Compositions and methods for wound and scar healing

Abstract

Methods of treating wounds and / or promoting wound healing in subjects are disclosed. Methods of treating or diminishing appearance of a scar or scarring in a subject are also disclosed. The methods generally include administering an emblica extract or a compound constituent of an emblica extract, or a fucus extract or a compound constituent of a fucus extract, or a chebula extract or a compound constituent of a chebula extract. Related compositions and wound dressings are also disclosed.

Description

[0001] PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0002] Docket No. Y2008-7007WG

[0003] COMPOSITIONS AND METHODS FOR WOUND AND SCAR HEALING

[0004] CROSS-REFERENCE TO RELATED APPLICATIONS

[0005] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application

[0006] 5 Serial No. 63 / 699,410 titled “COMPOSITIONS AND METHODS FOR WOUND HEALING” filed September 26, 2024, which is incorporated herein by reference in its entirety for all purposes.

[0007] FIELD OF TECHNOLOGY

[0008] 10 Aspects and embodiments disclosed herein relate to compositions and methods for delivery of emblica extract, chebula extract, and isolated constituents thereof. Aspects and embodiments disclosed herein relate to methods of treatment by administration of emblica extract, chebula extract, and isolated constituents thereof.

[0009] 15 BACKGROUND

[0010] Mitochondrial dysfunction, such as mitochondrial DNA (mtDNA) depletion, is involved in many diseases and conditions, such as mtDNA depletion syndromes, mitochondrial diseases, aging, aging-associated chronic diseases or conditions, reduced energy levels and vitality, characteristics of hair aging including hair loss and graying, characteristics of skin aging

[0011] 20 including skin wrinkles and senile lentigines, skin diseases and conditions, and other human pathologies. There is a need for compositions and treatment methods for diseases and conditions related to mitochondrial dysfunction, such as mtDNA depletion.

[0012] SUMMARY

[0013] In accordance with certain aspects, there is provided a method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a

[0014] 30 pharmaceutically acceptable form thereof. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0015] Docket No. Y2008-7007WO

[0016] In accordance with certain aspects, there is provided a method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fucus extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a fucus extract or having a similarity score

[0017] 5 of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.

[0018] In accordance with certain aspects, there is provided a method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of a chebula extract, or a pharmaceutically

[0019] 10 acceptable form thereof, or one or more compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.

[0020] In accordance with certain aspects, there is provided a method of treating or diminishing appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof.

[0021] In accordance with certain aspects, there is provided a method of treating or diminishing

[0022] 20 appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fucus extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.

[0023] 25 In accordance with certain aspects, there is provided a method of treating or diminishing appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a

[0024] 30 pharmaceutically acceptable form thereof. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0025] Docket No. Y20Q8-7007WO

[0026] In accordance with certain aspects, there is provided a wound dressing including any of the compositions as described herein.

[0027] In accordance with certain aspects, there is provided a kit including a wound dressing and a source of any of the compositions as described herein.

[0028] 5 The disclosure contemplates all combinations of any one or more of the foregoing aspects and / or embodiments, as well as combinations with any one or more of the embodiments set forth in the detailed description and any examples.

[0029] BRIEF DESCRIPTION OF THE DRAWINGS

[0030] 10 The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0031] The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures is represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:

[0032] FIGS. 1A-1D include graphs showing expression of COXII at 6, 12, 24, and 48 hours after in vitro administration of a chebulinic acid, optionally encapsulated in a delivery carrier, according to one embodiment;

[0033] 20 FIGS. 2A-2D include graphs showing expression of TFAM at 6, 12, 24, and 48 hours after in vitro administration of chebulinic acid, optionally encapsulated in a delivery carrier, according to one embodiment;

[0034] FIGS. 3A-3B include graphs showing expression of COXII at 6 hours after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one

[0035] 25 embodiment;

[0036] FIGS. 4A-4D include graphs showing expression of COXII at 6, 12, 24, and 48 hours after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one embodiment;

[0037] FIGS. 5A-5D include graphs showing expression of TFAM at 6, 12, 24, and 48 hours

[0038] 30 after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one embodiment; PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0039] Docket No. Y2008-7007WO

[0040] FIGS. 6A-6D include graphs showing expression of COXII at 6, 12, 24, and 48 hours after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one embodiment;

[0041] FIGS. 7A-7D include graphs showing expression of COXII at 6, 12, 24, and 48 hours

[0042] 5 after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one embodiment; and

[0043] FIGS. 8A-8D include graphs showing expression of TFAM at 6, 12, 24, and 48 hours after in vitro administration of emblica extract encapsulated in a delivery carrier, according to one embodiment;

[0044] 10 FIG. 9 is a heatmap of gene expression after administration of Y 100, according to one embodiment;

[0045] FIG. 10 is a Venn diagram showing gene expression in three subjects after administration of Y 100, according to one embodiment;

[0046] FIGS. 11A-11B are graphs showing gene expression of DNER and THRSP, respectively, on sun-exposed and non-exposed skin, according to certain embodiments;

[0047] FIGS. 12A-12C are graphs showing biological roles of differentially expressed genes as a whole from one subject, according to one embodiment;

[0048] FIGS. 13A-13C are graphs showing biological roles of differentially expressed genes as a whole from another subject, according to one embodiment

[0049] 20 FIGS. 14A-14C are graphs showing biological roles of differentially expressed genes as a whole from another subject, according to one embodiment;

[0050] FIGS. I5A-15C are graphs showing upregulation of COL1A1 at 6 hours, 12 hours, and 24 hours, respectively, after administration of Y100 in vitro, according to one embodiment;

[0051] FIGS. 16A-16B present data discussed in accompanying Example 5; and

[0052] 25 FIGS. 17A-17B present data discussed in accompanying Example 6.

