Stable, non-irritating topical formulations of hydroquinone

1. A method for increasing the efficacy of a hydroquinone-containing formulation, the formulation comprising an oil-in-water emulsion, comprising the step of adding a plurality of activating agents to the continuous phase of the formulation in an amount of about 8.5 to about 14.5% by weight of the formulation, thereby forming an improved hydroquinone containing formulation, wherein the activating agent is selected from the group consisting of niacinamide, alpha-arbutin, kojic acid, 1-methylhydantoine-2-imide, algae/mugwort extract, saccharomyces /xylinum/black tea ferment, palmaria palmate extract, brassica napus extract, hexapeptide-2 , glycrrhiza glabra root extract, and combinations thereof.

2. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows improvement from baseline after 12 weeks in overall photodamage in at least about 90% of the subjects.

3. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows improvement from baseline after 12 weeks in mottled pigmentation in at least about 95% of the subjects.

4. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows improvement from baseline after 12 weeks in color in at least about 96% of the subjects.

5. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average of at least about 18% improvement from baseline after 12 weeks in overall photodamage.

6. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average of at least about 25% improvement from baseline after 12 weeks in mottled pigmentation.

7. The method of claim 1 , wherein the improved hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average of at least about 23% improvement from baseline after 12 weeks in color.

8. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises surfactants and co-surfactants, in an amount of about 4.0 to about 10.0% by weight of the formulation, selected from the group consisting of ceteth-20, steareth-20, cetyl alcohol, glyceryl stearate, PEG-75 stearate, cetearyl alcohol and polyglyceryl-3 esters of acacia decurrents /jojoba/sunflower seed wax.

9. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises emollients, in an amount of about 10.0 to about 19.0% by weight of the formulation, selected from the group consisting of cyclomethicone, isononyl isononoate, C 12 -C 15 alkyl ethylhexanoate, dimethicone/divinyldimethicone/silsesquioxane crosspolymer, moringa oleifera seed oil, dimethicone, punica granatum seed oil, rubus occidentalis seed oil, vaccinium macrocarpon seed oil, citrullus lanatus seed oil, rubus idaeus seed oil, salvia hispanica seed oil, jojoba esters, moringa oil/hydrogenated moringa oil esters, and butyrospermum parkii butter.

10. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises humectants, in an amount of about 5.5 to about 9.5% by weight of the formulation, selected from the group consisting of pentylene glycol, glycerin and sodium hyaluronate.

11. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises thickeners, in an amount of about 0.7 to about 2.0% by weight of the formulation, selected from the group consisting of magnesium aluminum silicate, xanthan gum, dextran and hydroxyethylcellulose.

12. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises preservatives, in an amount of about 0.5 to about 3.5% by weight of the formulation, selected from the group consisting of chlorphenesin, sodium bisulfite, sodium sulfite, tocopheryl acetate, citric acid, potassium sorbate, sodium benzoate, BHT, disodium EDTA and phenoxyethanol.

13. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises anti-irritants, in an amount of about 0.5 to about 3.5% by weight of the formulation, selected from the group consisting of panthenol, avena sativa kernel extract, allantoin, bisabolol and stearyl glycyrrhetinate.

14. The method of claim 1 , wherein the improved hydroquinone-containing formulation further comprises: surfactants and co-surfactants, in an amount of about 4.0 to about 10.0% by weight of the formulation; emollients, in an amount of about 10.0 to about 19.0% by weight of the formulation; humectants, in an amount of about 5.5 to about 9.5% by weight of the formulation; thickeners, in an amount of about 0.7 to about 2.0% by weight of the formulation; preservatives, in an amount of about 0.5 to about 3.5% by weight of the formulation; anti-irritants, in an amount of about 0.5 to about 3.5% by weight of the formulation; and water, in an amount of about 50.0 to about 60.0% by weight of the formulation.

15. The method of claim 1 , wherein the improved hydroquinone-containing formulation consists essentially of, by weight of the formulation:

purified water

from about 30% to about 70%

hydrofluorocarbon 227ea

from about 6% to about 18%

pentylene glycol

from about 3% to about 7%

cyclomethicone

from about 3% to about 7%

niacinamide

from about 2% to about 6%

isononyl isononoate

from about 1% to about 4%

C12-C15 alkyl ethylhexanoate

from about 1% to about 4%

glycerin

from about 1% to about 3%

hydroquinone

from about 1% to about 3%

alpha-arbutin

from about 1% to about 3%

dimethicone/divinyldimethicone/

from about 1% to about 3%

silsesquioxane crosspolymer

moringa oleifera seed oil

from about 1% to about 3%

glyceryl stearate

from about 1% to about 3%

cetyl alcohol

from about 1% to about 3%

dimethicone

from about 0.5% to about 1.5%

cetearyl alcohol

from about 0.5% to about 1.5%

kojic acid

from about 0.5% to about 1.5%

panthenol

from about 0.5% to about 1.5%

1-methylhydantoine-2-imide

from about 0.5% to about 1.5%

algae extract and mugwort

from about 0.5% to about 1.5%

( artemisia vulgaris ) extract

magnesium aluminum silicate

from about 0.5% to about 1.5%

peg-75 stearate

from about 0.5% to about 1.5%

avena sativa (oat) kernel extract

from about 0.1% to about 1.0%

saccharomyces / xylinum /black tea

from about 0.2% to about 0.6%

ferment

palmaria palmata extract

from about 0.1% to about 0.4%

brassica napus extract

from about 0.3% to about 1.0%

punica granatum (pomegranate)

