IP Library Granted Patent US 12,485,085
Granted Patent B2
US 12,485,085 · App. 17/781,416 · Granted Dec 2, 2025

PPAR agonist complex and methods of use

Inventors: George P. Majewski (Walnut, CA); John Simon Craw (San Francisco, CA)
A61K8/9789A61K8/361A61K8/375A61Q17/00A61Q19/004A61Q19/007A61Q19/08
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Quick Facts
Patent No.
US 12,485,085
App. No.
17/781,416
Granted
Dec 2, 2025
Kind
B2
Abstract

Compositions and topical formulations comprising a PPAR agonist complex comprising glyceryl linoleate, glyceryl linolenate, xymenynic acid, and Pterocarpus marsupium bark extract are described herein. Methods of inducing skin barrier repair, increasing the biosynthesis of barrier lipids and proteins in the skin, stimulating hair growth, treating acne and combinations thereof utilizing the composition and topical formulations are also provided herein.

Claims (20)

1 . A composition comprising an effective amount of glyceryl linoleate, glyceryl linolenate, xymenynic acid, and Pterocarpus marsupium bark extract.

2 . The composition of claim 1 , wherein the effective amount of glyceryl linoleate is about 75% to about 94% by weight of the composition.

3 . The composition of claim 1 , wherein the effective amount of glyceryl linolenate is about 5% to about 10% by weight of the composition.

4 . The composition of claim 1 , wherein the effective amount of xymenynic acid is about 5% to about 10% by weight of the composition.

5 . The composition of claim 1 , wherein the effective amount of Pterocarpus marsupium bark extract is about 1% to about 5% by weight of the composition.

6 . The composition of claim 1 , wherein the effective amount of glyceryl linoleate is 75% to 94% by weight of the composition, glyceryl linolenate is 5% to 10% by weight of the composition, xymenynic acid is 5% to 10% by weight of the composition, and Pterocarpus Marsupium bark extract is 1% to 5% by weight of the composition.

7 . A topical formulation comprising a composition of an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, xymenynic acid, and Pterocarpus marsupium bark extract, and pharmaceutically or cosmetically acceptable excipients, wherein the formulation is suitable for topical administration.

8 . The topical formulation of claim 7 , wherein glyceryl linoleate is in an amount of about 0.375% to about 4.7% by weight of the topical formulation.

9 . The topical formulation of claim 7 , wherein glyceryl linolenate is in an amount of about 0.025% to about 0.5% by weight of the topical formulation.

10 . The topical formulation of claim 7 , wherein xymenynic acid is in an amount of about 0.025% to about 0.5% by weight of the topical formulation.

11 . The topical formulation of claim 7 , wherein Pterocarpus marsupium bark extract is in an amount of about 0.005% to about 0.25% by weight of the topical formulation.

12 . A method of inducing skin barrier repair comprising topically administering a topical formulation of claim 7 .

13 . The method of claim 12 , wherein inducing skin barrier repair results in the biosynthesis of barrier lipids and proteins in the skin selected from the group consisting of ceramides, filaggrin, trans-glutaminase 1, TGFB1, keratins, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF, and combinations thereof.

14 . The method of claim 12 , wherein inducing skin barrier repair results in the modulation of the expression of barrier genes in the skin selected from the group consisting of ceramides, filaggrin, trans-glutaminase 1, TGFB1, keratins, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF and combinations thereof.

15 . A method of improving aging skin comprising topically administering a topical formulation of claim 7 , wherein the improvement of aging skin is selected from the group consisting of smoothness, hydration and texture.

16 . A method of preventing skin damage comprising topically administering a topical formulation of claim 7 .

17 . A method of treating photo-damage and hyperpigmentation comprising topically administering a topical formulation of claim 7 .

18 . A method of improving skin barrier function comprising topically administering a topical formulation of claim 7 .

19 . A method of mitigating irritation comprising topically administering a topical formulation of claim 7 .

20 . A method of supporting the skin's natural ability to defend itself against environmental stressors comprising topically administering a topical formulation of claim 7 .

