IP Library › Granted Patent US 12,458,577
Granted Patent B2
US 12,458,577 · App. 17/556,778 · Granted Nov 4, 2025

Photoprotective compositions containing

Inventors: Michael Einziger (Malibu, CA); Ann Marie Simpson (Malibu, CA)
Assignee: VERSICOLOR TECHNOLOGIES, LLC
A61K8/492A61K8/4926A61K8/4953A61K8/4973A61K31/404A61K31/407A61K31/519A61P17/16A61Q17/04A61Q19/02
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,458,577
App. No.
17/556,778
Granted
Nov 4, 2025
Kind
B2
Abstract

The present invention relates to compounds, compositions, and methods for modulating skin pigmentation and treating or preventing UV-induced skin damage, erythema, aging of the skin, sunburn, and hyperpigmentation in a subject. The compounds, compositions, and methods of the present invention generally involve Malassezia -derived compounds, including malassezin and indirubin, and/or chemical analogs thereof. Other applications of the compounds and compositions disclosed herein include, but are not limited to, improving hyperpigmentation caused by a hyperpigmentation disorder, inducing melanocyte apoptosis, and modulating arylhydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogenesis, melanosome transfer, melanocyte activity, and melanin concentration.

Claims (28)

1 . A composition comprising one or more compounds selected from the group consisting of:

or a crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

2 . The composition of claim 1 , wherein the composition comprises a compound selected from the group consisting of:

or a crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

3 . The composition of claim 1 , wherein the composition comprises a compound selected from the group consisting of:

or a pharmaceutically or cosmetically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

4 . The composition of claim 1 , wherein the composition comprises a compound selected from the group consisting of:

or a pharmaceutically or cosmetically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

5 . The composition of claim 1 , wherein the composition comprises a compound of the following structure:

or a pharmaceutically or cosmetically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

6 . The composition of claim 5 , wherein the composition further comprises one or more of a perfume, a pigment, estrogen, vitamin A, vitamin C, vitamin E, alpha-hydroxy or alpha-keto acids, lanolin, vaseline, aloe vera, methyl paraben, and propyl paraben.

7 . The composition of claim 5 , wherein the composition is a powder, spray, paste, solution, patch, drop, emulsion, suspension, aerosol, inhalant, liquid, cream, oil, lotion, ointment, gel, or solid.

8 . The composition of claim 7 , wherein the composition is a topical composition.

9 . The composition of claim 5 , wherein the composition is a capsule, cachet, pill, tablet, dragee, powder, granule, an aqueous solution, a non-aqueous solution, an aqueous suspension, a non-aqueous suspension, an oil-in-water liquid emulsion, a water-in-oil liquid emulsion, a microemulsion, an elixir, a syrup, a pastille, a bolus, an electuary or a paste.

10 . The composition of claim 9 , wherein the composition is an oral composition.

11 . The composition of claim 9 , wherein the composition is an oral, liquid dosage form.

12 . The composition of claim 11 , wherein the composition further comprises one or more of a wetting agent, emulsifying agent, suspending agent, sweetening agent, flavoring agent, coloring agent, perfuming agent and preservative agent.

13 . A compound of the following structure:

or a pharmaceutically or cosmetically acceptable salt thereof.

14 . The composition of claim 4 , wherein the composition further comprises one or more of a perfume, a pigment, estrogen, vitamin A, vitamin C, vitamin E, alpha-hydroxy or alpha-keto acids, lanolin, vaseline, aloe vera, methyl paraben, and propyl paraben.

15 . The composition of claim 4 , wherein the composition is a powder, spray, paste, solution, patch, drop, emulsion, suspension, aerosol, inhalant, liquid, cream, oil, lotion, ointment, gel, or solid.

16 . The composition of claim 15 , wherein the composition is a topical composition.

17 . The composition of claim 4 , wherein the composition is a capsule, cachet, pill, tablet, dragee, powder, granule, an aqueous solution, a non-aqueous solution, an aqueous suspension, a non-aqueous suspension, an oil-in-water liquid emulsion, a water-in-oil liquid emulsion, a microemulsion, an elixir, a syrup, a pastille, a bolus, an electuary or a paste.

18 . The composition of claim 17 , wherein the composition is an oral composition.

19 . The composition of claim 17 , wherein the composition is an oral, liquid dosage form.

20 . The composition of claim 19 , wherein the composition further comprises one or more of a wetting agent, emulsifying agent, suspending agent, sweetening agent, flavoring agent, coloring agent, perfuming agent and preservative agent.

21 . The composition of claim 4 , wherein the composition further comprises one or more of pyruvic acid, lactic acid, and glycolic acid.

