PPAR agonist complex and method of use

Abstract

Described herein are compositions and topical formulations containing PPAR agonist complexes with glyceryl linoleate, glyceryl linolenate, ximenynic acid, and Pterocarpus Marsupium bark extract. Also provided herein are methods for inducing skin barrier repair, increasing skin barrier lipid and protein biosynthesis, stimulating hair growth, treating acne, and combinations thereof, using the compositions and topical formulations.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 62 / 955,055, filed on December 30, 2019, which is hereby incorporated by reference in its entirety.

Summary of the Invention

[0002] Embodiments disclosed herein relate to compositions having a combination of three or more PPAR agonists. Embodiments disclosed herein relate to compositions having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenic acid, and extract of bark of Pterocarpus Marsupium.

[0003] Embodiments disclosed herein relate to compositions having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenic acid, and extract of bark of Pterocarpus Marsupium.

[0004] Embodiments disclosed herein relate to topical formulations having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenic acid, and extract of bark of Pterocarpus Marsupium and a pharmaceutically or cosmetically acceptable excipient, and the topical formulations are suitable for topical administration.

[0005] Embodiments disclosed herein relate to topical formulations having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenic acid, and extract of bark of Pterocarpus Marsupium and a pharmaceutically or cosmetically acceptable excipient, and the topical formulations are suitable for topical administration.

[0006] Embodiments disclosed herein relate to a method for inducing skin barrier repair, comprising the step of topically administering a topical formulation having a composition containing an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration. Embodiments disclosed herein relate to a method for inducing skin barrier repair, comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration. In embodiments, induction of skin barrier repair results in the biosynthesis of skin barrier lipids and proteins selected from the group consisting of ceramide, filaggrin, trans-glutaminase 1, TGFB1, keratin, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF, and combinations thereof. In embodiments, induction of skin barrier repair results in the regulation of skin barrier gene expression selected from the group consisting of ceramide, filaggrin, trans-glutaminase 1, TGFB1, keratin, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF, and combinations thereof. The following are prior art documents related to the invention of this application (including documents cited in the international phase after the international filing date and documents cited when the application entered the national phase in other countries): (Prior art document) (Patent Document) (Patent Document 1) International Publication No. 2000 / 016752 (Patent Document 2) U.S. Patent Application Publication No. 2018 / 0140528 (Patent Document 3) International Publication No. 2004 / 037225 (Patent Document 4) U.S. Patent Application Publication No. 2014 / 0120141 (Patent Document 5) International Publication No. 2019 / 060357 (Non-patent literature) (Non-patent document 1) https: / / en.wikipedia.org / w / index.php?title=Ximenynic_acid&oldid=902336690 'Ximenynic acid' 18 June 2019, entire document esp pg 1 para 3, pg 2 para 1 (Non-patent document 2) https: / / www.cosmeticsandtoiletries.com / formulating / category / natural / Sabinsa-Cosmetics-pTeroWhite-505801751.html Schleehauf. 'Sabinsa Cosmetics TeroWhite' 13 February 2019 (13.02.2019), entire document esp pg 1 [Brief explanation of the drawing]

[0007] For a complete understanding of the nature and advantages of this embodiment, please refer to the following detailed description, which will be interpreted in relation to the attached drawings.

[0008] [Figure 1] Figure 1 shows the control ratio of each test material in the 250 μg / mL dilution in the PPAR-α-luciferase experiment. [Figure 2] Figure 2 shows the control ratio of each test material in the 500 μg / mL dilution in the PPAR-α-luciferase experiment. [Figure 3] Figure 3 shows the control ratio of each test material in the 50 μg / mL dilution in the PPAR-γ luciferase experiment. [Figure 4] Figure 4 shows the control ratio of each test material in the 200 μg / mL dilution in the PPAR-γ luciferase experiment. [Figure 5] Figure 5 shows that the 100 μg / mL test material suppresses melanin production. [Figure 6] Figure 6 shows that ceramide expression increases on day 1 in defatted explants. [Figure 7] Figure 7 shows the increase in transglutaminase-1 (TGM1) expression on day 1 in undefatted explants. [Figure 8] Figure 8 shows that filaggrin expression increases on day 1 in defatted explants. [Figure 9] Figure 9 shows the effect of the comparative mixture on the transcription of PPAR-α-regulated luciferase reporter genes. [Modes for carrying out the invention]

[0009] skin

[0010] Barrier lotions, creams, and ointments containing commercially available skin protectants generally approach the improvement of barrier function by physical methods such as occlusive hydrophobic barriers and film formers (i.e., petrolatum, dimethicone, lanolin), utilizing the chemical properties of the components. Such products have limitations because they only provide a temporary hydrophobic surface barrier effect and are not part of the natural and healthy barrier function of the skin. On the other hand, the direct administration of biomimetic and precursor topical components, i.e., ceramides, cholesterol, and other biomimetic lipids, has limitations such as restricted absorption and distribution of ceramides in the lamellar body and the issue of identifying which of the numerous epidermal ceramides should be utilized. Ceramides are classified into 19 types based on their sphingoid base and fatty acid moieties, and the value of using only one or two types topically may be limited. Preparing a truly biomimetic topical composition that is closest to the original composition of the skin is very difficult.

[0011] Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear hormone receptor involved in the transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant enzymes such as catalase, and its expression is decreased in aged human skin. The mRNA level of PPARα has been shown to be significantly decreased not only in UV-irradiated skin but also in human skin with intrinsic aging and photoaging. Furthermore, the increased expression of catalase due to PPARα activation leads to the elimination of ROS generated by UV irradiation or aging. Activation of PPARα induces the expression of catalase and the elimination of ROS, thereby protecting the skin from UV damage and intrinsic aging.

[0012] The PPAR agonist complex described herein activates the skin's natural biosynthetic barrier lipids and epidermal proteins, namely ceramides, filaggrin, and transglutaminase (also known as the "barrier repair cascade"). Embodiments described herein relate to topical PPAR agonist complex compositions having glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract. The PPAR agonist complex described herein is used to improve skin barrier function, improve the texture of the skin surface, provide exfoliation, improve skin whitening, relieve irritation, and support the skin's natural ability to defend itself against environmental stress factors.

[0013] Hair

[0014] Also, the PPAR pathway and activation are involved in the metabolic activities of both hair follicles and sebaceous glands and are involved in hair growth.

[0015] Peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear hormone receptor superfamily, is an important factor that controls epidermal development. PPAR alpha, -delta, and -gamma are expressed in both dermal and epithelial human hair follicle cells.

[0016] The PPAR agonist complex described herein activates hair follicles and sebaceous glands, i.e., by stimulating collagen 17, an important molecule for HFSC (hair follicle stem cell) maintenance. Embodiments described herein relate to topical PPAR agonist complex compositions having glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract. The PPAR agonist complex described herein is used to stimulate hair growth, maintain healthy hair, increase hair density and volume, and improve the appearance and feel of hair.

[0017] Acne

[0018] Acne is a disease characterized by excessive keratinocyte proliferation and abnormal desquamation, leading to clogged pores and hair follicles and inducing the pathogenic behavior of P. acnes. Increased sebum levels and hyperkeratosis of follicles are essential conditions for acne vulgaris. Peroxisome proliferator-activated receptors (PPARs) are known to regulate lipid metabolism in various human tissues and are thought to be involved in the pathogenesis of acne vulgaris. PPAR activators have anti-apoptotic effects, promote keratinocyte differentiation, and maintain epidermal homeostasis. Normalizing keratinocyte differentiation and desquamation is essential for managing the development of acne.

[0019] The primary function of human sebaceous glands is sebum excretion. PPAR agonists may regulate sebum secretion not only by increasing it but also by regulating sebaceous cell differentiation and lipid metabolism. Sebum composition and its clearance from ducts and hair follicles are important. Thick, sticky sebum can contribute to clogged hair follicles, which are known to promote the proliferation and pathogenic activity of P. acnes. Clogs can be relieved by increasing sebum secretion or thinning the sebum.

[0020] Additionally, PPAR agonists may offer beneficial anti-inflammatory activity to minimize the appearance of acne and soothe inflammation associated with acne scars.

[0021] The PPAR agonist complexes described herein are modulated by regulating the sebaceous glands, i.e., by activating two kinases, PKB / Akt and p44 / 42, which are involved in anti-apoptosis and proliferation, respectively, or by reducing arachidonic acid-derived keto metabolites (e.g., 5KETE, 12KETE) that are known to increase in acne-prone skin. Embodiments described herein relate to topical PPAR agonist complex compositions having glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus marsupium bark extract. The PPAR agonist complexes described herein are used for the treatment of acne vulgaris, reduction of inflammation and irritation caused by acne lesions, suppression of P. acnes, prevention of clogged follicular formation, and reduction of the number of acne lesions.

[0022] Without being bound by theory, glyceryl linoleate and glyceryl linolenic acid are not known to induce PPAR agonist activity. Hydrolysis by esterase enzymes in the skin leads to the release of known PPAR agonists (linoleic acid and linolenic acid). When tested with a combination of glyceryl linoleate and glyceryl linolenic acid, it does not show significant PPAR activity. The combination of glyceryl linoleate, glyceryl linolenic acid, and ximenic acid provides an excellent solvent for Pterocarpus Marsupium bark extract, forming a highly permeable polar oil carrier.

[0023] Without being constrained by theory, ximenynic acid (acetylene fatty acid) is a very mild PPARα agonist and a moderate PPARγ agonist that irreversibly binds to arachidonic acid. Furthermore, it has the advantage of being useful as a solvent aid in Pterocarpus Marsupium bark extract, helping to prevent crystallization during freeze-thaw cycles.

[0024] While not bound by theory, Pterocarpus Marsupium bark extract is not known to be a PPAR agonist, although major stilbenes (90% pterostilbene) are known to be PPAR agonists in their synthetic form. However, at concentrations necessary to produce beneficial effects, Pterocarpus Marsupium bark extract, when tested alone, did not exhibit PPAR agonist effects due to its high cytotoxicity. Pterocarpus Marsupium bark extract is beneficial because it does not change color over time like other stilbenes, activates sirtuins, is a COX-2 inhibitor, and possesses anti-glycation activity.

[0025] Various embodiments are described in detail below. However, such embodiments may be embodied in many different forms and should not be construed as being limited to the embodiments shown herein. Rather, these embodiments are provided so that this disclosure is thorough and complete and its scope is fully conveyed to those skilled in the art.

[0026] Where a range of values ​​is provided, each intervention value between the upper and lower limits of that range, as well as any other stated or intervening values ​​within that stated range, are intended to be included within this disclosure. For example, if a range from 1 wt% to 8 wt% is stated, then 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, and 7 wt% are also intended to be explicitly disclosed, as are the ranges of values ​​greater than or equal to 1 wt% and the ranges of values ​​less than or equal to 8 wt%.

[0027] All percentages, parts, and ratios are based on the total weight of the formulation and composition unless otherwise specified, and all measurements performed are at approximately 25°C.

[0028] The singular forms "a," "an," and "the" include multiple references unless the context clearly indicates otherwise. For example, a reference to "polymer" includes a single polymer as well as two or more identical or different polymers, and a reference to "excipient" includes a single excipient as well as two or more identical or different excipients, etc.

[0029] The word “approximately” preceding a number means a range of plus or minus 10% of that value. For example, “approximately 50” means 45 to 55, “approximately 25,000” means 22,500 to 27,500, etc., unless the context of this disclosure indicates otherwise or contradicts such interpretation. For example, in a list of numbers such as “approximately 49, approximately 50, approximately 55,” “approximately 50” means a range that extends to less than half the interval between the preceding and succeeding values, e.g., between 49.5 and 52.5. Furthermore, expressions such as “less than approximately” or “greater than approximately” for a given value should be understood in consideration of the definition of the term “approximately” provided herein.

[0030] As used herein, the terms “administer,” “administering process,” and “administer” mean directly administering a compound (also called the drug of interest) or a pharmaceutically acceptable salt or composition of the compound (the drug of interest) to a subject.

[0031] As used herein, the term “effective dose” is used herein to mean the amount of a composition that elicits a clinical or biological response in an individual’s skin as requested by a clinical professional or individual. A clinical or biological response may include improving or ameliorating a disease, condition, or disorder in an individual. For example, an effective dose is an amount that improves the appearance and feel of the skin, or an amount that improves the effects of aging on the skin.

[0032] As used herein, the term “excipient” means a material, composition, or vehicle, including carriers and diluents, that is involved in carrying or transporting pharmaceuticals, cosmetics, or other drugs across tissue layers such as the stratum corneum or stratum spinosum, such as liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials.

[0033] The transitional term “comprising,” which is synonymous with “including,” “containing,” and “characterized by,” is inclusive or open and does not exclude additional, uncited elements or steps of method. In contrast, the transitional expression “consisting of” excludes elements, steps, or components not specified in the claim. The transitional expression “consisting essentially of” limits the scope of the claim to a specified material or step that does not “materially affect the basic and novel properties” of the claimed. In some embodiments or claims in which the term “comprising” is used as a transitional phrase, such embodiments may also be expected to replace the term “comprising” with the term “consisting of” or “consisting essentially of.”