[0053] DETAILED DESCRIPTION

[0054] Mitochondrial dysfunction is associated with many mitochondrial diseases, many of which are the result of dysfunctional mitochondrial oxidative phosphorylation (OXPHOS).

[0055] 30 Mitochondrial OXPHOS accounts for the generation of most of the cellular adenosine triphosphate (ATP) in a cell. The OXPHOS function largely depends on the coordinated PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0056] Docket No. Y2008-7007WD expression of proteins encoded by both nuclear and mitochondrial genomes. The human mitochondrial genome encodes for 13 polypeptides of the OXPHOS system, and the nuclear genome encodes the remaining more than 85 polypeptides required for the assembly of OXPHOS system. mtDNA depletion impairs OXPHOS and leads to mtDNA depletion

[0057] 5 syndromes (Alberio,et al., Mitochondrion 7, 6-12, 2007; Ryan, Met al., Anna. Rev. Biochem. 76, 701-722, 2007). The mtDNA depletion syndromes are a heterogeneous group of disorders, characterized by low mtDNA levels in specific tissues. In different target organs, mtDNA depletion leads to specific pathological changes (Tuppen, et al., Biochim. Biophys. Acta 1797, 113-128, 201)). mtDNA depletion syndromes result from the genetic defects in the nuclear-

[0058] 10 encoded genes that participate in mtDNA replication, and mitochondrial nucleotide metabolism and nucleotide salvage pathway (Alberio,et al., Mitochondrion 7, 6-12, 2007). mtDNA depletion is also implicated in other human diseases and conditions, such as, but not limited to, mtDNA depletion syndromes, mitochondrial diseases, aging, aging-associated chronic diseases or conditions, reduced energy levels and vitality, characteristics of hair aging including hair loss and graying, characteristics of skin aging including skin wrinkles and senile lentigines, skin diseases and conditions, and other human pathologies.

[0059] A general decline in mitochondrial function has been extensively reported during aging. Furthermore, mitochondrial dysfunction is known to be a driving force underlying age-related human diseases. A mouse that carries a specific mtDNA mutation has been shown to present

[0060] 20 signs of premature aging (i.e., a mtDNA depleter mouse). In addition to mutations in mtDNA, studies also suggest a decrease in mtDNA content and mitochondrial copy number with age. Low mtDNA copy number is linked to frailty and, for a multiethnic population, is a predictor of all-cause mortality. A recent study revealed that humans on an average lose about four copies of mtDNA every ten years. This study also identified an association of decrease in mtDNA copy

[0061] 25 number with age-related physiological parameters.

[0062] Accumulating evidence suggests a strong link between mitochondrial dysfunction, mitochondrial diseases, aging, and aging-associated diseases. Notably, increased somatic mtDNA mutations and decline in mitochondrial functions have been extensively reported during human aging. Studies also suggest a decrease in mtDNA content and mitochondrial number with

[0063] 30 age. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0064] Docket No. Y2008-7007WO

[0065] Definitions

[0066] As used herein, the term “carrier” refers to a diluent or vehicle with which a compound is administered. The carrier may be a pharmaceutically acceptable carrier. The carrier may be a cosmetically acceptable carrier. Examples of suitable pharmaceutical carriers are described in

[0067] 5 “Remington’s Pharmaceutical Sciences” by E. W. Martin.

[0068] As used herein, “treatment” of a disease or condition refers to reducing or lessening the severity or frequency of at least one symptom of that disease or condition, compared to a similar but untreated patient. Treatment can also refer to halting, slowing, or reversing the progression of a disease or condition, compared to a similar but untreated patient. Treatment may comprise

[0069] 10 addressing the root cause of the disease and / or one or more symptoms.

[0070] As used herein, the term “effective amount” refers to an amount of a compound or composition of the disclosure administered to a subject, which is effective to provide a desired response and / or effect in the subject. The response and / or effect may be a cosmetic response and / or effect. The response and / or effect may be a therapeutic response and / or effect. The response and / or effect may be a prophylactic or preventative response and / or effect.

[0071] As used herein, the term “therapeutically effective amount” refers to an amount of compound or composition of the disclosure administered to a subject, which is effective to treat a disease or condition described herein in a subject and / or to produce a desired physiological response and / or therapeutic effect in the subject. One example of a desired physiological

[0072] 20 response includes increasing mtDNA copy number and / or concentration.

[0073] The actual dose which comprises the “effective amount” or “therapeutically effective amount” may depend upon the route of administration, the size and health of the subject, the disorder being treated, and the like.