Assignments (10)
ASSIGNMENT OF SECURITY INTERESTS IN PATENT COLLATERAL Recorded Feb 2, 2026
From: CITIBANK, N.A., IN ITS CAPACITY AS THE WITHDRAWING AGENT
To: ANKURA TRUST COMPANY, LLC, IN ITS CAPACITY AS SUCCESSOR AGENT
Reel/Frame 074643/0097 →
MERGER Recorded Oct 9, 2024
From: RODAN & FIELDS, LLC
To: RODAN & FIELDS BEAUTY, LLC
Reel/Frame 068844/0351 →
PATENT SECURITY AGREEMENT Recorded Sep 27, 2024
From: RODAN & FIELDS BEAUTY, LLC
To: ANKURA TRUST COMPANY, LLC, AS COLLATERAL AGENT
Reel/Frame 069066/0818 →
RELEASE OF SECURITY INTEREST IN PATENT COLLATERAL RECORDED ON APRIL 28, 2023, AT REEL/FRAME 063480/0786 Recorded Sep 27, 2024
From: ANKURA TRUST COMPANY, LLC, AS COLLATERAL AGENT
To: RODAN & FIELDS, LLC
Reel/Frame 069066/0803 →
PATENT SECURITY AGREEMENT Recorded Sep 27, 2024
From: RODAN & FIELDS BEAUTY, LLC
To: ANKURA TRUST COMPANY, LLC, AS COLLATERAL AGENT
Reel/Frame 069066/0810 →
SECURITY INTEREST Recorded May 2, 2023
From: RODAN & FIELDS, LLC
To: CITIBANK, N.A.
Reel/Frame 063501/0785 →
SECURITY INTEREST Recorded May 2, 2023
From: RODAN & FIELDS, LLC
To: ANKURA TRUST COMPANY, LLC
Reel/Frame 063501/0804 →
SECURITY INTEREST Recorded Apr 28, 2023
From: RODAN & FIELDS, LLC
To: ANKURA TRUST COMPANY, LLC
Reel/Frame 063480/0786 →
SECURITY INTEREST Recorded Apr 28, 2023
From: RODAN & FIELDS, LLC
To: ANKURA TRUST COMPANY, LLC
Reel/Frame 063480/0179 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2022
From: CRAW, JOHN SIMON; MAJEWSKI, GEORGE P.
To: RODAN & FIELDS, LLC
Reel/Frame 061245/0777 →
Continuity (2)
Provisional Application 62955055 · Dec 30, 2019
Related Publication 20230000759A1 · Jan 5, 2023
References Cited (96)
US 5641504A · Lee · 1997 [cited by examiner]
US 7838025B2 · Koenig et al. · 2010 [cited by applicant]
US 8133917B2 · Rimando et al. · 2012 [cited by applicant]
US 8252845B1 · Rimando et al. · 2012 [cited by applicant]
US 9980924B2 · Meyskens et al. · 2018 [cited by applicant]
US 20040115331A1 · Eggink et al. · 2004 [cited by applicant]
US 20040146482A1 · Pauly · 2004 [cited by examiner]
US 20050158258A1 · Fisher · 2005 [cited by examiner]
US 20060057231A1 · Rimando et al. · 2006 [cited by applicant]
US 20070020220A1 · Osborne · 2007 [cited by applicant]
US 20140120141A1 · Anton et al. · 2014 [cited by applicant]
US 20180140528A1 · Lee et al. · 2018 [cited by applicant]
CN 1905891A · 2007 [cited by applicant]
CN 101268145A · 2008 [cited by applicant]
CN 108883036A · 2018 [cited by applicant]
CN 110731929A · 2020 [cited by applicant]
WO 2000016752A2 · 2000 [cited by applicant]
WO 2004037225A2 · 2004 [cited by applicant]
WO 2016036999A1 · 2016 [cited by applicant]
WO 2019060357A1 · 2019 [cited by applicant]
Moy et al., “Sandalwood Album Oil as a Botanical Therapeutic in Dermatology,” J. Clin. Aesthet. Dermatol. 10(10):34-39 (2017). [cited by applicant]
Moya-Camarena et al., “Conjugated Linoleic Acid is a Potent Naturally Occurring Ligand and Activator of PPARalpha,” J. Lipid Res. 40(8):1426-1433 (1999). [cited by applicant]
Nugteren et al., “Naturally Occurring Conjugated Octadecatrienoic Acids are Strong Inhibitors of Prostaglandin Biosynthesis,” Prostaglandins 33(3):403-417 (1987). [cited by applicant]
Oh et al., “The Molecular Revolution in Cutaneous Biology: EDC and Locus Control,” J. Invest. Dermatol. 137(5):e101-e104 (2017). [cited by applicant]
