. While (CBEA-A), cannabielsoic acid B (CBEA-B), treatment with moisturizers and steroid creams may tempo (CBE), cannabinolic acid (CBNA), (CBN), can rarily control skin disorder and aging symptoms by reducing nabinol methylether (CBNM), cannabinol-C (CBN C), inflammation and Smoothing wrinkles, the relief is only (CBV), cannabinol-C (CBN C), cannabior temporary. There is no known cure for dermatitis, and col (CBN C), (CBND), cannabinodivarin systemic side effects prevent long term treatment of chronic (CBVD), cannabitriol (CBT), 10-ethoxy-9-hydroxy-delta dermatological conditions with steroids. 6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-6a-tetrahy US 2017/0042791 A1 Feb. 16, 2017 drocannabinol, cannabitriolvarin (CBTV), ethoxy-cannabit about 1 umol/cm. In one aspect of the invention, the subject riolvarin (CBTVE), dehydrocannabifuran (DCBF), is a mammal. In a preferred aspect of the invention, the cannabifuran (CBF), cannabichromanon (CBCN), can mammal is a human. nabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol 0017. In yet another embodiment, the invention provides (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5, a method for treating or preventing pruritus, dryness of the 6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-pro skin, skin rash, redness, Swelling of the skin, itching, crust pyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso ing, flaking, blistering, cracking, oozing, bleeding or blis HHCV), cannabiripsol (CBR) and trihydroxy-delta-9- tering of the skin in a Subject in need thereof, that comprises tetrahydrocannabinol (triCH-THC). topically administering to the Subject the composition of the 0011. In yet another aspect of the invention, the cannabi invention. In one aspect of the invention, the Subject has one noid is a agonist. Preferably, the can or more of eczema, psoriasis, dermatitis, itching dermatosis, nabinoid receptor agonist comprises one or more of a rosacea, perioral dermatitis, acne, non-melanoma cancer or naphthoylindole, a naphthylmethylindole, a naphthoylpyr melanoma. In one embodiment, the dermatitis is atopic role, a naphthylmethylindene, a phenylacetylindole and a dermatitis, contact dermatitis, Xerotic eczema, or seborrheic cyclohexylphenol. dermatitis. Preferably, the composition of the invention is 0012. In one embodiment of the invention, the hydroxy topically administered to the Subject in an amount between acid is present in the topical composition in a concentration about 100 nmol to about 1 Imol/cm. In one aspect of the between 0.1 and 10% by weight of the composition. In one invention, the Subject is a mammal. In a preferred aspect of aspect of the invention, the hydroxy acid is an alpha hydroxy the invention, the mammal is a human. acid, wherein the alpha hydroxy acid is lactic acid, citric 0018. The foregoing general description and following acid, glycolic acid, mandelic acid, benzylic acid, malic acid, brief description of the drawings and the detailed description tartaric acid, gluconolactone, galactonolactone, glucurono are exemplary and explanatory and are intended to provide lactone, galacturonolactone, gulonolactone, ribonolactone, further explanation of the invention as claimed. Other saccharic acid lactone, pantoylactone, glucoheptonolac objects, advantages, and novel features will be readily tone, mannonolactone, or galactoheptonolactone. In a dif apparent to those skilled in the art from the following ferent aspect of the invention, the hydroxy acid is a beta detailed description of the invention. hydroxy acid, and the beta hydroxy acid is salicylic acid or lipohydroxy acid. BRIEF DESCRIPTION OF THE DRAWINGS 0013 In one embodiment, the topical composition may 0019 FIG. 1 illustrates the chemical structure of some further comprise a stabilizer. Preferably, the stabilizer is cannabinoids for use according to the invention. selected from the group consisting of guar gum, Xanthan (0020 FIG. 2 illustrates the effect of the CBD-AHA day gum cellulose hyaluronic acid, polyvinyl pyrrolidone (PVP), cream composition on skin firmness, as measured by a alginate, chondritin Sulfate, poly gamma glutamic acid, Cutometer. Measurements were taken on the skin of the gelatin, chitisin, corn starch and flour, and is present in an Subjects on day one prior to the application of the compo amount from about 0.25% to about 30% (w/v). sition, and again after 28 days of daily use of the compo 0014. In a preferred aspect of the invention, the topical sition. The results show an average decrease of 1.09% in the composition is in the form of an ointment, a cream, an RO parameter, which represents the final distension of skin emulsion, a lotion, a paste, an unguent, a gel or a Sunscreen. on the test sites treated with the composition. In yet another preferred aspect, the carrier in the topical (0021 FIG. 3 illustrates the effect of the CBD-AHA night composition comprises hemp oil. cream composition on skin firmness, as measured by a 0015. In one embodiment, the topical composition further Cutometer. Measurements were taken on the skin of the comprises one or more of a thickening agent, an , Subjects on day one prior to the application of the compo an agent, an , an antibacterial agent, an sition, and again after 28 days of daily use of the compo or an antiviral agent. In one aspect of the inven sition. The results show an average decrease of 0.81% in the tion, the topical composition may further comprises a UV RO parameter, which represents the final distension of skin absorbing agent in an amount between 0.1 and 5% by weight on the test sites treated with the composition. of the composition. 0022 FIG. 4 illustrates the effect of the CBD-AHA-FS night cream composition on skin firmness, as measured by 0016. In a different embodiment, the invention provides a Cutometer. Measurements were taken on the skin of the a method of treating skin, treating a skin disorder, or Subjects on day one prior to the application of the compo improving a condition of the skin in a Subject in need thereof sition, and again after 28 days of daily use of the compo comprising topically administering to the Subject the topical sition. The results show an average decrease of 3.37% in the composition of the invention as described above. In one RO parameter, which represents the final distension of skin aspect of the invention, the skin disorder is one or more of eczema, psoriasis, dermatitis, itching dermatosis, rosacea, on the test sites treated with the composition. perioral dermatitis, acne, non-melanoma cancer or mela DETAILED DESCRIPTION OF THE noma. In another aspect of the invention, the Subject pres