[0074] In some embodiments, the “effective amount” or “therapeutically effective amount” in

[0075] 25 the context of the present disclosure is sufficient to induce mitochondrial biogenesis. The “effective amount” or “therapeutically effective amount” may be sufficient to induce mitochondrial biogenesis locally. The “effective amount” or “therapeutically effective amount” may be sufficient to induce mitochondrial biogenesis systemically.

[0076] In some embodiments, the “effective amount” or “therapeutically effective amount” in

[0077] 30 the context of the disclosure decreases an inflammatory phenotype, increases expression of mitochondrial oxidative phosphorylation complexes, increases stability of mitochondrial PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0078] Docket No. Y20Q8-7007WO oxidative phosphorylation complexes, alters, e.g., decreases expression of at least one gene selected from the group consisting of: NF-KB. COX-2, IXF-fiE CCE5, MMP1, MMP2, MMP9, MMP13, IGF1R, VEGF, and MRPS5, alters, e.g., increases expression of at least one gene selected from the group consisting of: TIMP1 KLOTHO, COL1A1, MTCO2, TFAM, and VDAC,

[0079] 5 activates a gene associated with mitochondrial health and activity, e.g., FGF2, FGFR1, COX7A1, PDK4, FAM 173 A. MRPL12, and WNT11 , increases mtDNA copy number or concentration and / or increases expression of at least one protein selected from PGC-la, TFAM, NRF-1, and COXII.

[0080] In some embodiments, the “effective amount” or “therapeutically effective amount” in

[0081] 10 the context of the disclosure increases mtDNA copy number or concentration by at least 5%, for example, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%. In each of the foregoing, when a reduction or increase is specified, such reduction or increase may be determined with respect to a subject or non-human animal that has not been treated with a compound or composition of the disclosure and that is suffering from a disease or condition described herein.

[0082] In some embodiments, the “effective amount” or “therapeutically effective amount” in the context of the disclosure prevents incidence of an inflammatory phenotype, prevents a

[0083] 20 decrease in expression of mitochondrial oxidative phosphorylation complexes, prevents a decrease in stability of mitochondrial oxidative phosphorylation complexes, prevents an increase in expression of at least one gene selected from the group consisting of: NF-KB, COX-2, INF- / 31, CCL5, MMP1, MMP2, MMP9, MMP13, IGF1R, VEGF, and MRPS5, prevents a decrease in expression of at least one gene selected from the group consisting of: TIMP1, KLOTHO,

[0084] 25 COL1A1, MTCO2, TFAM, and VDAC, prevents a deactivation of a gene associated with mitochondrial health and activity, e.g., FGF2, FGFR1, COX7A1, PDK4, FAM173A, MRPL12, and WNT11, prevents a decrease in mtDNA copy number or concentration, and / or prevents a decrease in expression of at least one protein selected from PGC-la, TFAM, NRF-1, and COXII.

[0085] As used herein, the term “excipient” means a substance formulated alongside the active

[0086] 30 ingredient of a composition included for purposes such as, but not limited to, long-term stabilization, bulking up solid formulations that contain potent active ingredients in small PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0087] Docket No. Y2008-7007WO amounts (thus often referred to as bulking agents, fillers, or diluents), or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerns such as by

[0088] 5 facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation over the expected shelf life. The excipient may be a pharmaceutically acceptable excipient. The excipient may be a cosmetically acceptable excipient. Examples of suitable excipients are described in “Remington’s Pharmaceutical Sciences” by E. W. Martin.

[0089] 10 As used herein, the term “in need of’ (such as in the phrase “in need of treatment”) refers to a judgment made by a healthcare professional that a subject requires or will benefit from administration of a compound of the disclosure. This judgment is made based on a variety of factors that are in the realm of a healthcare professional’s expertise, such as, but not limited to, the knowledge that the subject is ill, or will be ill, as the result of a disease or condition that is treatable by a method or drug composition of the disclosure.

[0090] As used herein, the term “pharmaceutically acceptable” refers to a compound that is compatible with the other ingredients of a composition and not deleterious to the subject receiving the compound or composition. In some embodiments, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or

[0091] 20 listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.

[0092] As used herein, the term “cosmetically acceptable” refers to a compound that is compatible with the other cosmetic ingredients of a composition and not deleterious to the subject receiving the compound or composition. A cosmetically acceptable composition or

[0093] 25 compound may be pharmaceutically acceptable. However, a cosmetically acceptable composition or compound need not be pharmaceutically acceptable.

[0094] As used herein, the term “pharmaceutically acceptable form” is meant to include known forms of a compound of the disclosure that may be administered to a subject, including, but not limited to, solvates, hydrates, prodrugs, isomorphs, polymorphs, pseudomorphs, neutral forms

[0095] 30 and salt forms of a compound of the disclosure. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0096] Docket No. Y2008-7007WO

[0097] As used herein, the term “pharmaceutically acceptable salt” refers to physiologically and pharmaceutically acceptable salts of the compounds of the invention: i.e., salts that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects to the compounds disclosed. For oligonucleotides, exemplary pharmaceutically

[0098] 5 acceptable salts include but are not limited to (a) salts formed with cations such as sodium, potassium, ammonium, magnesium, calcium, polyamines such as spermine and spermidine and the like; (b) acid addition salts formed with inorganic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; (c) salts formed with organic acids such as, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic

[0099] 10 acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p- toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (d) salts formed from elemental anions such as chlorine, bromine, and iodine.