Ohtera et al., “Identification of a New Type of Covalent PPARγ Agonist Using a Ligand-Linking Strategy,” ACS Chem. Biol. 10(12):2794-2804 (2015). [cited by applicant]
Li et al., “The Role of Ceramides in Skin Homeostasis and Inflammatory Skin Diseases,” J. Dermatol. Sci. 97(1):2-8 (2020). [cited by applicant]
Rageeb et al., “In Vitro Anti-Inflammatory Activity of Pterocarpus Marsupium Roxb. Stem Bark on Albino Rats,” Journal of Pharmaceutical and Scientific Innovation 1(2):21-25 (2012). [cited by applicant]
Rimando et al., “Pterostilbene, a New Agonist for the Peroxisome Proliferator-Activated Receptor Alpha-Isoform, Lowers Plasma Lipoproteins and Cholesterol in Hypercholesterolemic Hamsters,” J. Agric .Food Chem. 53(9):34… [cited by applicant]
Rivier et al., “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes,” J. Invest. Dermatol. 111(6):1116-1121 (1998). [cited by applicant]
Rivier et al., “Peroxisome Proliferator-Activated Receptor-Alpha Enhances Lipid Metabolism in a Skin Equivalent Model,” J. Invest. Dermatol. 114(4):681-687 (2000). [cited by applicant]
Robertshaw et al., “Pioglitazone: A Promising Therapy for Psoriasis,” Br. J. Dermatol. 152(1):189-191 (2005). [cited by applicant]
Roupe et al., “Pharmacometrics of Stilbenes: Seguing Towards the Clinic,” Curr. Clin. Pharmacol. 1(1):81-101 (2006). [cited by applicant]
Schleehauf, Sabinsa Cosmetics' pTeroWhite, Feb. 13, 2019, <https://www.cosmeticsandtoiletries.com/formulating/category/natural/Sabinsa-Cosmetics-pTeroWhite-505801751.html>. [cited by applicant]
Schmuth et al., “Role of PPAR, LXR, and PXR in Epidermal Homeostasis and Inflammation,” Biochim. Biophys. Acta. 1841(3):463-473 (2014). [cited by applicant]
Schütz et al., “Bio-Derived Hydroxystearic Acid Ameliorates Skin Age Spots and Conspicuous Pores,” Int. J. Cosmet. Sci. 41(3):240-256 (2019). [cited by applicant]
Sertznig et al., “Peroxisome Proliferator-Activated Receptors (PPARs) in Dermatology: Challenge and Promise,” Dermatoendocrinol. 3(3):130-135 (2011). [cited by applicant]
Shafiq et al., “Pilot Trial: Pioglitazone Versus Placebo in Patients with Plaque Psoriasis (the P6),” Int. J. Dermatol. vol. 44(4):328-333 (2005). [cited by applicant]
Shang et al., “Cooperative Cobinding of Synthetic and Natural Ligands to the Nuclear Receptor PPARγ,” eLife 7:e43320 (2018). [cited by applicant]
Sierra et al., “Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARalpha Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents,” J. Med. Chem. 50(4):685-695 (2007). [cited by applicant]
Takeda et al., “Strawberry Seed Extract and its Major Component, Tiliroside, Promote Ceramide Synthesis in the Stratum Corneum of Human Epidermal Equivalents,” PLoS One 13(10):e020561 (2018). [cited by applicant]
Wiechers et al., “A New Mechanism of Action for Skin Whitening Agents: Binding to the Peroxisome Proliferator- Activated Receptor,” Int. J. Cosmet. Sci. 27(2):123-132 (2005). [cited by applicant]
Ximenynic Acid, Jun. 18, 2019, entire document, https://en.wikipedia.org/w/index.php?title=Ximenynic_acid&oldid=902336690. [cited by applicant]
