WO2016183134A1 - Palmitoylethanolamide compositions - Google Patents

Palmitoylethanolamide compositions Download PDF

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Publication number
WO2016183134A1
WO2016183134A1 PCT/US2016/031742 US2016031742W WO2016183134A1 WO 2016183134 A1 WO2016183134 A1 WO 2016183134A1 US 2016031742 W US2016031742 W US 2016031742W WO 2016183134 A1 WO2016183134 A1 WO 2016183134A1
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Prior art keywords
composition
agent
fragrance
total concentration
group
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PCT/US2016/031742
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French (fr)
Inventor
Curtis W. SLIPMAN
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Cutting Edge Medical Solutions, Llc
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Publication of WO2016183134A1 publication Critical patent/WO2016183134A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • compositions comprising palmitoylethanolamide, and more particularly to compositions comprising palmitoylethanolamide and an antiinflammatory or anti-pain component.
  • Nutraceutical s are a class of natural products that are attracting increased attention in the medical and herbal supplement communities.
  • a nutraceutical is a food or food component that is believed to have beneficial effects on human health.
  • composition comprising:
  • composition comprising:
  • a composition provided herein further comprises one or more emulsifying agents.
  • each of the one or more emulsifying agents is a non-ionic emulsifying agent.
  • each of the one or more emulsifying agents is independently selected from the group consisting of a Cio- 30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, and a glycerol alkyl ether.
  • a composition provided herein further comprises one or more emulsifying agents selected from the group consisting of:
  • a composition provided herein further comprises one or more emollients.
  • each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, and a Cio-30 silicone.
  • each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, and a botanical oil.
  • a composition provided herein further comprises one or more emollients selected from the group consisting of:
  • a composition provided herein further comprises one or more preservatives.
  • each of the one or more preservatives is independently selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, and glycereth-2 cocoate,
  • a composition provided herein further comprises one or more preservatives selected from the group consisting of:
  • a composition provided herein further comprises one or more anti-static agents.
  • each of the one or more anti-static agents is independently selected from the group consisting of a Cio-30 amine, a Cio-30 amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, and cellulose or a derivative thereof.
  • a composition provided herein further comprises an anti-static agent, wherein the antistatic agent is hydroxypropyl methyl cellulose.
  • a composition provided herein further comprises one or more film forming agents.
  • each of the one or more film forming agents is independently selected from the group consisting of
  • a composition provided herein further comprises a film forming agent, wherein the film forming agent is selected from the group consisting of a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, and mixtures thereof.
  • composition provided herein further comprises one or more moisturizing agents. In some embodiments, each of the one or more
  • moisturizing agents is independently selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci-30 alkylene glycol.
  • a composition provided herein further comprises a moisturizing agent, wherein the moisturizing agent is aloe barbadensis leaf juice.
  • a composition provided herein further comprises one or more moisture barrier agents.
  • each of the one or more moisturizing barrier agents is independently selected from petroleum jelly and mineral oil.
  • a composition provided herein further comprises a moisture barrier agent, wherein the moisture barrier agent is mineral oil.
  • a composition provided herein further comprises one or more antioxidants.
  • each of the one or more antioxidants is independently selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, and an anthocyanin.
  • composition provided herein further comprises an antioxidant, wherein the antioxidant is ( ⁇ / ⁇ , ⁇ , ⁇ )- l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta- l,6-diene-3,5-dione.
  • a composition provided herein further comprises one or more bleaching agents.
  • each of the one or more bleaching agents is independently selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropylcatechol, and lemon juice.
  • a composition provided herein further comprises one or more bleaching agents selected from the group consisting of:
  • a composition provided herein further comprises one or more anti-foaming agents.
  • each of the one or more anti- foaming agents is independently selected from the group consisting of a silicone based anti-foaming agent, a water-based anti-foaming agent, and an oil-based anti- foaming agent.
  • a composition provided herein further comprises an anti-foaming agent, wherein the anti-foaming agent is dimethicone.
  • a composition provided herein further comprises one or more fragrance agents.
  • each of the one or more fragrance agents is independently selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, and mixtures of any two or more thereof.
  • a composition provided herein further comprises one or more of the following components:
  • the silica gel comprises trimethylated silica gel.
  • the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate. In some embodiments, the salicylate is triethanolamine salicylate.
  • each of the one or more solvents is independently selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
  • the solvent is water.
  • the total concentration of emulsifying agent is from about 1 to about 15 wt %. In some embodiments, the total concentration of emulsifying agent is from about 3 to about 15 wt %. In some embodiments, the total concentration of emulsifying agent is from about 5 to about 13 wt %.
  • the total concentration of emollient is from about 1 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 3 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 5 to about 20 wt %.
  • the total concentration of preservative is from about 0.05 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.1 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.2 to about 3 wt %.
  • the total concentration of anti-static agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of anti-static agent is from about 0.05 to about 2 wt %. In some embodiments, the total
  • concentration of anti- static agent is from about 0.1 to about 1.5 wt %. In some embodiments, the total concentration of film forming agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of film forming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of film forming agent is from about 0.1 to about 1.5 wt %.
  • the total concentration of moisturizing agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.1 to about 1.5 wt %.
  • the total concentration of moisture barrier agent is from about 1 to about 8 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 1.5 to about 7 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 2 to about 6 wt %.
  • the total concentration of antioxidant is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of antioxidant is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of antioxidant is from about 0.1 to about 1.5 wt %.
  • the total concentration of bleaching agent is from about 0.5 to about 6 wt %. In some embodiments, the total concentration of bleaching agent is from about 1 to about 5 wt %. In some embodiments, the total concentration of bleaching agent is from about 1.5 to about 4.5 wt %.
  • the total concentration of anti-foaming agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of anti- foaming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of anti-foaming agent is from about 0.1 to about 1.5 wt %.
  • the total concentration of fragrance agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of fragrance agent is from about 0.05 to about 2 wt %. In some embodiments, the total
  • concentration of fragrance agent is from about 0.1 to about 1.5 wt %.
  • dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis- Isobutyl PPG-20 crosspolymer is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.1 to about 1.5 wt %.
  • the total concentration of silica gel is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of silica gel is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of silica gel is from about 0.1 to about 1.5 wt %.
  • the total concentration of salicylate is from about 5 to about 15 wt %. In some embodiments, the total concentration of salicylate is from about 5 to about 12 wt %. In some embodiments, the total concentration of salicylate is from about 8 to about 12 wt %.
  • the total concentration of palmitoylethanolamide is from about 1 to about 5 wt %. In some embodiments, the total concentration of palmitoylethanolamide is from about 1 to about 3 wt %. In some embodiments, the total concentration of solvent is from about 35 to about 75 wt %.
  • the total concentration of solvent is from about 40 to about 70 wt %. In some embodiments, the total concentration of solvent is from about 45 to about 65 wt %.
  • the pharmaceutically acceptable salt thereof is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.1 to about 1.5 wt %.
  • composition comprising:
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • the present application further provides a composition, compri about 0.5 to about 3 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • the present application further provides a composition, compri about 1 to about 3 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 2 wt % of fragrance agent
  • the present application further provides a composition, comprising: about 0.5 to about 5 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • the present application further provides a composition, comprising: about 0.5 to about 3 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • composition comprising:
  • the emulsifying agent is selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, a glycerol alkyl ether, or any combination thereof.
  • the emulsifying agent is a combination of propylene glycol, glyceryl stearate, PEG- 100 stearate, and stearyl alcohol.
  • the emollient is selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, botanical oil, or any combination thereof.
  • the emollient is a combination of cetearyl alcohol, isopropyl palmitate, caprylic capric triglyceridy, dicaprylyl ether, isodecyl neopentanoate, dimethicone/bis-isobutyl PPG-20 crosspolymer, and Carthamus Tinctorius (Safflower) seed oil.
  • the preservative is selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, glycereth-2 cocoate, or any combination thereof.
  • the preservative is a combination of lecithin, isopropyl palmitate, sorbic acid, potassium sorbate, phenoxyethanol, benzoic acid, ethylhexylglycerin, and glycereth-2 cocoate.
  • the anti-static agent is selected from the group consisting of an aliphatic amine, an ethoxylated aliphatic amine, aliphatic amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, cellulose, a hydroxyalkyl alkyl cellulose derivative, or any combination thereof.
  • the anti-static agent is hydroxypropyl methyl cellulose.
  • the film forming agent is selected from the group consisting of polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof.
  • the film forming agent is a C4-30 acrylate, a (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer, or a combination thereof.
  • the moisturizing agent is selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci-30 alkylene glycols, or any combination thereof. In some embodiments, the moisturizing agent is aloe barbadensis leaf juice.
  • the moisture barrier agent is selected from the group consisting of petroleum jelly, mineral oil, or combinations thereof. In some embodiments, the moisture barrier agent is mineral oil.
  • the antioxidant is selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, an anthocyanin, or any combination thereof.
  • the antioxidant is (1£ ' ,6£)-1-(4- hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6- diene-3,5-dione.
  • the bleaching agent is selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropyl catechol, and lemon juice. In some embodiments, the bleaching agent is a combination of cetearyl alcohol and polysorbate 60.
  • the anti-foaming agent is selected from the group consisting of silicone based anti-foaming agents, water-based anti-foaming agents, oil-based anti-foaming agents, or any combination thereof. In some embodiments, the anti-foaming agent is dimethicone.
  • the fragrance agent is selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, or any combination thereof.
  • the crosspolymer is selected from the group consisting of (dimethicone)-(bis-isobutyl PPG-20) crosspolymer and (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer. In some embodiments, the crosspolymer is dimethicone/bis- isobutyl PPG-20 crosspolymer, or any combination thereof.
  • the silica gel is selected form the group consisting of hydrated silica gel, alkylated silica gel, hydroxylated silica gel, alkoxylated silica gel, or any combination thereof. In some embodiments, the silica gel is trimethylated silica gel.
  • the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate, or any combination thereof. In some embodiments, the salicylate is triethanolamine salicylate.
  • the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
  • composition provided here further comprises isododecane.
  • composition is suitable for topical administration.
  • composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
  • the present application further provides a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
  • the present application further provides a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
  • the present application further provides a method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein.
  • the method comprises topical administration of a composition provided herein.
  • the composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
  • composition comprising:
  • the composition comprises about 200 to about 800 mg palmitoylethanolamide. In some embodiments, the composition comprises about 400 to about 800 mg palmitoylethanolamide.
  • the composition comprises about 200 to about 800 mg of a curcuminoid. In some embodiments, the composition comprises about 300 to about 600 mg of a curcuminoid. In some embodiments, the curcuminoid is selected from the group consisting of (l J E , ,6£)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6- heptadiene-3 , 5 -dione (curcumin), ⁇ IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (desmethoxycurcumin), (lE,6E)-l,7-bis(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (bisdemethoxy curcumin), (1£ ' ,6£)-1-(4- hydroxy-3-me
  • the curcuminoid is ( IE, 6E)-l -(4-hy droxy-3 -methoxyphenyl)-7-(4-hydroxy-5- methoxycyclohex-3 -en- 1 -yl)hepta- 1 ,6-diene-3 ,5-dione.
  • composition provided herein further comprises a pharmaceutically acceptable excipient.
  • a composition provided herein further comprises a capsule.
  • the capsule is a methyl cellulose capsule.
  • the present application further provides a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
  • the present application further provides a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
  • the present application further provides a method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein.
  • the method comprises oral administration of a composition provided herein.
  • the term "therapeutically effective amount" of a composition with respect to the subject method of treatment refers to an amount of the
  • conjugate(s) in a preparation which, when administered as part of a desired dosage regimen (to a patient, e.g., a human) alleviates a symptom, ameliorates a condition, or slows the onset of conditions according to clinically acceptable standards for the disorder or condition to be treated or the cosmetic purpose, e.g., at a reasonable benefit/risk ratio applicable to any treatment.
  • treating includes reversing, reducing, or arresting the symptoms, clinical signs, and underlying pathology of a condition in manner to improve or stabilize a patient's condition.
  • wt % refers to the total percent by weight ⁇ i.e. total concentration by weight) of the composition.
  • a composition comprising about 1 to about 5 wt % of Component A is a composition wherein the total percent by weight of Component A in the composition is about 1 to about 5 wt %.
  • optionally substituted means unsubstituted or substituted.
  • substituted means that a hydrogen atom is removed and replaced by a substituent. It is to be understood that substitution at a given atom is limited by valency.
  • Cn-m indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include Ci-6, Cio-30, and the like.
  • a C4-30 acrylate refers to an acrylate having from 4 to 30 carbon atoms.
  • acrylamide refers to a group having formula
  • a C3-30 acrylamide refers to an acrylamide having from 3 to 30 carbon atoms.
  • Cn-m alkyl refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbon atoms.
  • a Ci-6 alkyl is an alkyl group having 1 to 6 carbon atoms and a Cio-30 alkyl is an alkyl group having 10 to 30 carbon atoms.
  • alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n- pentyl, 2-methyl-l -butyl, 3-pentyl, «-hexyl, 1,2,2-trimethylpropyl, and the like.
  • Cn-m alkenyl refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbon atoms.
  • a C2-6 alkenyl is an alkenyl group having 2 to 6 carbon atoms.
  • Example alkenyl groups include, but are not limited to, ethenyl, «-propenyl, isopropenyl, «-butenyl, sec- butenyl, and the like.
  • Cn-m alkynyl refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons.
  • a C2-6 alkynyl is an alkynyl group having 2 to 6 carbon atoms.
  • Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like.
  • Cn-m alkylene glycol refers to a linear, branched, or cyclic diol (i.e.., a compound having two -OH groups) having n to m carbon atoms.
  • a Ci-30 alkylene glycol is an alkylene glycol group having 1 to 30 carbon atoms.
  • Cn-m alkoxy refers to a group of formula -O-alkyl, wherein the alkyl group has n to m carbons.
  • a Ci-6 alkoxy is an alkoxy group having 1 to 6 carbon atoms.
  • Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., «-propoxy and isopropoxy), tert-butoxy, and the like.
  • Cn-m amine refers to a compound of formula R- H2, wherein R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms.
  • R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms.
  • a C 10-30 amine is an amine group having 10 to 30 carbon atoms.
  • Cio-30 amide refers to a compound of formula R- wherein R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms.
  • R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms.
  • a Cio-30 amide is an amide group having 10 to 30 carbon atoms.
  • Example Cio-30 amides include, but are not limited to decanamide,
  • dodecanamide 2-methyldecanamide, 2,6-dimethyldecanamide, and the like.
  • Ci-6 hydroxyalkyl refers to an alkyl group having n to m carbons and that is substituted by at least 1 hydroxyl group (OH group).
  • a Ci-6 hydroxyalkyl is a hydroxyalkyl group having 1 to 6 carbon atoms.