22 . The composition of claim 5 , wherein the composition further comprises one or more of pyruvic acid, lactic acid, and glycolic acid.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2023
From: EINZIGER, MICHAEL; SIMPSON, ANN MARIE
To: VERSICOLOR TECHNOLOGIES, LLC
Reel/Frame 062928/0266 →
Continuity (4)
Continuation 16549106 · Aug 23, 2019
Provisional Application 62722412 · Aug 24, 2018
Provisional Application 62742657 · Oct 8, 2018
Related Publication 20220110848A1 · Apr 14, 2022
References Cited (80)
US 9969686B2 · Tang et al. · 2018 [cited by applicant]
US 10131631B2 · Einziger · 2018 [cited by examiner]
US 10730833B2 · Tang et al. · 2020 [cited by applicant]
US 11104644B2 · Einziger · 2021 [cited by examiner]
US 11202748B2 · Einziger · 2021 [cited by examiner]
US 11220491B2 · Einziger · 2022 [cited by examiner]
US 11987555B2 · Einziger · 2024 [cited by examiner]
US 20090263339A1 · Kyono et al. · 2009 [cited by applicant]
US 20100324109A1 · Saurat · 2010 [cited by applicant]
US 20160039754A1 · Tang et al. · 2016 [cited by applicant]
US 20170260133A1 · Einziger et al. · 2017 [cited by applicant]
US 20180222861A1 · Tang et al. · 2018 [cited by applicant]
US 20180370913A1 · Einziger et al. · 2018 [cited by applicant]
US 20190337927A1 · Einziger et al. · 2019 [cited by applicant]
US 20190345140A1 · Einziger et al. · 2019 [cited by applicant]
US 20220106297A1 · Einziger et al. · 2022 [cited by applicant]
US 20220110848A1 · Einziger et al. · 2022 [cited by applicant]
CN 106916171A · 2017 [cited by applicant]
KR 20160128764A · 2016 [cited by applicant]
WO 0236561A1 · 2002 [cited by applicant]
WO 2014143125A1 · 2014 [cited by applicant]
WO WO2017156424A1 · 2017 [cited by applicant]
WO 2019200232A1 · 2019 [cited by applicant]
WO 2020041663A1 · 2020 [cited by applicant]
Adachi et al., “Indirubin and Indigo are Potent Aryl Hydrocarbon Receptor Ligands Present in Human Urine,” The Journal of Biological Chemistry, vol. 276, No. 34, p. 31475-31478 (Aug. 24, 2001). [cited by applicant]
Berridge et al., “The Biochemical and Cellular Basis of Cell Proliferation Assays That Use Tetrazolium Salts”, Biochemica, vol. 4 pp. 4-19 (1996). [cited by applicant]
Bergman, J. et al., “Synthesis of indolocarbazole quinones; potent aryl hydrocarbon receptor ligands,” Tetrahedron 58 (2002) 1443-1452. [cited by applicant]
Black, et al. “Athymic Nude Mice and Human Skin Grafting”, In: Maibach, et al. (eds.), Models in Dermatology vol. 1., Karger, Basel, pp. 228-239, (1985). [cited by applicant]
Costin, et al., “Optimized in vitro pigmentation screening assay using a reconstructed three dimensional human skin model”, Rom. J. Biochem, vol. 50 No. 1, pp. 15-27, (2013). [cited by applicant]
Crisan et al., “QSAR Study and Molecular Docking on Indirubin Inhibitors of Glycogen Synthase Kinase-3,” Cent. Eur. J. Chem., 11 (1), pp. 63-77 (2013). [cited by applicant]
Donato, et al., “A Microassay for Measuring Cytochrome P450IA1 and P450IIB1 Activities in Intact Human and Rat Hepatocytes Cultured on 96-Well Plates”, Anal Biochem, vol. 213, No. 1, pp. 29-33, (1993). [cited by applicant]
Elmore, “Apoptosis: A Review of Programmed Cell Death”, Toxicologic Pathology, vol. 35, pp. 495-516, (2007). [cited by applicant]
English Translation for KR 20160128764 A (2016). [cited by applicant]
Evdokimov et al., “Isatin derivatives with activity against apoptosis-resistant cancer cells”, Bioorganic Medicinal Chemistry Letters, vol. 26, No. 6, pp. 1558-1560, (2016). [cited by applicant]
Fitzpatrick et al., “The Validity and Practicality of Sun-Reactive Skin Types I Through VI”, Arch Dermatol, vol. 124, No. 6, pp. 869-871, (1988). [cited by applicant]
Gaitanis et al., “Skin Diseases Associated With [cited by applicant]
Gambichler et al., “Quantification of Ultraviolet Protective Effects of Pityriacitrin in Humans”, Archives of Dermatological Research; vol. 299, pp. 517-520, (2007). [cited by applicant]