Yamamoto et al., “Molecular Association Model of PPARα and its New Specific and Efficient Ligand, Pemafibrate: Structural Basis for SPPARMα,” Biochem. Biophys. Res. Commun. 499(2):239-245 (2018). [cited by applicant]
Zhang et al., “Topically Applied Ceramide Accumulates in Skin Glyphs,” Clin. Cosmet. Investig. Dermatol. 8:329-337 (2015). [cited by applicant]
Zoete et al., “Peroxisome Proliferator-Activated Receptor Structures: Ligand Specificity, Molecular Switch and Interactions with Regulators,” Biochim. Biophys. Acta. 1771(8):915-925 (2007). [cited by applicant]
Majewski et al., “Accelerated Barrier Repair in Human Skin Explants Induced with a Plant-Derived PPAR-a Activating Complex via Cooperative Interactions”, PMID: 34566418 PMCID: PMC8458040 DOI: 10.2147/CCID.S325967, Clin … [cited by applicant]
Al Yacoub et al., “PPARdelta is a Type 1 IFN Target Gene and Inhibits Apoptosis in T Cells,” J. Invest. Dermatol. 128(8):1940-1949 (2008). [cited by applicant]
Angeli et al., “Peroxisome Proliferator-Activated Receptor Gamma Inhibits the Migration of Dendritic Cells: Consequences for the Immune Response,” J. Immunol. 170(10):5295-5301 (2003). [cited by applicant]
Bais et al., “The Molecular Regulation of Stilbene Phytoalexin Biosynthesis in Vitis Vinifera During Grape Berry Development,” Aust. J. Plant Physiol. 27:425-433 (2000). [cited by applicant]
Batheja et al., “Effects of Growth Conditions on the Barrier Properties of a Human Skin Equivalent,” Pharm Res. 26(7):1689-1700 (2009). [cited by applicant]
Behshad et al., “A Retrospective Case Series Review of the Peroxisome Proliferator-Activated Receptor Ligand Rosiglitazone in the Treatment of Atopic Dermatitis,” Arch. Dermatol. 144(1):84-88 (2008). [cited by applicant]
Berger et al., “The Mechanisms of Action of PPARs,” Annu. Rev. Med. 53:409-435 (2002). [cited by applicant]
Billoni et al., “Expression of Peroxisome Proliferator Activated Receptors (PPARs) in Human Hair Follicles and PPAR alpha Involvement in Hair Growth,” Acta Derm. Venereol. 80(5):329-334 (2000). [cited by applicant]
Boguniewicz et al., “Atopic Dermatitis: A Disease of Altered Skin Barrier and Immune Dysregulation,” Immunol. Rev. 242(1):233-246 (2011). [cited by applicant]
Bongartz et al., “Treatment of Active Psoriatic Arthritis with the PPARgamma Ligand Pioglitazone: An Open-Label Pilot Study,” Rheumatology 44(1):126-129 (2005). [cited by applicant]
Braissant et al., “Differential Expression of Peroxisome Proliferator-Activated Receptor-alpha, -beta, and -gamma During Rat Embryonic Development,” Endocrinology 139(6): 2748-2754 (1998). [cited by applicant]
Braissant et al., “Differential Expression of Peroxisome Proliferator-Activated Receptors (PPARs): Tissue Distribution pf PPAR-alpha, -beta, and -gamma in the Adult Rat,” Endocrinology 137(1):354-366 (1996). [cited by applicant]
Chawla et al., “Nuclear Receptors and Lipid Physiology: Opening the X-Files,” Science 294(5548):1866-1870 (2001). [cited by applicant]
Chon et al., “Keratinocyte Differentiation and Upregulation of Ceramide Synthesis Induced by an Oat Lipid Extract via the Activation of PPAR Pathways,” Exp. Dermatol. 24(4):290-295 (2015). [cited by applicant]
Cox, “Rationally Designed PPARδ-Specific Agonists and Their Therapeutic Potential for Metabolic Syndrome,” Proc. Natl. Acad. Sci. USA 114(13):3284-3285 (2017). [cited by applicant]