  • Example Ci-6 hydroxyalkyl groups include hydroxymethyl, 1 -hydroxy ethyl, 2- hydroxyethyl, 2-hydroxypropyl, 2-hydroxyisoproyl, and the like.
  • halo refers to F, CI, Br, or I.
  • polyol refers to a compound having two or more - OH groups.
  • nutraceutical compositions comprising palmitoylethanolamide (PEA), a salicylate, and one or more solvents.
  • PDA palmitoylethanolamide
  • salicylate refers to salicylic acid or a salt or ester thereof.
  • Example salicylates include, but are not limited to methyl salicylate, ethyl salicylate, choline salicylate, triethanol amine salicylate, sodium salicylate, and magnesium salicylate.
  • the composition comprises from about 0.5 to about 5 wt % of palmitoylethanolamide, for example, about 0.5 to about 5 wt %, about 0.5 to about 4 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2.5 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 0.5 to about 1 wt %, about 1 to about 5 wt %, about 1 to about 4 wt %, about 1 to about 3 wt %, about 1 to about 2.5 wt %, about 1 to about 2 wt %, about 1 to about 1.5 wt %, about 1.5 to about 5 wt %, about 1.5 to about 4 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2.5 wt %, about 1.5 to about 2 wt %, about 5 to about 5 wt %, about 4 wt %, about 1.5 to
  • the composition comprises about 2 to about 4 wt % palmitoylethanolamide. In some embodiments, the composition comprises about 1 to about 3 wt % palmitoylethanolamide. In some embodiments, the composition comprises about 2 to about 3 wt %
  • the composition comprises about 2.5 wt % palmitoylethanolamide.
  • the composition comprises about 0.5 to about 15 wt % of a salicylate, for example, about 0.5 to about 15 wt %, about 0.5 to about 12 wt %, about 0.5 to about 10 wt %, about 0.5 to about 8 wt %, about 0.5 to about 6 wt %, about 0.5 to about 4 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1 wt %, about 1 to about 15 wt %, about 1 to about 12 wt %, about 1 to about 10 wt %, about
  • the total concentration of salicylate is from about 5 to about 12 wt %. In some embodiments, the total concentration of salicylate is from about 8 to about 12 wt %. In some embodiments, the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate. In some embodiments, the salicylate is triethanolamine salicylate.
  • the composition comprises from about 35 to about 75 wt % of one or more solvents, for example, about 35 to about 75 wt %, about 35 to about 65 wt %, about 35 to about 55 wt %, about 35 to about 45 wt %, about 45 to about 75 wt %, about 45 to about 65 wt %, about 45 to about 55 wt %, about 55 to about 75 wt %, about 55 to about 65 wt %, or about 65 to about 75 wt %.
  • the total concentration of solvent is from about 35 to about 75 wt %.
  • the total concentration of solvent is from about 40 to about 70 wt %.
  • the total concentration of solvent is from about 45 to about 65 wt %.
  • Example solvents may include, but are not limited to, water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
  • At least one of the one or more solvents is water.
  • the composition comprises one solvent.
  • the solvent is water.
  • the composition comprises:
  • composition provided herein further comprises allantoin, or a pharmaceutically a
  • the allantoin, or a pharmaceutically acceptable salt thereof is synthesized or isolated from botanical extracts (e.g., a comfrey plant). In some embodiments, the allantoin, or a pharmaceutically acceptable salt thereof, is synthesized or isolated from a mammalian byproduct (e.g., urine of a mammal).
  • botanical extracts e.g., a comfrey plant
  • the allantoin, or a pharmaceutically acceptable salt thereof is synthesized or isolated from a mammalian byproduct (e.g., urine of a mammal).
  • the composition comprises about 0.05 to about 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %,
  • the composition comprises about 0.05 to about 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 0.1 to about 1.5 wt % of allantoin, or a pharmaceutically acceptable salt thereof,
  • the composition comprises:
  • composition provided herein further comprises one or more independently selected additional agents provided herein.
  • each of the one or more additional agents is independently selected from the group consisting of an emulsifying agent, an emollient, a preservative, an anti-static agent, a film forming agent, a moisturizing agent, a moisture barrier agent, an antioxidant, an anti-foaming agent, a fragrance agent, a crosspolymer, a silica gel, or any combination thereof.
  • a composition provided herein further comprises one or more emulsifying agents.
  • emulsifying agent(s) refers to a compound or mixture of compounds having hydrophilic and lipophilic properties that is used to promote the mixture of compounds that are substantially immiscible in the absence of the emulsifying agent.
  • the emulsifying agent is a non-ionic emulsifying agent.
  • each of the one or more emulsifying agents is independently selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, a glycerol alkyl ether, or any combination thereof.
  • the composition further comprises one or more of the following emulsifying agents:
  • the total concentration of emulsifying agent is from about 1 to about 15 wt %, for example, from about 1 to about 15 wt %, from about 1 to about 13 wt %, from about 1 to about 10 wt %, from about 1 to about 8 wt %, from about 1 to about 5 wt %, from about 1 to about 2 wt %, from about 2 to about 15 wt %, from about 2 to about 13 wt %, from about 2 to about 10 wt %, from about 2 to about 8 wt %, from about 2 to about 5 wt %, from about 5 to about 15 wt %, from about 5 to about 13 wt %, from about 5 to about 10 wt %, from about 5 to about 8 wt %, from about 8 to about 15 wt %, from about 8 to about 13 wt %, from about 8 to about 10 wt %, from about 10 to about 15 wt %,
  • a composition provided herein further comprises one or more emollients.
  • emollient refers to a compound or a mixture of compounds used to soften or soothe a surface (e.g., reduce itchiness of dry skin, maintain moisture of skin, prevent skin cracking).
  • each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, a botanical oil, or any combination thereof.
  • botanical oil refers to a compound or a mixture of compounds that is synthesized or isolated from a botanical extract (e.g., a plant, a plant seed, a tree leave, tree bark, and the like).
  • Example botanical oils include, but are not limited to, calendula oil, yucca oil, horsetail oil, chamomile oil, nettle oil, white willow bark oil, red clover oil, rosemary oil, lavender oil, rose oil, lemon grass oil, peppermint oil, yarrow oil, sage oil, elderflower oil, safflower seed oil, and aloe barbadensis leaf juice (aloe vera).
  • the emollient is selected from the group consisting of: a) cetearyl alcohol;
  • the total concentration of emollient is from about 1 to about 25 wt %, for example, from about 1 to about 25 wt %, from about 1 to about 20 wt %, from about 1 to about 15 wt %, from about 1 to about 10 wt %, from about 1 to about 5 wt %, from about 1 to about 3 wt %, from about 1 to about 2 wt %, from about 2 to about 25 wt %, from about 2 to about 20 wt %, from about 2 to about 15 wt %, from about 2 to about 10 wt %, from about 2 to about 5 wt %, from about 2 to about 3 wt %, from about 3 to about 25 wt %, from about 3 to about 20 wt %, from about 3 to about 15 wt %, from about 3 to about 10 wt %, from about 3 to about 5 wt %, from about 5 to about 25 wt %, from
  • a composition provided herein further comprises one or more preservatives.
  • preservative(s) refers to a compound or mixture of compounds used to slow, mitigate, or prevent decomposition of a composition provided herein.
  • Example preservatives include, but are not limited to, organic acids, or salts and esters thereof ⁇ e.g., benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, levulinic acid, anisic acid), parabens ⁇ e.g., methylparaben, propylparaben, butylparaben), glycerins (e.g., ethylhexylglycerin), aryl glycol ethers (e.g., 2-phenoxyethanol), lecithin, and glycereth-2 cocoate.
  • organic acids, or salts and esters thereof ⁇ e.g., benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, levulinic acid, anisic acid
  • parabens ⁇ e.g., methylparaben, propylparaben, butylparaben
  • glycerins e.g., ethylhe
  • each of the one or more preservatives is independently selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, glycereth-2 cocoate, or any combination thereof.
  • composition further comprises one or more of the following preservatives:
  • the total concentration of preservative is from about 0.05 to about 5 wt %, for example, from about 0.05 to about 5 wt %, from about 0.05 to about 4 wt %, from about 0.05 to about 3 wt %, from about 0.05 to about 2 wt %, from about 0.05 to about 1 wt %, from about 0.05 to about 0.5 wt %, from about 0.05 to about 0.2 wt %, from about 0.05 to about 0.1 wt %, from about 0.1 to about 5 wt %, from about 0.1 to about 4 wt %, from about 0.1 to about 3 wt %, from about 0.1 to about 2 wt %, from about 0.1 to about 1 wt %, from about 0.1 to about 0.5 wt %, from about 0.1 to about 0.2 wt %, from about 0.2 to about 5 wt %, from about 0.2 to about 4 wt %, from about 0.1
  • a composition provided herein further comprises one or more anti-static agents.
  • anti-static agent refers to a compound or a mixture of compounds that is used to reduce or eliminate an excess accumulation of static electricity.
  • Example anti-static agents include, but are not limited to Cio-30 amines, Cio-30 amides, quaternary ammonium salts (e.g.,
  • behentrimonium chloride cocamidopropyl betaine
  • phosphoric acid esters polyethylene glycol esters, polyols, cellulose or derivatives thereof (e.g.,
  • hydroxypropyl methyl cellulose or any combination thereof.
  • each of the one or more anti-static agents is independently selected from one or more anti-static agents.
  • the composition comprises an anti-static agent, wherein the anti-static agent is hydroxypropyl methyl cellulose.
  • the total concentration of anti-static agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 0.2 to
  • a composition provided herein further comprises one or more film forming agents.
  • film forming agent(s) refers to a compound or mixture of compounds that maintain a cohesive and/or continuous covering over a surface (e.g., skin) upon application to the surface.
  • Example film forming agents include, but are not limited to polyvinylpyrrolidone, C3-30 acrylamides, C4-30 acrylates, (C 10-30 alkyl)-(C4-3o acrylate) crosspolymers, or any combination thereof.
  • each of the one or more film forming agents is independently selected from the group consisting of polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof.
  • the composition further comprises a film forming agent, wherein the film forming agent is selected from the group consisting of a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or a combination thereof.
  • the total concentration of film forming agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 0.2 to
  • concentration of film forming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of film forming agent is from about 0.1 to about 1.5 wt %.
  • a composition provided herein further comprises one or more moisturizing agents.
  • moisturizing agent(s) refers to a compound or a mixture of compounds that increases hydration of a surface (e.g., skin) by reducing evaporation from the surface.
  • moisturizing agents include, but are not limited to botanical oils, alpha hydroxyl acids, and Ci-30 alkylene glycols (e.g., propylene glycol, butylene glycol, hexylene glycol).
  • each of the one or more moisturizing agents is independently selected from the group consisting of a botanical oil, an alpha hydroxyl acid, a Ci-30 alkylene glycol, or any combination thereof.
  • the composition further comprises a moisturizing agent, wherein the moisturizing agent is a botanical oil.
  • the composition further comprises a moisturizing agent, wherein the moisturizing agent is aloe barbadensis leaf juice (aloe vera).
  • the total concentration of moisturizing agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 0.2 to
  • concentration of moisturizing agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.1 to about 1.5 wt %.
  • a composition provided herein further comprises one or more moisture barrier agents.
  • moisture barrier agent refers to a compound or mixture of compounds used to prevent excess moisture from contacting a surface and/or prevent excess moisture from leaving a surface (e.g., evaporate).
  • Example moisture barrier agents include but are not limited to petroleum jelly and mineral oil.
  • each of the one or more moisturizing barrier agents is independently selected from the group consisting of petroleum jelly and mineral oil, or any combination thereof .
  • the composition comprises a moisture barrier agent, wherein the moisture barrier agent is mineral oil.
  • the total concentration of moisture barrier agent is from about 1 to about 8 wt %, for example, about 1 to about 8 wt %, about 1 to about 7 wt %, about 1 to about 6 wt %, about 1 to about 5 wt %, about 1 to about 4 wt %, about 1 to about 3 wt %, about 1 to about 2 wt %, about 1 to about 1.5 wt %, about 1.5 to about 8 wt %, about 1.5 to about 7 wt %, about 1.5 to about 6 wt %, about 1.5 to about 5 wt %, about 1.5 to about 4 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, about 2 to about 8 wt %, about 2 to about 7 wt %, about 2 to about 6 wt %, about 2 to about 5 wt %, about 2 to about 4 wt %, about 2 to about 3 wt %,
  • a composition provided herein further comprises one or more antioxidants.
  • antioxidants include, but are not limited to curcuminoids (e.g., (lE,6E)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione (curcumin), (1E,6E)- 1 -(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta- 1,6- diene-3,5-dione (desmethoxycurcumin), (lE,6E)-l,7-bis(4-hydroxyphenyl)hepta-l,6- diene-3,5-dione (bisdemethoxycurcumin), (lE,6E)-l-(4-hydroxy-3-meth curcumin), (1E,6E)- 1 -(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta- 1,6- die
  • each of the one or more antioxidants is independently selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone
  • the composition further comprises an antioxidant, wherein the antioxidant is a curcuminoid. In some embodiments, the composition further comprises an antioxidant, wherein the antioxidant is (lE,6E)-l-(4-hydroxy-3- methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5- dione.
  • the total concentration of antioxidant is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %
  • a composition provided herein further comprises one or more bleaching agents.
  • bleaching agent(s) refers to a pharmaceutically acceptable compound or a pharmaceutically acceptable mixture of compounds that partially or fully bleach (i.e., lighten) a surface (e.g., skin) upon contact with the surface.
  • bleaching agents include, but are not limited to, cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid,
  • the bleaching agent is a pharmaceutically acceptable skin lightening agent.
  • each of the one or more bleaching agents is independently selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropylcatechol, lemon juice, or any combination thereof.
  • the composition comprises one or more of the following bleaching agents:
  • the total concentration of bleaching agent is from about 0.5 to about 6 wt %, for example, about 0.5 to about 6 wt %, about 0.5 to about 5.5 wt %, about 0.5 to about 5 wt %, about 0.5 to about 4.5 wt %, about 0.5 to about 4 wt %, about 0.5 to about 3.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2.5 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 0.5 to about 1 wt %, about 1 to about 6 wt %, about 1 to about 5.5 wt %, about 1 to about 5 wt %, about 1 to about 4.5 wt %, about 1 to about 4 wt %, about 1 to about 3.5 wt %, about 1 to about 3 wt %, about 1 to about 2.5 wt %,
  • the total concentration of bleaching agent is from about 1.5 to about 4.5 wt %.
  • a composition provided herein further comprises one or more anti-foaming agents.
  • anti-foaming agent(s) refers to a pharmaceutically acceptable compound or a pharmaceutically acceptable mixture of compounds that are used to reduce, mitigate, or prevent foaming of a composition.
  • Example anti-foaming agents include, but are not limited to silicone based anti- foaming agents, water-based anti-foaming agents, and oil-based anti-foaming agents.