[0100] As used herein, the term “pharmaceutical composition” refers to a mixture of one or more of the compounds of the disclosure, with other components, such as, but not limited to, pharmaceutically acceptable carriers and / or excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound of disclosure.

[0101] In some embodiments, a “cosmetically acceptable” excipient refers to a cosmetically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or

[0102] 20 encapsulating material. In some embodiments, each excipient is cosmetically acceptable in the sense of being compatible with the other ingredients of a cosmetic formulation, and suitable for use in contact with the tissue or organ of humans and animals without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0103] 25 As used herein, the term “solvate” means a compound of the disclosure, or a pharmaceutically acceptable salt thereof, wherein one or more molecules of a suitable solvent are incorporated in the crystal lattice. A suitable solvent is physiologically tolerable at the dosage administered. Examples of suitable solvents are ethanol, water and the like. When water is the solvent, the molecule may be referred to as a “hydrate.”

[0104] 30 As used herein, the terms “subject” or “patient” include all members of the animal kingdom including, but not limited to, vertebrates, mammals, animals (e.g., cats, dogs, horses, PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0105] Docket No. Y2008-7007WD swine, rodents, etc.) and humans. In certain embodiments, the subject is a human. In certain embodiments, the subject is an animal, e.g., a research animal, e.g., a mouse, a rat.

[0106] As used herein, the terms “similarity” or “similarity score” when used with respect to a compound refers to a degree of similarity between two or more compounds in chemical

[0107] 5 structure, chemical function, and / or one or more chemical properties. The compounds may be isolated from the same or different sources, e.g., isolated from the same or different extracts. One or more of the compounds may be synthetic. In certain embodiments, a compound having a high similarity score as another compound may be a chemically modified version of the other compound. The similarity score may be quantified by augmenting data generated by a deep

[0108] 10 neural network trained to model a plurality of chemical reactions for any given compound. The data may be augmented by a multi-dimensional vector defining a matrix of properties of the compound or a chemical reaction involving the compound to generate an embedding score for the compound. The embedding score for two or more compounds may be compared to generate the similarity score between the two or more compounds.

[0109] All patent applications, patents, and printed publications cited herein are incorporated herein by reference in their entireties, for all purposes.

[0110] Impact of Mitochondrial Function on Intrinsic and Extrinsic Aging

[0111] Mitochondrial dysfunction is implicated in both intrinsic and extrinsic aging. The

[0112] 20 presence of skin wrinkles, acanthosis, epidermal hyperplasia with hyperkeratosis, and marked inflammatory infiltrate in the skin has been observed in mtDNA-depleter mice (an animal model exhibiting a decrease in mtDNA copy number and / or concentration) and represent characteristics similar to the extrinsic aging of skin in humans. Furthermore, the changes in expression of intrinsic aging-associated genetic markers support intrinsic mechanisms underlying the

[0113] 25 phenotypic changes observed in mtDNA-depleter mice.

[0114] Loss of collagen fibers is reported to underlie skin wrinkles. A tight balance between the proteolytic matrix metalloprotease (MMP) enzymes and their tissue- specific inhibitor tissue inhibitor metalloproteinase- 1 (TIMP1) is essential to maintain the collagen fiber content in the skin. Expression of MMPs is altered in the aged skin. Consistent with these reports, the skin of

[0115] 30 mtDNA-depleter mice showed increased expression of MMPs and decreased expression of TIMP1, indicating loss of balance contributing to the development of skin wrinkles. Repletion of PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0116] Docket No. Y2008-7007WD mtDNA content (increase in mtDNA copy number and / or concentration) restored MMP expression leading to a reversal of wrinkled skin and hair loss. Thus, mitochondria have been shown to be regulators of aging. This observation is surprising and suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the

[0117] 5 restoration of normal skin and hair phenotype. mtDNA stress triggers inflammatory response. Inflammation also underlies aging and age-related diseases. Increased levels of markers of inflammation in the mtDNA-depleter mice indicate an activated immune response in the skin of mtDNA-depleter mice. Increased expression of NF-KB, a master regulator of the inflammatory response upon mtDNA depletion

[0118] 10 and its reduced expression after the restoration of mtDNA content suggests that NF-KB signaling is a critical mechanism contributing to the skin and hair follicle pathologies observed in mtDNA- depleter mice. Furthermore, a unique feature of proteins encoded by mtDNA is / V-formyl- methionine at the N terminus. N-formylated peptides when present in the extracellular space are known to act as mitochondrial damage-associated molecular patterns and activate neutrophils or activate keratinocyte-intrinsic responses resulting in the recruitment of immune cells.