from about 0.1% to about 0.4%

seed oil

rubus occidentalis (black

from about 0.1% to about 0.4%

raspberry) seed oil

vaccinium macrocarpon

from about 0.1% to about 0.4%

(cranberry) seed oil

citrullus lanatus (watermelon)

from about 0.01% to about 0.05%

seed oil

rubus idaeus (raspberry) seed oil

from about 0.01% to about 0.05%

salvia hispanica (chia) seed oil

from about 0.01% to about 0.05%

tetrahexadecyl ascorbate

from about 0.3% to about 0.7%

ceteth-20

from about 0.2% to about 0.6%

steareth-20

from about 0.2% to about 0.6%

allantoin

from about 0.3% to about 0.7%

chlorphenesin

from about 0.1% to about 0.4%

hexapeptide-2

from about 0.1% to about 1.0%

jojoba esters

from about 0.1% to about 0.4%

moringa oil/hydrogenated

from about 0.1% to about 0.4%

moringa oil esters

bisabolol

from about 0.1% to about 0.3%

fragrance

from about 0.1% to about 0.3%

sodium bisulfite

from about 0.02% to about 0.07%

sodium sulfite

from about 0.02% to about 0.07%

tocopheryl acetate

from about 0.05% to about 0.15%

xanthan gum

from about 0.05% to about 0.15%

citric acid

from about 0.1% to about 0.3%

potassium sorbate

from about 0.1% to about 0.3%

sodium benzoate

from about 0.1% to about 0.3%

dextran

from about 0.1% to about 1.0%

sodium hyaluronate

from about 0.005% to about 0.015%

BHT

from about 0.1% to about 0.3%

stearyl glycyrrhetinate

from about 0.05% to about 0.15%

disodium EDTA

from about 0.05% to about 0.15%

phenoxyethanol

from about 0.01% to about 0.10%

hydroxyethylcellulose

from about 0.1% to about 1.0%

glycyrrhiza glabra (licorice)

from about 0.02% to about 0.07%

root extract.

16. The method of claim 1 , wherein the improved hydroquinone-containing formulation consists essentially of, by weight of the formulation:

purified water

from about 30% to about 70%

hydrofluorocarbon 227ea

from about 6% to about 18%

pentylene glycol

from about 3% to about 7%

cyclomethicone

from about 1% to about 2%

niacinamide

from about 2% to about 6%

isononyl isononoate

from about 1% to about 3%

C 12 -C 15 alkyl ethylhexanoate

from about 1% to about 3%

glycerin

from about 1% to about 3%

hydroquinone

from about 1% to about 3%

alpha-arbutin

from about 1% to about 3%

dimemicone/divinyldimethicone/

from about 1% to about 3%

silsesquioxane crosspolymer

glyceryl stearate

from about 1% to about 3%

cetyl alcohol

from about 1% to about 3%

dimethicone

from about 0.5% to about 1.5%

cetearyl alcohol

from about 0.5% to about 1.5%

kojic acid

from about 0.5% to about 1.5%

panthenol

from about 0.5% to about 1.5%

1-methylhydantoine-2-imide

from about 0.5% to about 1.5%

algae extract and mugwort

from about 0.5% to about 1.5%

( artemisia vulgaris ) extract

magnesium aluminum silicate

from about 0.5% to about 1.5%

PEG-75 stearate

from about 0.5% to about 1.5%

avena sativa (oat) kernel extract

from about 0.1% to about 1.0%

saccharomyces / xylinum /black tea

from about 1% to about 4%

ferment

palmaria palmata extract

from about 0.1% to about 0.5%

brassica napus extract

from about 0.04% to about 0.1%

punica granatum (pomegranate)

from about 0.3% to about 0.9%

seed oil

rubus occidentalis (black

from about 0.3% to about 0.9%

raspberry) seed oil

vaccinium macrocarpon

from about 0.3% to about 0.9%

(cranberry) seed oil

citrullus lanatus (watermelon)

from about 0.06% to about 0.13%

seed oil

rubus idaeus (raspberry) seed oil

from about 0.06% to about 0.13%

salvia hispanica (chia) seed oil

from about 0.06% to about 0.13%

tetrahexadecyl ascorbate

from about 0.2% to about 0.7%

cetem-20

from about 0.1% to about 0.5%

steareth-20

from about 0.1% to about 0.5%

allantoin

from about 0.2% to about 0.7%

chlorphenesin

from about 0.1% to about 0.5%

hexapeptide-2

from about 0.1% to about 1.0%

bisabolol

from about 0.1% to about 0.3%

fragrance

from about 0.1% to about 0.3%

sodium bisulfite

from about 0.02% to about 0.07%

sodium sulfite

from about 0.02% to about 0.07%

tocopheryl acetate

from about 0.2% to about 0.7%

xanthan gum

from about 0.05% to about 0.15%

citric acid

from about 0.05% to about 0.20%

potassium sorbate

from about 0.05% to about 0.20%

sodium benzoate

from about 0.05% to about 0.20%

dextran

from about 0.1% to about 1.0%

sodium hyaluronate

from about 0.005% to about 0.015%

bht

from about 0.1% to about 0.3%

stearyl glycyrrhetinate

from about 0.05% to about 0.15%

disodium edta

from about 0.05% to about 0.15%

phenoxyethanol

from about 0.05% to about 0.1%

hydroxyethylcellulose

from about 0.1% to about 1.0%

glycyrrhiza glabra (licorice)

from about 0.02% to about 0.07%

root extract

acacia decurrens /jojoba/

from about 1% to about 3%

sunflower seed wax polyglyceryl-

3 esters

butyrospermum parkii (shea)

from about 1% to about 3%

butter.