  • the one or more anti-foaming agents are selected from the group consisting of silicone based anti-foaming agents, water-based anti-foaming agents, oil-based anti-foaming agents, or any combination thereof.
  • the composition comprises an anti-foaming agent, wherein the anti- foaming agent is a silicone based anti-foaming agent.
  • the anti- foaming agent is dimethicone.
  • the total concentration of anti-foaming agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 0.2 to
  • concentration of anti-foaming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of anti-foaming agent is from about 0.1 to about 1.5 wt %.
  • the composition further comprises one or more fragrance agents.
  • the one or more fragrance agents are selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, or any
  • the composition further comprises a fragrance agent, wherein the fragrance agent is a combination of fresh rain and aloe fragrance.
  • the total concentration of fragrance agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3
  • concentration of fragrance agent is from about 0.1 to about 1.5 wt %.
  • a composition provided herein further comprises one or more crosspolymers.
  • crosspolymer(s) refers to a mixture of independently selected polymers that are partially or fully crosslinked.
  • Example crosspolymers may be found, for example, in Gottschalck T.E., and Breslawec H.P., International Cosmetic Ingredient Dictionary and Handbook, 14 th ed. Washington, D.C., Personal Care Products Council, 2012.
  • the composition further comprises a crosspolymer selected from the group consisting of (dimethicone)-(bis-isobutyl PPG-20) crosspolymer, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof.
  • a composition provided herein further comprises isododecane.
  • dimethicone/bis-isobutyl PPG-20 crosspolymer is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5
  • the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis- Isobutyl PPG-20 crosspolymer is from about 0.1 to about 1.5 wt %.
  • a composition provided herein further comprises silica gel.
  • the silica gel is selected from the group consisting of hydrated silica gel, alkylated silica gel, hydroxylated silica gel, alkoxylated silica gel, or any combination thereof.
  • the silica gel is alkylated silica gel.
  • the silica gel is trimethylated silica gel.
  • the total concentration of silica gel is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 0.2 to
  • the composition comprises one or more emulsifying agents, one or more emollients, one or more preservatives, one or more anti-static agents, one or more film forming agents, one or more moisturizing agents, one or more moisture barrier agents, one or more antioxidants, one or more anti-foaming agents, one or more fragrance agents, one or more crosspolymers, and one or more silica gels.
  • a composition provided herein further comprises isododecane.
  • the composition comprises palmitoylethanolamide, a salicylate, one or more solvents, and one or more emulsifying agents.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, a salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, and one or more emulsifying agents.
  • the composition comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, and one or more emollients.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, and one or more emollients.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, one or more emollients, and one or more moisturizing agents.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, one or more emollients, and one or more moisturizing agents.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, one or more emollients, one or more moisturizing agents, and one or more antioxidants.
  • the composition comprises:
  • the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, one or more emollients, one or more moisturizing agents, and one or more antioxidants.
  • the composition comprises:
  • a composition provided herein comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • a composition provided herein comprises: about 0.5 to about 3 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • a composition provided herein comprises: about 1 to about 3 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 2 wt % of fragrance agent
  • a composition provided herein comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
  • fragrance agent about 0.05 to about 3 wt % of fragrance agent
  • a composition provided herein comprises: about 0.5 to about 3 wt % of palmitoylethanolamide;
  • composition provided herein comprises:
  • fragrance agent about 0.05 to about 2 wt % of fragrance agent
  • the composition is suitable for topical administration.
  • the composition is in the form of an ointment, a lotion, a cream, a gel, a liquid, a foam, or an oil.
  • the composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
  • the present application further provides a composition comprising palmitoylethanolamide and a curcuminoid.
  • curcuminoid refers dicycloheptanoid of the following formula: or a pharmaceutically acceptable salt thereof, wherein:
  • each represents a single or double bond
  • each R is independently selected from the group consisting of OH, SH, CN, NO2, halo, oxo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 hydroxyalkyl, and Ci-6 alkoxy; and
  • each n is independently 0, 1, 2, 3, 4, or 5.
  • Example curcuminoids include, but are not limited to:
  • the composition comprises about 100 to about 1000 mg of palmitoylethanolamide, for example, about 100 to 1000 mg, about 100 to about 900 mg, about 100 to about 800 mg, about 100 to about 700 mg, about 100 to about 600 mg, about 100 to about 500 mg, about 100 to about 400 mg, about 100 to about 300 mg, about 100 to about 200 mg, about 200 to 1000 mg, about 200 to about 900 mg, about 200 to about 800 mg, about 200 to about 700 mg, about 200 to about 600 mg, about 200 to about 500 mg, about 200 to about 400 mg, about 200 to about 300 mg, about 300 to 1000 mg, about 300 to about 900 mg, about 300 to about 800 mg, about 300 to about 700 mg, about 300 to about 600 mg, about 300 to about 500 mg, about 300 to about 400 mg, about 400 to 1000 mg, about 400 to 1000 mg, about 400 to 1000 mg, about 400 to about 900 mg, about 400 to about 800 mg, about 400 to about 700 mg, about 400 to about 600 mg, about 400 to about 500 mg, about 500 to about 900 mg, about 500 to
  • the composition comprises about 100 to about 1000 mg of a curcuminoid, for example, about 100 to 1000 mg, about 100 to about 900 mg, about 100 to about 800 mg, about 100 to about 700 mg, about 100 to about 600 mg, about 100 to about 500 mg, about 100 to about 400 mg, about 100 to about 300 mg, about 100 to about 200 mg, about 200 to 1000 mg, about 200 to about 900 mg, about 200 to about 800 mg, about 200 to about 700 mg, about 200 to about 600 mg, about 200 to about 500 mg, about 200 to about 400 mg, about 200 to about 300 mg, about 300 to 1000 mg, about 300 to about 900 mg, about 300 to about 800 mg, about 300 to about 700 mg, about 300 to about 600 mg, about 300 to about 500 mg, about 300 to about 400 mg, about 400 to 1000 mg, about 400 to 1000 mg, about 400 to 1000 mg, about 400 to about 900 mg, about 400 to about 800 mg, about 400 to about 700 mg, about 400 to about 600 mg, about 400 to about 500 mg, about 500 to about 900 mg, about 500 to
  • the composition comprises about 300 to about 600 mg of a curcuminoid.
  • the curcuminoid is a natural curcuminoid.
  • the composition comprises:
  • the curcuminoid is selected from the group consisting of:
  • the composition comprises:
  • the composition comprises:
  • the composition comprises:
  • the composition comprises:
  • the curcuminoid is ( IE, 6E)-l -(4-hy droxy-3 - methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5- dione.
  • the composition comprises 600 mg of
  • the composition is suitable for oral administration.
  • the composition further comprises a pharmaceutically acceptable excipient.
  • the pharmaceutically acceptable excipient is a diluent.
  • the pharmaceutically acceptable excipient is a coating or a binding agent.
  • the composition further comprises a capsule. In some embodiments, the composition is housed within the capsule. In some embodiments, the capsule is a hard-shelled capsule or a soft-shelled capsule. In some embodiments, the capsule is a methyl cellulose capsule.
  • compositions provided herein can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated.
  • the administration is topical (e.g. transdermal, epidermal, ophthalmic, and administration through mucous membranes, including intranasal, vaginal and rectal administration).
  • administration is oral.
  • compositions for topical administration may include, but are not limited to, transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders.
  • Composition for oral administration may include, but are not limited to tablets, pills, powders, lozenges, elixirs, suspensions, emulsions, solutions, syrups, and soft or hard capsules.
  • compositions which contain one or more pharmaceutically acceptable carriers (e.g., pharmaceutically acceptable excipients).
  • the active ingredient is typically mixed with an excipient, diluted by an excipient, or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container.
  • compositions provided herein can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, ointments containing, soft and hard gelatin capsules, suppositories, and sterile packaged powders.
  • the present application further provides methods of reducing or alleviating pain, reducing or alleviating inflammation, and improving the health or nutrition of a subject.
  • the term "subject” refers to any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans.
  • the subject is a human.
  • the method comprises administering to the subject a composition provided herein.
  • the method is a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of reducing pain. In some embodiments, the method is a method of alleviating pain. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
  • the method is a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of reducing inflammation. In some embodiments, the method is a method of alleviating inflammation. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
  • the method is a method of improving heath or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of improving the health of a subject. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
  • composition for topical administration was prepared using the components provided in Table 1.
  • Example 2 Oral Composition A composition for oral administration was prepared and housed within a methyl cellulose tablet, using the components provided in Table 2.

Abstract

The present application provides compositions comprising palmitoylethanolamide, and an anti-inflammatory or anti-pain component. Methods of reducing pain and inflammation are also provided.

Description

Palmitoylethanolamide Compositions
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U. S. Provisional Application Serial No. 62/160,207, filed May 12, 2015, the disclosure of which is incorporated herein by reference in its entirety.
TECHNICAL FIELD
This invention relates to compositions comprising palmitoylethanolamide, and more particularly to compositions comprising palmitoylethanolamide and an antiinflammatory or anti-pain component.
BACKGROUND
Nutraceutical s are a class of natural products that are attracting increased attention in the medical and herbal supplement communities. A nutraceutical is a food or food component that is believed to have beneficial effects on human health.
SUMMARY
The present application provides, inter alia, a composition, comprising:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; and
about 35 to about 75 wt % of one or more solvents.
The present application further provides a composition, comprising:
about 0.5 to 5 wt % of palmitoylethanolamide;
about 5 to 15 wt % of a salicylate;
about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof; and
about 35 to about 75 wt % of one or more solvents.
In some embodiments, a composition provided herein further comprises one or more emulsifying agents. In some embodiments, each of the one or more emulsifying agents is a non-ionic emulsifying agent. In some embodiments, each of the one or more emulsifying agents is independently selected from the group consisting of a Cio- 30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, and a glycerol alkyl ether. In some embodiments, a composition provided herein further comprises one or more emulsifying agents selected from the group consisting of:
a) propylene glycol;
b) glyceryl stearate
c) PEG- 100 stearate; and
d) stearyl alcohol.
In some embodiments, a composition provided herein further comprises one or more emollients. In some embodiments, each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, and a Cio-30 silicone. In some embodiments, each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, and a botanical oil. In some embodiments, a composition provided herein further comprises one or more emollients selected from the group consisting of:
a) cetearyl alcohol;
b) isopropyl palmitate;
c) caprylic capric triglyceride;
d) dicaprylyl ether;
e) isodecyl neopentanoate; and
f) Carthamus Tinctorius (Safflower) Seed Oil.
In some embodiments, a composition provided herein further comprises one or more preservatives. In some embodiments, each of the one or more preservatives is independently selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, and glycereth-2 cocoate, In some embodiments, a composition provided herein further comprises one or more preservatives selected from the group consisting of:
a) lecithin;
b) isopropyl palmitate;
c) sorbic acid; d) potassium sorbate; and
e) phenoxyethanol;
f) benzoic acid;
g) ethylhexylglycerin; and
h) glycereth-2 cocoate.
In some embodiments, a composition provided herein further comprises one or more anti-static agents. In some embodiments, each of the one or more anti-static agents is independently selected from the group consisting of a Cio-30 amine, a Cio-30 amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, and cellulose or a derivative thereof. In some embodiments, a composition provided herein further comprises an anti-static agent, wherein the antistatic agent is hydroxypropyl methyl cellulose.
In some embodiments, a composition provided herein further comprises one or more film forming agents. In some embodiments, each of the one or more film forming agents is independently selected from the group consisting of
polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, and mixtures thereof. In some embodiments, a composition provided herein further comprises a film forming agent, wherein the film forming agent is selected from the group consisting of a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, and mixtures thereof.
In some embodiments, a composition provided herein further comprises one or more moisturizing agents. In some embodiments, each of the one or more
moisturizing agents is independently selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci-30 alkylene glycol. In some embodiments, a composition provided herein further comprises a moisturizing agent, wherein the moisturizing agent is aloe barbadensis leaf juice.
In some embodiments, a composition provided herein further comprises one or more moisture barrier agents. In some embodiments, each of the one or more moisturizing barrier agents is independently selected from petroleum jelly and mineral oil. In some embodiments, a composition provided herein further comprises a moisture barrier agent, wherein the moisture barrier agent is mineral oil. In some embodiments, a composition provided herein further comprises one or more antioxidants. In some embodiments, each of the one or more antioxidants is independently selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, and an anthocyanin. In some embodiments, a composition provided herein further comprises an antioxidant, wherein the antioxidant is (Ι/ί,ό,Ε)- l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta- l,6-diene-3,5-dione.
In some embodiments, a composition provided herein further comprises one or more bleaching agents. In some embodiments, each of the one or more bleaching agents is independently selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropylcatechol, and lemon juice. In some embodiments, a composition provided herein further comprises one or more bleaching agents selected from the group consisting of:
a) cetearyl alcohol; and
b) polysorbate 60.
In some embodiments, a composition provided herein further comprises one or more anti-foaming agents. In some embodiments, each of the one or more anti- foaming agents is independently selected from the group consisting of a silicone based anti-foaming agent, a water-based anti-foaming agent, and an oil-based anti- foaming agent. In some embodiments, a composition provided herein further comprises an anti-foaming agent, wherein the anti-foaming agent is dimethicone.
In some embodiments, a composition provided herein further comprises one or more fragrance agents. In some embodiments, each of the one or more fragrance agents is independently selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, and mixtures of any two or more thereof. In some embodiments, a composition provided herein further comprises one or more of the following components:
a) isododecane;
b) dimethicone/bis-isobutyl PPG-20 crosspolymer; and
c) silica gel.
In some embodiments, the silica gel comprises trimethylated silica gel.
In some embodiments, the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate. In some embodiments, the salicylate is triethanolamine salicylate.
In some embodiments, each of the one or more solvents is independently selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof. In some embodiments, the solvent is water.
In some embodiments, the total concentration of emulsifying agent is from about 1 to about 15 wt %. In some embodiments, the total concentration of emulsifying agent is from about 3 to about 15 wt %. In some embodiments, the total concentration of emulsifying agent is from about 5 to about 13 wt %.
In some embodiments, the total concentration of emollient is from about 1 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 3 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 5 to about 20 wt %.
In some embodiments, the total concentration of preservative is from about 0.05 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.1 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.2 to about 3 wt %.
In some embodiments, the total concentration of anti-static agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of anti-static agent is from about 0.05 to about 2 wt %. In some embodiments, the total
concentration of anti- static agent is from about 0.1 to about 1.5 wt %. In some embodiments, the total concentration of film forming agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of film forming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of film forming agent is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of moisturizing agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of moisture barrier agent is from about 1 to about 8 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 1.5 to about 7 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 2 to about 6 wt %.
In some embodiments, the total concentration of antioxidant is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of antioxidant is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of antioxidant is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of bleaching agent is from about 0.5 to about 6 wt %. In some embodiments, the total concentration of bleaching agent is from about 1 to about 5 wt %. In some embodiments, the total concentration of bleaching agent is from about 1.5 to about 4.5 wt %.