[0119] While previous animal models have shown alternations in mtDNA homeostasis and / or mtDNA copy number or concentration using a localized approach (for example targeting only a specific cell type), other animal models have been shown to provide for the global and targeted disruption of mtDNA homeostasis and / or mtDNA copy number of concentration in a controlled

[0120] 20 manner. Using such an animal model, whole plant extracts were previously identified that are effective in treating diseases and conditions relating to mitochondrial dysfunction in a background of significant mtDNA depletion. In addition, the such extracts reverse the physiological and phenotypic effects mediated by mitochondrial dysfunction. Exemplary physiological and phenotypic effects of intrinsic and extrinsic aging reversed include a decrease

[0121] 25 in skin wrinkles, a decrease in hair loss, an increase in hair follicles in growth phase, decreased inflammatory gene expression, decreased inflammatory infiltrate in the skin and hair follicles, and increased collagen content in the skin.

[0122] Further, due to the short lifespan of the animal models of the conventional practice, prior studies were prevented from determining the effect of mitochondrial dysfunction on the aging

[0123] 30 process and such studies did not observe the appearance of many of the physiological and phenotypic changes related to mitochondrial dysfunction. As such, the conventional practice was PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0124] Docket No. Y2008-7007WG not capable of identifying compounds effective to treat such physiological and phenotypic changes related to mitochondrial dysfunction reported herein.

[0125] The foregoing limitations make identifying effective treatments for the skin diseases and conditions where mitochondrial dysfunction is at issue difficult. In addition, due to aberrations in

[0126] 5 normal epithelial development and hair follicle morphogenesis in current models, the issue of false positive and false negative results is high. An inducible non-human animal model expressing a mutated POLG1 polypeptide (such as, but not limited to, a POLG1 polypeptide expressing a dominant-negative (DN) mutation) that induces mitochondrial dysfunction (for example by depletion of mtDNA) in the whole animal or selected cells / tissues was previously

[0127] 10 disclosed in International Application Publication No. WO / 2022 / 198066, titled “COMPOSITIONS AND METHODS FOR IMPROVING MITOCHONDRIAL FUNCTION,” which is herein incorporated by reference in its entirety for all purposes.

[0128] The non-human animal model was used to identify whole extracts effective in treating mtDNA-related diseases and conditions. Further in vitro and human studies have been performed to identify specific compounds, such as isolated compounds, and formulations, such as amorphous silica particle formulations, that are effective in treating mtDNA-related diseases and conditions.

[0129] Methods of Treatment

[0130] 20 The disclosure provides compounds and compositions effective to treat or prevent diseases and conditions related to mitochondrial dysfunction, including mtDNA depletion. In certain embodiments, the diseases and conditions related to mitochondrial dysfunction, including mtDNA depletion, include treating or preventing an aging-associated chronic disease or condition, improving or preventing a decrease in energy levels and vitality treating or preventing

[0131] 25 a characteristic of aging, and / or treating, improving, or preventing skin diseases or conditions. While not being bound to any particular theory, such compounds may exert the observed effects through inhibiting a decrease in mitochondrial DNA copy number or concentration, inhibiting depletion of mitochondrial DNA, inhibiting degradation of mitochondrial DNA, contributing to an increase in mitochondrial DNA copy number or concentration, repleting mitochondrial DNA,

[0132] 30 and / or promoting increased activity of mitochondrial DNA.

[0133] In one embodiment, the disclosure provides a method for treating or preventing PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0134] Docket No. Y2008-7007WO mitochondrial dysfunction in a subject, the method comprising administering to said subject an effective amount of a preparation of the disclosure, or a pharmaceutically acceptable form thereof.

[0135] In one embodiment, the disclosure provides a method for treating or preventing a disease

[0136] 5 or condition associated with mitochondrial dysfunction or a symptom thereof in a subject, the method comprising administering to said subject an effective amount of a preparation of the disclosure, or a pharmaceutically acceptable form thereof.

[0137] In one embodiment, the disclosure provides a method of treating a wound or promoting wound healing in a subject.

[0138] 10 In one embodiment, the disclosure provides a method of treating a scar or scarring in a subject. In one embodiment, the disclosure provides a method of diminishing appearance of a scar or scarring in a subject.

[0139] In some embodiments, the wound is an open wound. For example, the open wound may be a penetrating wound such as a cut, scrape, bruise, or scratch, a puncture wound, a surgical wound, an environmental wound (e.g. thermal, chemical or electric bum), a bite (e.g. animal), a sting or a high velocity wound (e.g. gunshot wound). The open wound may be a blunt force trauma wound such as an abrasion, laceration, puncture or skin tear (abulsion).

[0140] In some embodiments, the wound is a closed wound. For example, the closed wound may be a contusion, a blister, a seroma, a hematoma or a crush injury.

[0141] 20 In some embodiments, the scar or scarring is a fine line, surface line, pitted hole, abnormal overgrowth of tissue or deep furrow.

[0142] In some embodiments, the scar or scarring is associated with a sunburn, bed sore, wound, inflammatory lesion, or burn.

[0143] In some embodiments, the wound may be an ulcer, e.g. a pressure ulcer, a venous ulcer,

[0144] 25 an arterial ulcer, a diabetic ulcer or a neuropathic ulcer.

[0145] In one embodiment, the disclosure provides a method for improving or preventing a skin disease or condition in a subject, the method comprising administering to said subject an effective amount of a preparation of the disclosure, or a pharmaceutically acceptable form thereof.