ents a symptom which is one or more of pruritus, dryness, INVENTION skin rash, redness, Swelling of the skin, itching, crusting, 0023 Cannabinoids are terpenophenolic compounds flaking, blistering, cracking, oozing, or bleeding. In yet found in sativa, an annual plant belonging to the another aspect, the dermatitis is atopic dermatitis, contact Cannabaceae family. The plant contains more than 400 dermatitis, Xerotic eczema, or seborrheic dermatitis. Prefer chemicals and approximately 80 cannabinoids. The latter ably, the composition of the invention is topically adminis accumulate mainly in the glandular trichomes. Natural phy tered to the subject in an amount between about 100 nmol to tocannabinoids occur in the free acid forms within plant US 2017/0042791 A1 Feb. 16, 2017 tissue. For instance, the psychoactive cannabinoids tetrahy alpha-hydroxy acids and beta-hydroxy acids can penetrate drocannbinol (THC), cannabidiol (CBD), cannabichromene the stratum corneum and act as exfoliants. Small molecule (CBC) and cannabigerol (CBG) exist in their corresponding alpha-hydroxy acids, such as glycolic acid and lactic acid, carboxylic acid forms THCA, CBDA, CBCA and CBGA are best Suited to penetrate dry skin and act as humectants within plant tissue and are converted to their active forms via and moisturizers. On the other hand, oil-soluble beta non-enzymatic decarboxylation that occurs upon the drying hydroxy acids are best Suited to penetrate into pores clogged of the plant tissue, or during storage or Smoking. with oily cells and sebum. 0024. The most active of the naturally occurring cannabi 0030 The present inventors have unexpectedly discov noids is tetrahydrocannabinol (THC), which is used for ered that compositions containing hydroxy acids in combi treating a wide range of medical conditions, including nation with one or more cannabinoids provide a number of glaucoma, AIDS wasting, neuropathic pain, treatment of advantages not found when either active agent is used by spasticity associated with multiple Sclerosis, fibromyalgia itself, including reduced skin irritation and fast healing of and chemotherapy-induced nausea. Additionally, THC has any skin condition that is enhanced by inflammation includ been reported to be effective for the treatment of allergies, ing, but not limited to, acne, aging spots, Scar formation, inflammation, , epilepsy, depression, migraine, eczema and wrinkles. Without being bound to any theory, it bipolar disorders, anxiety disorder, drug dependency and is believed that the cannabinoids of the inventive composi drug withdrawal syndromes. tions modulate the cannabinoid receptors CBR and CBR 0025 Cannabidiol (CBD), an isomer of THC, is a potent located in the skin and involved in the attenuation of pain antioxidant and anti-inflammatory compound known to pro and contact allergic reaction, and thus stimulate the prolif vide protection against acute and chronic neurodegenera eration, growth and differentiation of keratinocytes in the tion, and relief from chronic pain, inflammation, migraines, skin as well as their immune competence and/or tolerance, arthritis, spasms, epilepsy and Schizophrenia. while neutralizing the irritating effects of the hydroxy acids. 0026 Cannabigerol (CBG), which is found in high con Furthermore, it is believed that the combination of the centrations in hemp, acts as a high affinity C-adrenergic cannabinoids with the hydroxy acids results in an unex receptor agonist, moderate affinity 5-HT, receptor antago pected Synergic anti-inflammatory effect due to the anti nist and low affinity CB receptor antagonist, and thus may inflammatory properties of the cannabinoids, and contrib have anti-depressant activity. Cannabichromene (CBC) pos utes to the total wellness of the skin. In fact, skin irritation sesses anti-inflammatory, anti-fungal and anti-viral proper tests using repeated "open patch' applications of the com ties. Tetrahydrocannabivarin (THCV) is known as an appe positions of the invention on the back of 50 subjects for at tite Suppressant. least three weeks showed no adverse reactions of any kind 0027. The use of cannabinoids in topical compositions is and no irritation of the skin in any subject. Accordingly, the limited by the fact that cannabinoids, because of their compositions containing a combination of one or more hydrophobic nature, must be dissolved in organic solvents hydroxy acids and one or more cannabinoids according to that may irritate the skin. the invention provide greater skin improvement effects than 0028. Alpha and beta hydroxy acids are chemical exfo the same compositions comprising either a hydroxy acid or liants. Alpha hydroxy acids are carboxylic acids character a cannabinoid alone. ized by the presence of one hydroxyl group attached to the 0031. As used herein, the terms “cannabinoid’ and “can C-position of the carboxyl group, known for their beneficial nabinoids' include, but are not limited to, natural phytocan exfoliating properties and for inducing skin proliferation and nabinoids, organic cannabinoids, endocannabinoids, can new cell growth. Exemplary alpha-hydroxy acids include, nabinoid analogs, cannabinoid derivatives, synthetic but are not limited to, glycolic acid, lactic acid, malic acid, cannabinoids and cannabinoid receptor agonists. citric acid and tartaric acid. Alpha-hydroxy acids are differ 0032 Examples of organic cannabinoids include, but are ent from beta-hydroxy acids, such as B-hydroxybutanoic not limited to, hemp oil and human breast milk. acid, which are carboxylic acids characterized by having one 0033 Examples of cannabinoids, cannabinoid analogs hydroxyl group attached to the B-position of the carboxyl and cannabinoid derivatives include, but are not limited to, group, as shown in the figure below. cannabigerolic acid (CBGA), cannabigerolic acid monom ethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CB O GVA), cannabigerovarin (CBGV), cannabichromenic acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic HO OH acid (CBDA), cannabidiol (CBD), cannabidiol monomethy Alpha hydroxy acid lether (CBDM), cannabidiol-C (CBD-C), cannabidivarinic O acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD-C), delta-9-tetrahydrocannabinolic acid A (THCA A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta B OH 9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannab OH inolic acid-C (THCA-C), delta-9-tetrahydrocannabinol-C (THC-C), delta-9-tetrahydrocannabivarinic acid (THCVA), Beta hydroxy acid delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydro cannabiorcolic acid (THCA-C), delta-9-tetrahydrocan 0029. These differences in