In some embodiments, the total concentration of anti-foaming agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of anti- foaming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of anti-foaming agent is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of fragrance agent is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of fragrance agent is from about 0.05 to about 2 wt %. In some embodiments, the total
concentration of fragrance agent is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of isododecane and
dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis- Isobutyl PPG-20 crosspolymer is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of silica gel is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of silica gel is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of silica gel is from about 0.1 to about 1.5 wt %.
In some embodiments, the total concentration of salicylate is from about 5 to about 15 wt %. In some embodiments, the total concentration of salicylate is from about 5 to about 12 wt %. In some embodiments, the total concentration of salicylate is from about 8 to about 12 wt %.
In some embodiments, the total concentration of palmitoylethanolamide is from about 1 to about 5 wt %. In some embodiments, the total concentration of palmitoylethanolamide is from about 1 to about 3 wt %. In some embodiments, the total concentration of solvent is from about 35 to about 75 wt %.
In some embodiments, the total concentration of solvent is from about 40 to about 70 wt %. In some embodiments, the total concentration of solvent is from about 45 to about 65 wt %.
In some embodiments, the total concentration of allantoin, or a
pharmaceutically acceptable salt thereof, is from about 0.05 to about 3 wt %. In some embodiments, the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.1 to about 1.5 wt %.
The present application further provides a composition, comprising:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti- static agent;
about 0.05 to about 3 wt % of film forming agent; about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
The present application further provides a composition, compri about 0.5 to about 3 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 40 to about 70 wt % of solvent;
about 3 to about 15 wt % of emulsifying agent;
about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti-static agent;
about 0.05 to about 2 wt % of film forming agent;
about 0.05 to about 2 wt % of moisturizing agent;
about 1.5 to about 7 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
The present application further provides a composition, compri about 1 to about 3 wt % of palmitoylethanolamide;
about 5 to about 12 wt % of a salicylate;
about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent;
about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative; about 0.1 to about 1.5 wt % of anti-static agent;
about 0.1 to about 1.5 wt % of film forming agent;
about 0.1 to about 1.5 wt % of moisturizing agent;
about 2 to about 6 wt % of moisture barrier agent;
about 0.05 to about 2 wt % of antioxidant;
about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent;
about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
The present application further provides a composition, comprising: about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti-static agent;
about 0.05 to about 3 wt % of film forming agent;
about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
The present application further provides a composition, comprising: about 0.5 to about 3 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; about 0.05 to 2 wt % allantoin, or a pharmaceutically acceptable salt thereof, about 40 to about 70 wt % of solvent;
about 3 to about 15 wt % of emulsifying agent;
about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti-static agent;
about 0.05 to about 2 wt % of film forming agent;
about 0.05 to about 2 wt % of moisturizing agent;
about 1.5 to about 7 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
The present application further provides a composition, comprising:
about 1 to about 3 wt % of palmitoylethanolamide;
about 5 to about 12 wt % of a salicylate;
about 0.1 to 1.5 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent;
about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative;
about 0.1 to about 1.5 wt % of anti -static agent;
about 0.1 to about 1.5 wt % of film forming agent;
about 0.1 to about 1.5 wt % of moisturizing agent;
about 2 to about 6 wt % of moisture barrier agent;
about 0.05 to about 2 wt % of antioxidant;
about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent; about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
In some embodiments, the emulsifying agent is selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, a glycerol alkyl ether, or any combination thereof. In some embodiments,the emulsifying agent is a combination of propylene glycol, glyceryl stearate, PEG- 100 stearate, and stearyl alcohol.
In some embodiments, the emollient is selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, botanical oil, or any combination thereof. In some embodiments, the emollient is a combination of cetearyl alcohol, isopropyl palmitate, caprylic capric triglyceridy, dicaprylyl ether, isodecyl neopentanoate, dimethicone/bis-isobutyl PPG-20 crosspolymer, and Carthamus Tinctorius (Safflower) seed oil.
In some embodiments, the preservative is selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, glycereth-2 cocoate, or any combination thereof. In some embodiments, the preservative is a combination of lecithin, isopropyl palmitate, sorbic acid, potassium sorbate, phenoxyethanol, benzoic acid, ethylhexylglycerin, and glycereth-2 cocoate.
In some embodiments, the anti-static agent is selected from the group consisting of an aliphatic amine, an ethoxylated aliphatic amine, aliphatic amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, cellulose, a hydroxyalkyl alkyl cellulose derivative, or any combination thereof. In some embodiments, the anti-static agent is hydroxypropyl methyl cellulose.
In some embodiments, the film forming agent is selected from the group consisting of polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof. In some
embodiments, the film forming agent is a C4-30 acrylate, a (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer, or a combination thereof.
In some embodiments, the moisturizing agent is selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci-30 alkylene glycols, or any combination thereof. In some embodiments, the moisturizing agent is aloe barbadensis leaf juice.
In some embodiments, the moisture barrier agent is selected from the group consisting of petroleum jelly, mineral oil, or combinations thereof. In some embodiments, the moisture barrier agent is mineral oil.
In some embodiments, the antioxidant is selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, an anthocyanin, or any combination thereof. In some embodiments, the antioxidant is (1£',6£)-1-(4- hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6- diene-3,5-dione.
In some embodiments, the bleaching agent is selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropyl catechol, and lemon juice. In some embodiments, the bleaching agent is a combination of cetearyl alcohol and polysorbate 60.
In some embodiments, the anti-foaming agent is selected from the group consisting of silicone based anti-foaming agents, water-based anti-foaming agents, oil-based anti-foaming agents, or any combination thereof. In some embodiments, the anti-foaming agent is dimethicone.
In some embodiments, the fragrance agent is selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, or any combination thereof.
In some embodiments, the crosspolymer is selected from the group consisting of (dimethicone)-(bis-isobutyl PPG-20) crosspolymer and (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer. In some embodiments, the crosspolymer is dimethicone/bis- isobutyl PPG-20 crosspolymer, or any combination thereof. In some embodiments, the silica gel is selected form the group consisting of hydrated silica gel, alkylated silica gel, hydroxylated silica gel, alkoxylated silica gel, or any combination thereof. In some embodiments, the silica gel is trimethylated silica gel.
In some embodiments, the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate, or any combination thereof. In some embodiments, the salicylate is triethanolamine salicylate.
In some embodiments, the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
In some embodiments, a composition provided here further comprises isododecane.
In some embodiments, a composition provided herein is suitable for topical administration. In some embodiments, composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
The present application further provides a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
The present application further provides a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
The present application further provides a method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein.
In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
The present application further provides a composition, comprising:
about 100 to about 1000 mg palmitoylethanolamide; and
about 100 to about 1000 mg of a curcuminoid. In some embodiments, the composition comprises about 200 to about 800 mg palmitoylethanolamide. In some embodiments, the composition comprises about 400 to about 800 mg palmitoylethanolamide.
In some embodiments, the composition comprises about 200 to about 800 mg of a curcuminoid. In some embodiments, the composition comprises about 300 to about 600 mg of a curcuminoid. In some embodiments, the curcuminoid is selected from the group consisting of (lJE,,6£)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6- heptadiene-3 , 5 -dione (curcumin), {IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (desmethoxycurcumin), (lE,6E)-l,7-bis(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (bisdemethoxy curcumin), (1£',6£)-1-(4- hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6- diene-3,5-dione, and mixtures of two or more thereof. In some embodiments, the curcuminoid is ( IE, 6E)-l -(4-hy droxy-3 -methoxyphenyl)-7-(4-hydroxy-5- methoxycyclohex-3 -en- 1 -yl)hepta- 1 ,6-diene-3 ,5-dione.
In some embodiments, a composition provided herein further comprises a pharmaceutically acceptable excipient.
In some embodiments, a composition provided herein further comprises a capsule. In some embodiments, the capsule is a methyl cellulose capsule.
The present application further provides a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
The present application further provides a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein.
The present application further provides a method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein.
In some embodiments, the method comprises oral administration of a composition provided herein.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.
DETAILED DESCRIPTION
Definitions
For the terms "for example" and "such as" and grammatical equivalences thereof, the phrase "and without limitation" is understood to follow unless explicitly stated otherwise. As used herein, the term "about" is meant to account for variations due to experimental error. All measurements reported herein are understood to be modified by the term "about", whether or not the term is explicitly used, unless explicitly stated otherwise. As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.
As used herein, the term "therapeutically effective amount" of a composition with respect to the subject method of treatment, refers to an amount of the
conjugate(s) in a preparation which, when administered as part of a desired dosage regimen (to a patient, e.g., a human) alleviates a symptom, ameliorates a condition, or slows the onset of conditions according to clinically acceptable standards for the disorder or condition to be treated or the cosmetic purpose, e.g., at a reasonable benefit/risk ratio applicable to any treatment.
As used herein, the term "treating" or "treatment" includes reversing, reducing, or arresting the symptoms, clinical signs, and underlying pathology of a condition in manner to improve or stabilize a patient's condition.
As used herein, the term "wt %" or "weight percent" refers to the total percent by weight {i.e. total concentration by weight) of the composition. For example, it is understood that a composition comprising about 1 to about 5 wt % of Component A is a composition wherein the total percent by weight of Component A in the composition is about 1 to about 5 wt %. As used herein, the phrase "optionally substituted" means unsubstituted or substituted. As used herein, the term "substituted" means that a hydrogen atom is removed and replaced by a substituent. It is to be understood that substitution at a given atom is limited by valency.
Throughout the definitions, the term "Cn-m" indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include Ci-6, Cio-30, and the like.
As used herein, the term "acrylate" refers to group having formula
-(CH=CH)C(=0)0-. For example a C4-30 acrylate refers to an acrylate having from 4 to 30 carbon atoms.
As used here, the term "acrylamide" refers to a group having formula
-(CH=CH)C(=0) H-. For example, a C3-30 acrylamide refers to an acrylamide having from 3 to 30 carbon atoms.
As used herein, the term "Cn-m alkyl", employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbon atoms. For example a Ci-6 alkyl is an alkyl group having 1 to 6 carbon atoms and a Cio-30 alkyl is an alkyl group having 10 to 30 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n- pentyl, 2-methyl-l -butyl, 3-pentyl, «-hexyl, 1,2,2-trimethylpropyl, and the like.
As used herein, "Cn-m alkenyl" refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbon atoms. For example, a C2-6 alkenyl is an alkenyl group having 2 to 6 carbon atoms. Example alkenyl groups include, but are not limited to, ethenyl, «-propenyl, isopropenyl, «-butenyl, sec- butenyl, and the like.
As used herein, "Cn-m alkynyl" refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. For example, a C2-6 alkynyl is an alkynyl group having 2 to 6 carbon atoms. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like.
As used herein, the term "Cn-m alkylene glycol" refers to a linear, branched, or cyclic diol (i.e.., a compound having two -OH groups) having n to m carbon atoms. For example, a Ci-30 alkylene glycol is an alkylene glycol group having 1 to 30 carbon atoms.
As used herein, the term "Cn-m alkoxy", refers to a group of formula -O-alkyl, wherein the alkyl group has n to m carbons. For example, a Ci-6 alkoxy is an alkoxy group having 1 to 6 carbon atoms. Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., «-propoxy and isopropoxy), tert-butoxy, and the like.
As used herein, the term "Cn-m amine" refers to a compound of formula R- H2, wherein R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms. For example, a C 10-30 amine is an amine group having 10 to 30 carbon atoms.
As used herein, the term "Cn-m amide" refers to a compound of formula R-
Figure imgf000018_0001
wherein R is a linear, branched, or cyclic carbon chain comprising n to m carbon atoms. For example, a Cio-30 amide is an amide group having 10 to 30 carbon atoms. Example Cio-30 amides include, but are not limited to decanamide,
dodecanamide, 2-methyldecanamide, 2,6-dimethyldecanamide, and the like.
As used herein, the term "Cn-mhydroxyalkyl" refers to an alkyl group having n to m carbons and that is substituted by at least 1 hydroxyl group (OH group). For example, a Ci-6 hydroxyalkyl is a hydroxyalkyl group having 1 to 6 carbon atoms. Example Ci-6 hydroxyalkyl groups include hydroxymethyl, 1 -hydroxy ethyl, 2- hydroxyethyl, 2-hydroxypropyl, 2-hydroxyisoproyl, and the like.
As used herein, "halo" refers to F, CI, Br, or I.
As used herein, the term "polyol" refers to a compound having two or more - OH groups.
As used herein, "oxo" refers to a group of formula "=0".
It is understood that any compound name or structure provided herein as one particular tautomeric form is intended to include other tautomeric forms unless otherwise specified.
Compositions
The present application provides, inter alia, nutraceutical compositions comprising palmitoylethanolamide (PEA), a salicylate, and one or more solvents. As used herein, the term "salicylate" refers to salicylic acid or a salt or ester thereof. Example salicylates include, but are not limited to methyl salicylate, ethyl salicylate, choline salicylate, triethanol amine salicylate, sodium salicylate, and magnesium salicylate.
In some embodiments, the composition comprises from about 0.5 to about 5 wt % of palmitoylethanolamide, for example, about 0.5 to about 5 wt %, about 0.5 to about 4 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2.5 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 0.5 to about 1 wt %, about 1 to about 5 wt %, about 1 to about 4 wt %, about 1 to about 3 wt %, about 1 to about 2.5 wt %, about 1 to about 2 wt %, about 1 to about 1.5 wt %, about 1.5 to about 5 wt %, about 1.5 to about 4 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2.5 wt %, about 1.5 to about 2 wt %, about 2 to about 5 wt %, about 2 to about 4 wt %, about 2 to about 3 wt %, about 2 to about 2.5 wt %, about 2.5 to about 5 wt %, about 2.5 to about 4 wt %, about 2.5 to about 3 wt %, about 3 to about 5 wt %, about 3 to about 4 wt %, or about 4 to about 5 wt %. In some embodiments, the composition comprises about 2 to about 4 wt % palmitoylethanolamide. In some embodiments, the composition comprises about 1 to about 3 wt % palmitoylethanolamide. In some embodiments, the composition comprises about 2 to about 3 wt %
palmitoylethanolamide. In some embodiments, the composition comprises about 2.5 wt % palmitoylethanolamide.