[0034] The term "cosmetics" means any substance applied to and / or intended to be applied to the human body for the purpose of cleansing, beautifying, enhancing attractiveness, altering the appearance of the skin, or a combination thereof.

[0035] As used herein, the term “composition” means a combination or mixture of two or more different components, constituents, or substances.

[0036] As used herein, the term "keratin fiber" refers to any tissue containing keratin as a fibrous structural protein, including, but not limited to, skin, hair, and nails.

[0037] As used herein, the term “regulation” refers to both the upregulation and / or downregulation of genes as described herein.

[0038] "Pharmacologically acceptable" or "cosmetically acceptable" are used herein to mean a drug / compound, salt, composition, dosage form, etc. of interest that is within the bounds of sound medical judgment suitable for use in contact with human and / or other mammalian tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, commensurate with a reasonable benefit / risk ratio. In some embodiments, pharmacopoeia means that it is approved by a federal or state regulatory agency or is listed in the United States Pharmacopeia or other generally accepted pharmacopoeias for use in mammals (e.g., animals), more specifically, in humans.

[0039] The terms “patient” and “subject” are interchangeable and can be considered to mean any living organism that can be administered and / or treated with the compounds or compositions provided herein. Thus, the terms “patient” and “subject” may include, but are not limited to, any non-human mammal, primate or human. In some embodiments, “patient” or “subject” is a mammal such as a mouse, rat, other rodent, rabbit, dog, cat, pig, cattle, sheep, horse, primate or human. In some embodiments, the patient or subject is an adult, child or infant. In some embodiments, the patient or subject is a human.

[0040] As used herein, the terms “topically” and “locally” refer to the application of a composition to the surface of skin, mucous membrane cells, and keratin. Examples of keratin include skin, nails, and hair.

[0041] As used herein, the term “to treat” refers to a method of treating a skin disorder or systemic condition, and generally includes the administration of a compound or composition that reduces the frequency of symptoms of the condition, delays its onset, or enhances the feel, appearance, color, sensation, or hydration of an intended tissue treatment area on the tissue surface of the subject, compared to a subject that does not receive the compound or composition. This is a method of improving or stabilizing the condition of the subject, and may include reversing, reducing, or cessating the symptoms, clinical signs, and underlying pathology of the condition.

[0042] You may, for any reason, claim anything that falls short of the full scope of this disclosure, by hereby reserving the right to exclude any individual member of any such group, including any sub-scope or combination of sub-scopes within a group, which may be claimed in accordance with the scope or a similar manner. Furthermore, you may, for any reason, claim anything that falls short of the full scope of this disclosure, by hereby reserving the right to exclude any individual substituent, analogue, compound, ligand, structure, or any group thereof, or any member of the claimed group, proviso to this agreement.

[0043] This disclosure references various patents, patent applications, and publications. The disclosures of these patents, patent applications, and publications are incorporated by reference to better describe the state of the art as known to those skilled in the art as of the date of this disclosure. This disclosure applies in the event of any inconsistency between the cited patents, patent applications, and publications and this disclosure.

[0044] For convenience, the specific terms used in this specification, examples, and claims are set forth herein. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs.

[0045] composition Embodiments disclosed herein relate to compositions comprising a combination of three or more PPAR agonists. Embodiments disclosed herein relate to compositions having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract.

[0046] Embodiments disclosed herein relate to compositions having effective amounts of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract: glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract.

[0047] Pterocarpus Marsupium bark extract (CAS No. 537-42-8) is an extract of the bark of Pterocarpus Marsupium. Pterocarpus Marsupium bark extract contains at least 90% pterostilbene. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 1% to 5% by weight of the topical composition. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 1.5% to 4% by weight of the topical composition. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 2% by weight of the topical composition. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 3% by weight of the topical composition. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 4% by weight of the topical composition. In some embodiments, the effective amount of Pterocarpus Marsupium bark extract is about 5% by weight of the topical composition.

[0048] Ximenynic acid (CAS No. 557-58-4) is empirically formulated C 18 H 30 It contains O2 and can be represented by the following formula. [ka] Ximeninic acid is also known as (E)-octadec-11-ene-9-ic acid, 11-octadecene-9-ic acid, or ximeninic acid. In some embodiments, the effective amount of ximeninic acid is about 5% to about 10% by weight of the topical composition. In some embodiments, the amount of ximeninic acid is about 6% to about 9% by weight of the topical composition. In some embodiments, the amount of ximeninic acid is about 6% by weight of the topical composition. In some embodiments, the amount of ximeninic acid is about 7% by weight of the topical composition. In some embodiments, the amount of ximeninic acid is about 8% by weight of the topical composition. In some embodiments, the amount of ximeninic acid is about 9% by weight of the topical composition.

[0049] Glyceryl linolenate (CAS No. 18465-99-1) is a monoester of glycerin and linolenic acid, empirically formulated C 21 H 36 It contains O4 and can be represented by the following formula. [ka] Glyceryl linolenate is also known as 2,3-dihydroxypropyl 9,12,15-octadecatrienoate, glyceryl monolinolenate, linolenic acid monoester with 1,2,3-propanetriol, or 2,3-dihydroxypropyl 9,12,15-octadecatrienoate. In some embodiments, the effective amount of glyceryl linolenate is about 5% to about 10% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linolenate is about 6% to about 9% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linolenate is about 6% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linolenate is about 7% by weight of the topical composition. In some embodiments, glyceryl linolenate is about 8% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linolenate is about 9% by weight of the topical composition.

[0050] Glyceryl linoleate (CAS No. 2277-28-3) is a monoester of glycerin and linoleic acid, empirically formulated C 21 H 38 It contains O4 and can be represented by the following formula. [ka] Glyceryl linoleate is also known as 2,3-dihydroxypropyl 9,12-octadecadienoate, glycerol monolinoleate, linoleic acid monoester with glycerol monolinoleate and 1,2,3-propanetriol, monolinolein, 9,12-octadecadienoic acid, 2,3-dihydroxypropyl ester, 9,12-octadecadienoic acid monoester with 1,2,3-propanetriol, or 9,12-octadecadienoic acid (Z,Z)-monoester with 1,2,3-propanetriol. In some embodiments, the effective amount of glyceryl linoleate is greater than 50% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linoleate is about 75% to about 94% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linoleate is about 75% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linoleate is about 80% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linoleate is about 85% by weight of the topical composition. In some embodiments, the effective amount of glyceryl linoleate is about 90% by weight of the topical composition.

[0051] In some embodiments, a mixture of glyceryl linolenate and glyceryl linoleate is used. In some embodiments, the mixture of glyceryl linolenate and glyceryl linoleate is known as vitamin F glyceryl ester CLR and mainly contains esterified essential unsaturated fatty acids rich in biologically active linoleic acid, and is obtained from vegetable oils such as peanut oil, soybean oil, and rapeseed oil. Therefore, the mixture of glyceryl linolenate and glyceryl linoleate may also contain additional proportions of C16 and C18 fatty acids, which are present in about 1% to about 40% by weight of the mixture of glyceryl linolenate and glyceryl linoleate. In some embodiments, the effective amount of the mixture of glyceryl linolenate and glyceryl linoleate is about 85% to about 94% by weight of the topical composition. In some embodiments, the effective amount of the mixture of glyceryl linolenate and glyceryl linoleate is about 90% by weight of the topical composition.

[0052] In certain embodiments, the ratio of glyceryl linoleate to glyceryl linolenate to ximenylic acid to Pterocarpus Marsupium bark extract is approximately 25:2:2:1 to approximately 50:5:5:1. In certain embodiments, the ratio of glyceryl linoleate to glyceryl linolenate to ximenylic acid to Pterocarpus Marsupium bark extract is approximately 5:0.1:0.1:0.001 to approximately 10:1:1:0.1. In certain embodiments, when a mixture of glyceryl linolenate and glyceryl linoleate is used, the ratio of the glyceryl linoleate / glyceryl linolenate mixture to ximenylic acid to Pterocarpus Marsupium bark extract is approximately 9:7:3 to approximately 10:5:1. In certain embodiments, the ratio of glyceryl linoleate to glyceryl linolenate to ximenic acid is approximately 25:2:2 to approximately 50:5:5. In certain embodiments, the ratio of glyceryl linoleate to glyceryl linolenate to Pterocarpus Marsupium bark extract is approximately 25:2:1 to approximately 50:5:1. In certain embodiments, the ratio of glyceryl linolenate to ximenic acid to Pterocarpus Marsupium bark extract is approximately 2:2:1 to approximately 5:5:1. In certain embodiments, the ratio of glyceryl linoleate to ximenic acid to Pterocarpus Marsupium bark extract is approximately 25:2:1 to approximately 50:5:1.

[0053] Embodiments disclosed herein relate to topical formulations comprising a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0054] Embodiments disclosed herein relate to topical formulations comprising compositions having effective amounts of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenic acid, and Pterocarpus Marsupium bark extract, and pharmaceutically or cosmetically acceptable excipients, which are suitable for topical administration.

[0055] In certain embodiments, the composition is part of the final formulation in an amount of about 0.5% to about 5% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 1% to about 4% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 0.5% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 1% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 3% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 5% by weight. In certain embodiments, the composition is part of the final formulation in an amount of about 0.5% to about 10%. In certain embodiments, the composition is part of the final formulation in an amount of about 1.5%. In certain embodiments, the composition is part of the final formulation in an amount of about 2.0%. In certain embodiments, the composition is part of the final formulation in an amount of about 2.5%. In certain embodiments, the composition is part of the final formulation in an amount of about 3.0%. In certain embodiments, the composition constitutes approximately 3.5% of the final formulation and is part of the final formulation.

[0056] In certain embodiments, Pterocarpus Marsupium bark extract is part of the final formulation in an amount of about 0.005% to about 0.25% by weight. In certain embodiments, Pterocarpus Marsupium bark extract is part of the final formulation in an amount of about 0.005% to about 0.05% by weight. In certain embodiments, Pterocarpus Marsupium bark extract is part of the final formulation in an amount of about 0.025% to about 0.25% by weight.

[0057] In certain embodiments, glyceryl linoleate is a component of the final formulation in an amount of about 0.375% to about 4.7% by weight. In certain embodiments, glyceryl linoleate is a component of the final formulation in an amount of about 0.375% to about 3.75% by weight. In certain embodiments, glyceryl linoleate is a component of the final formulation in an amount of about 0.47% to about 4.7% by weight.

[0058] In certain embodiments, glyceryl linolenate is a component of the final formulation in an amount of about 0.025% to about 0.5% by weight. In certain embodiments, glyceryl linolenate is a component of the final formulation in an amount of about 0.025% to about 0.25% by weight. In certain embodiments, glyceryl linolenate is a component of the final formulation in an amount of about 0.05% to about 0.5% by weight.

[0059] In certain embodiments, ximenylic acid is a component of the final formulation in an amount of about 0.025% to about 0.5% by weight. In certain embodiments, ximenylic acid is a component of the final formulation in an amount of about 0.025% to about 0.25% by weight. In certain embodiments, ximenylic acid is a component of the final formulation in an amount of about 0.05% to about 0.5% by weight.

[0060] In certain embodiments, the composition is part of the final formulation at approximately 4 μg / ml to approximately 500 μg / ml. In certain embodiments, the composition is part of the final formulation at approximately 4 μg / ml. In certain embodiments, the composition is part of the final formulation at approximately 20 μg / ml. In certain embodiments, the composition is part of the final formulation at approximately 100 μg / ml. In certain embodiments, the composition is part of the final formulation at approximately 200 μg / ml. In certain embodiments, the composition is part of the final formulation at approximately 500 μg / ml.

[0061] In certain embodiments, the final formulation is selected from the group consisting of neck cream, neck lotion, body lotion, body cream, face lotion, face cream, eyelash treatment, hair moisturizer, hair conditioner, hair and scalp oil, cellulite treatment, nail conditioner, gel, emulsion, silicone gel, water gel, oil-in-water emulsion, or water-in-oil emulsion.

[0062] In some embodiments, the pharmaceutically or cosmetically acceptable excipient is a solvent. In some embodiments, the solvent is selected from the group consisting of pentylene glycol, butylene glycol, water, glycol, propylene glycol, isopropylene glycol, coco-caprylic / capric acid, 1,2-hexanediol, glycerin, cetyl alcohol, and combinations thereof. In some embodiments, the pharmaceutically or cosmetically acceptable excipient is selected from the group consisting of diluents, fillers, disintegrants, binders, lubricants, surfactants, hydrophobic vehicles, water-soluble vehicles, emulsifiers, buffers, wetting agents, humectants, solubilizers, preservatives, colorants, plasticizers, carriers, excipients, and combinations thereof. Those skilled in the art can refer to various pharmaceutical literature, such as Modern Pharmaceutics, Banker & Rhodes, Marcel Dekker, Inc. (1979) and Goodman & Gilman's The Pharmaceutical Basis of Therapeutics, 6th Edition, MacMillan Publishing Co, New York (1980), as guidance in determining the amount of such components in embodiments of a composition.