structure are reflected in dif nabiorcol (THC-C), delta-7-cis-iso-tetrahydrocannabi ferences in Solubility, as alpha-hydroxy acids are water varin, delta-8-tetrahydrocannabinolic acid (A-THCA), soluble, whereas beta-hydroxy acids are lipid-soluble. Both delta-8-tetrahydrocannabinol (A-THC), cannabicyclolic US 2017/0042791 A1 Feb. 16, 2017 acid (CBLA), cannabicyclol (CBL), cannabicyclovarin compounds of the molecular formula CHO represented (CBLV), cannnabielsoic acid A (CBEA-A), cannabielsoic by the structure: acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C (CBN C), cannabivarin (CBV), OH cannabinol-C (CBN C), cannabiorcol (CBN C), can nabinodiol (CBND), cannabinodivarin (CBVD), cannabit riol (CBT), 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocan nabinol, 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin (CBTVE), dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hy droxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano ru 2H-1-benzoxocin-5-methanol (OH-iso-HHCV), cannabiripsol (CBR) and trihydroxy-delta-9-tetrahydrocan compounds of the molecular formula C2HNO repre nabinol (triCH-THC). sented by the structure: 0034 Cannabinoid receptor agonists as used herein may include natural and synthetic compounds that are structur ally related to natural cannabinoids, and natural and Syn thetic compounds that are not structurally related to natural cannabinoids, all of which interact with at least one of the cannabinoid receptors CBR and CBR. Cannabinoid recep toragonists that can be used according to the invention exert the same function as natural cannabinoids and share one or more common features with natural cannabinoids. For example, cannabinoid receptor agonists that are not struc turally related to natural cannabinoids are lipid soluble and non-polar, consist of 22 to 26 carbon atoms and have a side-chain comprising more than four and up to nine satu rated carbon atoms. Non-limiting examples of cannabinoid receptor agonists that are not structurally related to natural cannabinoids include naphthoylindoles, naphthylmethylin doles, naphthoylpyrroles, naphthylmethylindenes, pheny lacetylindoles, such as benzoylindoles, and cyclohexylphe nols. 0035 Exemplary cannabinoid receptor agonists include, and compounds of the molecular formula C2HNO rep but are not limited to, compounds of the molecular formula resented by the structure: CHO represented by the structure:

compounds of the molecular formula C5H8O. represented by the structure:

0036. Accordingly, the present invention provides a topi cal composition and methods for the treatment of a skin disorder or rejuvenation of the skin that comprise adminis tering a topical composition, wherein the topical composi tion comprises a therapeutically effective amount of at least one cannabinoid and a therapeutically effective amount of at least one hydroxy acid in a pharmaceutically acceptable carrier. Preferably, the carrier is an oil. Even more prefer ably, the oil is hemp oil. The use of refined hemp oil in the topical compositions and methods of the invention is par US 2017/0042791 A1 Feb. 16, 2017 ticularly advantageous, as hemp oil has a high content of acid (alpha hydroxymyristic acid) (C. Has) (H) C (OH) antioxidants and cannabinoids having anti-inflammatory COOH: 2-hydroxyhexadecanoic acid (alpha hydroxypalm effects. Such as cannabidiol. Hemp oil is also enriched in itic acid) C. Ho) (H) C (OH) COOH: 2-hydroxyoctade omega-6 fatty acids and has a 3:1 ratio of omega-6 to canoic acid (alpha hydroxy stearic acid) (C. Ha) (H) C omega-3 essential fatty acids, which matches the balance (OH) COOH: 2-hydroxyeicosanoic acid (alpha hydrox required by the human body. yarachidonic acid) (C, H,) (H) C (OH) COOH. 0037. In one aspect of the invention, the cannabinoids are 0041 Aralkyl and aryl alpha hydroxy acids include, but present in the topical composition in a concentration are not limited to, 2-phenyl 2-hydroxyethanoic acid (man between 0.1 and 30% by weight of the composition. Pref delic acid) (CH) (H) C (OH) COOH: 2,2-diphenyl 2-hy erably, the cannabinoids are one or more of tetrahydrocan droxyethanoic acid (benzylic acid) (CHS) (CH) C (OH) nbinol (THC), cannabidiol (CBD), cannabigerol (CBG). COOH: 3-pphenyl 2-hydroxypropanoic acid (phenylactic cannabichromene (CBC), tetrahydrocannabivarin (THCV), acid) (C. H. CH-) (H) C (OH) COOH:2-pphenyl 2-methyl analogs thereof, derivatives thereof, organic and synthetic 2-hydroxyethanoic acid (atrolactic acid) (C HS) (CH) C cannabinoids and cannabinoid receptor agonists as (OH) COOH: 2-(4'-hydroxyphenyl)2-hydroxyethanoic acid described above. In one aspect of the invention, the can (4-hydroxymandelic acid) (HO C. Ha) (H) C (OH) nabinoids in the topical composition comprise one or more COOH: 2-(4-chlorophenyl) 2-hydroxyethanoic acid of a natural phytocannabinoid, an organic cannabinoid, an (4-chloromandelic acid) (C1 C. Ha) (H) C (OH) COOH: endocannabinoid, a cannabinoid analog, a cannabinoid 2-(3'-hydroxy-4-methoxyphenyl) 2-hydroxyethanoic acid derivative, a synthetic cannabinoid and a cannabinoid recep (3-hydroxy-4-methoxymandelic acid) (HO—, CH, O C. toragonist. The cannabinoid receptor agonist may comprise H) (H) C (OH) COOH: 2-(4'-hydroxy-3-methoxyphenyl) one or more of a naphthoylindole, a naphthylmethylindole, 2-hydroxyethanoic acid (4-hydroxy-3-methoxymandelic a naphthoylpyrrole, a naphthylmethylindene, a pheny acid) (HO , CH, O C H) (H) C (OH) COOH: 3-(2- lacetylindole and a cyclohexylphenol. hydroxyphenyl)2-hydroxypropanoic acid 3-(2-hydroxy 0038. As used herein, the term “hydroxy acid' includes, phenyl) lactic acid HO C H CH (H) C (OH) COOH: but is not limited to, alpha-hydroxy acid and beta-hydroxy 3-(4-hydroxyphenyl) 2-hydroxypropanoic acid 3-(4-hy acid. The hydroxy acids are present in the topical compo droxyphenyl) lactic acid HO C CH (H) C (OH) sition in a concentration between 0.1 and 10% by weight of COOH; and 2-(3',4'-dihydroxyphenyl) 2-hydroxyethanoic the composition. Alpha hydroxy acids that may be used acid (3,4-dihydroxymandelic acid) HO , HO C. H. (H) according to the invention comprise, but are not limited to, C (OH) COOH. organic carboxylic acids in which one hydroxyl group is 0042 Polyhydroxy alpha hydroxy acids include, but are attached to the alpha carbon of the acids. The generic not limited to, 2,3-dihydroxypropanoic acid (glyceric acid) structure of alpha hydroxy acids may be represented by the (HOCH) (H) C (OH) COOH: 2,3,4-trihydroxybutanoic formula (Ra) (Rb) C (OH) COOH: wherein Ra and Rb are acid (isomers; erythronic acid, threonic acid) HOCH (HO) each H, F, Cl, Br, alkyl, aralkyl or aryl group of saturated