In some embodiments, the composition comprises about 0.5 to about 15 wt % of a salicylate, for example, about 0.5 to about 15 wt %, about 0.5 to about 12 wt %, about 0.5 to about 10 wt %, about 0.5 to about 8 wt %, about 0.5 to about 6 wt %, about 0.5 to about 4 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1 wt %, about 1 to about 15 wt %, about 1 to about 12 wt %, about 1 to about 10 wt %, about
1 to about 8 wt %, about 1 to about 6 wt %, about 1 to about 4 wt %, about 1 to about
2 wt %, about 2 to about 15 wt %, about 2 to about 12 wt %, about 2 to about 10 wt %, about 2 to about 8 wt %, about 2 to about 6 wt %, about 2 to about 4 wt %, about 4 to about 15 wt %, about 4 to about 12 wt %, about 4 to about 10 wt %, about 4 to about 8 wt %, about 4 to about 6 wt %, about 6 to about 15 wt %, about 6 to about 12 wt %, about 6 to about 10 wt %, about 6 to about 8 wt %, about 8 to about 15 wt %, about 8 to about 12 wt %, about 8 to about 10 wt %, about 10 to about 15 wt %, about 10 to about 12 wt %, or about 12 to about 15 wt %. In some embodiments, the total concentration of salicylate is from about 5 to about 12 wt %. In some embodiments, the total concentration of salicylate is from about 8 to about 12 wt %. In some embodiments, the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate. In some embodiments, the salicylate is triethanolamine salicylate.
In some embodiments, the composition comprises from about 35 to about 75 wt % of one or more solvents, for example, about 35 to about 75 wt %, about 35 to about 65 wt %, about 35 to about 55 wt %, about 35 to about 45 wt %, about 45 to about 75 wt %, about 45 to about 65 wt %, about 45 to about 55 wt %, about 55 to about 75 wt %, about 55 to about 65 wt %, or about 65 to about 75 wt %. In some embodiments, the total concentration of solvent is from about 35 to about 75 wt %. In some embodiments, the total concentration of solvent is from about 40 to about 70 wt %. In some embodiments, the total concentration of solvent is from about 45 to about 65 wt %.
Example solvents may include, but are not limited to, water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof. In some
embodiments, at least one of the one or more solvents is water. In some embodiments, the composition comprises one solvent. In some embodiments, the solvent is water.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; and
about 35 to about 75 wt % of one or more solvents.
In some embodiments, a composition provided herein further comprises allantoin, or a pharmaceutically a
Figure imgf000020_0001
1 -(2,5-dioxoimidazolidin-4-yl)urea
"Allantoin"
In some embodiments, the allantoin, or a pharmaceutically acceptable salt thereof, is synthesized or isolated from botanical extracts (e.g., a comfrey plant). In some embodiments, the allantoin, or a pharmaceutically acceptable salt thereof, is synthesized or isolated from a mammalian byproduct (e.g., urine of a mammal). In some embodiments, the composition comprises about 0.05 to about 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the composition comprises about 0.05 to about 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 0.1 to about 1.5 wt % of allantoin, or a pharmaceutically acceptable salt thereof,
In some embodiments, the composition comprises:
about 0.5 to 5 wt % of palmitoylethanolamide;
about 5 to 15 wt % of a salicylate;
about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof; and
about 35 to about 75 wt % of one or more solvents.
In some embodiments, a composition provided herein further comprises one or more independently selected additional agents provided herein. In some
embodiments, each of the one or more additional agents is independently selected from the group consisting of an emulsifying agent, an emollient, a preservative, an anti-static agent, a film forming agent, a moisturizing agent, a moisture barrier agent, an antioxidant, an anti-foaming agent, a fragrance agent, a crosspolymer, a silica gel, or any combination thereof.
In some embodiments, a composition provided herein further comprises one or more emulsifying agents. As used herein, the term "emulsifying agent(s)" refers to a compound or mixture of compounds having hydrophilic and lipophilic properties that is used to promote the mixture of compounds that are substantially immiscible in the absence of the emulsifying agent. In some embodiments, the emulsifying agent is a non-ionic emulsifying agent. In some embodiments, each of the one or more emulsifying agents is independently selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, a glycerol alkyl ether, or any combination thereof. In some embodiments, the composition further comprises one or more of the following emulsifying agents:
a) propylene glycol;
b) glyceryl stearate
c) PEG- 100 stearate; and
d) stearyl alcohol.
In some embodiments, the total concentration of emulsifying agent is from about 1 to about 15 wt %, for example, from about 1 to about 15 wt %, from about 1 to about 13 wt %, from about 1 to about 10 wt %, from about 1 to about 8 wt %, from about 1 to about 5 wt %, from about 1 to about 2 wt %, from about 2 to about 15 wt %, from about 2 to about 13 wt %, from about 2 to about 10 wt %, from about 2 to about 8 wt %, from about 2 to about 5 wt %, from about 5 to about 15 wt %, from about 5 to about 13 wt %, from about 5 to about 10 wt %, from about 5 to about 8 wt %, from about 8 to about 15 wt %, from about 8 to about 13 wt %, from about 8 to about 10 wt %, from about 10 to about 15 wt %, from about 10 to about 13 wt %, or from about 13 to about 15 wt %, In some embodiments, the total concentration of emulsifying agent is from about 3 to about 15 wt %. In some embodiments, the total concentration of emulsifying agent is from about 5 to about 13 wt %.
In some embodiments, a composition provided herein further comprises one or more emollients. As used herein, the term "emollient" refers to a compound or a mixture of compounds used to soften or soothe a surface (e.g., reduce itchiness of dry skin, maintain moisture of skin, prevent skin cracking).
In some embodiments, each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, a botanical oil, or any combination thereof.
As used herein, the term "botanical oil" refers to a compound or a mixture of compounds that is synthesized or isolated from a botanical extract (e.g., a plant, a plant seed, a tree leave, tree bark, and the like). Example botanical oils include, but are not limited to, calendula oil, yucca oil, horsetail oil, chamomile oil, nettle oil, white willow bark oil, red clover oil, rosemary oil, lavender oil, rose oil, lemon grass oil, peppermint oil, yarrow oil, sage oil, elderflower oil, safflower seed oil, and aloe barbadensis leaf juice (aloe vera).
In some embodiments, the emollient is selected from the group consisting of: a) cetearyl alcohol;
b) isopropyl palmitate;
c) caprylic capric triglyceride;
d) dicaprylyl ether;
e) isodecyl neopentanoate; and
f) Carthamus Tinctorius (Safflower) seed oil.
In some embodiments, the total concentration of emollient is from about 1 to about 25 wt %, for example, from about 1 to about 25 wt %, from about 1 to about 20 wt %, from about 1 to about 15 wt %, from about 1 to about 10 wt %, from about 1 to about 5 wt %, from about 1 to about 3 wt %, from about 1 to about 2 wt %, from about 2 to about 25 wt %, from about 2 to about 20 wt %, from about 2 to about 15 wt %, from about 2 to about 10 wt %, from about 2 to about 5 wt %, from about 2 to about 3 wt %, from about 3 to about 25 wt %, from about 3 to about 20 wt %, from about 3 to about 15 wt %, from about 3 to about 10 wt %, from about 3 to about 5 wt %, from about 5 to about 25 wt %, from about 5 to about 20 wt %, from about 5 to about 15 wt %, from about 5 to about 10 wt %, from about 10 to about 25 wt %, from about 10 to about 20 wt %, from about 10 to about 15 wt %, from about 15 to about 25 wt %, from about 15 to about 20 wt %, or from about 20 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 3 to about 25 wt %. In some embodiments, the total concentration of emollient is from about 5 to about 20 wt %.
In some embodiments, a composition provided herein further comprises one or more preservatives. As used herein, the term "preservative(s)" refers to a compound or mixture of compounds used to slow, mitigate, or prevent decomposition of a composition provided herein. Example preservatives include, but are not limited to, organic acids, or salts and esters thereof {e.g., benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, levulinic acid, anisic acid), parabens {e.g., methylparaben, propylparaben, butylparaben), glycerins (e.g., ethylhexylglycerin), aryl glycol ethers (e.g., 2-phenoxyethanol), lecithin, and glycereth-2 cocoate.
In some embodiments, each of the one or more preservatives is independently selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, glycereth-2 cocoate, or any combination thereof.
In some embodiments, the composition further comprises one or more of the following preservatives:
a) lecithin;
b) isopropyl palmitate;
c) sorbic acid;
d) potassium sorbate; and
e) phenoxyethanol;
f) benzoic acid;
g) ethylhexylglycerin; and
h) glycereth-2 cocoate.
In some embodiments, the total concentration of preservative is from about 0.05 to about 5 wt %, for example, from about 0.05 to about 5 wt %, from about 0.05 to about 4 wt %, from about 0.05 to about 3 wt %, from about 0.05 to about 2 wt %, from about 0.05 to about 1 wt %, from about 0.05 to about 0.5 wt %, from about 0.05 to about 0.2 wt %, from about 0.05 to about 0.1 wt %, from about 0.1 to about 5 wt %, from about 0.1 to about 4 wt %, from about 0.1 to about 3 wt %, from about 0.1 to about 2 wt %, from about 0.1 to about 1 wt %, from about 0.1 to about 0.5 wt %, from about 0.1 to about 0.2 wt %, from about 0.2 to about 5 wt %, from about 0.2 to about 4 wt %, from about 0.2 to about 3 wt %, from about 0.2 to about 2 wt %, from about 0.2 to about 1 wt %, from about 0.2 to about 0.5 wt %, from about 0.5 to about 5 wt %, from about 0.5 to about 4 wt %, from about 0.5 to about 3 wt %, from about 0.5 to about 2 wt %, from about 0.5 to about 1 wt %, from about 1 to about 5 wt %, from about 1 to about 4 wt %, from about 1 to about 3 wt %, from about 1 to about 2 wt %, from about 2 to about 5 wt %, from about 2 to about 4 wt %, from about 1 to about 3 wt %, from about 3 to about 5 wt %, from about 3 to about 4 wt %, or from about 4 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.1 to about 5 wt %. In some embodiments, the total concentration of preservative is from about 0.2 to about 3 wt %.
In some embodiments, a composition provided herein further comprises one or more anti-static agents. As used here, the term "anti-static agent" refers to a compound or a mixture of compounds that is used to reduce or eliminate an excess accumulation of static electricity. Example anti-static agents include, but are not limited to Cio-30 amines, Cio-30 amides, quaternary ammonium salts (e.g.,
behentrimonium chloride, cocamidopropyl betaine), phosphoric acid esters, polyethylene glycol esters, polyols, cellulose or derivatives thereof (e.g.,
hydroxypropyl methyl cellulose), or any combination thereof.
In some embodiments, each of the one or more anti-static agents is
independently selected from the group consisting of a Cio-30 amine, Cio-30 amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, cellulose or a derivative thereof, or any combination thereof. In some embodiments, the composition comprises an anti-static agent, wherein the anti-static agent is hydroxypropyl methyl cellulose.
In some embodiments, the total concentration of anti-static agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total concentration of antistatic agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of anti- static agent is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises one or more film forming agents. As used herein, the term "film forming agent(s)" refers to a compound or mixture of compounds that maintain a cohesive and/or continuous covering over a surface (e.g., skin) upon application to the surface. Example film forming agents include, but are not limited to polyvinylpyrrolidone, C3-30 acrylamides, C4-30 acrylates, (C 10-30 alkyl)-(C4-3o acrylate) crosspolymers, or any combination thereof.
In some embodiments, each of the one or more film forming agents is independently selected from the group consisting of polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (C 10-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof. In some embodiments, the composition further comprises a film forming agent, wherein the film forming agent is selected from the group consisting of a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or a combination thereof.
In some embodiments, the total concentration of film forming agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total
concentration of film forming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of film forming agent is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises one or more moisturizing agents. As used herein, the term "moisturizing agent(s)" refers to a compound or a mixture of compounds that increases hydration of a surface (e.g., skin) by reducing evaporation from the surface. Example moisturizing agents include, but are not limited to botanical oils, alpha hydroxyl acids, and Ci-30 alkylene glycols (e.g., propylene glycol, butylene glycol, hexylene glycol).
In some embodiments, each of the one or more moisturizing agents is independently selected from the group consisting of a botanical oil, an alpha hydroxyl acid, a Ci-30 alkylene glycol, or any combination thereof. In some embodiments, the composition further comprises a moisturizing agent, wherein the moisturizing agent is a botanical oil. In some embodiments, the composition further comprises a moisturizing agent, wherein the moisturizing agent is aloe barbadensis leaf juice (aloe vera).
In some embodiments, the total concentration of moisturizing agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total
concentration of moisturizing agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of moisturizing agent is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises one or more moisture barrier agents. As used herein, the term "moisture barrier agent" refers to a compound or mixture of compounds used to prevent excess moisture from contacting a surface and/or prevent excess moisture from leaving a surface (e.g., evaporate). Example moisture barrier agents include but are not limited to petroleum jelly and mineral oil.
In some embodiments, each of the one or more moisturizing barrier agents is independently selected from the group consisting of petroleum jelly and mineral oil, or any combination thereof . In some embodiments the composition comprises a moisture barrier agent, wherein the moisture barrier agent is mineral oil.
In some embodiments, the total concentration of moisture barrier agent is from about 1 to about 8 wt %, for example, about 1 to about 8 wt %, about 1 to about 7 wt %, about 1 to about 6 wt %, about 1 to about 5 wt %, about 1 to about 4 wt %, about 1 to about 3 wt %, about 1 to about 2 wt %, about 1 to about 1.5 wt %, about 1.5 to about 8 wt %, about 1.5 to about 7 wt %, about 1.5 to about 6 wt %, about 1.5 to about 5 wt %, about 1.5 to about 4 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, about 2 to about 8 wt %, about 2 to about 7 wt %, about 2 to about 6 wt %, about 2 to about 5 wt %, about 2 to about 4 wt %, about 2 to about 3 wt %, about 3 to about 8 wt %, about 3 to about 7 wt %, about 3 to about 6 wt %, about 3 to about 5 wt %, about 3 to about 4 wt %, about 4 to about 8 wt %, about 4 to about 7 wt %, about 4 to about 6 wt %, about 4 to about 5 wt %, about 5 to about 8 wt %, about 5 to about 7 wt %, about 5 to about 6 wt %, about 6 to about 8 wt %, about 6 to about 7 wt %, or about 7 to about 8 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 1.5 to about 7 wt %. In some embodiments, the total concentration of moisture barrier agent is from about 2 to about 6 wt %.
In some embodiments, a composition provided herein further comprises one or more antioxidants. As used here, the term "antioxidant" refers to a compound or a mixture of compounds useful for inhibiting, preventing, or reducing, oxidation in other compounds. Example antioxidants include, but are not limited to curcuminoids (e.g., (lE,6E)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione (curcumin), (1E,6E)- 1 -(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta- 1,6- diene-3,5-dione (desmethoxycurcumin), (lE,6E)-l,7-bis(4-hydroxyphenyl)hepta-l,6- diene-3,5-dione (bisdemethoxycurcumin), (lE,6E)-l-(4-hydroxy-3-methoxyphenyl)- 7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5-dione,), natural vitamins (e.g., Vitamin A, Vitamin C, Vitamin E), flavones (e.g., apigenin, luteolin, tangeritin), flavonols, (e.g., isorhamnetin, kaempferol, myricetin), flavanones (e.g., eriodictyol, hesperetin), flavanols and polymerized flavanols (e.g., catechin, gallocatechin and their corresponding gallate esters, epicatechin, epigallocatechin and their corresponding gallate esters, theaflavin and its corresponding gallate esters), isoflavone phytoestrogens (e.g., daidzein, genistein, glycitein), stilbenoids (e.g., resveratrol, pterostilbene), and anthocyanins (e.g., cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin).