[0063] The compounds used to activate PPAR transcription, hydroxystearic acid (12-HSA, 10-HSA) and octadecendioic acid (ODA), are waxy solid substances that present formulation and formulation challenges / limitations at effective levels of use. These components, 12-HSA, 10-HSA, and ODA, increase the viscosity of the final product to a heavy, poorly spreading paste-like structure that is aesthetically and sensorially undesirable for consumer products of the end use. Advantageously, the topical compositions described herein are liquid component blends with a highly desirable sensory profile. The topical compositions described herein can be readily incorporated into a wide range of final product viscosities and compositions, providing good spreading, bioavailability, and rapid absorption.

[0064] In some embodiments, the topical composition further comprises a pharmaceutical or cosmetic active ingredient. In some embodiments, the pharmaceutical or cosmetic active ingredient is selected from the group consisting of vitamins, cosmetic peptides, oil control agents, sensory modifiers, whitening agents, hydrated agents, sunscreens, compounds that absorb or reflect UV photons, other skincare agents, and combinations thereof. In some embodiments, the pharmaceutical or cosmetic active ingredient is hydroxyacetophenone, sodium phytate, caprylic / capric triglyceride, sodium acrylate copolymer, octyldodecanol, octyldodecylxyloside, PEG-30 dipolyhydroxystearate, jojoba esters, sunflower seed wax, acacia decarens flower wax, polyglycerin-3, acrylamide / sodium acryloyldimethyltaurate copolymer, isohexadecane, polysorbate 80, cyclopentasiloxane, dimethicone, dimethicone / bis-isobutyl PPG Selected from the group consisting of 20 crosspolymer, dimethicone / vinyl dimethicone crosspolymer, ethylhexylglycerin, magnesium sulfate heptahydrate, isononylisononanoic acid, polyglyceryl-2 dipolyhydroxystearate, butyrospermum perky (shea) butter, hexyl laurate, triethylhexanoin, coconut oil, bisabolol, tetrahexyldecyl ascorbate, sodium benzoate, niacinamide, sodium PCA, glyceryl stearate, PEG-75 stearate, ceteth-20, steareth-20, squalane, behenyl alcohol, caproyl phytosphingosine, adenosine, xanthan gum, lecithin, sclerotium gum, pullulan, polyacrylate-13, polyisobutene, polysorbate 20, phenoxyethanol, ethylhexylglycerin, tetrapeptide-2,1, and combinations thereof.

[0065] In some embodiments, pharmaceutically or cosmetically acceptable excipients, pharmaceutically or cosmetically acceptable active ingredients, or any combination thereof may be present in concentrations of approximately 10% to approximately 99.5% w / w, approximately 10% to approximately 97% w / w, approximately 10% to approximately 95% w / w, approximately 10% to approximately 90% w / w, approximately 10% to approximately 85% w / w, approximately 10% to approximately 80% w / w, approximately 10% to approximately 75% w / w, and approximately 1 It is present in the topical formulations described herein in amounts selected from the group consisting of 0% to approximately 70% w / w, approximately 10% to approximately 65% ​​w / w, approximately 10% to approximately 60% w / w, approximately 10% to approximately 55% w / w, approximately 10% to approximately 50% w / w, approximately 10% to approximately 45% w / w, approximately 10% to approximately 40% w / w, approximately 10% to approximately 35% w / w, approximately 10% to approximately 30% w / w, and approximately 10% to approximately 25% w / w. In some embodiments, pharmaceutically or cosmetically acceptable excipients, pharmaceutically or cosmetically active ingredients, or any combination thereof are present in the topical formulations described herein in amounts selected from the group consisting of about 99.5% to about 95.0% w / w, about 99.5% to about 90.0% w / w, about 99.5% w / w, about 97.0% w / w, about 95.0% w / w, and about 90% w / w.

[0066] In some embodiments, the topical formulation may contain water in a proportion selected from the group consisting of about 50% to about 90% w / w, about 60% to about 90% w / w, about 70% to about 90% w / w, and about 80% to about 90% w / w.

[0067] In some embodiments, the topical formulation may further contain abrasives, anti-acne agents, anti-dandruff agents, antifungal agents, antibacterial agents, antioxidants, lotions, moisturizers, skin conditioning agents, wetting agents, emollients, occlusive agents, skin bleaching or whitening agents, proteins, cleansing agents, hair conditioners, preservatives, film-forming polymers, and the like.

[0068] Abrasives may be used to remove dead skin cells and unwanted skin such as skin indurations. In some embodiments, abrasives include alumina, aluminum silicate, apricot kernel powder, attapulgite, avocado powder, bamboo powder, barley flour, bentonite, calcium carbonate, calcium phosphate, calcium pyrophosphate, calcium sulfate, chalk, chitin, coconut shell powder, colloidal oatmeal, comfrey leaf powder, corn cob powder or powder, corn flour, cornmeal, corn starch, diamond powder, diatomaceous earth, dicalcium phosphate, dehydrated dicalcium phosphate, eggshell powder, fuller's earth, hydrated silica, hydroxyapatite, kaolin, kiwi seed, lauryl acrylate polymer, yellow clay, and potassium magnesium fluorosilicate. Selected from the group consisting of magnesium trisilicate, microcrystalline cellulose, montmorillonite, Moroccan lava clay, oat bran, oat flour, oatmeal, oyster shell powder, peach pit powder, peanut flour, pecan shell powder, polyethylene, pumice, raspberry seeds, rice bran, rye flour, sand, silica, sodium bicarbonate, sodium hydroxypropyl starch phosphate, sodium magnesium fluorosilicate, sodium silicate aluminate, soy flour, sweet almond meal, talc, tin oxide, tricalcium phosphate, walnut shell powder, wheat bran, wheat flour powder, wheat starch, wood flour, zirconium silicate, and combinations thereof.

[0069] Anti-acne agents may be used to treat blemishes, acne, blackheads, and whiteheads. In some embodiments, the anti-acne agent is selected from the group consisting of salicylic acid, benzoyl peroxide, carbamide peroxide, glycolic acid, retinal, retinalaldehyde, vitamin A, vitamin A derivatives, azelaic acid, or sulfur, and their derivatives and combinations thereof.

[0070] Anti-dandruff agents may be used to treat dandruff, seborrheic dermatitis, or psoriasis. In some embodiments, anti-dandruff agents are selected from the group consisting of coal tar, salicylic acid, selenium sulfide, sulfur, zinc pyrithione, and their derivatives and combinations thereof.

[0071] Antifungal agents include those that inhibit the growth and reproduction of fungal cells or reduce the number of fungi present. In some embodiments, the antifungal agent is selected from the group consisting of calcium undecylenate, ketoconazole, povidone-iodine (PVP-iodine), tea tree oil, undecylenic acid, zinc undecylenate, and their derivatives and combinations thereof.

[0072] Antimicrobial agents include agents that kill microorganisms, agents that prevent or inhibit the growth and reproduction of microorganisms, or agents that help prevent infection in minor cuts, scrapes, and burns. In some embodiments, antimicrobial agents are selected from the group consisting of low-chain (C1-C4) alcohols, quaternary ammonium compounds such as benzalkonium chloride and benzethonium chloride, clindamycin, methylbenzethonium chloride, hydrogen peroxide, oligopeptide-10, phenol, tea tree oil, triclosan, povidone-iodine (PVP-iodine) and their derivatives and combinations thereof.

[0073] Antioxidants include agents characterized as free radical scavengers that help reverse skin damage caused by free radicals. In some embodiments, antioxidants include acetylcysteine, alpha-lipoic acid, arbutin, ascorbic acid (vitamin C), ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, caffeic acid, camellia oil, carotenoids, ascorbic acid chitosan, glycolate chitosan, salicylic acid chitosan, chlorogenic acid, CoQ10, corticone, cysteine, and cysteine. Stain HC1, Decyl mercaptomethylimidazole, Diamylhydroquinone, Di-t-butylhydroquinone, Dicetyl thiodipropionate, Dicyclopentadiene / t-butylcresol copolymer, Digalloyl trioleate, Dilauryl thiodipropionate, Dimyristyl thiodipropionate, Dioleyl tocopheryl methylsilanol, Diosmin, Disodium ascorbyl sulfate, Disodium rutinyl disulfate, Distearyl thiodipropionate, Ditridecyl thiodipropionate, Dodecyl gallate Dunaliella salina extract, erythorbic acid, ethyl ferulate, ferulic acid, hydroquinone, p-hydroxyanisole, hydroxylamine HCl, hydroxylamine sulfate, hydroxytyrosol, isooctyl thioglycolate, isoquercitrin, kojic acid, madecasicoside, magnesium ascorbate, magnesium ascorbyl phosphate, melatonin, methoxy-PEG-7 rutinyl succinate, methylenedi-t-butylcresol, methylsilanol ascorbate, nordihydroguaiyale Tincture, octyl gallate, phenylthioglycolic acid, phloroglucinol, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, resveratrol, rosmarinic acid, rutin, siltunis, sodium ascorbate, sodium ascorbyl / cholesteryl phosphate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, sodium thioglycolate, sorbityl furfural, tea tree oil, tetrahexyldecyl ascorbate,The following are selected from the group consisting of tetrahydrodiferroylmethane, thiodiglycol, thiodiglycolamide, thiodiglycolic acid, thiolactic acid, thiosalicylic acid, thiotaurine, tocophereth derivatives, tocopherol (vitamin E), tocofersolan, tocopherol acetate, tocopherol linoleate, tocopherol linoleate / oleate, tocopherol nicotinate, tocopherol succinate, tocoquinone, o-tolylbiguanide, tri(nonylphenyl) phosphate, ubiquinone, vitamin D, zinc dibutyldithiocarbamate, and their derivatives and combinations thereof.

[0074] The toner contains agents that cause a tightening or tingling sensation in the skin. In some embodiments, the toner contains ammonium alum, calcium chloride, calcium lactate, dimethyl MEA, gallic acid, lentil seed extract, potassium alum, sodium alum, sodium aluminum chlorohydroxylactate, sodium aluminum lactate, tannic acid, thioxolone, tranexamic acid, zinc acetate, zinc chloride, zinc lactate, zinc phenolsulfonate, zinc sulfate, zirconium chloride hydrate, witch hazel, denatured alcohol, alcohol derivatives such as SD alcohol, aluminum acetate, aluminum bromide, aluminum chloride, aluminum chlorohydrex, aluminum citrate, aluminum diacetate, aluminum dichlorohydrate, aluminum dichlorohydrex The following are selected from the group consisting of aluminum derivatives such as aluminum glycinate, aluminum lactate, aluminum phenolsulfonate, aluminum sesquichlorohydrate, aluminum sesquichlorohydrex, and aluminum sulfate, aluminum zirconium derivatives such as aluminum zirconium octachlorohydrex, aluminum zirconium pentachlorohydrate, aluminum zirconium pentachlorohydrex, aluminum zirconium tetrachlorohydrate, aluminum zirconium tetrachlorohydrex, aluminum zirconium trichlorohydrate, and aluminum zirconium trichlorohydrate, and combinations thereof with these derivatives.

[0075] Skin conditioning agents or moisturizers can be classified into different groups such as emollients, wetting agents, and occlusive agents. Emollients include agents that remain on the upper layers of the skin, act as lubricants, and improve appearance. In some embodiments, emollients are selected from the group consisting of petrolatum, petrolatum and volatile silicones, cold cream (USP), hydrophilic ointment (USP), lanolin, glycerides, fruit oils, nut oils, vegetable oils, dimethicone, methicone, cyclomethicone, domin, fatty acids, myristic acid derivatives such as butyl myristate and myristyl myristate, oleic acid derivatives, C1-C4 glycols, fatty acid glycols, glycol esters, glycerin, glycerol, paraffin, rapeseed oil, long-chain alcohols, olive oil, jojoba oil, castor oil, and their derivatives and combinations thereof. Wetting agents include agents that increase the moisture content of the uppermost layer of the skin. In some embodiments, the wetting agent is selected from the group consisting of allatoin, agarose, arginine, benzyl hyaluronate, chitosan, copper, corn glycerides, gluconolactone, lactic acid, lactobionic acid, lactose, lysine, kombucha, maltitol, maltose, mannitol, propylene glycol, butylene glycol, pentylene glycol, propanediol, sodium aspartate, fructose, honey, glycerin, diglycerin, betaine, diols, hydroxyethyl urea, 1,2-hexanediol, D-ribose, glucose, sorbitol, dextrose, urea, 2-pyrrolidone-5-carboxylic acid and related salts, sea salt, inorganic citrate, inorganic lactate, ectoin, glycolic acid and its derivatives, and combinations thereof. The occlusive agent slows down the evaporation of moisture from the skin. In some embodiments, the occlusive agent is selected from the group consisting of petrolatum, shea butter, dimethicone, avocado, canola, cod liver, and other plant and animal oils such as corn, mineral oil, olive oil, soybean oil, lanolin, glycerides, beeswax, triglycerides, long-chain fatty alcohols, coco butter, coconut oil, jojoba oil, propylene glycol and their derivatives, and combinations thereof.

[0076] In addition to skin conditioning agents that provide moisturizing effects, there are also other skin conditioning agents that improve the appearance of the skin. In some embodiments, the skin conditioning agent is selected from the group consisting of cholesterol, cystine, hyaluronic acid, keratin, egg yolk, glycine, gluconolactone, lactic acid, lactobionic acid, panthenol, retinol, salicylic acid, vegetable oil, protein, vitamin, bisabolol, ceramide, coenzyme A, lecithin and its derivatives and combinations thereof.