or CH (H) C (OH) COOH: 2,3,4,5-tetrahydroxypentanoic acid unsaturated, isomeric or non-isomeric, straight or branched (isomers; ribonic acid, arabinoic acid, Xylonic acid, lyxonic chain or cyclic form, having 1 to 25 carbon atoms. Ra and acid) HOCH (HO) CH(HO) CH (H) C (OH) COOH: Rb may also carry an OH, CHO, COOH or alkoxy group 2,3,4,5,6-pentahydroxyhexanoic acid (Isomers; allonic acid, having 1 to 9 carbon atoms. The hydroxy acids may be altronic acid, gluconic acid, mannoic acid, gulonic acid, present in the topical composition as a free acid or in lactone idonic acid, galactonic acid, talonic acid) HOCH (HO)CH form, or in a salt form with an organic base or an inorganic (HO)CH (HO)CH, C (OH) COOH; and 2,3,4,5,6,7-hexa alkali. The hydroxy adds may also exist as Stereoisomers as hydroxyheptanoic acid (isomers; glucoheptonic acid, galac D. L., and DL forms when Ra and Rb are not identical. toheptonic acid etc.) HOCH (HO) CH (HO) CH (HO) 0039 Typical alkyl, aralkyl and aryl groups for Ra and CH (HO) CH (H) C (OH) COOH: Rb include, but are not limited to, methyl, ethyl, propyl. 0043 Polycarboxylic alpha hydroxy acids include, but isopropyl, butyl, pentyl, octyl, lauryl, Stearyl, benzyl and are not limited to, 2-hydroxypropane-1,3-dioic acid (tar phenyl. Alpha hydroxy acids include (1) alkyl alpha tronic acid) HOOC (H) C (OH) COOH: 2hydroxybutane-1, hydroxyacids; (2) aralkyl and aryl alpha hydroxyacids, (3) 4-dioic acid (malic acid) HOOC CH (H) C (OH) COOH: polyhydroxy alpha hydroxyacids; and (4) polycarboxylic 2,3-dihydroxybutane-1,4-dioic acid (tartaric acid) HOOC alpha hydroxyacids. (HO)CH (H) C (OH) COOH:2-hydroxy-2-carboxypentane 0040 Alkyl alpha hydroxy acids include, but are not 1,5-dioic acid (citric acid) HOOC CH, C (OH) (COOH) limited to, 2-hydroxyethanoic acid (glycolic acid, hydroxy CH COOH: 2, 3,4,5-tetrahydroxyhexane-1,6-dioic acid ) (H) (H) c (OH) COOH: 2-hydroxypropanoic (isomers; saccharic acid, mucic acid etc.) HOOC (CHOH), acid (lactic acid) (CH) (s) C (OH) COOH: 2-methyl 2-hy COOH: droxypropanoic acid (methylactic acid) (CH) (CH) C 0044 Lactone forms include, but are not limited to, (OH) COOH: 2-hydroxybutanoic acid (C, Hs) (H) C (OH) gluconolactone, galactonolactone, glucuronolactone, galac COOH: 2-hydroxypentanoic acid (C, H,) (H) C (OH) turonolactone, gulonolactone, ribonolactone, saccharic acid COOH: 2-hydroxyhexanoic acid (C Ho) (H) C (OH) lactone, pantoylactone, glucoheptonolactone, mannonolac COOH: 2-hydroxyheptanoic acid (Cs H (H) C (OH) tone, and galactoheptonolactone. COOH: 2-hydroxyoctanoic acid (C, H) (H) C (OH) 0045. In a preferred aspect of the invention, the alpha COOH: 2-hydroxynonanoic acid (C, Hs) (H) C (OH) hydroxy acid is lactic acid, citric acid, glycolic acid, man COOH: 2-hydroxydecanoic acid C. Hz) (H) C (OH) delic acid, benzylic acid, malic acid, tartaric acid, glucono COOH: 2-hydroxyundecanoic acid (C, Ho) (H) C (OH) lactone, galactonolactone, glucuronolactone, galacturono COOH: 2-hydroxydodecanoic acid (alpha hydroxylauric lactone, gulonolactone, ribonolactone, saccharic acid acid) (CoH) (H) C (OH) COOH:2-hydroxytetradecanoic lactone, pantoylactone, glucoheptonolactone, mannonolac US 2017/0042791 A1 Feb. 16, 2017 tone, or galactoheptonolactone. In an additional preferred cefotaxime, cefpodoxime proxetil, ceftazidime, ceftizoxime, aspect of the invention, the beta-hydroxy acid is salicylic ceftriaxone, cefepime, azithromycin, clarithromycin, clin acid. damycin, dirithromycin, erythromycin, lincomycin, trolean 0046. In one embodiment, the topical composition may domycin, cinoxacin, ciprofloxacin, enoxacin, gatifloxacin, further comprise a stabilizer. Preferably, the stabilizer is grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, selected from the group consisting of guar gum, Xanthan nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trova gum cellulose hyaluronic acid, polyvinyl pyrrolidone (PVP), floxacin, oxolinic acid, gemifloxacin, perfloxacin, imi alginate, chondritin Sulfate, poly gamma glutamic acid, penemi-cilastatin, meropenem, and aztreonam. In one gelatin, chitisin, corn starch and flour, and is present in an embodiment, the amount of the antibiotic in the composition amount from about 0.25% to about 30% (w/v). is from 0.01 to 5% by weight of the total composition. 0047. In a preferred aspect of the invention, the topical 0056 Antiseptic compounds include, but are not limited composition is in the form of an ointment, a cream, an to, iodine, manuka honey, octenidine dihydrochloride, phe emulsion, a lotion, a paste, an unguent, a gel or a Sunscreen. nol, polyhexanide, Sodium chloride, Sodium hypochlorite, In yet another preferred aspect, the carrier in the topical calcium hypochlorite, sodium bicarbonate, methyl paraben, composition comprises hemp oil. and sodium dehydroacetate. In one embodiment, the amount 0048 Creams according to the inventions include water of the antiseptic compound in the topical formulation is from in-oil or oil-in-water emulsions and may further comprise a 0.01 to 5% by weight of the total composition. cleansing agent, an emollient and an aromatic chemical 0057 Antifungal agents include, but are not limited to, compound. , , filipin, , , 0049 Ointments and unguents according to the invention , rimocidin, , , , optionally contain oil and water in a ratio from 2:1 to 7:1, , , , , luli and may further comprise a wax, alcohols and petroleum conazole, , omoconazole, , Sertacon based mollifying agents. , , , , , 0050 Gels according to the invention optionally contain isavuconazole, , , , a vegetable oil up to 5% by weight of the total composition, , , , amorolfin, , water and a thickening agent. Preferably, the thickening , , , , mica agent is a natural polysaccharide, such as Xanthan gum, fungin, benzoic acid, , , , carrageen, an alginate or cellulose gum. , , , , and 0051 Pastes according to the invention may optionally balsam of Peru. In one embodiment, the amount of the contain aloe gel and beeswax. antifungal agent in the topical formulation is from 0.01 to 0052 Lotions according to the invention include oil-in 5% by weight of the total composition. water or water-in-oil emulsions and may comprise cetyl 0.058 Analgesic agents include, but are not limited to, alcohol, an emulsifier, a fragrance, glycerol, petroleum jelly, , codeine, morphine, methadone, pethidine, a dye, one or more preservatives and a stabilizing agent. buprenorphine, hydromorphine, levorphanol, oxycodone, 0053 A sunscreen composition according to the inven fentanyl, and a non-steroidal anti-inflammatory drug. The tion may further comprise a UV absorbing agent in an amount of the analgesic agent in the topical formulation is amount between 0.1 and 5% by weight of the composition. from 0.01 to 5% by weight of the total composition. Exemplary UV-absorbing compounds include, but are not 0059 Anti-viral agents include, but are not limited to, limited to, benzone compounds, glyceryl PABA, roXadi acyclovir, famciclovir, penciclovir, Valacyclovir, trifluridine, mate, octocrylene, octyl methoxycinnamate, ethoxyethyl docosanol, amantadine, rimantadine, oseltamivir, and Zan p-methoxycinnamate, homomenthyl salicylate, ethylhexyl amivir. The amount of the anti-viral agent in the topical salicylate, trolamine salicylate, ecamsule, ensulizole, bemo formulation is from 0.01 to 5% by weight of the total trizinol and bisoctrizole. composition. 