[0146] 30 In any of the methods, and any of the aspects of the foregoing, the subject animal is a vertebrate. In any of the methods, and any aspects of the foregoing, the subject is a mammal. In PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0147] Docket No. Y2008-7007WD any of the methods, and any aspects of the foregoing, the subject is a human. In any of the methods, and any of aspects of the foregoing, the subject is a non-human mammal, e.g., a rodent, e.g., a mouse.

[0148] In some aspects, the subject may be female. In some aspects, the subject may be male.

[0149] 5 The subject may be characterized as one of the following ethnicity / race: Asian, Black or African American, Hispanic or Latino, white, or multi-racial. The subject may have a Fitzpatrick Scale score of from I to IV. The subject may be of an age less than 1, or between 1-5, 5-10, 10-20, 20- 30, 30-40, 40-50, 50-60, or over 60 years.

[0150] In any of the methods, and any aspects of the foregoing, the compound or the extract is

[0151] 10 administered in an effective amount. Suitable effective amounts are described in more detail herein. In any of the methods, and any of the aspects of the foregoing, the compound or the extract is administered in a therapeutically effective amount. In any of the methods, and any aspects of the foregoing, the administering step may comprise administering a single dose of a compound or extract according to a course of treatment (where the dose may contain an effective amount). In any of the methods, and any aspects of the foregoing, the administering step may comprise administering more than one dose of a compound or extract according to a course of treatment (where one or more doses may contain an effective amount). The amount of a compound or extract in each dose administered during a course of treatment is not required to be the same. For example, the administering step may comprise administering at least one loading

[0152] 20 dose and at least one maintenance dose during a course of treatment. Dosing is described in more detail herein.

[0153] The compound may be administered as a prophylactic treatment. The compound may be administered as a cosmetic or therapeutic treatment.

[0154] The compounds disclosed herein may be used in various applications, e.g., cosmetic

[0155] 25 and / or therapeutic applications. The compounds may be administered in an effective amount for an intended use, e.g., a cosmetic or a therapeutic application. In some embodiments, a composition may comprise a concentration or amount, e.g., an effective amount, of the compound sufficient to have a desired cosmetic effect. In some embodiments, a composition may comprise a concentration or amount, e.g., an effective amount, of the compound sufficient

[0156] 30 to have a desired therapeutic effect.

[0157] An amount and / or frequency of administration may be sufficient to induce mitochondrial PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0158] Docket No. Y2008-7007WO biogenesis. An amount and / or a frequency of administration may be sufficient to treat, inhibit, or prevent the progression of at least one of mitochondrial dysfunction, a disease or condition associated with mitochondrial dysfunction or a symptom thereof, an aging- associated chronic condition associated with mitochondrial dysfunction or a symptom thereof, and / or a decrease in

[0159] 5 energy level or vitality. An amount and / or frequency of administration may be sufficient to modify a score of a parameter on a qualitative scale, as graded by the subject or a clinical grader. The qualitative scale may comprise the following categories: none (best possible condition), mild, moderate, severe (worst possible condition). The qualitative scale may refer to perceived or actual energy levels and / or vitality.

[0160] 10 In some aspects, administering an effective amount of the compound may limit or inhibit at least one of mitochondrial dysfunction, a disease or condition associated with mitochondrial dysfunction or a symptom thereof, an aging-associated chronic condition associated with mitochondrial dysfunction or a symptom thereof, and / or a decrease in energy level or vitality. For example, the effective amount of the compound may slow progression of the at least one of mitochondrial dysfunction, a disease or condition associated with mitochondrial dysfunction or a symptom thereof, an aging-associated chronic condition associated with mitochondrial dysfunction or a symptom thereof, and / or a decrease in energy level or vitality. In some embodiments, administering an effective amount of the compound may promote mitochondrial biogenesis, mitochondrial function, and / or an increase in energy level or vitality.

[0161] 20 In some aspects, the compound may be administered prior to onset of the disease or condition in the subject. The compound may be administered during incidence of the disease or condition in the subject. The compound may be administered subsequent to at least partial reduction of the disease or condition in the subject. The compound may be administered in response to a trigger or warning sign of a mitochondrial dysfunction or aging-associated

[0162] 25 condition, e.g., aging, premature aging, habitual sleep conditions, habitual sleep position, habitual facial expression, weight loss, ultraviolet (UV) light exposure, treatment with a chemical or therapeutic agent, e.g., chemotherapy and / or radiation therapy, smoking, dehydration, or immersion. The subject may be predisposed for a mitochondrial dysfunction condition, e.g., based on age, race, skin type, eye color, habit, or heredity. A method may further

[0163] 30 comprise determining whether the subject is in need of treatment. The composition comprising the compound may additionally comprise a moisturizing agent, deodorizing agent, scent, PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0164] Docket No. Y2008-7007WG colorant, insect repellant, cleansing agent, or UV-blocking agent. The composition may include microspheres or microcapsules.