In some embodiments, each of the one or more antioxidants is independently selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone
phytoestrogen, a stilbenoid, an anthocyanin, or any combination thereof. In some embodiments, the composition further comprises an antioxidant, wherein the antioxidant is a curcuminoid. In some embodiments, the composition further comprises an antioxidant, wherein the antioxidant is (lE,6E)-l-(4-hydroxy-3- methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5- dione.
In some embodiments, the total concentration of antioxidant is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total concentration of antioxidant is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of antioxidant is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises one or more bleaching agents. As used herein, the term "bleaching agent(s)" refers to a pharmaceutically acceptable compound or a pharmaceutically acceptable mixture of compounds that partially or fully bleach (i.e., lighten) a surface (e.g., skin) upon contact with the surface. Example bleaching agents include, but are not limited to, cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid,
isopropyl catechol, and lemon juice.
In some embodiments, the bleaching agent is a pharmaceutically acceptable skin lightening agent. In some embodiments, each of the one or more bleaching agents is independently selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropylcatechol, lemon juice, or any combination thereof. In some embodiments, the composition comprises one or more of the following bleaching agents:
a) cetearyl alcohol; and
b) polysorbate 60.
In some embodiments, the total concentration of bleaching agent is from about 0.5 to about 6 wt %, for example, about 0.5 to about 6 wt %, about 0.5 to about 5.5 wt %, about 0.5 to about 5 wt %, about 0.5 to about 4.5 wt %, about 0.5 to about 4 wt %, about 0.5 to about 3.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2.5 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 0.5 to about 1 wt %, about 1 to about 6 wt %, about 1 to about 5.5 wt %, about 1 to about 5 wt %, about 1 to about 4.5 wt %, about 1 to about 4 wt %, about 1 to about 3.5 wt %, about 1 to about 3 wt %, about 1 to about 2.5 wt %, about 1 to about 2 wt %, about 1 to about 1.5 wt %, about 1.5 to about 6 wt %, about 1.5 to about 5.5 wt %, about 1.5 to about 5 wt %, about 1.5 to about 4.5 wt %, about 1.5 to about 4 wt %, about 1.5 to about 3.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2.5 wt %, about 1.5 to about 2 wt %, about 2 to about 6 wt %, about 2 to about 5.5 wt %, about 2 to about 5 wt %, about 2 to about 4.5 wt %, about 2 to about 4 wt %, about 2 to about 3.5 wt %, about 2 to about 3 wt %, about 2 to about 2.5 wt %, about 2.5 to about 6 wt %, about 2.5 to about 5.5 wt %, about 2.5 to about 5 wt %, about 2.5 to about 4.5 wt %, about 2.5 to about 4 wt %, about 2.5 to about 3.5 wt %, about 2.5 to about 3 wt %, about 3 to about 6 wt %, about 3 to about 5.5 wt %, about 3 to about 5 wt %, about 3 to about 4.5 wt %, about 3 to about 4 wt %, about 3 to about 3.5 wt %, about 3.5 to about 6 wt %, about 3.5 to about 5.5 wt %, about 3.5 to about 5 wt %, about 3.5 to about 4.5 wt %, about 3.5 to about 4 wt %, about 4 to about 6 wt %, about 4 to about 5.5 wt %, about 4 to about 5 wt %, about 4 to about 4.5 wt %, about 4.5 to about 6 wt %, about 4.5 to about 5.5 wt %, about 4.5 to about 5 wt %, about 5 to about 6 wt %, about 5 to about 5.5 wt %, or about 5.5 to about 6 wt %. In some embodiments, the total concentration of bleaching agent is from about 1 to about 5 wt %. In some
embodiments, the total concentration of bleaching agent is from about 1.5 to about 4.5 wt %.
In some embodiments, a composition provided herein further comprises one or more anti-foaming agents. As used herein, the term "anti-foaming agent(s)" refers to a pharmaceutically acceptable compound or a pharmaceutically acceptable mixture of compounds that are used to reduce, mitigate, or prevent foaming of a composition. Example anti-foaming agents include, but are not limited to silicone based anti- foaming agents, water-based anti-foaming agents, and oil-based anti-foaming agents.
In some embodiments, the one or more anti-foaming agents are selected from the group consisting of silicone based anti-foaming agents, water-based anti-foaming agents, oil-based anti-foaming agents, or any combination thereof. In some embodiments, the composition comprises an anti-foaming agent, wherein the anti- foaming agent is a silicone based anti-foaming agent. In some embodiments, the anti- foaming agent is dimethicone.
In some embodiments, the total concentration of anti-foaming agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total
concentration of anti-foaming agent is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of anti-foaming agent is from about 0.1 to about 1.5 wt %.
In some embodiments, the composition further comprises one or more fragrance agents. In some embodiments, the one or more fragrance agents are selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, or any
combination thereof. In some embodiments, the composition further comprises a fragrance agent, wherein the fragrance agent is a combination of fresh rain and aloe fragrance.
In some embodiments, the total concentration of fragrance agent is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total concentration of fragrance agent is from about 0.05 to about 2 wt %. In some embodiments, the total
concentration of fragrance agent is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises one or more crosspolymers. As used herein, the term "crosspolymer(s)" refers to a mixture of independently selected polymers that are partially or fully crosslinked. Example crosspolymers may be found, for example, in Gottschalck T.E., and Breslawec H.P., International Cosmetic Ingredient Dictionary and Handbook, 14th ed. Washington, D.C., Personal Care Products Council, 2012.
In some embodiments, the composition further comprises a crosspolymer selected from the group consisting of (dimethicone)-(bis-isobutyl PPG-20) crosspolymer, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof. In some embodiments, a composition provided herein further comprises isododecane.
In some embodiments, the total concentration of isododecane and
dimethicone/bis-isobutyl PPG-20 crosspolymer is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of isododecane and dimethicone/bis- Isobutyl PPG-20 crosspolymer is from about 0.1 to about 1.5 wt %.
In some embodiments, a composition provided herein further comprises silica gel. In some embodiments, the silica gel is selected from the group consisting of hydrated silica gel, alkylated silica gel, hydroxylated silica gel, alkoxylated silica gel, or any combination thereof. In some embodiments, the silica gel is alkylated silica gel. In some embodiments, the silica gel is trimethylated silica gel.
In some embodiments, the total concentration of silica gel is from about 0.05 to about 3 wt %, for example, about 0.05 to about 3 wt %, about 0.05 to about 2 wt %, about 0.05 to about 1.5 wt %, about 0.05 to about 0.5 wt %, about 0.05 to about 0.2 wt %, about 0.05 to about 0.1 wt %, about 0.1 to about 3 wt %, about 0.1 to about 2 wt %, about 0.1 to about 1.5 wt %, about 0.1 to about 0.5 wt %, about 0.1 to about 0.2 wt %, about 0.2 to about 3 wt %, about 0.2 to about 2 wt %, about 0.2 to about 1.5 wt %, about 0.2 to about 0.5 wt %, about 0.5 to about 3 wt %, about 0.5 to about 2 wt %, about 0.5 to about 1.5 wt %, about 1.5 to about 3 wt %, about 1.5 to about 2 wt %, or about 2 to about 3 wt %. In some embodiments, the total concentration of silica gel is from about 0.05 to about 2 wt %. In some embodiments, the total concentration of silica gel is from about 0.1 to about 1.5 wt %.
In some embodiments, the composition comprises one or more emulsifying agents, one or more emollients, one or more preservatives, one or more anti-static agents, one or more film forming agents, one or more moisturizing agents, one or more moisture barrier agents, one or more antioxidants, one or more anti-foaming agents, one or more fragrance agents, one or more crosspolymers, and one or more silica gels. In some embodiments, a composition provided herein further comprises isododecane.
In some embodiments, the composition comprises palmitoylethanolamide, a salicylate, one or more solvents, and one or more emulsifying agents.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent; and
about 1 to about 15 wt % of emulsifying agent.
In some embodiments, the composition comprises palmitoylethanolamide, a salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, and one or more emulsifying agents.
In some embodiments, the composition comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 0.05 to 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof; and
about 1 to about 15 wt % of emulsifying agent.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, and one or more emollients.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent; and
about 1 to about 25 wt % of emollient.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, and one or more emollients.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 0.05 to 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 1 to about 15 wt % of emulsifying agent; and
about 1 to about 25 wt % of emollient.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, one or more emollients, and one or more moisturizing agents.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient; and
about 0.05 to about 3 wt % of moisturizing agent.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, one or more emollients, and one or more moisturizing agents.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 0.05 to 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient; and
about 0.05 to about 3 wt % of moisturizing agent.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, one or more emulsifying agents, one or more emollients, one or more moisturizing agents, and one or more antioxidants.
In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 3 wt % of moisturizing agent; and
about 0.05 to about 3 wt % of antioxidant.
In some embodiments, the composition comprises palmitoylethanolamide, salicylate, one or more solvents, allantoin, or a pharmaceutically acceptable salt thereof, one or more emulsifying agents, one or more emollients, one or more moisturizing agents, and one or more antioxidants. In some embodiments, the composition comprises:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 0.05 to 2 wt % of allantoin, or a pharmaceutically acceptable thereof;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 3 wt % of moisturizing agent; and
about 0.05 to about 3 wt % of antioxidant.
In some embodiments, a composition provided herein comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti- static agent;
about 0.05 to about 3 wt % of film forming agent;
about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
In some embodiments, a composition provided herein comprises: about 0.5 to about 3 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 40 to about 70 wt % of solvent;
about 3 to about 15 wt % of emulsifying agent; about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti- static agent;
about 0.05 to about 2 wt % of film forming agent;
about 0.05 to about 2 wt % of moisturizing agent;
about 1.5 to about 7 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
In some embodiments, a composition provided herein comprises: about 1 to about 3 wt % of palmitoylethanolamide;
about 5 to about 12 wt % of a salicylate;
about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent;
about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative;
about 0.1 to about 1.5 wt % of anti -static agent;
about 0.1 to about 1.5 wt % of film forming agent;
about 0.1 to about 1.5 wt % of moisturizing agent;
about 2 to about 6 wt % of moisture barrier agent;
about 0.05 to about 2 wt % of antioxidant;
about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent;
about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
In some embodiments, a composition provided herein comprises: about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti- static agent;
about 0.05 to about 3 wt % of film forming agent;
about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
In some embodiments, a composition provided herein comprises: about 0.5 to about 3 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 0.05 to 2 wt % of allantoin, or a pharmaceutically acceptable salt thereof,
about 40 to about 70 wt % of solvent;
about 3 to about 15 wt % of emulsifying agent;
about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti-static agent;
about 0.05 to about 2 wt % of film forming agent;
about 0.05 to about 2 wt % of moisturizing agent;
about 1.5 to about 7 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent; about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
In some embodiments, a composition provided herein comprises:
about 1 to about 3 wt % of palmitoylethanolamide;
about 5 to about 12 wt % of a salicylate;
about 0.1 to 1.5 wt % of allantoin, or a pharmaceutically acceptable salt thereof;
about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent;
about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative;
about 0.1 to about 1.5 wt % of anti-static agent;
about 0.1 to about 1.5 wt % of film forming agent;
about 0.1 to about 1.5 wt % of moisturizing agent;
about 2 to about 6 wt % of moisture barrier agent;
about 0.05 to about 2 wt % of antioxidant;
about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent;
about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
In some embodiments, the composition is suitable for topical administration. In some embodiments, the composition is in the form of an ointment, a lotion, a cream, a gel, a liquid, a foam, or an oil. In some embodiments, the composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
The present application further provides a composition comprising palmitoylethanolamide and a curcuminoid.
As used herein, the term "curcuminoid" refers dicycloheptanoid of the following formula:
Figure imgf000039_0001
or a pharmaceutically acceptable salt thereof, wherein:
each = represents a single or double bond; and
each R is independently selected from the group consisting of OH, SH, CN, NO2, halo, oxo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 hydroxyalkyl, and Ci-6 alkoxy; and
each n is independently 0, 1, 2, 3, 4, or 5.
Example curcuminoids include, but are not limited to:
l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione;
l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-l,6-diene-3,5- dione;
l,7-bis(4-hydroxyphenyl)hepta-l,6-diene-3,5-dione;
1 -(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en- 1 - yl)hepta-l,6-diene-3,5-dione;
(lJE',6JE)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione (curcumin);
(IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4-hy droxyphenyl)hepta- 1 , 6- diene-3,5-dione (desmethoxy curcumin);
(IE, 6E)- 1 ,7-bi s(4-hy droxyphenyl)hepta- 1 , 6-diene-3 , 5 -dione
(bisdemethoxycurcumin); and
(lJE',6JE)-l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex- 3 -en- 1 -yl)hepta- 1 ,6-diene-3 ,5-dione.
In some embodiments, the composition comprises about 100 to about 1000 mg of palmitoylethanolamide, for example, about 100 to 1000 mg, about 100 to about 900 mg, about 100 to about 800 mg, about 100 to about 700 mg, about 100 to about 600 mg, about 100 to about 500 mg, about 100 to about 400 mg, about 100 to about 300 mg, about 100 to about 200 mg, about 200 to 1000 mg, about 200 to about 900 mg, about 200 to about 800 mg, about 200 to about 700 mg, about 200 to about 600 mg, about 200 to about 500 mg, about 200 to about 400 mg, about 200 to about 300 mg, about 300 to 1000 mg, about 300 to about 900 mg, about 300 to about 800 mg, about 300 to about 700 mg, about 300 to about 600 mg, about 300 to about 500 mg, about 300 to about 400 mg, about 400 to 1000 mg, about 400 to about 900 mg, about 400 to about 800 mg, about 400 to about 700 mg, about 400 to about 600 mg, about 400 to about 500 mg, about 500 to 1000 mg, about 500 to about 900 mg, about 500 to about 800 mg, about 500 to about 700 mg, about 500 to about 600 mg, about 600 to 1000 mg, about 600 to about 900 mg, about 600 to about 800 mg, about 600 to about 700 mg, about 700 to 1000 mg, about 700 to about 900 mg, about 700 to about 800 mg, about 800 to 1000 mg, about 800 to about 900 mg, or about 900 to about 1000 mg. In some embodiments, the composition comprises about 200 to about 800 mg palmitoylethanolamide. In some embodiments, the composition comprises about 400 to about 800 mg palmitoylethanolamide.