Dahten et al., “Systemic PPARgamma Ligation Inhibits Allergic Immune Response in the Skin,” J. Invest. Dermatol. 128(9):2211-2218 (2008). [cited by applicant]
Del Rosso et al., “Understanding the Epidermal Barrier in Healthy and Compromised Skin: Clinically Relevant Information for the Dermatology Practitioner,” J. Clin. Aesthet. Dermatol. 9(4 suppl 1):S2-S8 (2016). [cited by applicant]
Demento et al. “Improving the Quality of Skin Barrier Function with PPAR-Activating Technology,” Journal of the American Academy of Dermatology 70:AB64 (2014). [cited by applicant]
Downie et al., “Peroxisome Proliferator-Activated Receptor and Farnesoid X Receptor Ligands Differentially Regulate Sebaceous Differentiation in Human Sebaceous Gland Organ Cultures in vitro,” British J. Dermatol. 151(4… [cited by applicant]
Dubrac et al., “Peroxisome Proliferator-Activated Receptor-alpha Activation Inhibits Langerhans Cell Function,” J. Immunol. 178(7):4362-4372 (2007). [cited by applicant]
Dubrac et al., “PPAR-alpha in Cutaneous Inflammation,” Dermatoendocrinol. 3(1):23-26 (2011). [cited by applicant]
Dwivedi et al., “Chemopreventive Effects of Sandalwood Oil on Skin Papillomas in Mice,” Eur. J. Cancer Prev. 6(4):399-401 (1997). [cited by applicant]
Eastham et al., “PPARalpha/gamma Expression and Activity in Mouse and Human Melanocytes and Melanoma Cells,” Pharm. Res. 25(6):1327-1333 (2008). [cited by applicant]
Eissa et al., “Human Tissue Kallikreins as Promiscuous Modulators of Homeostatic Skin Barrier Functions,” Biol. Chem. 389(6):669-680 (2008). [cited by applicant]
Elias et al., “Interactions Among Startum Corneum Defensive Functions,” Exp. Dermatol. 14(10):719-726 (2005). [cited by applicant]
Evans et al., “PPARs and the Complex Journey to Obesity,” Nat. Med. 10(4):355-361 (2004). [cited by applicant]
Faveeuw et al., “Peroxisome Proliferator-Activated Receptor gamma Activators Inhibit Interleukin-12 Production in Murine Dendritic Cells,” FEBS Lett. 486(3):261-266 (2000). [cited by applicant]
Fluhr et al., “Topical Peroxisome Proliferator Activated Receptor Activators Accelerate Postnatal Stratum Corneum Acidification,” J. Invest. Dermatol. 129(2):365-374 (2009). [cited by applicant]
Forman et al., “15-Deoxy-delta 12, 14-prostaglandin J2 is a Ligand for the Adipocyte Determination Factor PPAR Gamma,” Cell 83(5):803-812 (1995). [cited by applicant]
Forman et al., “Hypolipidemic Drugs, Polyunsaturated Fatty Acids, and Eicosanoids are Ligands for Peroxisome Proliferator-Activated Receptors Alpha and Delta,” Proc. Natl. Acad. Sci. U S A 94(9):4312-4317 (1997). [cited by applicant]
Goleva et al., “Epithelial Barrier Repair and Prevention of Allergy,” J. Clin. Investl. 129(4):1463-1474 (2019). [cited by applicant]
Greene et al., “PPARgamma: Observations in the Hematopoietic System,” Prostaglandins Other Lipid Mediat. 62(1):45-73 (2000). [cited by applicant]
Hanley et al., “Fetal Epidermal Differentiation and Barrier Development In Vivo is Accelerated by Nuclear Hormone Receptor Activators,” J. Invest. Dermatol. 113(5):788-795 (1999). [cited by applicant]
Hanley et al., “Glucosylceramide Metabolism is Regulated During Normal and Hormonally Stimulated Epidermal Barrier Development in the Rat,” J. Lipid Res. 38(3):576-584 (1997). [cited by applicant]