[0077] Skin bleaching or whitening agents contain agents that lighten skin pigment. A preferred skin bleaching agent is hydroquinone. In some embodiments, the glossing agent is selected from the group consisting of azelaic acid, bearberry, deoxyarbutene, licorice root extract, kojic acid, peat extract, and their derivatives and combinations thereof.

[0078] Hair conditioners contain agents that improve the appearance and feel of hair by improving properties such as shine, texture, or body. In some embodiments, the hair conditioner is selected from the group consisting of lanolin, silicone, dimethicone, amino acids, proteins such as collagen and keratin, vitamins, betaine surfactants, amine oxide surfactants, ceramides, fatty acids, egg, milk, natural plant and animal oils, mineral oil, olive oil, polyquaternium, and derivatives thereof, as well as combinations thereof.

[0079] Proteins include animal, plant, fungal, yeast, and bacterial proteins that have skin health benefits. In some embodiments, proteins include collagen, keratin, soy protein, wheat protein, palmitic acid, ascorbic acid polypeptide, amino acids, casein, cholecalciferol polypeptide, rice protein, silk protein, gluten protein, lysine, acetylglucosamine, actin, actizyme, egg white, conchiolin protein, corn protein, egg protein, elastin, fibronectin, cod protein, hemoglobin, hexapeptide-21, lactalbumin, lupine protein, European maple protein, milk protein, myristoyl pentapeptide-8, myristoyl tetrapeptide-8, oat protein, oligopeptide-10, palmitoyl hexapeptide-14, palmitoyl Selected from the group consisting of ligopeptides, palmitoyl tetrapeptides-7, pea protein, potato protein, recline, rice bran protein, serum protein, sweet almond protein, tetrapeptide-16, vegetable protein, yeast protein, palmitoyl oligopeptides, pantothenic acid polypeptides, milk solids, sericin, albumen, amylase, amyloglucosidase, arginine, bromelain, catalase, gelatin, zein, crystallin, cytochrome C, deoxyribonuclease, gliadin, glucose oxidase, glycoproteins, lactoferrin, lactoglobulin, lactoperoxidase, lipase, nisin, oxidoreductases, papain, pepsin, subtilisin, stylains, and combinations thereof with their derivatives.

[0080] Detergents include agents used to cleanse skin and hair by solubilizing oils and lifting dirt. Detergents may be foaming or non-foaming. Exemplary detergents are typically surfactants, which can be characterized as nonionic, anionic, or zwitterionic. In some embodiments, detergents are selected from the group consisting of taurates, sulfates, sulfonates, carboxylates, sulfosuccinates, sarcosinates, zwitterionic betaines, fatty acid and fatty alcohol derivatives, as well as alkyl polyglucoside and amine oxide surfactants. In some embodiments, detergents may be combined with some abrasives, such as clay and sulfur, to provide mild exfoliation.

[0081] In some embodiments, the topical formulation further comprises a gelling agent. In some embodiments, the gelling agent is an aqueous gelling agent. In some embodiments, the aqueous gelling agent is selected from the group consisting of xanthan gum, gellan gum, carrageenan, biosaccharide gum-I, sclerotium gum, pectin, pullulan, guar gum, acacia gum, chondroitin, sulfuric acid, alginic acid, sodium hyaluronate, hydrolyzed sodium hyaluronate polyglutamic acid, chitin, chitosan, starch, and combinations thereof. In some embodiments, the gelling agent is xanthan gum.

[0082] In some embodiments, the topical formulation may further include an oil control agent. The oil control agent is a compound useful for regulating the production of skin oil, i.e., sebum, and for improving the appearance of oily skin. In some embodiments, the oil control agent is selected from the group consisting of salicylic acid, dehydroacetic acid, benzoyl peroxide, vitamin B3 (e.g., niacinamide), their isomers, esters, salts and derivatives, and combinations thereof.

[0083] In some embodiments, the topical formulation may further include other skincare agents selected from the group consisting of retinol, steroids, sunscreens, salicylates, minocycline, antifungal agents, peptides, antibodies, lidocaine, and combinations thereof. In some embodiments, the other skincare agents include N-acyl amino acid compounds, such as N-acylphenylalanine, N-acyltyrosine, their D and L isomers, salts, derivatives, and mixtures thereof. A suitable example of an N-acyl amino acid is N-undecylenoyl-L-phenylalanine, which is commercially available under the trade name SEPIWHITE®. Other dermatolytic agents include Lavandox, Thallasine 2, Argireline NP, Gatuline In-Tense and Gatuline Expression, Myoxinol LS 9736, Syn-ake and Instensyl®, Sesaflash®, N-acetyl-D-glucosamine, panthenol (e.g., DL panthenol available from Alps Pharmaceutical Inc.), tocopherol nicotinate, benzoyl peroxide, 3-hydroxybenzoic acid, flavonoids (e.g., flavanone, chalcone), farnesol, phytantriol, glycolic acid, lactic acid, 4-hydroxybenzoic acid, acetylsalicylic acid, and 2-hydroxybutanoic acid.This includes, but is not limited to, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, cis-retinoic acid, trans-retinoic acid, retinol, retinyl esters (e.g., retinyl propionate), phytic acid, N-acetyl-L-cysteine, lipoic acid, tocopherol and its esters (e.g., tocopherol acetate: DL-α-tocopherol acetate available from Eisai), azelaic acid, arachidonic acid, tetracycline, ibuprofen, naproxen, ketoprofen, hydrocortisone, acetominphen, resorcinol, phenoxyethanol, phenoxapropanol, phenoxapropanol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, octopirox, lidocaine hydrochloride, clotrimazole, miconazole, ketoconazole, neomycin sulfate, theophylline, and mixtures thereof. Further skincare agents are disclosed in U.S. Publication No. 2007 / 0020220A1, and their ingredients / components are incorporated herein by reference in their entirety.

[0084] In some embodiments, the topical formulation may further contain an anti-aging ingredient selected from the group consisting of ascorbic acid compounds, vitamin B3 compounds, azelaic acid, butylhydroxyanisole, gallic acid and its derivatives, glycyrrhizic acid, hydroquinone, kojic acid, arbutin, mulberry extract, and combinations thereof. In some embodiments, the topical composition may contain Ovaliss ((S)-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo[de,g]quinoline, 1,2-octanediol, D-glucopyranose, oligomer, C10-16-alkyl glycoside, water, ethyl alcohol, and glycerin), whey protein, MPC (milk protein complex), Sesaflash (glycerin, acrylic acid copolymer, PVP / polycarbamyl polyglycol ester, hydrolyzed sesame protein PG-propylmethylsilanediol), Majestem (glycerin, edelweiss callus culture extract, and xanthan gum), or Idealift (butylene glycol, sorbitan laurin, hydroxyethylcellulose, and acetyl dipeptide-1 cetyl ester).

[0085] In some embodiments, the topical formulation contains para-aminobenzoic acid (PABA), PABA esters (glyceryl PABA, amyldimethyl PABA, and octyldimethyl PABA), benzophenone (oxybenzone, sulisobenzone), cinnamate (octylmethoxycinnamate, and cinoxate), salicylic acid (homomethylsalicylic acid), anthranilic acid, TiO2, avobenzone, bemotoridinol, bisoctrizole, 3-(4-methylbenzylidene) camphor, cinoxate, and diethylaminohydroxy The sunscreen may further be selected from the group consisting of hexyl benzoyl benzoate, dioxybenzone, drometrizole trisiloxane, ecamsul, ethylhexyl triazone, homosalate, menthyl anthranylate, octocrylene, octyl salicylate, isotridinol, isopentenyl-4-methoxycinnamate, octyl-dimethyl-p-aminobenzoic acid, octyl methoxycinnamate, oxybenzone, polysilicone-15, trolamine salicylate, ZnO, and combinations thereof.

[0086] In some embodiments, the topical formulation may contain a sensory modifier selected from the group consisting of coolants, warmants, relaxants or sedatives, stimulants or refreshers, and combinations thereof.

[0087] In some embodiments, the coolant is menthol; menthol isomers, menthol derivatives; 4-methyl-3-(1-pyrrolidinyl)-2[5H]-furanone; WS-23, ishirin, ishirin Unilever analogs, 5-methyl-4-(1-pyrrolidinyl)-3[2H]-furanone; 4,5-dimethyl-3-(1-pyrrolidinyl)-2[5H]-furanone; isopuregol, 3-(1-menthoxy)propane-1,2-diol, 3-(1-menthoxy)-2-methylpropane-1,2-diol, p-menthane-2,3-diol, p-menthane-3,8-diol, 6-isopropyl-9-methyl-1,4-dioxas-pyro[4,5]decane-2-methanol, menthyl succinate and its alkaline earth metal salts, trimethylcyclohexanol, N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide, peppermint (Mentha Selected from the group consisting of arvensis oil, peppermint oil, menthone, menthol glycoside ketal, menthyl lactate, 3-(1-menthoxy)ethane-1-ol, 3-(1-menthoxy)propane-1-ol, 3-(1-menthoxy)butan-1-ol, 1-menthyl acetate N-ethylamide, 1-menthyl-4-hydroxypentanoic acid, 1-menthyl-3-hydroxybutyric acid, N,2,3-trimethyl-2-(1-methylethyl)butanamide, spearmint oil, and combinations thereof.

[0088] In some embodiments, the warming agent is selected from the group consisting of polyhydric alcohols, capsaicin, chili pepper powder, chili pepper tincture, chili pepper extract, capsaicin, witch hazel, homocapsaicin, homodihydrocapsaicin, nonanoyl vanillylamide, vanillyl nonanoate ether, vanillyl ethyl ether, vanillyl butyl ether, vanillyl pentyl ether, and vanillyl alcohol alkyl ether derivatives such as vanillyl hexyl ether, isovanillyl alcohol alkyl ether, ethyl vanillyl alcohol alkyl ether, veratrillyl alcohol derivative, substituted benzyl alcohol derivative, substituted benzyl alcohol alkyl ether, vanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal, ginger extract, ginger oil, gingerol, zingerone, and combinations thereof.

[0089] In some embodiments, the relaxant or sedative is a mixture of herbal extracts, aloe vera, alpha-bisabolol, D-panthenol, allantoin, witch hazel, chamomile, yarrow; calendula, comfrey, American witch hazel and other astringents, seaweed, and oat extract; oils selected from the group consisting of almond oil, avocado oil, and comfrey; essential oils selected from the group consisting of cardamom, eucalyptus, peppermint, hyssop, and rosemary; waxy or oily substances selected from the group consisting of lanolin or petrolatum jelly; zinc oxide, calamine, and selenium Minerals selected from the group consisting of; vitamins selected from the group consisting of tocopherol acetate (vitamin E); and pharmaceuticals selected from the group consisting of analgesics, anesthetics, anti-inflammatory agents, antihistamines, and muscle relaxants; menthol, camphor, eugenol, eucalyptol, safrole, methyl salicylate, menthyl lactate, menthyl ethoxyacetate, menthol glycerin acetal, 3-1-menthoxypropane-1,2-diol, 1-menthyl carbonate, (1S,3S,4R)-p-menth-8-en-3-ol, menthyl pyrrolidone carboxylate, N-substituted-p-menthane-3-carboxamide; selected from the group consisting of witch hazel extract, ginger oil, and combinations thereof.

[0090] In some embodiments, the stimulant or refresher is selected from the group consisting of alcohol, L-menthol, camphor, mint oil, chili pepper extract, capsaicin, benzyl nicotinate, salicylate, salicylate glycol, acetylcholine, serotonin, histamine, prostaglandins, neurotransmitters, CNS stimulants, caffeine, kinins, and combinations thereof.

[0091] In some embodiments, the topical formulation has a pH less than about 6.0. In some embodiments, the topical formulation has a pH less than about 5.5. In some embodiments, the topical formulation has a pH selected from the group consisting of about 4.0 to about 6.0, about 4.5 to about 5.0, and about 4.4 to about 4.7.

[0092] In certain embodiments, topical formulations are formulated in a form selected from the group consisting of solutions, fluids, emulsions, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, films, or transdermal patches, and include liquids, creams, ointments, gels, aerosols, neck creams, neck lotions, body lotions, body creams, face lotions, face creams, eyelash treatments, hair moisturizers, hair conditioners, hair and scalp oils, cellulite treatments, nail conditioners, gels, emulsions, silicone gels, water gels, oil-in-water emulsions, or water-in-oil emulsions.

[0093] Liquid dosage forms for topical administration may contain diluents such as alcohols, glycols, oils, or water. Such compositions may also contain wetting agents or emulsifiers.