In some embodiments, the composition comprises about 100 to about 1000 mg of a curcuminoid, for example, about 100 to 1000 mg, about 100 to about 900 mg, about 100 to about 800 mg, about 100 to about 700 mg, about 100 to about 600 mg, about 100 to about 500 mg, about 100 to about 400 mg, about 100 to about 300 mg, about 100 to about 200 mg, about 200 to 1000 mg, about 200 to about 900 mg, about 200 to about 800 mg, about 200 to about 700 mg, about 200 to about 600 mg, about 200 to about 500 mg, about 200 to about 400 mg, about 200 to about 300 mg, about 300 to 1000 mg, about 300 to about 900 mg, about 300 to about 800 mg, about 300 to about 700 mg, about 300 to about 600 mg, about 300 to about 500 mg, about 300 to about 400 mg, about 400 to 1000 mg, about 400 to about 900 mg, about 400 to about 800 mg, about 400 to about 700 mg, about 400 to about 600 mg, about 400 to about 500 mg, about 500 to 1000 mg, about 500 to about 900 mg, about 500 to about 800 mg, about 500 to about 700 mg, about 500 to about 600 mg, about 600 to 1000 mg, about 600 to about 900 mg, about 600 to about 800 mg, about 600 to about 700 mg, about 700 to 1000 mg, about 700 to about 900 mg, about 700 to about 800 mg, about 800 to 1000 mg, about 800 to about 900 mg, or about 900 to about 1000 mg. In some embodiments, the composition comprises about 200 to about 800 mg of a
curcuminoid. In some embodiments, the composition comprises about 300 to about 600 mg of a curcuminoid. In some embodiments, the curcuminoid is a natural curcuminoid.
In some embodiments, the composition comprises:
about 100 to about 1000 mg of palmitoylethanolamide; and
about 100 to about 1000 mg of a curcuminoid. In some embodiments, the curcuminoid is selected from the group consisting of:
(lJE',6JE)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione (curcumin);
(IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4-hy droxyphenyl)hepta- 1 , 6- diene-3,5-dione (desmethoxy curcumin);
(IE, 6E)- 1 ,7-bi s(4-hy droxyphenyl)hepta- 1 , 6-diene-3 , 5 -dione
(bisdemethoxy curcumin);
(lJE',6JE)-l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex- 3 -en- 1 -yl)hepta- 1 ,6-diene-3 ,5-dione;
and mixtures of two or more thereof.
In some embodiments, the composition comprises:
about 100 to about 1000 mg of palmitoylethanolamide; and
about 100 to about 1000 mg of a curcuminoid.
In some embodiments, the composition comprises:
about 200 to about 800 mg of palmitoylethanolamide; and
about 200 to about 800 mg of a curcuminoid.
In some embodiments, the composition comprises:
about 200 to about 800 mg of palmitoylethanolamide; and
about 200 to about 800 mg of a curcuminoid.
In some embodiments, the composition comprises:
about 400 to about 800 mg of palmitoylethanolamide; and
about 400 to about 800 mg of a curcuminoid.
In some embodiments, the curcuminoid is ( IE, 6E)-l -(4-hy droxy-3 - methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5- dione.
In some embodiments, the composition comprises 600 mg of
palmitoylethanolamide and 500 mg (lJE',6JE)-l-(4-hydroxy-3-methoxyphenyl)-7-(4- hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene-3,5-dione.
In some embodiments, the composition is suitable for oral administration. In some embodiments, the composition further comprises a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutically acceptable excipient. In some embodiments, the pharmaceutically acceptable excipient is a diluent. In some embodiments, the pharmaceutically acceptable excipient is a coating or a binding agent.
In some embodiments, the composition further comprises a capsule. In some embodiments, the composition is housed within the capsule. In some embodiments, the capsule is a hard-shelled capsule or a soft-shelled capsule. In some embodiments, the capsule is a methyl cellulose capsule.
The compositions provided herein can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated. In some embodiments, the administration is topical (e.g. transdermal, epidermal, ophthalmic, and administration through mucous membranes, including intranasal, vaginal and rectal administration). In some embodiments, administration is oral.
Compositions for topical administration may include, but are not limited to, transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Composition for oral administration may include, but are not limited to tablets, pills, powders, lozenges, elixirs, suspensions, emulsions, solutions, syrups, and soft or hard capsules.
The present application also provides compositions which contain one or more pharmaceutically acceptable carriers (e.g., pharmaceutically acceptable excipients). In making the compositions provided herein, the active ingredient is typically mixed with an excipient, diluted by an excipient, or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. When a
pharmaceutically acceptable excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier, or medium for the active ingredient. Thus, the compositions provided herein can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, ointments containing, soft and hard gelatin capsules, suppositories, and sterile packaged powders. Methods of Use
The present application further provides methods of reducing or alleviating pain, reducing or alleviating inflammation, and improving the health or nutrition of a subject. As used herein, the term "subject" refers to any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans. In some embodiments, the subject is a human. In some embodiments, the method comprises administering to the subject a composition provided herein.
In some embodiments, the method is a method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of reducing pain. In some embodiments, the method is a method of alleviating pain. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
In some embodiments, the method is a method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of reducing inflammation. In some embodiments, the method is a method of alleviating inflammation. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
In some embodiments, the method is a method of improving heath or nutrition in a subject, comprising administering to the subject an effective amount of a composition provided herein. In some embodiments, the method is a method of improving the health of a subject. In some embodiments, the method comprises topical administration of a composition provided herein. In some embodiments, the method comprises oral administration of a composition provided herein.
EXAMPLES
The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.
Example 1. Topical Composition
A composition for topical administration was prepared using the components provided in Table 1.
Table 1. Topical Composition Components
Figure imgf000045_0001
Example 2. Oral Composition A composition for oral administration was prepared and housed within a methyl cellulose tablet, using the components provided in Table 2.
Table 2. Oral Composition Components
Figure imgf000046_0001
OTHER EMBODIMENTS
It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:
1. A composition, comprising:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate; and
about 35 to about 75 wt % of one or more solvents.
2. A composition, comprising:
about 0.5 to 5 wt % of palmitoylethanolamide;
about 5 to 15 wt % of a salicylate;
about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof; and
about 35 to about 75 wt % of one or more solvents.
3. The composition of claim 1 or 2, further comprising one or more emulsifying agents.
4. The method of claim 3, wherein each of the one or more emulsifying agents is a non-ionic emulsifying agent.
5. The composition of claim 3, wherein each of the one or more emulsifying agents is independently selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, and a glycerol alkyl ether.
6. The composition of any one of claims 1 to 3, further comprising one or more emulsifying agents selected from the group consisting of:
a) propylene glycol;
b) glyceryl stearate
c) PEG- 100 stearate; and
d) stearyl alcohol.
7. The composition of any one of claims 1 to 6, further comprising one or more emollients.
8. The composition of claim 7, wherein each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, and a Cio-30 silicone.
9. The composition of claim 7 or 8, wherein each of the one or more emollients is independently selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, and a botanical oil.
10. The composition of any one of claims 1 to 7, further comprising one or more emollients selected from the group consisting of:
a) cetearyl alcohol;
b) isopropyl palmitate;
c) caprylic capric triglyceride;
d) dicaprylyl ether;
e) isodecyl neopentanoate; and
f) Carthamus Tinctorius (Safflower) Seed Oil.
1 1. The composition of any one of claims 1 to 10, further comprising one or more preservatives.
12. The composition of claim 1 1, wherein each of the one or more preservatives is independently selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, and glycereth-2 cocoate,
13. The composition of any one of claims 1 to 1 1, further comprising one or more preservatives selected from the group consisting of:
a) lecithin;
b) isopropyl palmitate;
c) sorbic acid;
d) potassium sorbate; and
e) phenoxyethanol;
f) benzoic acid;
g) ethylhexylglycerin; and
h) glycereth-2 cocoate.
14. The composition of any one of claims 1 to 13, further comprising one or more anti- static agents.
15. The composition of claim 14, wherein each of the one or more anti-static agents is independently selected from the group consisting of a Cio-30 amine, a Cio-30 amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, and cellulose or a derivative thereof.
16. The composition of any one of claims 1 to 13, further comprising an anti-static agent, wherein the anti-static agent is hydroxypropyl methyl cellulose.
17. The composition of any one of claims 1 to 16, further comprising one or more film forming agents.
18. The composition of claim 17, wherein each of the one or more film forming agents is independently selected from the group consisting of polyvinylpyrrolidone, a C3- 30 acrylamide, a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, and mixtures thereof.
19. The composition of any one of claims 1 to 17, further comprising a film forming agent, wherein the film forming agent is selected from the group consisting of a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, and mixtures thereof.
20. The composition of any one of claims 1 to 19, further comprising one or more moisturizing agents.
21. The composition of claim 20, wherein each of the one or more moisturizing agents is independently selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci-30 alkylene glycol.
22. The composition of any one of claims 1 to 20, further comprising a moisturizing agent, wherein the moisturizing agent is aloe barbadensis leaf juice.
23. The composition of any one of claims 1 to 22, further comprising one or more moisture barrier agents.
24. The composition of claim 23, wherein each of the one or more moisturizing barrier agents is independently selected from petroleum jelly and mineral oil.
25. The composition of any one of claims 1 to 23, further comprising a moisture barrier agent, wherein the moisture barrier agent is mineral oil.
26. The composition of any one of claims 1 to 25, further comprising one or more antioxidants.
27. The composition of claim 26, wherein each of the one or more antioxidants is independently selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, and an anthocyanin.
28. The composition of any one of claims 1 to 26, further comprising an antioxidant, wherein the antioxidant is (lJE',6JE)-l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5- methoxycyclohex-3 -en- 1 -yl)hepta- 1 ,6-diene-3 ,5-dione.
29. The composition of any one of claims 1 to 28, further comprising one or more bleaching agents.
30. The composition of claim 29, wherein each of the one or more bleaching agents is independently selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropylcatechol, and lemon juice.
31. The composition of any one of claims 1 to 29, further comprising one or more bleaching agents selected from the group consisting of:
a) cetearyl alcohol; and
b) polysorbate 60.
32. The composition of any one of claims 1 to 31, further comprising one or more anti-foaming agents.
33. The composition of claim 32, wherein each of the one or more anti-foaming agents is independently selected from the group consisting of a silicone based anti- foaming agent, a water-based anti-foaming agent, and an oil-based anti-foaming agent.
34. The composition of any one of claims 1 to 32, further comprising an anti-foaming agent, wherein the anti-foaming agent is dimethicone.
35. The composition of any one of claims 1 to 34, further comprising one or more fragrance agents.
36. The composition of claim 35, wherein each of the one or more fragrance agents is independently selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, and mixtures of any two or more thereof.
37. The composition of any one of claims 1 to 36, wherein the composition further comprises one or more of the following components:
a) isododecane;
b) dimethicone/bis-isobutyl PPG-20 crosspolymer; and
c) silica gel.
38. The composition of claim 37, wherein the silica gel comprises trimethylated silica gel.
39. The composition of any one of claims 1 to 38, wherein the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate.
40. The composition of any one of claims 1 to 38, wherein the salicylate is triethanolamine salicylate.
41. The composition of any one of claims 1 to 40, wherein each of the one or more solvents is independently selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
42. The composition of any one of claims 1 to 40, wherein the solvent is water.
43. The composition of any one of claims 3 to 42, wherein the total concentration of emulsifying agent is from about 1 to about 15 wt %.
44. The composition of any one of claims 3 to 42, wherein the total concentration of emulsifying agent is from about 3 to about 15 wt %.
45. The composition of any one of claims 3 to 42, wherein the total concentration of emulsifying agent is from about 5 to about 13 wt %.
46. The composition of any one of claims 7 to 45, wherein the total concentration of emollient is from about 1 to about 25 wt %.
47. The composition of any one of claims 7 to 45, wherein the total concentration of emollient is from about 3 to about 25 wt %.
48. The composition of any one of claims 7 to 45, wherein the total concentration of emollient is from about 5 to about 20 wt %.
49. The composition of any one of claims 11 to 48, wherein the total concentration of preservative is from about 0.05 to about 5 wt %.
50. The composition of any one of claims 11 to 48, wherein the total concentration of preservative is from about 0.1 to about 5 wt %.
51. The composition of any one of claims 11 to 48, wherein the total concentration of preservative is from about 0.2 to about 3 wt %.
52. The composition of any one of claims 14 to 51, wherein the total concentration of anti- static agent is from about 0.05 to about 3 wt %.
53. The composition of any one of claims 14 to 51, wherein the total concentration of anti -static agent is from about 0.05 to about 2 wt %.
54. The composition of any one of claims 14 to 51, wherein the total concentration of anti -static agent is from about 0.1 to about 1.5 wt %.
55. The composition of any one of claims 17 to 54, wherein the total concentration of film forming agent is from about 0.05 to about 3 wt %.
56. The composition of any one of claims 17 to 54, wherein the total concentration of film forming agent is from about 0.05 to about 2 wt %.
57. The composition of any one of claims 17 to 54, wherein the total concentration of film forming agent is from about 0.1 to about 1.5 wt %.
58. The composition of any one of claims 20 to 57, wherein the total concentration of moisturizing agent is from about 0.05 to about 3 wt %.
59. The composition of any one of claims 20 to 57, wherein the total concentration of moisturizing agent is from about 0.05 to about 2 wt %.
60. The composition of any one of claims 20 to 57, wherein the total concentration of moisturizing agent is from about 0.1 to about 1.5 wt %.
61. The composition of any one of claims 23 to 60, wherein the total concentration of moisture barrier agent is from about 1 to about 8 wt %.
62. The composition of any one of claims 23 to 60, wherein the total concentration of moisture barrier agent is from about 1.5 to about 7 wt %.
63. The composition of any one of claims 23 to 60, wherein the total concentration of moisture barrier agent is from about 2 to about 6 wt %.
64. The composition of any one of claims 26 to 63, wherein the total concentration of antioxidant is from about 0.05 to about 3 wt %.
65. The composition of any one of claims 26 to 63, wherein the total concentration of antioxidant is from about 0.05 to about 2 wt %.
66. The composition of any one of claims 26 to 63, wherein the total concentration of antioxidant is from about 0.1 to about 1.5 wt %.
67. The composition of any one of claims 29 to 66, wherein the total concentration of bleaching agent is from about 0.5 to about 6 wt %.
68. The composition of any one of claims 29 to 66, wherein the total concentration of bleaching agent is from about 1 to about 5 wt %.
69. The composition of any one of claims 29 to 66, wherein the total concentration of bleaching agent is from about 1.5 to about 4.5 wt %.
70. The composition of any one of claims 32 to 69, wherein the total concentration of anti-foaming agent is from about 0.05 to about 3 wt %.
71. The composition of any one of claims 32 to 69, wherein the total concentration of anti-foaming agent is from about 0.05 to about 2 wt %.
72. The composition of any one of claims 32 to 69, wherein the total concentration of anti-foaming agent is from about 0.1 to about 1.5 wt %.