Gueho et al., “The Genus [cited by applicant]
He, Y. et al., “Substrate-Controlled Regioselective Arylations of 2-Indolylmethanols with Indoles: Synthesis of Bis(idolyl)methane and 3,3′-Bisindole Derivatives”, The Journal of Organic Chemistry 82 (2017) 2462-2471. [cited by applicant]
International Search Report and Written Opinion for PCT/US2019/047831, dated Jan. 8, 2020. [cited by applicant]
Karchner, et al., “Identification and Functional Characterization of Two Highly Divergent Aryl Hydrocarbon Receptors (AHR1 and AHR2) in the Teleost Fundulus heteroclitus”, The Journal of Biological Chemistry, vol. 274, … [cited by applicant]
Kramer et al., “Malassezin, a Novel Agonist of the Aryl Hydrocarbon Receptor from the Yeast [cited by applicant]
Lee, et al., “Comparison of Gene Expression Profiles Between Keratinocytes, Melanocytes and Fibroblasts”, Ann Dermatol, vol. 25, No. 1, pp. 35-45, (2013). [cited by applicant]
Machowinski et al., “Pityriacitrin—A Potent UV filter Produced by [cited by applicant]
Manning, et al., “Maintenance of Skin Xenografts of Widely Divergent Phylogenetic Origin on Congenitally Athymic (Nude) Mice”, J Exp Med, vol. 138, pp. 488-494, (1973). [cited by applicant]
Mayser et al., “Pityriacitrin—An Ultraviolet-Absorbing Indole Alkaloid from the Yeast [cited by applicant]
Mayser et al., “Pityrialactone—A New Fluorochrome from the Tryptophan Metabolism of [cited by applicant]
Nazzaro-Porro, et al., “Identification of Tyrosinase Inhibitors in Cultures of Pityrosporum”, The Journal of Investigative Dermatology, vol. 71, pp. 205-208, (1978). [cited by applicant]
Noakes, “The Aryl Hydrocarbon Receptor: A Review of Its Role in the Physiology and Pathology of the Integument and Its Relationship to the Tryptophan Metabolism”, Journal of Tryptophan Research, vol. 8, pp. 17-18, (2015… [cited by applicant]
Otulakowski et al., “Use of a Human Skin-Grafted Nude Mouse Model for the Evaluation of Topical Retinoic Acid Treatment”, J Invest Dermatol, vol. 102, pp. 515-518, (1994). [cited by applicant]
Park et al., “Inhibitory effect of 2-methyl-naphtho[1,2,3-de]quinolin-8-one on melanosome transport and skin pigmentation”, Sci. Rep., vol. 6 No. 29189, Doi: 10.1038/srep29189, (2016). [cited by applicant]
Pillaiyar, T. et al., “A rapid, efficient and versatile green synthesis of 3,3′-diidolvlmethanes,” Arkivoc (2018) Part III, 1-19. [cited by applicant]
Pillaiyar, T. et al., “Supplementary Material: A rapid, efficient and versatile green synthesis of diindolylmethanes” Arkivoc (2018) Part III, S1-S61. [cited by applicant]
Plenat et al. “Host-Donor Interactions in Healing of Human Split-Thickness Skin Grafts Onto Nude Mice: In Situ Hybridization, Immunohistochemical and Histochemical Studies”, Transplantation, vol. 53, pp. 1002-1010, (199… [cited by applicant]
Reed et al., “Long-Term Maintenance of Normal Human Skin on Congenitally Athymic (Nude) Mice”, Proc Soc Exp Biol Med, vol. 143, pp. 350-353, (1973). [cited by applicant]
Scott et al., “The Permeability of Grafted Human Transplant Skin in Athymic Mice”, J Pharm Pharmacol, vol. 40, pp. 128-129, (1988). [cited by applicant]
Song et al., “A Ligand for the Aryl Hydrocarbon Receptor Isolated From Lung”, PNAS, vol. 99, No. 23, pp. 14694-14699, (2002). [cited by applicant]
Taylor et al., “The Taylor Hyperpigmentation Scale: a new visual assessment tool for the evaluation of skin color and pigmentation”, Cutis, vol. 76, No. 4, pp. 270-274, (2005). [cited by applicant]
Wang et al., “Stress-Induced RNASET2 Overexpression Mediates Melanocyte Apoptosis Via the TRAF2 Pathway In Vitro”, Cell Death and Disease, 5:e1022, (2014). [cited by applicant]
Wasmeier, et al. “Melanosomes at a Glance”, Journal of Cell Science, vol. 121, pp. 3995-3999, (2008). [cited by applicant]