[0094] Creams include water-in-oil (w / o) emulsions, in which the aqueous phase is dispersed in the oil phase, and oil-in-water (o / w) emulsions, in which the oil is dispersed in the aqueous base. Ointments generally refer to oil-in-water creams, which have a higher viscosity. Conventional ointment bases (i.e., carriers) include hydrocarbons (petrolatum, beeswax, etc.), vegetable oils, fatty alcohols (cholesterol, lanoyl phosphate, wool alcohol, stearyl alcohol, etc.), or silicones. Insoluble solids such as starch, zinc oxide, calcium carbonate, or talc can also be used in ointments and creams. Gel forms of the above compositions can be formed by encapsulating a large amount of aqueous or aqueous-alcoholic liquid within a polymer network or colloidal solid particles. Such polymers or colloids (gelling agents or thickeners) are typically present at concentrations of less than 10% w / w and include carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, sodium alginate, alginic acid, pectin, tragacanth, carrageenan, agar, clay, aluminum silicate, carbomer, and the like.

[0095] In aerosols, the composition is dissolved in a propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas, and in a cosolvent such as ethanol, acetone, hexadecyl alcohol, or combinations thereof.

[0096] Hydrogels are typically prepared by crosslinking various monomers and / or polymers to provide a three-dimensional polymer network. Non-limiting examples of polymers include polyoxyethylene-polypropylene block copolymers, ionic polysaccharides such as chitosan or sodium alginate, biodegradable polymers such as cellulose, polylactic acid (PLA) and polyglycolide (PGA), butylene succinate (PBS), polyhydroxyalkanoate (PHA), polycaprolactonic acid lactone (PCL), polyhydroxybutyrate (PHB), glycolamyl (PHV), PHB and PHV copolymer (PHBV), and polylactic acid (PLA)-polyethylene glycol (PEG) copolymer (PLEG).

[0097] The transdermal patch can be any conventional form, such as a strip, gauze, or film. The patch material may be nonwoven or woven (e.g., a gauze dressing). Layers may also be laminated during processing. It may be non-occlusive or occlusive, but the backing layer is preferably the latter. The patch is preferably sealed for storage (e.g., foil packaging). The patch can be retained on the skin, and the components of the patch can be held together using various adhesives. For example, the transdermal patch may be in the form of a band-aid type device, or it may be packaged in a small metal or plastic "cup," which is strapped to the appropriate site using adhesive, tape, or an outer cloth or leather strap similar to those worn as part of a watch. The entire patch may be disposable or refillable. In embodiments, the composition may be compounded with a latex polymer, and the composition is applied to the skin to form an occlusive film.

[0098] In some embodiments, the topical formulations disclosed herein may be applied to a bandage, mixed with a bioadhesive, or contained within a bandage.

[0099] In some embodiments, the topical formulations disclosed herein can be used in combination with cosmetic devices.

[0100] In some embodiments, the topical formulations disclosed herein can be used in combination with a patch.

[0101] In some embodiments, the topical formulation is part of an anti-aging regimen. In some embodiments, the topical formulation is part of an after-sun care regimen. In some embodiments, the topical formulation is part of a photoprotection regimen. In some embodiments, the photoprotection regimen is a sunscreen regimen or sunscreen. In some embodiments, the topical formulation is part of a skin lightening regimen. In some embodiments, the topical formulation is part of a skin brightening regimen. In some embodiments, the topical formulation is part of a regimen for acne treatment. In some embodiments, the topical formulation is part of a regimen for inflammation treatment. In some embodiments, the topical formulation is part of a color cosmetics regimen. In some embodiments, the topical formulation is part of a hair treatment regimen. In some embodiments, the topical formulation is part of a scalp treatment regimen.

[0102] Methods using the compositions described herein Embodiments disclosed herein relate to a method for inducing skin barrier repair, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0103] Embodiments disclosed herein relate to a method for inducing skin barrier repair, the method comprising the step of topically administering a topical formulation comprising a composition of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0104] In certain embodiments, induction of skin barrier repair results in the biosynthesis of barrier lipids and proteins in the skin selected from the group consisting of ceramide, filaggrin, trans-glutaminase 1, TGFB1, keratin, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF and combinations thereof. R This results in the regulation of skin barrier gene expression selected from the group consisting of P, FIAF, and combinations thereof.

[0105] In certain embodiments, ceramide expression is increased. Ceramide is a lipid component of the lipid bilayer; in addition to providing structural support to cells, ceramide is involved in various cellular signaling pathways, including regulating cell differentiation, proliferation, and programmed cell death (PCD). In some embodiments, the ceramide is CERS3, a ceramide synthase. In certain embodiments, ceramide expression is constant and does not decrease.

[0106] In certain embodiments, filaggrin expression is increased. Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells. In certain embodiments, filaggrin expression remains constant and does not decrease.

[0107] In certain embodiments, the expression of trans-glutaminase 1 (TGM1) is increased. TGM1 encodes the transglutaminase enzyme in keratinocytes. In certain embodiments, the expression of TGM1 remains constant and does not decrease.

[0108] In certain embodiments, TGFB1 expression increases. TGFB1 (Transforming Growth Factor Beta-1 or TGF-β1) is a cytokine and a major regulator of the skin's anti-aging process and wound healing. In certain embodiments, TGFB1 expression remains constant and does not decrease.

[0109] In certain embodiments, keratin expression is regulated. Keratin is a fibrous structural protein known as a scleral protein. In certain embodiments, KRT1 is decreased. In certain embodiments, KRT5 is increased. In certain embodiments, KRT6B is increased. In certain embodiments, KRT17 is decreased.

[0110] In certain embodiments, LCE1D expression is increased. LCE1D is a late keratinization protein and a precursor of the keratinization envelope of the stratum corneum. In certain embodiments, LCE1D expression remains constant and does not decrease.

[0111] In certain embodiments, CDH1 expression is increased. CDH1 is an e-cadherin Ca(2+)-dependent cell-cell adhesion molecule. In certain embodiments, CDH1 expression remains constant and does not decrease.

[0112] In certain embodiments, FOXO1 expression increases. FOXO1 is a keratinocyte differentiation molecule. In certain embodiments, FOXO1 expression remains constant and does not decrease.

[0113] In certain embodiments, the expression of aquaporin 3 (AQP3) is increased. AQP3 is a membrane transporter for water and glycerol expressed on the cell membrane of basal layer keratinocytes in the epidermis. In certain embodiments, the expression of AQP3 remains constant and does not decrease.

[0114] In certain embodiments, the expression of involucrin and loricrin increases. Involucrin is a protein component of human skin and is encoded in humans by the IVL gene. In binding with the protein loricrin, involucrin contributes to the formation of a cellular envelope that protects skin keratinocytes. In certain embodiments, the expression of involucrin and loricrin remains constant and does not decrease.

[0115] In certain embodiments, HSP27 expression is increased. Heat shock protein 27 (Hsp27) is a member of the small Hsp family that functions as a molecular chaperone, protecting cells from environmental stress. Hsp27 is expressed in the upper epidermis of normal human skin and has been reported to be involved in keratinocyte differentiation and apoptosis. In certain embodiments, HSP27 expression remains constant and does not decrease.

[0116] In certain embodiments, the expression of β-glucocerebrosidase is increased. β-glucocerebrosidase (also called acid β-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase, or GCase) is a glucosylceramidase-active enzyme required to hydrolyze the β-glucosidic bond of glucocerebroside, a chemical intermediate in glycolipid metabolism that is abundant in cell membranes (particularly skin cells). In certain embodiments, the expression of β-glucocerebrosidase remains constant and does not decrease.

[0117] In certain embodiments, ABCA12 expression is increased. ABCA12 belongs to a group of genes called the ATP-binding cassette family and produces a protein that transports molecules across the cell membrane. This protein appears to be essential for the normal development of skin, which provides a barrier between the body and its surrounding environment. It transports epidermoside, a glucosylceramide, out of keratinocytes in the stratum corneum of the epidermis. In certain embodiments, ABCA12 expression remains constant and does not decrease.

[0118] In certain embodiments, increased expression means increased gene expression and increased encoded protein. In certain embodiments, decreased expression means decreased gene expression and decreased encoded protein. In certain embodiments, gene expression is measured by isolating the RNA of interest, performing qPCR, and quantifying the expression level compared to a housekeeping gene or a control sample. In certain embodiments, protein expression is measured by Western blot analysis, where the protein of interest is identified and quantified using an appropriate antibody compared to a housekeeping protein or a control sample.

[0119] Embodiments disclosed herein relate to a method for improving skin barrier function, comprising the step of topically administering a topical formulation having a composition containing an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration.

[0120] The embodiment relates to a method for improving skin barrier function, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0121] Embodiments disclosed herein relate to a method for improving the texture of the skin surface, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0122] The embodiment relates to a method for improving the texture of the skin surface, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0123] Embodiments disclosed herein relate to a method for inducing desquamation, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0124] The embodiment relates to a method for inducing desquamation, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0125] Embodiments disclosed herein relate to a method for improving skin whitening, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration.

[0126] The embodiment relates to a method for improving skin whitening, and the method comprises the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenic acid, and Pterocarpus Marsupium bark extract, as well as a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration.

[0127] Embodiments disclosed herein relate to a method for alleviating irritation, comprising the step of topically administering a topical formulation having a composition comprising an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration.

[0128] The embodiment relates to a method for alleviating irritation, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0129] Embodiments disclosed herein relate to a method for supporting the skin's inherent ability to withstand environmental stressors, the method comprising the step of topically administering a topical formulation having a composition comprising an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and pharmaceutically or cosmetically acceptable excipients, the topical formulation being suitable for topical administration.

[0130] The embodiment relates to a method for supporting the skin's inherent ability to withstand environmental stressors, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0131] The embodiments relate to a method for improving aged skin, comprising the step of topically administering a composition having a combination of three or more PPAR agonists described herein. The embodiments disclosed herein relate to a method for improving aged skin, comprising an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract, as well as pharmaceutically or cosmetically acceptable excipients. The embodiments disclosed herein relate to a method for improving aged skin, comprising an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenate, ximenic acid, and Pterocarpus Marsupium bark extract, as well as pharmaceutically or cosmetically acceptable excipients.

[0132] In certain embodiments, improvement of aged skin is selected from the group consisting of smoothness, hydration, texture, skin tone, brightness and radiance of skin lightness, elasticity and firmness, smooth fine lines associated with photodamage and aging, as well as relief of dry, irritated and itchy skin, and reduction of transepidermal water loss (TEWL).

[0133] Embodiments disclosed herein relate to a method for preventing skin damage, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0134] The embodiment relates to a method for preventing skin damage, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0135] Embodiments disclosed herein relate to a method for improving the appearance of skin, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0136] The embodiment relates to a method for improving the appearance of the skin, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0137] Embodiments disclosed herein relate to a method for calming and soothing inflamed skin, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0138] The embodiment relates to a method for calming and soothing inflamed skin, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0139] In the embodiments described herein, improving the appearance of the skin is equivalent to improving the properties of the skin. In some embodiments, the properties of the skin are selected from the group consisting of firmness, elasticity, fine lines, texture, skin tone, appearance, and any combination thereof. In some embodiments, improving the appearance of the skin results in skin that looks smoother, firmer, and younger. In some embodiments, improving the appearance of the skin results in a brighter complexion, improved texture, and a more even-looking skin.

[0140] In the embodiments described herein, improving the appearance of the skin results in smoother skin, firmer skin, softer skin, a brighter complexion, improved skin texture, more even-looking skin, improved discoloration, disappearance of scars, reduced redness, or younger-looking skin. In some embodiments, improving the appearance of the skin results in an anti-inflammatory effect. In some embodiments, improving the appearance of the skin results in increased skin elasticity, reduced fine lines, reduced wrinkles, more consistent skin tone, and any combination thereof.

[0141] Embodiments disclosed herein relate to a method for treating fibrous skin, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0142] The embodiments relate to a method for treating fibrous skin, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration. In some embodiments, the fibrous skin condition is selected from the group consisting of atopic dermatitis, eczema, scleroderma, nephrogenic fibrous dermatosis, mixed connective tissue disease, scleral edema, scleroderma, eosinophilic fasciitis, and combinations thereof. In some embodiments, the fibrous skin disease is eczema.

[0143] Embodiments disclosed herein relate to methods for treating photodamage and hyperpigmentation, the method comprising the step of topically administering a topical formulation having a composition comprising an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0144] The embodiments relate to a method for treating photodamage and hyperpigmentation, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration. In some embodiments, the topical formulation inhibits melanin production activity both intracellularly and extracellularly.

[0145] Embodiments disclosed herein relate to a method for stimulating hair growth, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0146] The embodiment relates to a method for stimulating hair growth, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0147] Embodiments disclosed herein relate to a method for maintaining healthy hair, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0148] The embodiment relates to a method for maintaining healthy hair, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0149] Embodiments disclosed herein relate to a method for increasing hair density and volume, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0150] The embodiment relates to a method for increasing hair density and volume, and comprises the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, as well as a pharmaceutically or cosmetically acceptable excipient, wherein the topical formulation is suitable for topical administration.

[0151] Embodiments disclosed herein relate to a method for improving the appearance and feel of hair, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0152] The embodiment relates to a method for improving the appearance and feel of hair, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0153] Embodiments disclosed herein relate to a method for treating acne, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0154] Embodiments relate to a method for treating acne, the method comprising the step of topically administering a topical formulation having a composition containing an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration. In some embodiments, the topical formulation modulates the proliferation and differentiation of sebaceous gland cells.