73. The composition of any one of claims 35 to 72, wherein the total concentration of fragrance agent is from about 0.05 to about 3 wt %.
74. The composition of any one of claims 35 to 72, wherein the total concentration of fragrance agent is from about 0.05 to about 2 wt %.
75. The composition of any one of claims 35 to 72, wherein the total concentration of fragrance agent is from about 0.1 to about 1.5 wt %.
76. The composition of any one of claims 37 to 75, wherein the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 3 wt %.
77. The composition of any one of claims 37 to 75, wherein the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.05 to about 2 wt %.
78. The composition of any one of claims 37 to 75, wherein the total concentration of isododecane and dimethicone/bis-Isobutyl PPG-20 crosspolymer is from about 0.1 to about 1.5 wt %.
79. The composition of any one of claims 37 to 78, wherein the total concentration of silica gel is from about 0.05 to about 3 wt %.
80. The composition of any one of claims 37 to 78, wherein the total concentration of silica gel is from about 0.05 to about 2 wt %.
81. The composition of any one of claims 37 to 78, wherein the total concentration of silica gel is from about 0.1 to about 1.5 wt %.
82. The composition of any one of claims 1 to 81, wherein the total concentration of salicylate is from about 5 to about 15 wt %.
83. The composition of any one of claims 1 to 81, wherein the total concentration of salicylate is from about 5 to about 12 wt %.
84. The composition of any one of claims 1 to 81, wherein the total concentration of salicylate is from about 8 to about 12 wt %.
85. The composition of any one of claims 1 to 84, wherein the total concentration of palmitoylethanolamide is from about 1 to about 5 wt %.
86. The composition of any one of claims 1 to 84, wherein the total concentration of palmitoylethanolamide is from about 1 to about 3 wt %.
87. The composition of any one of claims 1 to 86, wherein the total concentration of solvent is from about 35 to about 75 wt %.
88. The composition of any one of claims 1 to 86, wherein the total concentration of solvent is from about 40 to about 70 wt %.
89. The composition of any one of claims 1 to 86, wherein the total concentration of solvent is from about 45 to about 65 wt %.
90. The composition of any one of claims 2 to 89, wherein the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.05 to about 3 wt %.
91. The composition of any one of claims 2 to 89, wherein the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.05 to about 2 wt %.
92. The composition of any one of claims 2 to 89, wherein the total concentration of allantoin, or a pharmaceutically acceptable salt thereof, is from about 0.1 to about 1.5 wt
%.
93. A composition, comprising:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti- static agent;
about 0.05 to about 3 wt % of film forming agent;
about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
94. A composition, comprising:
about 0.5 to about 3 wt % of palmitoylethanolamide; about 5 to about 15 wt % of a salicylate;
about 40 to about 70 wt % of solvent;
about 3 to about 15 wt % of emulsifying agent; about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti- static agent; about 0.05 to about 2 wt % of film forming agent; about 0.05 to about 2 wt % of moisturizing agent; about 1.5 to about 7 wt % of moisture barrier agent; about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent; about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and about 0.05 to about 3 wt % of silica gel.
95. A composition, comprising:
about 1 to about 3 wt % of palmitoylethanolamide; about 5 to about 12 wt % of a salicylate;
about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent; about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative;
about 0.1 to about 1.5 wt % of anti-static agent; about 0.1 to about 1.5 wt % of film forming agent; about 0.1 to about 1.5 wt % of moisturizing agent; about 2 to about 6 wt % of moisture barrier agent; about 0.05 to about 2 wt % of antioxidant; about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent;
about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
96. A composition, comprising:
about 0.5 to about 5 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 0.05 to 3 wt % of allantoin, or a pharmaceutically acceptable salt thereof; about 35 to about 75 wt % of solvent;
about 1 to about 15 wt % of emulsifying agent;
about 1 to about 25 wt % of emollient;
about 0.05 to about 5 wt % of preservative;
about 0.05 to about 3 wt % of anti- static agent;
about 0.05 to about 3 wt % of film forming agent;
about 0.05 to about 3 wt % of moisturizing agent;
about 1 to about 8 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel.
97. A composition, comprising:
about 0.5 to about 3 wt % of palmitoylethanolamide;
about 5 to about 15 wt % of a salicylate;
about 0.05 to 2 wt % allantoin, or a pharmaceutically acceptable salt thereof, about 40 to about 70 wt % of solvent; about 3 to about 15 wt % of emulsifying agent;
about 3 to about 25 wt % of emollient;
about 0.1 to about 5 wt % of preservative;
about 0.05 to about 2 wt % of anti- static agent;
about 0.05 to about 2 wt % of film forming agent;
about 0.05 to about 2 wt % of moisturizing agent;
about 1.5 to about 7 wt % of moisture barrier agent;
about 0.05 to about 3 wt % of antioxidant;
about 0.5 to about 6 wt % of bleaching agent;
about 0.05 to about 3 wt % of anti-foaming agent;
about 0.05 to about 3 wt % of fragrance agent;
about 0.05 to about 3 wt % of crosspolymer; and
about 0.05 to about 3 wt % of silica gel. A composition, comprising:
about 1 to about 3 wt % of palmitoylethanolamide;
about 5 to about 12 wt % of a salicylate;
about 0.1 to 1.5 wt % of allantoin, or a pharmaceutically acceptable salt thereof; about 45 to about 65 wt % of solvent;
about 5 to about 13 wt % of emulsifying agent;
about 5 to about 20 wt % of emollient;
about 0.2 to about 3 wt % of preservative;
about 0.1 to about 1.5 wt % of anti-static agent;
about 0.1 to about 1.5 wt % of film forming agent;
about 0.1 to about 1.5 wt % of moisturizing agent;
about 2 to about 6 wt % of moisture barrier agent;
about 0.05 to about 2 wt % of antioxidant;
about 1 to about 5 wt % of bleaching agent;
about 0.05 to about 2 wt % of anti-foaming agent;
about 0.05 to about 2 wt % of fragrance agent; about 0.05 to about 2 wt % of crosspolymer; and
about 0.05 to about 2 wt % of silica gel.
99. The composition of any one of claims 93 to 98, wherein the emulsifying agent is selected from the group consisting of a Cio-30 aliphatic alcohol, a C2-30 glycol, a polyethylene glycol stearate, a glucoside alkyl ether, a glycerol alkyl ether, or any combination thereof.
100. The composition of any one of claims 93 to 98, wherein the emulsifying agent is a combination of propylene glycol, glyceryl stearate, PEG- 100 stearate, and stearyl alcohol.
101. The composition of any one of claims 93 to 100, wherein the emollient is selected from the group consisting of a Cio-30 aliphatic acid, a Cio-30 aliphatic alcohol, a Cio-30 aliphatic ester, a Cio-30 silicone, botanical oil, or any combination thereof.
102. The composition of any one of claims 93 to 100, wherein the emollient is a combination of cetearyl alcohol, isopropyl palmitate, caprylic capric triglyceridy, dicaprylyl ether, isodecyl neopentanoate, dimethicone/bis-isobutyl PPG-20 crosspolymer, and Carthamus Tinctorius (Safflower) seed oil.
103. The composition of any one of claims 93 to 102, wherein the preservative is selected from the group consisting of an organic acid, an organic acid salts, an organic acid ester, a paraben, a glycerin, an aryl glycol ether, lecithin, glycereth-2 cocoate, or any combination thereof.
104. The composition of any one of claims 93 to 102, wherein the preservative is a combination of lecithin, isopropyl palmitate, sorbic acid, potassium sorbate,
phenoxyethanol, benzoic acid, ethylhexylglycerin, and glycereth-2 cocoate.
105. The composition of any one of claims 93 to 104, wherein the anti-static agent is selected from the group consisting of an aliphatic amine, an ethoxylated aliphatic amine, aliphatic amide, a quaternary ammonium salt, a phosphoric acid ester, a polyethylene glycol ester, a polyol, cellulose, a hydroxyalkyl alkyl cellulose derivative, or any combination thereof.
106. The composition of any one of claims 93 to 105, wherein the anti-static agent is hydroxypropyl methyl cellulose.
107. The composition of any one of claims 93 to 106, wherein the film forming agent is selected from the group consisting of polyvinylpyrrolidone, a C3-30 acrylamide, a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or any combination thereof.
108. The composition of any one of claims 93 to 106, wherein the film forming agent is a C4-30 acrylate, a (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer, or a combination thereof.
109. The composition of any one of claims 93 to 108, wherein the moisturizing agent is selected from the group consisting of a botanical oil, an alpha hydroxyl acid, and a Ci- 30 alkylene glycols, or any combination thereof.
1 10. The composition of any one of claims 93 to 108, wherein the moisturizing agent is aloe barbadensis leaf juice.
1 1 1. The composition of any one of claims 93 to 1 10, wherein the moisture barrier agent is selected from the group consisting of petroleum jelly, mineral oil, or
combinations thereof.
1 12. The composition of any one of claims 93 to 1 10, wherein the moisture barrier agent is mineral oil.
1 13. The composition of any one of claims 93 to 1 12, wherein the antioxidant is selected from the group consisting of a curcuminoid, a natural vitamin, a flavone, a flavonol, a flavanones, a flavanol, a polymerized flavanol, an isoflavone phytoestrogen, a stilbenoid, an anthocyanin, or any combination thereof.
1 14. The composition of any one of claims 93 to 1 12, wherein the antioxidant is (IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4-hy droxy-5 -methoxy cy clohex-3 -en- 1 - yl)hepta-l,6-diene-3,5-dione.
1 15. The composition of any one of claims 93 to 1 14, wherein the bleaching agent is selected from the group consisting of cetearyl alcohol, polysorbate 60, hydroquinone, aloesin, gentisic acid, isopropyl catechol, and lemon juice.
1 16. The composition of any one of claims 93 to 1 14, wherein the bleaching agent is a combination of cetearyl alcohol and polysorbate 60.
1 17. The composition of any one of claims 93 to 1 16, wherein the anti-foaming agent is selected from the group consisting of silicone based anti-foaming agents, water-based anti-foaming agents, oil-based anti-foaming agents, or any combination thereof.
1 18. The composition of any one of claims 93 to 1 16, wherein the anti-foaming agent is dimethicone.
1 19. The composition of any one of claims 93 to 1 18, wherein the fragrance agent is selected from the group consisting of aloe fragrance, anise fragrance, apple fragrance, banana fragrance, berry fragrance, black currant fragrance, camphor fragrance, cherry fragrance, cherry cream fragrance, cinnamon fragrance, citrus fragrance, citrus cream fragrance, eucalyptus fragrance, fresh rain fragrance, grape fragrance, grapefruit fragrance, honey fragrance, lemon fragrance, lime fragrance, lemon cream fragrance, mixed berry fragrance, orange fragrance, pear fragrance, peach fragrance, peppermint fragrance, peppermint cream fragrance, raspberry fragrance, strawberry fragrance, strawberry cream fragrance, tangerine fragrance, vanilla fragrance, or any combination thereof.
120. The composition of any one of claims 93 to 1 19, wherein the crosspolymer is selected from the group consisting of (dimethicone)-(bis-isobutyl PPG-20) crosspolymer and (Cio-30 alkyl)-(C4-3o acrylate) crosspolymer.
121. The composition of any one of claim 93 to 1 19, wherein the crosspolymer is dimethicone/bis-isobutyl PPG-20 crosspolymer, or any combination thereof.
122. The composition of any one of claims 93 to 121, wherein the silica gel is selected form the group consisting of hydrated silica gel, alkylated silica gel, hydroxylated silica gel, alkoxylated silica gel, or any combination thereof.
123. The composition of any one of claims 93 to 121, wherein the silica gel is trimethylated silica gel.
124. The composition of any one of claims 93 to 123, wherein the salicylate is selected from the group consisting of methyl salicylate, ethyl salicylate, choline salicylate, triethanolamine salicylate, sodium salicylate, and magnesium salicylate, or any combination thereof.
125. The composition of any one of claims 93 to 123, wherein the salicylate is triethanolamine salicylate.
126. The composition of any one of claims 93 to 125, wherein the solvent is selected from the group consisting of water, methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, benzyl alcohol, diethylene glycol monoethyl ether, propylene glycol, or any combination thereof.
127. The composition of any one of claims 93 to 125, wherein the composition further comprises isododecane.
128. The composition of any one of claims 1 to 127, wherein the composition is suitable for topical administration.
129. The composition of claim 128, wherein composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
130. A method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 1 to 129.
131. A method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 1 to 129.
132. A method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition of any one of claims 1 to 129.
133. The method of any one of claims 130 to 132, wherein the method comprises topical administration of the composition of any one of claims 1 to 129.
134. The method of any one of claims 130 to 133, wherein the composition is in the form of an ointment, a lotion, a cream, a gel, a foam, or an oil.
135. A composition, comprising:
about 100 to about 1000 mg palmitoylethanolamide; and
about 100 to about 1000 mg of a curcuminoid.
136. The composition of claim 135, wherein the composition comprises about 200 to about 800 mg palmitoylethanolamide.
137. The composition of claim 135, wherein the composition comprises about 400 to about 800 mg palmitoylethanolamide.
138. The composition of any one of claims 135 to 137, wherein the composition comprises about 200 to about 800 mg of a curcuminoid.
139. The composition of any one of claims 135 to 137, wherein the composition comprises about 300 to about 600 mg of a curcuminoid.
140. The composition of any one of claims 135 to 137, wherein the curcuminoid is selected from the group consisting of (lJE,,6£)-l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6- heptadiene-3 , 5 -dione (curcumin), {IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (desmethoxycurcumin), (lE,6E)-l,7-bis(4- hydroxyphenyl)hepta-l,6-diene-3,5-dione (bisdemethoxy curcumin), (1£',6£)-1-(4- hydroxy-3-methoxyphenyl)-7-(4-hydroxy-5-methoxycyclohex-3-en-l-yl)hepta-l,6-diene- 3,5-dione, and mixtures of two or more thereof.
141. The composition of any one of claims 135 to 137, wherein the curcuminoid is (IE, 6E)- 1 -(4-hy droxy-3 -methoxyphenyl)-7-(4-hy droxy-5 -methoxy cy clohex-3 -en- 1 - yl)hepta-l,6-diene-3,5-dione.
142. The composition of any one of claims 135 to 141, further comprising a pharmaceutically acceptable excipient.
143. The composition of any one of claims 135 to 142, further comprising a capsule.
144. The composition of claim 143, wherein the capsule is a methyl cellulose capsule.
145. A method of reducing or alleviating pain in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 135 to 144.
146. A method of reducing or alleviating inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a composition of any one of claims 135 to 144.
147. A method of improving health or nutrition in a subject, comprising administering to the subject an effective amount of a composition of any one of claims 135 to 144.
148. The method of any one of claims 145 to 147, wherein the method comprises oral administration of the composition of any one of claims 135 to 144.
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