0054. In some embodiments, the topical compositions of 0060. In some embodiments, the topical composition of the invention may further comprise one or more active the invention may further comprise a stabilizer selected from agents, such as an antibiotic, an antiseptic agent, an anti the group consisting of guar gum, Xanthan gum cellulose fungal, an antibacterial agent, an analgesic or an antiviral hyaluronic acid, polyvinyl pyrrolidone (PVP), alginate, agent. In additional embodiments, the topical compositions chondritin Sulfate, poly gamma glutamic acid, gelatin, chiti of the invention may further comprise anesthetics, anti sin, corn starch and flour, in an amount from about 0.25% to cancer agents, antiacne agents, humectants, such as cationic, about 2% (w/v). ionic and non-ionic Surfactant, moisturizers, antipruritic 0061. In some embodiments, the composition for topical agents, antiperspirants, antipsoriatic agents, antiseborrheic application to the skin comprises a therapeutically effective agents, antiaging and anti-Wrinkle agents, skin lightening amount of at least one cannabinoid, a therapeutically effec agents, depigmenting agents and Vitamins. tive amount of an alpha hydroxy acid, and hemp oil. 0055 Exemplary include, but are not limited 0062. The cannabinoids according to the invention may to, amplicillin, bacampicillin, carbenicillin indanyl, meZlo be obtained as an extract from a cannabis plant for medical cillin, piperacillin, ticarcillin, amoxicillin-clavulanic acid, use, such as Cannabis sativa and Cannabis indica, by ampicillin-Sulbactam, benzylpenicillin, cloxacillin, dicloxa extracting the trichomes of the plants in a solvent and cillin, methicillin, oxacillin, penicillin G, penicillin V, pip heating the mixture to evaporate the Solvent. Examples of eracillin taZobactam, ticarcillin clavulanic acid, nafcillin, extraction technologies that may be used include, but are not procaine penicillin, cefadroxil, cefazolin, cephalexin, cepha limited to, CO extraction and microwave extraction. The lothin, cephapirin, cephradine, cefaclor, cefamandol, cefo cannabinoids according to the invention may also be nicid, cefotetan, cefoxitin, cefprozil, ceftmetazole, cefurox obtained as an extract from a cannabis transgenic plant that ime, loracarbefcefdinir, ceftibuten, cefoperaZone, cefixime, overexpresses one or more particular cannabinoids or that US 2017/0042791 A1 Feb. 16, 2017

does not express or under-expresses one or more particular EXAMPLES cannabinoids. may be prepared according to the technologies known to those skilled in the Example 1 art. In the alternative, endogenous nucleic acid sequences may be extracted from a cannabis plant and used to produce Preparation of Topical Compositions Comprising cannabinoids by recombinant technology. Alpha Hydroxy Acid and Cannabinoids 0067 A. Preparation of Alpha Hydroxy Acid Composi 0063. The topical compositions of the invention may be tions in Alcohol prepared by dissolving the dry extracts of cannabinoids in an 0068, 5.0 grams of lactic acid, glycolic acid, citric acid, oil, preferably hemp oil, and by adding the cannabinoid mandelic acid, benzylic acid, malic acid, tartaric acid or Solution to a composition containing the hydroxy acids. The gluconolactone are dissolved in propylene glycol. The mix hydroxy acid composition may be an alcohol solution in ture is shaken and 4.0 grams of hydroxypropylcellulose are which the hydroxy acids are dissolved, or the hydroxy acids slowly added to the mixture to avoid clamping. may be dissolved in an alcohol-free Solution. In an alterna 0069 B. Preparation of Cannabinoid Compositions tive embodiment, the hydroxy acids are dissolved in a 0070 Trichomes and leaves are collected from Cannabis composition comprising hemp oil or one or more cannabi sativa and Cannabis indica, dried in air after harvest, finely noid, analogs thereof, derivatives thereof, organic and Syn ground and dissolved into a solvent in a volume ratio of 1:5. thetic cannabinoids and cannabinoid receptor agonists as The solution is heated to evaporate the solvent and the dry described above, wherein the one or more cannabinoids, mixture is dissolved in hemp oil. analogs thereof, derivatives thereof, organic and synthetic 0071 C. Preparation of Topical Compositions cannabinoids and cannabinoid receptor agonists are dis 0072 The solution of alpha hydroxy acid is added to the solved in an oil. Preferably, the oil is a vegetable oil. Even hemp oil composition containing the cannabinoids and the more preferably the vegetable oil is hemp oil. mixture is agitated and formulated into compositions for 0064. In a different embodiment, the invention provides topical administration. a method to treat a skin disorder or rejuvenate the skin in a Subject in need thereof, that comprises topically administer Example 2 ing to the Subject the topical composition of the invention as Preparation of Topical Compositions Comprising described above. The skin disorder may be one or more of eczema, psoriasis, dermatitis, itching dermatosis, rosacea, Alpha Hydroxy Acid and Hemp Oil perioral dermatitis, acne, non-melanoma cancer or mela 0073 5.0 grams of lactic acid, glycolic acid, citric acid, noma. The Subject may present the first signs of irritation, or mandelic acid, malic acid, tartaric acid or gluconolactone are presents a severe symptom which is one or more of pruritus, dissolved in hemp oil and the solution is formulated into dryness, skin rash, redness, Swelling of the skin, itching, compositions for topical administration. crusting, flaking, blistering, cracking, oozing, and bleeding. The dermatitis may be atopic dermatitis, contact dermatitis, Example 3 xerotic eczema, or seborrheic dermatitis. In a preferred embodiment, the composition of the invention is topically Treatment of Dermatitis administered to the subject in an amount between about 100 0074 20 subjects with