[0155] Embodiments disclosed herein relate to a method for reducing inflammation and irritation caused by acne lesions, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0156] The embodiment relates to a method for reducing inflammation and irritation caused by acne lesions, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0157] Embodiments disclosed herein relate to a method for inhibiting P. acnes, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0158] The embodiment relates to a method for inhibiting P. acnes, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0159] Embodiments disclosed herein relate to a method for preventing hair follicle clogging, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0160] The embodiment relates to a method for preventing hair follicle blockage, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0161] Embodiments disclosed herein relate to a method for reducing the number of acne lesions, the method comprising the step of topically administering a topical formulation having a composition having an effective amount of three or more PPAR agonists selected from the group consisting of glyceryl linoleate, glyceryl linolenate, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0162] The embodiment relates to a method for reducing the number of acne lesions, the method comprising the step of topically administering a topical formulation having an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient, the topical formulation being suitable for topical administration.

[0163] In the embodiments described herein, the subjects are infants, children, adolescents, or adults.

[0164] In the embodiments described herein, topical formulations are formulated as topical formulations for anti-aging, after-sun care, skin whitening, acne treatment, inflammation treatment, hair treatment, or scalp treatment.

[0165] In some embodiments, the topical formulation can be applied to the skin once, twice, three, four, five or more times daily, and the application can be carried out for a period of at least one month, two months, three months, four months, six months, eight months, or twelve months.

[0166] In some embodiments, the topical formulation may be administered once, or, as needed, in administration cycles such as once daily, twice daily, three times daily, once weekly, twice weekly, every other week, or every other day. An administration cycle may consist of approximately 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, or 10 weeks of administration. After this cycle, the next cycle may be initiated approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks later. The treatment regimen may consist of 1, 2, 3, 4, 5, or 6 cycles, with each cycle spaced approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks apart.

[0167] In some embodiments, the method may include various additional steps, such as cleaning, polishing, microdermabrasion, and toning of the surface tissue of the application site.

[0168] Method for preparing the compositions described herein Broadly speaking, compositions and formulations can be prepared by combining the components as described herein, at temperatures and times sufficient to provide an acceptable composition or topical formulation.

[0169] In some embodiments, the composition is prepared by blending glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus Marsupium bark extract in the proportions listed in Table 1. Transfer phase A1 to a kettle using a nitrogen blanket, although this is not essential. Begin heating to 65-70°C. Add phase A2, a pre-weighed solid, while stirring. Once dissolved, add phase A3, a pre-weighed solid. Maintain a temperature of 65-70°C for approximately 30 minutes to 3 hours, stirring with a propeller, until completely dissolved. Check for small crystals or particles; if white crystals are present, continue mixing at 65-70°C for another hour. Once completely dissolved and free of colored insoluble particles and plant fibers, cool to room temperature and pump through a 10-micron sock filter to remove any remaining insoluble plant fibers. It is preferable to cover the drum / pail with nitrogen before transport. [Table 1]

[0170] In some embodiments, the composition is prepared as a finished topical formulation. In some embodiments, the topical formulation is an oil-in-water (O / W) emulsion containing a silicone emulsion, and the composition described herein is incorporated into the oil phase at about 0.5% to 5% before emulsification. In some embodiments, the topical formulation is an oil-in-water (O / W) emulsion containing a silicone emulsion, and the composition described herein is dispersed in the emulsion phase at about 0.5% to 5% with stirring. In some embodiments, the topical formulation is an oil-in-water (O / W) emulsion containing a silicone emulsion, and the composition described herein is not exposed to temperatures above 75°C.

[0171] In some embodiments, the composition is prepared as a finished topical formulation. In some embodiments, the topical formulation is a water-in-oil (W / O) emulsion containing a silicone emulsion, and the composition described herein is incorporated into the oil phase at about 0.5% to 5% before emulsification. In some embodiments, the topical formulation is a water-in-oil (W / O) emulsion containing a silicone emulsion, and the composition described herein is dispersed in the emulsion phase at about 0.5% to 5% with stirring. In some embodiments, the topical formulation is a water-in-oil (W / O) emulsion containing a silicone emulsion, and the composition described herein is not exposed to temperatures above 75°C.

[0172] In some embodiments, the composition is prepared as a finished topical formulation. In some embodiments, the topical formulation is anhydrous oil, ointment, or hot-cast wax (i.e., a continuous-phase formulation), and the composition described herein is incorporated into the oil phase at about 0.5–5% with minimal propeller stirring at room temperature. In some embodiments, the oil phase is a polar oil.

[0173] Next, the subject matter will be described with reference to the following examples. These examples are provided for illustrative purposes only, and the claims should not be construed as being limited in any way to these examples, but rather as encompassing any and all variations that become apparent as a result of the teachings provided herein. Those skilled in the art will readily recognize a variety of non-essential parameters that can be changed or modified to obtain essentially similar results.

[0174] Examples Example 1: Antioxidant activity of RFV3 and THD ascorbate in Lipo-ORAC testing.

[0175] Oxidative stress damages vital biological systems and is believed to be involved in over 100 diseases and aging processes. The purpose of this study is to measure the antioxidant capacity of the test materials shown in Table I using a lipophilic oxygen radical absorbance (Lipo-ORAC) assay (stock solutions were prepared at 2% acetone and diluted with 7% RMCD immediately before the experiment).

[0176] The Lipo-ORAC assay measures the ability of antioxidant compounds to suppress the reduction of fluorescein disodium (FL) fluorescence caused by 2',2'-azobis(2-amidinopropane) dihydrochloride (AAPH), a peroxyl radical generator. Peroxyl radicals are one of the most commonly found reactive oxygen species (ROS) in the body. This procedure incorporates randomly methylated beta-cyclodextrin as a solubility enhancer, allowing for the quantification of the antioxidant capacity of lipophilic samples using Trolox as a standard. An Applied Biosystems Cytofluor 4000 fluorometer and software were used for quantification in this assay. The detection threshold was set to a readout of 2.5 μg / mL, equivalent to or greater than that of Trolox.

[0177] Results and Discussion: As shown in Table 1, RFV3 had a LIPO-ORAC value of 400 μmol TE / g, which was considered high. THD ascorbate did not show activity in this assay system. Trolox yielded the expected ORAC score of ~4000 μmol TE / g across the entire concentration range tested, technically validating this experiment. Lipophilic oxygen radical absorbance (Lipo-ORAC) score is given in Trolox equivalents. Antioxidant activity was confirmed to be maintained even after treatment of the mixture at high temperatures. Linoleic acid and its derivatives can be oxidized to form free radicals. The results are shown in Table 2. [Table 2]

[0178] Example 2: Evaluation of the skin irritant activity of RFV3 in the reconstructed human epidermal model EpiDerm

[0179] The purpose of this assay was to investigate whether RFV3 has irritant activity in a reconstructed epidermal model. It was determined that RFV3 diluted to 10% (v:v) with Finsolv did not show irritant activity in this model.

[0180] Materials and Methods: 30 μm of each sample was applied onto an EpiDerm skin substitute. RFV3 was tested at 10% with Finsolv TN C12-15 alkyl benzoate as the diluent / solvent.

[0181] EpiDerm skin substitute (cat.EPI-200-SIT; Lot#29690) and 5% SDS solution (positive control) were obtained from MatTek (Ashland, MA). The tests were generally performed according to MatTek's protocol. This test was conducted in accordance with the requirements of OECD GD 34 and the ECVAM Performance Criteria document, and applied in vitro skin stimulation to a human skin model. This protocol effectively measures the cytotoxicity of the test material at the skin level by utilizing the readout of cytotoxicity based on MTT as the experimental endpoint. MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, tetrazole] is yellow but is reduced to purple formazan in living cells, and this conversion is measured by a colorimetric assay. The MTT assay measures the activity of succinate dehydrogenase, a key enzyme in the mitochondrial respiratory electron transport system, and is generally known as a test for measuring cytotoxicity.

[0182] Test materials were assayed in duplicate. Controls were assayed in triplicate. Negative controls were type I sterile water and Finsolv. Positive control was 5% SDS. All incubations were performed at 37°C. Pre-incubation time 1 (tissue acclimatization time) was overnight, and sample exposure was 60 minutes. Subsequently, tissues were washed with sterile PBS and placed in fresh culture medium. Post-incubation time 1 was 24 hours, after which the medium was collected and stored at -20°C for later interleukin quantification, and the tissues were placed in fresh medium. Post-incubation time 2 was 18 hours (both post-incubation times are to allow for full expression of potential irritant results), MTT test (irritant readout) was 3 hours, and extracts were left overnight. Extracted formazan (MTT conversion product, proportional to cell viability) was quantified by colorimetric analysis using a Molecular Devices MAX190 microplate reader. Signal quantification was performed using SoftMax 3.1.2 PRO at 560 nm. For IL-8 quantification (a complementary method for evaluating skin irritation), 100 μl samples of medium from each well were tested in triple replication using CytoSet antibody pairs for ELISA from Thermo Fischer Scientific (Waltham, Massachusetts; cat.#133301) according to the manufacturer's instructions. Colorimetric signals proportional to the IL-8 concentration in the tissue-modified medium were acquired using a Molecular Devices MAX190 microplate reader.

[0183] A statistically significant variation was defined as a variation of 15% or more from the water control, and a p-value of <0.05 calculated using a two-tailed t-test was used.

[0184] Results and Discussion: The colorimetric quantification of the MTT metabolic product (formazan) is provided in Table 2. As reported in Table 3 below, the viability of tissues treated under all experimental conditions except the positive control (SDS) was greater than 50% of the water (negative) control, classifying 10% of RFV3 as non-irritating and non-cytotoxic in this model system. Table 2 also summarizes the non-irritating (NI) or irritating (I) classification of all materials and controls used in this assay. Treatment with the positive control, 5% SDS detergent, was cytotoxic as expected, with only 12% of cells surviving. Replication met the standard deviation (SD) criterion defined in the protocol, i.e., SD < 18%, and the viability of the positive control (5% SDS) tissue was less than 20% of the negative control. Table 2 shows the results of IL-8 quantification in media prepared with EpiDerm tissues exposed to different experimental conditions. The levels of IL-8 detected in the EpiDerm-prepared media correlated with the irritation rate and are a secondary readout method. The test material did not stimulate IL-8 output. SDS (positive control) induced a 55% reduction in IL-8 levels due to cytotoxicity, technically validating the experiment. [Table 3]

[0185] Example 3: Transcriptional control by PPAR-α

[0186] Peroxisome proliferator-activated receptor alpha (PPAR-α) is a nuclear receptor protein encoded by the PPARA gene. This transcription factor belongs to the steroid hormone receptor superfamily and regulates the expression of target genes involved in cell proliferation, cell differentiation, immune and inflammatory responses. PPAR ligands (peroxisome proliferators) increase the size and number of peroxisomes, which are intracellular organelles found in plants and animals that are involved in maintaining energy homeostasis and cholesterol and lipid metabolism.

[0187] The objective of this project was to determine the effects of the test materials listed in Table 4 on the transcriptional regulatory activity of PPARα in a luciferase reporter assay system. [Table 4]

[0188] The effects of various samples on the transcription of the PPAR-α-regulated luciferase reporter gene were tested. CHO cells, an epithelial cell line derived from the ovaries of Chinese hamsters, were used. Positive control: 300 nM GW590735 is a potent and selective agonist of PPARα. Table 3 shows the composition of each test sample.

[0189] PPAR-α luciferase experiment. The composition was tested with a 250 μg / mL dilution in DMSO (Figure 1) and a 500 μg / mL dilution in DMSO (Figure 2). Positive control: 300 nM GW590735 is a potent and selective agonist of PPARα.

[0190] PPAR-γ luciferase experiment. The composition was tested with a 50 μg / mL dilution in DMSO (Figure 3) and a 200 μg / mL dilution in DMSO (Figure 4). Positive control: 300 nM rosiglitazone is a potent and selective agonist of PPARγ.

[0191] Table 5 summarizes the effects of different concentrations of test substances on transcriptional activation of the luciferase reporter gene under the PPAR-α-regulatory promoter (two separate experiments: Experiment 1 with water sample pretreatment and Experiment 2 with DMSO sample pretreatment). RFV3 had a statistically significant dose-dependent stimulating effect. Importantly, no signal was registered with RFV3 alone (without cells), indicating that this effect is not due to the inherent properties of the test material. Linefil (manufactured by PROVITAL: caprylic / capric triglyceride 55-75%, dimethyl isosorbide 25-40%, Sesamum Indicum (sesame) seed extract 3-5%, tocopherol 0.2-0.3%) registered a stimulating effect at the highest concentration tested, but it was not statistically significant. Statistically significant stimulating effects were observed under all non-cytotoxic experimental conditions except GLGL. The positive control GW590735 strongly upregulated reporter gene expression, technically demonstrating the effectiveness of the experiment. [Table 5] TIFF0007833253000009.tif235164

[0192] Example 4: Effects of RFV3 on metabolism, proliferation, IL-8, and type I collagen production in a model of human adult dermal fibroblasts subjected to photooxidative stress.