[0165] The subject may be characterized as having normal mitochondrial function. The subject may be characterized as having reduced mitochondrial function. The subject may be

[0166] 5 characterized as experiencing premature aging or a symptom of premature aging. In certain embodiments, the subject may be characterized by one or more of: an inflammatory phenotype in the skin, a change in mitochondrial protein expression, reduced expression of mitochondrial oxidative phosphorylation complexes, reduced stability of mitochondrial oxidative phosphorylation complexes, a decrease in collagen content of the skin, increased epidermal

[0167] 10 thickness, increased epidermal hyperplasia, acanthosis, hyperkeratosis, increased expression of at least one gene selected from the group consisting of: NF-KB, COX-2, INF-pi, CCL5, MMP1, MMP2, MMP9, MMP13, IGF1R, VEGF, and MRPS5, decreased expression of at least one of gene selected from the ground consisting of TIMP1, KLOTHO, COL1A1, MTC02, TFAM, and VDAC, and increased inflammatory infiltrate in skin. The subject may be characterized as having decreased expression at least one protein selected from PGC-la, TFAM, NRF-1, and COXII.

[0168] Methods of Treating Wounds and / or Scars; Methods of Promoting Wound and / or Scar Healing

[0169] 20 In accordance with one or more aspects, a method of treating skin of a subject is disclosed. The method may comprise administering to said subject an effective amount of a preparation of the disclosure, or a pharmaceutically acceptable form thereof, thereby treating the skin of the subject.

[0170] The subject may be diagnosed with a scar or scarring. In some aspects, at least one scar

[0171] 25 may comprise a fine line, surface line, pitted hole, abnormal overgrowth of tissue or deep furrow. In some aspects, the scar may be associated with a sunbum, bed sore, wound, inflammatory lesion, or burn. An amount and / or a frequency of administration may be sufficient to decrease an appearance, e.g., severity, of scarring in the subject. An amount and / or a frequency of administration may be sufficient to decrease a width of scarring in the subject. An amount and / or

[0172] 30 a frequency of administration may be sufficient to decrease a length of scarring in the subject. An amount and / or a frequency of administration may be sufficient to decrease a depth of scarring PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0173] Docket No. Y2008-7007WO in the subject. An amount and / or a frequency of administration may be sufficient to promote scar fading. An amount and / or frequency of administration may be sufficient to inhibit or prevent the progression of a scar.

[0174] The subject may be diagnosed with a wound. An amount and / or a frequency of

[0175] 5 administration may be sufficient to treat the wound and / or promote wound healing. An amount and / or frequency of administration may be sufficient to inhibit or prevent the progression of a wound. An amount and / or frequency of administration may be sufficient to promote wound closure, e.g. reduce one or more of a wound width, length and depth.

[0176] An amount and / or frequency of administration may be sufficient to promote visual and / or

[0177] 10 tactile smoothness of skin associated with a wound or scar in a subject.

[0178] In some aspects, treating a wound and / or promoting wound healing may address one or more symptoms or side effects of the wound, e.g. scarring, pain, swelling, bleeding, soreness, redness, oozing, pus or infection.

[0179] In some aspects, a desired degree of wound closure and / or scar diminishment (fading) is achieved.

[0180] In some aspects, the composition is administered in connection with a second wound treatment protocol.

[0181] In some aspects, the composition is administered in connection with a second scar treatment protocol.

[0182] 20 In some aspects, the composition may be applied to a wound dressing (e.g. bandage) and then the bandage may, in turn, be applied to the wound or scar.

[0183] In some aspects, a wound dressing (e.g. bandage) may be imbued with the composition and applied to the wound or scar.

[0184] In some aspects, a kit may include a wound dressing (e.g. bandage) and a source of the

[0185] 25 composition for treatment of a wound or a scar as described herein.

[0186] An amount and / or frequency of administration may be sufficient to modify or reduce a score of a parameter on the Griffiths’ 10-point scale, for example, as graded by the subject or a clinical grader, according to the following medical definitions (with half-point scores assigned as necessary to accurately describe the skin condition):

[0187] 30 0 = none (best possible condition)

[0188] 1 to 3 = mild PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0189] Docket No. Y2008-7007WO

[0190] 4 to 6 = moderate

[0191] 7 to 9 = severe (worst possible condition).

[0192] Exemplary parameters include oily appearance (shine and feel) with 0 = no shine, flat / matte appearance and 9 = strong shiny / oily appearance; pore appearance with 0 = small,

[0193] 5 tight, barely perceptible pores and 9 = large, noticeable pores; radiance with 0 = radiant, luminous appearance and 9 = dull / matte and or sallow appearance; blotchiness with 0 = no blotchiness / clear and 9 = blotchy skin appearance; skin tone (color) evenness with 0 = even, healthy skin color and 9 = uneven, discolored appearance; visual smoothness with 0 = smooth, even looking skin texture and 9 = rough, uneven looking skin texture; and tactile smoothness

[0194] 10 with 0 = smooth, even feeling skin texture and 9 = rough, uneven feeling skin texture. The modification or reduction of score may be by 9 points, 8 points, 7 points, 6 points, 5 points, 4 points, 3 points, 2 points, or 1 point.

[0195] In some aspects, administering an effective amount of the compound may limit or inhibit injury to skin integrity of a cutaneous layer of skin in the subject. Administering an effective amount of the compound may prevent an undesired topographical change of the cutaneous layer of skin in the subject. Administering an effective amount of the compound may slow progression from a first topographical, structural, or matrix profile to a second topographical, structural, or matrix profile associated with the cutaneous layer of skin in the subject. In some aspects, the cutaneous layer may pertain to an epidermis (e.g. stratum comeum, stratum lucidum, stratum

[0196] 20 granulosum, stratum spinosum, or stratum basalis), a basement membrane, a dermal-epidermal junction, a dermis (e.g. papillary dermis, reticular dermis, or any vasculature comprising the dermis), or subcutis (e.g. subcutaneous fat layer) of the subject.