severe dermatitis are divided into nmol to about 1 umol/cm. In one aspect of the invention, four groups, 5 subjects per group. The Subjects are instructed the Subject is a mammal. In a preferred aspect of the to topically apply a lotion two times daily for two weeks. invention, the mammal is a human. Group one is treated for two weeks with a lotion containing 0065. In yet another embodiment, the invention provides hydroxy acids. Group two is treated for two weeks with a a method for treating or preventing pruritus, dryness of the lotion containing cannabinoids. Group three is treated for skin, skin rash, redness, Swelling of the skin, itching, crust two weeks with a lotion containing hydroxy acids and ing, flaking, blistering, cracking, oozing, bleeding or blis cannabinoids in hemp oil prepared according to Example 1. tering of the skin in a Subject in need thereof, that comprises Group four is treated for two weeks with a lotion containing topically administering to the Subject the composition of the hydroxy acids and hemp oil prepared according to Example invention. The subject may be disease-free or may be 2. The effects of the different treatments are evaluated after Suspected of having or have one or more skin conditions, two weeks. Such as eczema, psoriasis, dermatitis, itching dermatosis, rosacea, perioral dermatitis, acne, non-melanoma cancer or Example 4 melanoma. The dermatitis may be atopic dermatitis, contact dermatitis, Xerotic eczema, or seborrheic dermatitis. In a Topical Anti-Aging Compositions preferred embodiment, the composition of the invention is 0075. Three different anti-aging compositions, “CBD topically administered to the Subject in an amount between AHA day cream,” “CBD-AHA night cream” and “CBD about 100 nmol to about 1 Imol/cm. In one aspect of the AHA-FS night cream” were used in this set of experiments. invention, the Subject is a mammal. In a preferred aspect of Each composition contained the following ingredients: the invention, the mammal is a human. (0076 CBD-AHA-Day Cream 0066. The present invention thus generally described, 0077. Ingredients: Aqua (Deionized Water), Aloe Bar will be understood more readily by reference to the follow badensis Leaf (Aloe Vera Gel) Juice, Glycerin, Cetearyl ing examples, which are provided by way of illustration Olivate, Sorbitan Olivate, Stearic Acid, Cetyl Alcohol, Gly only, and are not intended to be limiting the present inven colic Acid, Saccharide Isomerate. Butylene Glycol, Car tion. bomer, Polysorbate 20, Palmitoyl Oligopeptide, Palmitoyl US 2017/0042791 A1 Feb. 16, 2017

Tetrapeptide-7, Cannabis Sativa (Hemp) Seed Oil, Hespe daily use of the composition. All readings were totaled and ridin Methyl Chalcone, Steareth-20, Dipeptide-2, Xanthan reported as average scores. The data thus obtained were Gum, Mangifera Indica (Mango) Seed Butter. Butyrosper quoted as percentage differences from baseline at each time mum Parkii (Shea) Butter, Caprylic/Capric Triglyceride, point. Comparison of baseline measurements and post Simmondsia Chinensis (Jojoba) Seed Oil, Cocos Nucifera treatment measurements was analyzed using a two-tailed, (coconut) Oil, Allantoin, Citrullus Vulgaris (Watermelon) paired t-test (p<0.05). Fruit Extract, Camellia Sinensis (Green Tea) Leaf Extract, 0085. Results Punica Granatum (Pomegranate) Extract, Cucumis Sativus I0086. With regard to the CBD-AHA day cream, 90% of (Cucumber) Extract, Glycyrrhiza Glabra (Licorice) Root the subject reported rejuvenation of the skin and an overall Extract, Astaxanthin, Cranberry Seed Oil. Thioctic Acid, improvement in the skin feel and texture after 28 days of Hyaluronic Acid, Ascorbic Acid (), Retinyl Palmi daily application. With regard to the CBD-AHA night tate (Vitamin A), Tocopheryl Acetate (Vitamin E), Soluble cream, 90% of the subject reported an overall improvement Collagen, Phenoxyethanol, Ethylhexylglycerin. in skin's clarity, tone and radiance, and a reduction in lines 0078 CBD-AHA-Night Cream and wrinkles after 28 days of daily application. With regard 0079 Ingredients: Aqua (Deionized Water), Aloe Bar to the CBD-AHA-FS night cream, 70% of the subject badensis Leaf (Aloe Vera Gel) Juice, Cetearyl Olivate, reported an overall improvement in skin's clarity, tone and Sorbitan Olivate, Cetyl Alcohol, Glycerin, Stearic Acid, radiance, and a reduction in lines and wrinkles after 28 days Glycolic Acid, Saccharide Isomerate, Cannabis Sativa of daily application. All three compositions were effective in (Hemp) Seed Oil, Xanthan Gum, Mangifera Indica (Mango) improving the overall condition of the skin in the face area Seed Butter, Butyrospermyn Parkii (Shea) Butter, Caprylic/ after 28 days of daily use. The results are reproduced below. Capric Triglyceride, Simmondsia Chinensis (Jojoba) Seed I0087 CBD-AHA-Day Cream Oil, Cocos Nucifera (Coconut) Oil, Allantoin, Citrullus Vulgaris (Watermelon) Fruit Extract, Camelia Sinensis TABLE 1. (Green Tea) Leaf Extract, Punica Granatum (Pomegranate) Extract, Cucumis Sativus (Cucumber) Extract, Glycyrrhiza Skin Firmness Glabra (Licorice) Root Extract, Astaxanthin, Cranberry Panelist ID No. Baseline Day 28 Individual % Difference Seed Oil. Thioctic Acid, Sodium Hyaluronate, Salicylic 60 1825 O.29 O.285 -1.72% Acid, Ascorbic Acid (Vitamin C). Retinyl Palmitate (Vita S6 3884 O.235 0.2375 1.06% min A), Tocopheryl Acetate (Vitamin E), Soluble Collagen, 62 5219 O.2775 0.2825 1.8% Phenoxyethanol, Ethylhexylglycerin. S8 7412 0.275 O.2729 -0.78% 0080 CBD-AHA-FS Night Cream 39 1287 O.35 O.34 -2.86% 54 4408 0.2975 O.2988 O.42% 0081 Ingredients: Aqua (Deionized Water), Aloe Bar 62 O798 O.39 0.375 -3.85% badensis Leaf (Aloe Vera Gel) Juice, Glycerin, Cetearyl 64 7718 O.405 O.385 -4.94% Olivate, Sorbitan Olivate, Cetyl Alcohol, Glycerin, Stearic 92 S874 O.3638 0.3525 -3.09% Acid, Glycolic Acid, Cannabis Sativa (Hemp) Seed Oil, 60 7847 O.2925 O.312S 6.84% Mean O.3176 O3142 Saccharide Isomerate, Xanthan Gum, Mangifera Indica % Difference -1.09% (Mango) Seed Butter. Butyrospermyn Parkii (Shea) Butter, P O.366 Caprylic/Capric Triglyceride, Simmondsia Chinensis (Jo T O.926 joba) Seed Oil, Cocos Nucifera (Coconut) Oil, Potassium or Sodium Iodide 8 to 20 g/l. Natural Mono or Oligo and Polysaccharide 120 g/l. Iodine 8 g/l. Natural Proteins 11 g/l. I0088. The skin firmness data presented in Table 1 show Allantoin, Citrullus Vulgaris (Watermelon) Fruit Extract, a decrease of up to 4.94% in the RO parameter, which Camellia Sinensis (Green Tea) Leaf Extract, Punica Gra represented the final distension of skin on the test site. These natum (Pomegranate) Extract, Cucumis Sativus (Cucumber) results indicated tightness and elasticity on the test sites Extract, Glycyrrhiza Glabra (Licorice) Root Extract, Astax treated with the CBD-AHA day cream. anthin, Cranberry Seed Oil. Thioctic Acid, Sodium Hyaluro I0089 CBD-AHA-Night Cream nate, Salicylic Acid, Ascorbic Acid (Vitamin C). Retinyl Palmitate (Vitamin A), Tocopheryl Acetate (Vitamin E), TABLE 2 Soluble Collagen, Phenoxyethanol, Ethylhexylglycerin. Skin Firmness Example 5 Panelist ID No. Baseline Day 28 Individual % Difference 46 2263 O.345 O.385 11.59% Efficacy of Topical Anti-Aging Compositions 38 3147 O.395 O.385 -2.53% 64 1074 O.312S O3O2S -3.2% 0082 Evaluation 56 7836 O.305 0.2675 -12.3% 0083. The efficacy of three different anti-aging composi 44 S227 O.305 0.2575 -15.57% tions, “CBD-AHA day cream,” “CBD-AHA night cream” 46 9007 O.26 0.255 -1.92% 78 1833 O.32 O.3475 8.59% and “CBD-AHA-FS night cream” was evaluated. 