[0193] PPARγ activation increases mitochondrial biosynthesis, oxygen consumption, ΔΨm, and antioxidant defense, regulates autophagy, and increases transcription factors such as PGC1α, NRF1-2, and TFAM. Furthermore, PPARγ agonists regulate apoptosis and suppress inflammation. Thus, PPARγ agonists regulate the expression of several target genes, improving mitochondrial function and increasing redox capacity. The experimental conditions tested were UVA-irradiated adult human dermal fibroblasts (HDF).

[0194] The objective of this project was to clarify the effects of test materials on a series of skin-related parameters, in terms of total mitochondrial metabolism and proliferation, in adult human dermal fibroblasts (HDFs) exposed to UVA irradiation.

[0195] Materials and Methods: The test material was dissolved in DMSO at 100 mg / ml and further diluted with distilled water (dH2O). The sample was added in triplicate to exponentially growing mature human dermal fibroblasts (HDF; 10,000 cells / well in a 96-well plate; p.12 Cell Applications, San Diego, California, cat.#106-05a; lot#3014). The culture was maintained in DMEM / 10% FBS, and 24 hours after sample addition, it was exposed to UVA lamp UVA-28T (Ultra-lumen) at 5.2 mW / cm². 2 The plasma membrane and mitochondrial membrane were irradiated for 30 minutes to induce photooxidative stress. After 72 hours, the experiment was terminated, and type I collagen in the cell culture medium (soluble fraction) and on fixed cells (insoluble fraction) was quantified by ELISA. IL-8 was also measured in the cell culture medium. To investigate the effect of the test material on cell proliferation (cell number or cell count), total insoluble (cytoskeletal) proteins were quantified. Furthermore, using these values, the output data for type I collagen and IL-8 were standardized to cell number using the following formula.

[0196] [Raw reading of target macromolecule] / [Raw reading of cell number]

[0197] This standardization was performed individually for each well. Each experimental condition and control was assayed at least three times. The effect of the test material on mitochondrial metabolism was measured by the MTT assay, which measures the activity of mitochondrial dehydrogenases, such as succinate dehydrogenase, that are involved in the respiratory electron transport chain in mitochondria. All colorimetric measurements were performed using Molecular Devices' MAX190 microplate reader and SoftMax 3.1.2 PRO software. Statistical significance was assessed by paired Student's t-tests. A deviation of 20% or more compared to the water control and a p-value of less than 0.05 were considered statistically significant.

[0198] Results and Discussion: UVA radiation is the most common component of the solar ultraviolet spectrum and is the main effector of photoaging. It penetrates deeper into the skin than UVB, inducing photooxidative stress not only in the epidermis but also in the dermis. The UVA irradiation protocol (with modifications) used in this project was designed to investigate the effects of carotenoids on human dermal fibroblasts (HDFs) subjected to photooxidative stress.

[0199] The results (Table 6) suggest that UVA irradiation caused an increase in soluble type I collagen, likely partly due to an increase in metalloproteinase activity. This is supported by the slight (10%) decrease in deposited insoluble collagen after UVA irradiation. A slight (15%) increase in IL-8 secretion was also detected in UVA-irradiated cells. [Table 6]

[0200] Table 6 shows that RFV3 exhibited cytotoxicity at the highest concentration tested (500 μg / ml). This data established an upper limit on the concentration range to be adopted in further cell-based assays using this material. Table 7 also shows that RFV3 at non-cytotoxic concentrations of 20 μg / ml and 100 μg / ml did not have a statistically significant effect on cell proliferation, type I collagen production (soluble and insoluble), or interleukin-8 secretion into cell culture media. However, it significantly promoted mitochondrial metabolism (bold). Importantly, this increase was dose-dependent. These results suggest that RFV3 may provide mitochondrial health-related benefits to the skin across a wide range of concentrations without irritating side effects. These mitochondrial health-related benefits may include increased ATP production, upregulation of oxidative respiration (as opposed to glycolysis, which is more heavily used by cancer cells), and enhanced energy and macromolecular output for skin regeneration. [Table 7]

[0201] Example 5: Effect of RFV3 on melanin levels in melanocytes and melanocyte-prepared culture media.

[0202] This project aimed to evaluate the effects of test materials on the amount of melanin in human melanocytes.

[0203] Materials and Methods: On the day of the experiment, the test material was dissolved in DMSO at 100 mg / ml, diluted with sterile distilled water, and the sample was double-added to confluent cultures of C57BL / 6 mouse melanocytes in well plates. The cell growth medium was Opti-MEM supplemented with 7% horse serum (ThermoFisher Scientific, Waltham, Massachusetts) and antibiotics. The medium was replaced with fresh medium on day 0 of the experiment. Cells were cultured in the presence of the test material for 3 days, then frozen at -20°C, thawed at 37°C for 60 minutes in a Solvable (Perkin Elmer, Waltham, Massachusetts), and colorimetric quantification was performed at 490 nm using a Molecular Devices (Sunnyvale, California) microplate reader MAX190. Kojic acid (100 μg / ml and 200 μg / ml) was used as a positive control. Statistically significant variation was defined as a variation of 20% or more from the water control, and a p-value of <0.05 calculated by a two-tailed t-test was considered.

[0204] Results and Discussion: As reported in Table 8, neither RFV3 nor the positive control kojic acid had a statistically significant effect on extracellular and intracellular melanin levels at all concentrations tested. However, a moderate inhibitory trend was observed for both compounds. PPARα agonists are known to inhibit melanocyte proliferation. Although not statistically significant, the results in Figure 5 demonstrate the melanin production trend and the benefits of RFV3 as a skin-whitening and beautifying composition. PCR also demonstrated a decrease in HGF in RFV3-tested cells. [Table 8]

[0205] Example 6: Effects of RFV3 on the expression of gene panels related to epidermal structure and function in 3D tissue surrogate models.

[0206] The objective of this project was to clarify the effects of the test material (RFV3) on the expression of a gene panel related to epidermal structure and function using a three-dimensional tissue surrogate model.

[0207] Materials and methods:

[0208] Glycerin (99.7% USP) was used as a negative control. Epidermal substitutes (cat.#102-3D-12; lot#2744) were obtained from Cell Applications (San Diego, California). These were prepared in vitro in PCF inserts from neonatal keratinocytes and fibroblasts and differentiated into laminar squamous epithelium over approximately two weeks. Such three-dimensional cultures closely resemble human epidermis and are commonly used in the study of skin aging. The tissues were equilibrated in a cell culture incubator for 60 minutes and then triple-exposed to 2% test material (diluted with glycerin) and negative control (glycerin) for 24 hours. At the end of the culture (24 hours), the tissue was washed, RNA was extracted, and purified using the Macherey-Nagel NucleoSpin RNA Kit (cat.#740955.240C; Bethlehem, Pennsylvania) at a QiaCube robotic station (Qiagen, Germantown, Maryland). Purified total RNA was evaluated at 260 nm and 280 nm using NanoDrop Lite (Thermo Fisher Scientific, Waltham, Massachusetts). Pure samples with A260A / 280 and A260 / 230 ratios >1.7 were standardized, and the expression levels of the gene panel of interest were quantified by qPCR using the BioRad iCycler iQ Detection System with Realtimeprimers (RTP; Elkins Park, Pennsylvania), 5x All-In-One 1st Strand cDNA Synthesis Mix (cat.# AZ-1996, Azura Genomics / RTP), and Fast Green qPCR Master Mix-Fluor (cat.#4375; Azura Genomics / RTP). After standardizing gene expression to eight housekeeping genes, the efficiency ΔΔCt method was used to quantify the results. A gene was considered to have expression differences if its expression level was moderately high (detection cycles were 30 or less), the p-value was <0.05, and the modulation degree (magnification change) was ≥2.

[0209] Results and Discussion: The PCR array experiment was successful in that it was possible to collect high-purity (A260 / A280 ratio > 1.7) total RNA from all tissues. RNA samples were converted to DNA, and PCR reactions were performed using the array panel. Gene expression in tissues treated with the test material was compared with that of a control treated with glycerol. For each probe, the magnification change compared to the control was confirmed.

[0210] Conclusion: In summary, RFV3 appears to have a complex interplay of effects, ranging from immunomodulatory activity (e.g., upregulation of S100A8 and TLR2, downregulation of IL-6 and S100A9) to support for epidermal structure, differentiation, and barrier function [upregulation of AQP3 water channels, CDH1, filaggrin, several keratins, late keratinocytes, and membrane bilayer ceramides (due to increased CERS3)].

[0211] Example 7: Evaluation of the product's skin barrier repair activity against human skin edible samples in ex vivo.

[0212] The purpose of this study was to evaluate the skin barrier repair activity of products tested at three concentrations in ex vivo human living skin explants. This activity was assessed by controlling cell viability, immunostaining of ceramides, immunostaining of filaggrin, and immunostaining of transglutaminase-1 (TGM1).

[0213] Explant preparation: From a 54-year-old Caucasian woman with type II light type (see P2129-AB54), 66 explants with an average diameter of 11 mm (±1 mm), including 33 defatted explants, were prepared from abdominal reconstruction. These explants were kept alive in BEM medium (BIO-EC explant medium) at 37°C and 5% CO2 humidity.

[0214] Degreasing: On day 0, the abdominal formation was degreased by applying a 1:1 (v:v) ether:acetone mixture to a demarcated area for 2 minutes twice, followed by wiping the skin surface with a paper tissue. In this degreased area, 33 skin explants, named "D" with an average diameter of 11 mm (±1 mm), were prepared and kept alive as described above.

[0215] Explant distribution: As shown in Table 9, the explants were distributed into 12 batches. [Table 9]

[0216] Product application: On day 0 immediately after degreasing, products P1, P2, P3, and placebo E were applied topically to each explant at a rate of 2 μl (2 mg / cm2) and spread using a small spatula. Control explant T received no treatment.

[0217] Sampling: On day 0, three explants were collected from batches T0 and D0 (immediately after degreasing) and divided into two halves. Half were fixed in buffered formalin solution, and the other half were frozen at -80°C. On day 0+3h (3 hours after degreasing) and day 1 (24 hours after degreasing), three explants were collected from each batch and treated in the same manner as T0.

[0218] Histological preparation. After fixing in buffered formalin for 24 hours, the samples were dehydrated using a Leica PEARL dehydration automat and impregnated in paraffin. The samples were embedded using a Leica EG 1160 embedding station. 5 μm thick sections were prepared using a Leica RM 2125 Minot-type microtome and mounted on Superfrost® histological slides. Frozen samples were cut into 7 μm thick sections using a Leica CM 3050 cryostat. The sections were mounted on silane-treated Superfrost® Plus slides. Microscopic observation was performed using a Leica DMLB or Olympus BX43 microscope. Photographs were digitized using an Olympus DP72 camera and CellD preservation software.

[0219] Cell viability: Cell viability of epidermal and dermal structures was assessed by microscopic observation of paraffinized sections after Masson trichrome staining, using the Goldner variant. Staining was evaluated by microscopic observation. Applicable batch: All.

[0220] Ceramide immunostaining: Ceramide immunostaining was performed on formalin-fixed paraffin-embedded specimens at room temperature for 1 hour using monoclonal anti-ceramide antibody (Glycobiotech, reference: MAB_0013, clone S58-9) diluted 1:25 in PBS, 0.3% BSA, and Tween20 (0.05%). Amplification with a biotin / streptavidin system revealed the purple substrate of VIP (Vectore, reference: PK-7200). Immunostaining was performed using an automated slide processing system (Dako, AutostainerPlus) and evaluated by microscopic observation. Applicable batches: All.

[0221] Filaggrin immunostaining: Filaggrin immunostaining was performed on formalin-fixed, paraffin-embedded sections at room temperature for 1 hour using monoclonal anti-filaggrin antibody (Santa Cruz, ci: sc-66192, clone AKH1) diluted 1:1000 in PBS, 0.3% BSA, and Tween 20 (0.05%), and revealed using Alexafluoro 488 (Lifetechnologies, ci: A11001). Nuclei were counterstained with propidium iodide. Immunostaining was performed using an automated slide processing system (Dako, AutostainerPlus) and evaluated by microscopic observation. Applicable batches: All.

[0222] TGM1 immunostaining: TGM1 immunostaining was performed on paraffin-embedded sections fixed in formalin at room temperature for 1 hour using polyclonal anti-TGM1 antibody (Novus biologicals, reference: NB100-1844) diluted 1:100 in PBS, 0.3% BSA, and Tween20 (0.05%). The stains were amplified with a biotin / streptavidin system and presented as a purple substrate in VIP (Vector, reference: PK-7200). Immunostaining was performed using an automated slide processing system (Dako, AutostainerPlus) and evaluated by microscopic observation. Applicable batch: All.

[0223] Ceramides: The stratum corneum (SC) is the outermost layer of the skin and consists of 5 to 30 layers of cells. The main building blocks of the SC are keratinocytes, which are nucleated cells filled with hydrophilic keratin filaments and surrounded by a lipid-rich extracellular matrix. The most important intercellular lipids in keratinocytes are ceramides, cholesterol, and fatty acids, accounting for 50%, 25%, and 10% of the total lipid content of keratinocytes, respectively. Intercellular lipids, including ceramides, limit transepidermal water loss (TEWL). Ceramides also form a substantial barrier protecting the epidermis from external stimuli. Ceramides are precursors to all sphingolipids. Ceramides are formed by the bonding of fatty acids and sphingoid bases; sphingosine forms ceramide, and dehydrosphingosine forms dehydroceramide. Phytoceramides, in which phytosphingosine is bonded to a C-4 hydroxyl group, are also included in the SC.