Hanley et al., “Keratinocyte Differentiation is Stimulated by Activators of the Nuclear Hormone Receptor PPARalpha,” J. Invest. Dermatol. 110(4):368-375 (1998). [cited by applicant]
Hettiarachchi et al., “Western Australian Sandalwood Seed Oil: New Opportunities,” Lipid Technology 2(2):27-29 (2010). [cited by applicant]
International Search Report and Written Opinion for PCT/US2020/064798 mailed Mar. 22, 2021. [cited by applicant]
Jung et al., “Peroxisome Proliferator-Activated Receptor γ-Mediated Suppression of Dendritic Cell Function Prevents the Onset of Atopic Dermatitis in NC/Tnd Mice,” J. Allergy Clin. Immunol. 127(2):420-429 (2011). [cited by applicant]
Kang et al., “Peroxisome Proliferator-Activated Receptors-Gamma Activator, Ciglitazone, Inhibits Human Melanocyte Growth Through Induction of Apoptosis,” Arch. Dermatol. Res. 297(10):472-476 (2006). [cited by applicant]
Kezic et al., “Filaggrin and Skin Barrier Function,” Curr. Probl. Dermatol. 49:1-7 (2016). [cited by applicant]
Kim et al., “Limited Cooperation Between Peroxisome Proliferator-Activated Receptors and Retinoid X Receptor Agonists in Sebocyte Growth and Development,” Mol. Genet. Metab. 74(3):362-369 (2001). [cited by applicant]
Kuwabara et al., “Peroxisome Proliferator-Activated Receptors (PPARs) have Multiple Binding Points that Accommodate Ligands in Various Conformations: Phenylpropanoic Acid-Type PPAR Ligands Bind to PPAR in Different Conf… [cited by applicant]
Kypriotou et al., “The Human Epidermal Differentiation Complex: Cornified Envelope Precursors, S100 Proteins and the ‘Fused Genes’ Family,” Exp. Dermatol. 21(9):643-649 (2012). [cited by applicant]
Kömüves et al., “Keratinocyte Differentiation in Hyperproliferative Epidermis: Topical Application of PPARalpha Activators Restores Tissue Homeostasis,” J. Invest. Dermatol. 115(3):361-367 (2000). [cited by applicant]
Kömüves et al., “Ligands and Activators of Nuclear Hormone Receptors Regulate Epidermal Differentiation During Fetal Rat Skin Development,” J. Invest. Dermatol. 111(3):429-433 (1998). [cited by applicant]
Lee et al., “PPAR-Gamma Agonist, Ciglitazone, Increases Pigmentation and Migration of Human Melanocytes,” Exp. Dermatol. 16(2):118-123 (2007). [cited by applicant]
Li et al., “Growth Inhibition and Differentiation Induced by Peroxisome Proliferator Activated Receptor Gamma Ligand Rosiglitazone in Human Melanoma Cell Line A375,” Med. Oncol. 23(3):393-402 (2006). [cited by applicant]
Li et al., “Comparative Effects of Sandalwood Seed Oil on Fatty Acid Profiles and Inflammatory Factors in Rats,” Lipids 48(2):105-113 (2013). [cited by applicant]
Michalik et al., “Peroxisome Proliferator-Activated Receptors (PPARs) in Skin Health, Repair and Disease,” Biochim. Biophys. Acta 1771(8):991-998 (2007). [cited by applicant]
Mittal et al., “Efficacy and Safety of Combination Acitretin and Pioglitazone Therapy in Patients with Moderate to Severe Chronic Plaque-Type Psoriasis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial,” Ar… [cited by applicant]
Mizutani et al., “Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide During Keratinocyte Differentiation,” PLoS One 8(6):e67317 (2013). [cited by applicant]