Whyte et al., “Ethoxyresorufin-O-deethylase (EROD) Activity in Fish as a Biomarker of Chemical Exposure”, Critical Reviews in Toxicology, vol. 30, No. 4, pp. 347-570, (2000). [cited by applicant]
Wille et al., “Malassezin—A Novel Agonist of the Arylhydrocarbon Receptor From the Yeast [cited by applicant]
Winston-McPherson, et al., “Synthesis and Biological Evaluation of 2,3′-diindolylmethanes as Agonists of Aryl Hydrocarbon Receptor”, Bioorganic & Medicinal Chemistry Letters, vol. 24, No. 16, pp. 4023-4025, (2014). [cited by applicant]
Yamaguchi et al., “Melanocytes and Their Diseases”, Cold Spring Harb Perspect Med, vol. 4, a017046, (2014). [cited by applicant]
Zhang et al., “Environmental adaptability and quorum sensing: Iron uptake regulation during biofilm formation by [cited by applicant]
Zonios et al., “Skin Melanin, Hemoglobin, and Light Scattering Properties can be Quantitatively Assessed In Vivo Using Diffuse Reflectance Spectroscopy”, J Invest Dermatol, vol. 117, pp. 1452-1457, (2001). [cited by applicant]
Tholander et al. (Mar. 19, 1998) “Synthesis of 6-Formylindolo[3,2-b]Carbazole, an Extremely Potent Ligand for the Aryl Hydrogen (Ah) Receptor”, Tetrahedron Letters, 39:1619-1622. [cited by applicant]
Wahlstroem et al. (2004) “Synthesis of 2,3′-Diindolylmethanes and Substituted Indolo[3,2-b]Carbazoles, Synthesis”, Synthesis, (8):1187-1197. [cited by applicant]
Waller et al. (1995) “Three-Dimensional Quantitative Structure-Activity Relationships of Dioxins and Dioxin-like Compounds: Model Validation and Ah Receptor Characterization.”, Chemical research in toxicology, 8:847-858. [cited by applicant]
Zeng et al. (2005) “Novel Method for Synthesis of Unsymmetrical Bis(indolyl)alkanes Catalyzed by Ceric Ammonium Nitrate (CAN) Under Ultrasonic Irradiation”, Tetrahedron, 61(43):10235-10241. [cited by applicant]
Boudreault et al. (Oct. 2010) “Synthesis and characterization of soluble indolo[3,2-b]carbazole derivatives for organic field-effect transistors”, Organic Electronics, 11(10):1649-1659. [cited by applicant]
Colombo et al. (2008) “Three-Component Indium-Mediated Domino Allylation of 1H-Indole-3-carbaldehyde with Electron-Rich (Hetero)arenes: Highly Efficient Access to Variously Functionalized Indolylbutenes”, European Journ… [cited by applicant]
Liang et al. (Jan. 8, 2015) “A Biomimetic Method to Synthesise Indolo[3,2-a]Carbazoles”, Tetrahedron Letters, 56(2): 434-436. [cited by applicant]
Lin et al. (1998) “Indole-Carbonyl Coupling Reactions Promoted by Samarium Diiodide. Application to the Synthesis of Indole-Fused Compounds”, The Journal of Organic Chemistry, 63(9):2909-2917. [cited by applicant]
Luecke et al. (2010) “The Aryl Hydrocarbon Receptor (AHR), A Novel Regulator of Human Melanogenesis”, Pigment Cell Melanoma Research, 23(6):828-833. [cited by applicant]
Tholander et al. (1999) “Syntheses of 6, 12-Disubstituted 5,11-Dihydroindolo[3,2-b]Carbazoles, Including 5,11-Dihydroindolo[3,2-b]Carbazole-6,12-Dicarbaldehyde, an Extremely Efficient Ligand for the TCDD (Ah) Receptor”,… [cited by applicant]
Tholander et al. (1999) “Syntheses of 6-Substituted Indolo[3,2-b]Carbazoles, Including 6-Formylindolo[3,2-b] Carbazole, an Extremely Efficient Ligand for the TCDD (Ah) Receptor”, Tetrahedron, 55:6243-6260. [cited by applicant]
Gibbs et al., “Aminocatalytic Preparation of Bisindolylalkanes”, Organic & Biomolecular Chemistry, 2005, 3 (22):4043-4045. [cited by applicant]
Nguyen et al., “D-Amino Acid Oxidase Generates Agonists of the Aryl Hydrocarbon Receptor from D-Tryptophan”, Chemical Research on Toxicology, 2009, 22(12):1897-1904. [cited by applicant]
Wahlstrom et al., “Synthesis of Metabolites of the Ah Receptor Ligand 6-Formylindolo[3,2-b]carbazole”, European Journal of Organic Chemistry, 2004, 2004(12):2593-2602. [cited by applicant]