68 3246 0.27 O3O2S 12.04% 0084. The effectiveness of each composition was 72 3479 0.3175 O.3 -5.51% assessed in 10 different subjects using a Cutometer SEM 575 46 7249 0.2575 O.26 O.97% Mean O3O88 O.3063 to measure firmness, and a NOVAR Dermal Phase Meter to % Difference -0.81% determine the content of retained water in the skin. For each P O.791 composition, skin firmness measurements via Cutometer T O-269 were performed on the subjects on day one prior to the application of the composition, and again after 28 days of US 2017/0042791 A1 Feb. 16, 2017

0090 The skin firmness data presented in Table 2 show between 0.1 and 30% by weight of the composition; wherein a decrease of up to 15.57% in the RO parameter, which the hydroxy acid is present in a concentration between 0.1 represented the final distension of skin on the test site. These and 10% by weight of the composition; and wherein the results indicated tightness and elasticity on the test sites cannabinoid is one or more of a natural phytocannabinoid, treated with the CBD-AHA night cream. an organic cannabinoid, an endocannabinoid, a cannabinoid 0091 CBD-AHA-FS Night Cream analog, a cannabinoid derivative, a synthetic cannabinoid and a cannabinoid receptor agonist. TABLE 3 2. The topical composition of claim 1, wherein the organic Skin Firmness cannabinoid is hemp oil or human breast milk. 3. The topical composition of claim 1, wherein the can Panelist ID No. Baseline Day 28 Individual % Difference nabinoid is one or more of cannabigerolic acid (CBGA), 62 2435 0.3725 0.355 -4.7% cannabigerolic acid monomethylether (CBGAM), cannab 62 6204 0.3515 O.3425 -2.56% igerol (CBG), cannabigerol monomethylether (CBGM), 627072 O.395 0.37 -6.33% cannabigerovarinic acid (CBGVA), cannabigerovarin S4 1210 O.36 O.325 -9.72% 6O 8470 0.375 0.3575 -4.67% (CBGV), cannabichromenic acid (CBCA), cannabi 60 S848 O.3137 O.3325 5.99% chromene (CBC), cannabichromevarinic acid (CBCVA), SO 2032 O.3475 O.312S -10.07% cannabichromevarin (CBCV), cannabidiolic acid (CBDA), 62. 3438 O.325 0.3175 -2.31% cannabidiol (CBD), cannabidiol monomethylether 685565 O4O75 O4OS -0.61% S84837 O.32 O.33 3.13% (CBDM), cannabidiol-C (CBD-C), cannabidivarinic acid Mean O.3568 O.3448 (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD % Difference -3.37% C), delta-9-tetrahydrocannabinolic acid A (THCA-A), P O.061 delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9- T 1991 tetrahydrocannabinol (THC), delta-9-tetrahydrocannabino lic acid-C (THCA-C), delta-9-tetrahydrocannabinol-C 0092. The skin firmness data presented in Table 3 show (THC-C), delta-9-tetrahydrocannabivarinic acid (THCVA), a decrease of up to 10.07% in the RO parameter, which delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydro represented the final distension of skin on the test site. These cannabiorcolic acid (THCA-C), delta-9-tetrahydrocan results indicated tightness and elasticity on the test sites nabiorcol (THC-C), delta-7-cis-iso-tetrahydrocannabi treated with the CBD-AHA-FS night cream. varin, delta-8-tetrahydrocannabinolic acid (A-THCA), delta-8-tetrahydrocannabinol (A-THC), cannabicyclolic Example 6 acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannnabielsoic acid A (CBEA-A), cannabielsoic Evaluation of Skin Irritation or Sensitization by the acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid Topical Anti-Aging Compositions (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C (CBN C), cannabivarin (CBV), 0093. A Repeat Insult Patch Test (RIPT) was used to cannabinol-C (CBN C), cannabiorcol (CBN C), can assess the irritation and sensitization potential of two dif nabinodiol (CBND), cannabinodivarin (CBVD), cannabit ferent anti-aging compositions, the “CBD-AHA day cream,” riol (CBT), 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocan and the “CBD-AHA-FS night cream” as described above. nabinol, 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, 0094. The effect of each composition was assessed in 50 cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin different Subjects by applying nine "open patch' applica (CBTVE), dehydrocannabifuran (DCBF), cannabifuran tions on the subjects back each week for three consecutive (CBF), cannabichromanon (CBCN), cannabicitran (CBT), weeks. In the event of an adverse reaction, the area of 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis erythema and edema would be measured, and Subjects tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hy would be given 10 to 14 days of rest before the next droxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano application. The edema would be estimated by evaluating 2H-1-benzoxocin-5-methanol (OH-iso-HHCV), the skin with respect to the contour of the unaffected normal cannabiripsol (CBR) and trihydroxy-delta-9-tetrahydrocan skin. Each reaction was scored just before application two through nine. nabinol (triOH-THC). 0.095 Results 4. The topical composition of claim 1, wherein the can 0096. None of the subjects showed any adverse reactions nabinoid receptor agonist comprises one or more of a to the application of the two anti-aging compositions, the naphthoylindole, a naphthylmethylindole, a naphthoylpyr “CBD-AHA day cream,” and the “CBD-AHA-FS night role, a naphthylmethylindene, a phenylacetylindole and a cream’ (data not shown). These results indicate that the cyclohexylphenol. compositions of the invention are safe for topical application 5. The topical composition of claim 1, wherein the to human skin and do not cause skin irritation or sensitiza hydroxy acid is an alpha hydroxy acid, a beta hydroxy acid tion. or a combination thereof. What is claimed is: 6. The topical composition of claim 5, wherein the alpha 1. A topical composition for the rejuvenation or treatment hydroxy acid is lactic acid, citric acid, glycolic acid, man of skin in the form of an ointment, a cream, an emulsion, a delic acid, benzylic acid, malic acid, tartaric acid, glucono lotion, a paste, an unguent, a gel or a Sunscreen comprising lactone, galactonolactone, glucuronolactone, galacturono therapeutically effective amounts of at least one cannabinoid lactone, gulonolactone, ribonolactone, saccharic acid and at least one hydroxy acid in a topically acceptable lactone, pantoylactone, glucoheptonolactone, mannonolac carrier, wherein the cannabinoid is present in a concentration tone or galactoheptonolactone. US 2017/0042791 A1 Feb. 16, 2017