[0224] Filaggrin: Profilaggrin, a precursor of filaggrin, is a protein of approximately 400 kDa that is phosphorylated and insoluble. It is a major component of keratohyalin granules in the granular layer. In the later stages of the epidermal differentiation program, profilaggrin is dephosphorylated and cleaved into several filaggrin monomers by caspase 14. Subsequently, filaggrin binds to keratin filaments and is involved in aggregation into microfibrils and the formation of keratinized extracellular space. This proteolysis is a central step in the formation of natural moisturizing factors (NMF). Due to its hygroscopic properties, NMF is directly involved in the hydration of the stratum corneum.

[0225] Transglutaminase 1: Epidermal keratinocytes undergo terminal differentiation, involving keratin aggregation, nuclear degradation, and replacement of the cell membrane with a tough, insoluble protein capsule, forming a keratinized capsule crosslinked with extracellular lipids, thereby exhibiting barrier function. Transglutaminase (TGM) is a Ca2+-dependent crosslinking enzyme that catalyzes acyl transfer reactions between the carboxamide group of glutamine bound to proteins and various primary amines, particularly the -amino group of lysine residues, forming isopeptide bonds between proteins and creating insoluble macromolecular aggregates. Four of the seven human TGases (1, 2, 3, and 5) are expressed in terminally differentiated epithelium, including the skin. TGase 1 is essential for crosslinking substrates such as loricrin, trichohyalin, SPR1, 2, and 3. Transglutaminase-mediated protein crosslinking enhances resistance to protein degradation.

[0226] Epidermal lipid synthesis and metabolism are regulated by nuclear hormone receptors (NHRs), and epidermal lipid metabolites are known to function as ligands for NHRs. NHRs form a large receptor superfamily that regulates gene transcription through DNA binding. Subgroups of these receptors are ligand-activated and heterodimerize with retinoid X receptors, including peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), and pregnane X receptors (PXRs).

[0227] Table 10 provides the composition of the test samples. [Table 10]

[0228] In the ex vivo study, Myritol® 318 (INCI name: caprylic / capric triglyceride) was selected as the solvent. Abdominal skin lipids are composed of approximately 25% triglycerides.

[0229] The parameters evaluated were filaggrin, ceramide, and TGM1, as analyzed by image analysis. Table 11 summarizes the results. DJ1 refers to day 1 of the degreasing batch, and DEJ1 refers to day 1 of the solvent-treated degreasing batch. [Table 11]

[0230] See Table 12 for raw image analysis data of ceramides, surface percentage in the stratum corneum. [Table 12]

[0231] See Table 13 for raw image analysis data of filaggrin, surface percentage in the stratum corneum. [Table 13]

[0232] See Table 14 for raw image analysis data of TGM1, surface percentage in the stratum corneum. [Table 14]

[0233] Figure 6 shows the increase in ceramide expression on day 1 in defatted explants. Figure 7 shows the increase in transglutaminase-1 (TGM1) expression on day 1 in unremoved explants. Figure 8 shows the increase in filaggrin expression on day 1 in defatted explants.

[0234] Conclusions from the ex vivo barrier repair test report using samples taken from living human skin: All products are well-integrated into the skin and do not cause changes in cell viability in either the epidermis or dermis. The cosmetic-grade excipient (CCT) experimental sample (E) induced significant changes in ceramide content (day 0 + 3h, day 1) and transglutaminase expression (day 1) when degreasing was not performed, but showed no significant effect after degreasing. The cosmetic-grade experimental sample of product P1 (0.5% RFv3) showed moderate skin barrier repair activity. P1 was shown to partially suppress the degreasing-induced decrease in ceramide (after 3 hours, after 24 hours), TGM1 (after 24 hours), and filaggrin (after 3 hours) due to degreasing. P1 completely suppressed the decrease in filaggrin due to degreasing (after 24 hours). The cosmetic-grade experimental sample of product P2 (3% RFv3) showed fairly good skin barrier repair activity. P2 partially suppressed the decrease in ceramide due to degreasing (after 3 hours). P2 was able to completely suppress the degreasing-induced decrease of ceramide (after 24 hours), TGM1 (after 24 hours), and filaggrin (after 3 hours and 24 hours). Experimental samples of product P3 (5% RFv3) cosmetic grade showed good skin barrier repair activity. P3 partially suppressed the degreasing-induced decrease of ceramide (after 3 hours) and TGM1 (after 3 hours). It was confirmed that P3 completely suppressed the degreasing-induced decrease of ceramide (after 24 hours), TGM1 (after 24 hours), and filaggrin (after 3 hours and 24 hours).

[0235] These studies further confirmed increases in TGFB1, a major regulator of skin anti-aging processes and wound healing; changes in keratin expression, namely a decrease in krt1, an increase in krt5, an increase in krt6B, and a decrease in krt17; an increase in LCE1D, a late keratinization envelope protein; an increase in CERS3, a ceramide synthase; an increase in CDH1, which is Ca(2+)-dependent e-cadherin intercellular adhesion; and an increase in FOXO1, which is keratinocyte differentiation.

[0236] Example 8: Comparative formulation test

[0237] The control formulation ("EQB Blend") is a control containing 90% glyceryl oleate (representing 90% glyceryl esters of omega fatty acids), 7% palmitic acid (representing 7% plant-derived fatty acids), and 3% hydroxyresveratrol (representing 3% stilbene antioxidant). The experimental formulation ("RFV3 Blend") contains 90% glyceryl linoleate and glyceryl linolenate (representing 90% glyceryl esters of omega fatty acids), 7% ximenylic acid (representing 7% plant-derived fatty acids), and 3% Asana (Pterocarpus Marsupium) bark extract (representing 3% stilbene antioxidant). Each component, namely glyceryl linoleate and glyceryl linolenate, ximenylic acid, and Asana (Pterocarpus Marsupium) bark extract, was also tested. GW590735 was used as a positive control.

[0238] As a result, RFV3 was demonstrated to produce high PPAR agonist activity. The chemically similar EQB blend showed minimal activity. Individual components of the RFV3 blend were either inactive or cytotoxic. Figure 9 shows the effects of the above test samples on the transcription of the PPAR-α regulatory luciferase reporter gene in CHO cells, an epithelial cell line derived from the ovaries of Chinese hamsters. Each was diluted to 500 μg / mL with DMSO. Water (H2O) was used as a blank. Positive control: GW590735, a potent and selective agonist of PPARα. The EQB blend, RFV3 blend, glyceryl linoleate, and glyceryl linolenic acid were non-cytotoxic. Ximenylic acid and Pterocarpus Marsupium bark extract were cytotoxic.

[0239] Example 9: Oil-in-water barrier repair emulsion formulation

[0240] Table 15 shows an oil-in-water barrier repair emulsion formulation containing the presence of each component in the phases necessary for manufacturing a topical formulation. The oil-in-water barrier repair emulsion is prepared by mixing Phase A, heating it to 75°C with stirring, mixing B1, heating it to 75°C until dissolved, adding the B2 premix to B1 with stirring, adding A to B under homogeneous stirring while maintaining the temperature at 75°C for 20 minutes, adding C to A / B under homogeneous stirring for 20 minutes while maintaining the temperature at 75°C. After replacing the homogenizer with a sweep anchor mixer, cooling to 30°C, adding at 30°C, and continuing mixing until the product is completely homogeneous, adjusting the pH to 5.3 as necessary.

Table 15

[0241] Example 10: Water-in-oil type whitening barrier emulsion formulation

[0242] Table 16 provides a water-in-oil whitening barrier emulsion formulation containing the presence of each component in the phases necessary for manufacturing a topical formulation. The water-in-oil barrier repair emulsion is prepared by mixing Phase A with stirring and heating to 85°C, mixing Phase B with stirring and heating to 85°C, slowly adding Phase B to Phase A while intensively homogenizing, cooling to 35°C with a sweep mixer, and adding the Phase C components one by one and homogenizing until homogeneous.

Table 16

[0243] Example 11: Anhydrous OTC skin protectant ointment containing a barrier repair formulation

[0244] Table 17 provides a formulation of an anhydrous OTC skin protectant ointment with barrier repair containing the presence of each component in a topical formulation. The anhydrous OTC skin protectant ointment with barrier repair is prepared by combining the components and mixing them under high shear at room temperature conditions until they are uniformly dispersed.

Table 17

[0245] Example 12: Hair and scalp oil formulation

[0246] Table 18 provides a formulation of a hair and scalp oil preparation containing the presence of each component in a topical preparation. The hair and scalp oil is prepared by combining the components by blending until they are uniformly dispersed by high-shear mixing under room temperature conditions.

Table 18

[0247] Example 13: Deep Conditioning Hair Mask Formulation

[0248] Table 19 provides a formulation of a deep conditioning hair mask containing the presence of each component in a topical preparation. The deep conditioning hair mask is prepared by the following steps: 1) filling phase A into a tank and heating it to 80°C, 2) preparing phase B and heating it to 80°C, 3) combining phase B and phase A under high-shear conditions, 4) maintaining high-shear mixing until emulsification, 5) cooling the batch to 50°C, 6) adding C under appropriate mixing conditions, and 7) adjusting the pH to 5.0 - 6.0.

Table 19

[0249] Example 14: Acne treatment with a sebum control formulation

[0250] Table 20 provides a formulation of an acne treatment drug with sebum control, including the content of each component in the topical formulation. The acne treatment drug with sebum control is prepared by the following steps: 1) heating water to 80°C and slowly adding VEEGUM and xanthan gum as a dry blend while mixing with a high-shear propeller; 2) adding the remaining Phase A component and maintaining the temperature at 80-85°C; 3) combining the Phase B component and heating to 80°C; 4) slowly adding Phase B to Phase A while homogenizing; 5) gradually cooling while sweeping; and 6) adding Phase C at 30°C to adjust the pH. [Table 20] TIFF0007833253000026.tif60160

[0251] The disclosures of each patent, patent application, publication and acceptance number cited herein are incorporated herein by reference in their entirety.

[0252] While this disclosure has been made with reference to various embodiments, it will be apparent that other embodiments and variations of these can be devised by those skilled in the art without departing from the true spirit and scope of this disclosure. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

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

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

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

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

5. A composition according to claim 1, wherein the effective amount of the Asana (Pterocarpus Marsupium) bark extract is 1% to 5% by weight of the composition.

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

7. A topical formulation comprising an effective amount of the following PPAR agonists: glyceryl linoleate, glyceryl linolenic acid, ximenic acid, and Pterocarpus marsupium bark extract, and a pharmaceutically or cosmetically acceptable excipient.

8. A topical preparation according to claim 7, wherein the amount of glyceryl linoleate is 0.375% to 4.7% by weight of the topical preparation.

9. A topical preparation according to claim 7, wherein the amount of glyceryl linolenate is 0.025% to 0.5% by weight of the topical preparation.

10. A topical preparation according to claim 7, wherein the ximenynic acid is present in an amount of 0.025% to 0.5% by weight of the topical preparation.

11. A topical preparation according to claim 7, wherein the amount of the Pterocarpus Marsupium bark extract is 0.005% to 0.25% by weight of the topical preparation.

12. The use of effective amounts of the following PPAR agonists in the preparation of the topical formulation according to claim 7 for inducing skin barrier repair: glyceryl linoleate, glyceryl linolenic acid, ximenylic acid, and Pterocarpus marsupium bark extract.

13. In the use according to claim 12, the induction of skin barrier repair results in the biosynthesis of skin barrier lipids and proteins selected from the group consisting of ceramide, filaggrin, trans-glutaminase 1, TGFB1, keratin, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucoceresidase, aquaporin 3, ABCA12, ADRP, FIAF, and combinations thereof.

14. In the use according to claim 12, the induction of skin barrier repair results in the regulation of the expression of skin barrier genes selected from the group consisting of ceramide, filaggrin, trans-glutaminase 1, TGFB1, keratin, LCE1D, CERS3, CDH1, FOXO1, HSP27, involucrin, loricrin, beta-glucocerebrosidase, aquaporin 3, ABCA12, ADRP, FIAF, and combinations thereof.

15. a. Improvement of aged skin, wherein the improvement of aged skin is selected from the group consisting of smoothness, hydration and texture, b. Prevention of skin damage, c. Improvement of skin appearance, d. Calming and soothing inflamed skin, e. Treatment of atopic dermatitis (eczema) f. Treatment of photodamage and hyperpigmentation, g. Improvement of skin barrier function, h. Improvement of skin surface texture, i. Desquamation, j. Improvement of skin whitening, k. Relaxation of stimulation, l. Supporting the skin's natural defense mechanisms against environmental stressors. m. Stimulation of hair growth, n. Maintaining healthy hair, o. Increase in hair density and volume, p. Improvement of the appearance and feel of hair, Q. Treatment of acne, r. Reduction of inflammation and irritation caused by acne lesions. Suppression of s. P. acnes, t. Prevention of clogged hair follicles, and / or, u. Reduction in the number of acne lesions, A topical formulation according to claim 7 for use in [the specified purpose].