7. The topical composition of claim 5, wherein the beta cannabivarinic acid (THCVA), delta-9-tetrahydrocannabi hydroxy acid is salicylic acid or lipohydroxy acid. varin (THCV), delta-9-tetrahydrocannabiorcolic acid 8. The topical composition of claim 1, further comprising (THCA-C), delta-9-tetrahydrocannabiorcol (THC-C), a stabilizer selected from the group consisting of guar gum, delta-7-cis-iso-tetrahydrocannabivarin, delta-8-tetrahydro Xanthan gum cellulose hyaluronic acid, polyvinyl pyrroli cannabinolic acid (A-THCA), delta-8-tetrahydrocannabinol done (PVP), alginate, chondritin Sulfate, poly gamma glu (A-THC), cannabicyclolic acid (CBLA), cannabicyclol tamic acid, gelatin, chitisin, corn starch and flour, in an (CBL), cannabicyclovarin (CBLV), cannnabielsoic acid A amount from about 0.25% to about 30% (w/v). (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin 9. The topical composition of claim 1, wherein the carrier (CBE), cannabinolic acid (CBNA), cannabinol (CBN), can comprises hemp oil and wherein the topical composition nabinol methylether (CBNM), cannabinol-C (CBN C), further comprises one or more of a thickening agent, an cannabivarin (CBV), cannabinol-C (CBN C), cannabior antibiotic, an antiseptic agent, an antifungal, an antibacterial col (CBN C), cannabinodiol (CBND), cannabinodivarin agent, an analgesic, an antiviral agent or a UV absorbing (CBVD), cannabitriol (CBT), 10-ethoxy-9-hydroxy-delta agent in an amount between 0.1 and 5% by weight of the 6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-6a-tetrahy composition. drocannabinol, cannabitriolvarin (CBTV), ethoxy-cannabit 10. A method to treat a skin disorder or rejuvenate the skin riolvarin (CBTVE), dehydrocannabifuran (DCBF), in a subject in need thereof comprising topically adminis cannabifuran (CBF), cannabichromanon (CBCN), can tering to the Subject a composition in the form of an nabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol ointment, a cream, an emulsion, a lotion, a paste, an unguent, (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5, a gel or a Sunscreen comprising therapeutically effective 6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-pro amounts of at least one cannabinoid and at least one hydroxy pyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso acid in a pharmaceutically acceptable carrier, wherein the HHCV), cannabiripsol (CBR) and trihydroxy-delta-9- cannabinoid is present in a concentration between 0.1 and tetrahydrocannabinol (triCH-THC). 30% by weight of the composition; wherein the hydroxy 16. The method of claim 10, wherein the cannabinoid acid is present in a concentration between 0.1 and 10% by receptor agonist comprises one or more of a naphthoylin weight of the composition; and wherein the cannabinoid is dole, a naphthylmethylindole, a naphthoylpyrrole, a naph one or more of a natural phytocannabinoid, an organic thylmethylindene, a phenylacetylindole and a cyclohexyl cannabinoid, an endocannabinoid, a cannabinoid analog, a phenol. cannabinoid derivative, a synthetic cannabinoid and a can 17. The method of claim 10, wherein the hydroxy acid is nabinoid receptor agonist. an alpha hydroxy acid, a beta hydroxy acid or a combination 11. The method of claim 10, wherein the skin disorder is thereof. one or more of eczema, psoriasis, dermatitis, itching der 18. The method of claim 17, wherein the alpha hydroxy matosis, rosacea, perioral dermatitis, acne, non-melanoma acid is lactic acid, citric acid, glycolic acid, mandelic acid, cancer or melanoma. benzylic acid, malic acid, tartaric acid, gluconolactone, 12. The method of claim 10, wherein the subject presents galactonolactone, glucuronolactone, galacturonolactone, a symptom which is one or more of pruritus, dryness, skin gulonolactone, ribonolactone, Saccharic acid lactone, pan rash, redness, Swelling of the skin, itching, crusting, flaking, toylactone, glucoheptonolactone, mannonolactone, or blistering, cracking, oozing, or bleeding of the skin. galactoheptonolactone. 13. The method of claim 11, wherein the dermatitis is 19. The method of claim 17, wherein the beta hydroxy atopic dermatitis, contact dermatitis, Xerotic eczema, or acid is salicylic acid or lipohydroxy acid. seborrheic dermatitis. 20. The method of claim 10, wherein the composition 14. The method of claim 10, wherein the organic can further comprises a stabilizer selected from the group con nabinoid is hemp oil or human breast milk. sisting of guar gum, Xanthan gum cellulose hyaluronic acid, 15. The method of claim 10, wherein the cannabinoid is one or more of cannabigerolic acid (CBGA), cannabigerolic polyvinyl pyrrolidone (PVP), alginate, chondritin sulfate, acid monomethylether (CBGAM), cannabigerol (CBG), polygamma glutamic acid, gelatin, chitisin, corn starch and cannabigerol monomethylether (CBGM), cannabigero flour, in an amount from about 0.25% to about 30% (w/v). varinic acid (CBGVA), cannabigerovarin (CBGV), cannabi 21. The method of claim 10, wherein the carrier comprises chromenic acid (CBCA), cannabichromene (CBC), cannabi hemp oil and wherein the composition further comprises one chromevarinic acid (CBCVA), cannabichromevarin or more of a thickening agent, an antibiotic, an antiseptic (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), agent, an antifungal, an antibacterial agent, an analgesic, an cannabidiol monomethylether (CBDM), cannabidiol-C antiviral agent or a UV absorbing agent in an amount (CBD-C), cannabidivarinic acid (CBDVA), cannabidivarin between 0.1 and 5% by weight of the composition. (CBDV), cannabidiorcol (CBD-C), delta-9-tetrahydrocan 22. The method of claim 10, wherein the subject is a nabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic human and wherein the composition is topically adminis acid B (THCA-B), delta-9-tetrahydrocannabinol (THC), tered to the subject in an amount between about 100 nmol to delta-9-tetrahydrocannabinolic acid-C (THCA-C), delta about 1 umol/cm. 9-tetrahydrocannabinol-C (THC-C), delta-9-tetrahydro