[0197] In some aspects, the skin of the subject may be substantially non-diseased. The skin of the subject may be substantially uninjured. The skin of the subject may be substantially free of

[0198] 25 inflammatory lesions. The skin of the subject may be substantially free of a mild to severe crack, fissure, or wrinkle. The skin of the subject may be substantially free of a mild to severe scar (e.g., scar relating to sunburn, bed sore, wound, inflammatory lesion, or burn) or stretch mark. The skin of the subject may be substantially free of a mild to severe sun spot, dark patch, or age spot. The skin of the subject may be substantially free of a mild to severe heloma, skin

[0199] 30 thickening, skin tag, or keloid scar. The skin of the subject may be substantially free of an appearance of a varicose vein or a spider vein. The skin of the subject may be substantially free PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0200] Docket No. Y2008-7007WO of a mild to severe appearance of pores. The skin of the subject may be substantially free of mild to severe cellulitis.

[0201] Preparations Including Extracts and / or Constituents Thereof and Similar Compounds

[0202] 5 The methods disclosed herein may comprise administering to said subject an effective amount of a promoter of mtDNA. The methods disclosed herein may comprise administering to said subject an effective amount of an inhibitor of mtDNA.

[0203] Certain extracts have been identified as comprising one or more compounds that promote and / or inhibit mtDNA. Emblica extract, fucus extract, and chebula extract are described herein.

[0204] 10 It should be understood that similar extracts, in particular, extracts comprising one or more compounds disclosed herein, compounds that are constituents of an extract disclosed herein, optionally isolated from an extract disclosed herein or synthetic compounds, and / or compounds having a similarity score of at least 95% with one or more compounds disclosed herein, are expected to provide similar mtDNA promotion and / or inhibition. Accordingly, other extracts, compounds derived from, constituents of, or purified from other extracts, and compounds having a similarity score of at least 95% with compounds derived from, constituents of, or purified from other extracts are within the scope of the disclosure.

[0205] Exemplary extracts include extracts of extract of Emblica officinalis, Terminilia chebula, Terminalia arborea, or Eumnitzera racemose. Other exemplary extracts include extracts of

[0206] 20 Fucus vesiculosus, Fucus serratus, Fucus, spiralis, Fucus guiryi, Polygonum aviculare extract, Physalis gngulata extract, Dunaliella salina extract, Camellia sinensis leaf extract, Tremella fuciformis sporocarp extract, Alteromonas ferment extract, Theobroma cacao (cocoa) seed extract, Vitis vinifera (grape) flower cell extract, Mirabilis jalapa callus extract, Alteromonas ferment extract, and Vibrio alginolyticus ferment filtrate.

[0207] 25 Accordingly, the compounds described herein may be derived from, purified from, or isolated from the extract. The compounds described herein may be derived from, purified from, or isolated from a source other than the extract. A compound constituent of an extract may be derived from, purified from, or isolated from another natural or artificial source. In other embodiments, the compounds described herein may be synthetic. For instance, the compounds of

[0208] 30 the disclosure may be synthesized in a laboratory, manufacturing, or other setting. The above applies to compounds contained in or constituents of an extract, as well as compounds having a PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0209] Docket No. Y2008-7007WD high similarity score thereof.

[0210] The methods disclosed herein may comprise administering to said subject an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof.

[0211] The methods disclosed herein may comprise administering to said subject an effective

[0212] 5 amount of a compound derived from, constituent of, or purified from an emblica extract, or a pharmaceutically acceptable form thereof, or a compound having a similarity score of at least 95% with the compound derived from, constituent of, or purified from an emblica extract, or a pharmaceutically acceptable form thereof.

[0213] The methods disclosed herein may comprise administering to said subject an effective

[0214] 10 amount of a fucus extract, or a pharmaceutically acceptable form thereof.

[0215] The methods disclosed herein may comprise administering to said subject an effective amount of a compound derived from, constituent of, or purified from a fucus extract, or a pharmaceutically acceptable form thereof, or a compound having a similarity score of at least 95% with the compound derived from, constituent of, or purified from a fucus extract, or a pharmaceutically acceptable form thereof.

[0216] The methods disclosed herein may comprise administering to said subject an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof.

[0217] The methods disclosed herein may comprise administering to said subject an effective amount of a compound derived from, constituent of, or purified from a chebula extract, or a

[0218] 20 pharmaceutically acceptable form thereof, or a compound having a similarity score of at least 95% with the compound derived from, constituent of, or purified from a chebula extract, or a pharmaceutically acceptable form thereof.

[0219] The disclosure may generally be related to extracts and compounds derived from, constituents of, or purified from extracts. It should be understood that compounds having a

[0220] 25 similarity score of at least 95%, for example, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9%, at least 99.95%, at least 99.99%, at least 99.995%, or at least 99.999% with a compound derived from, constituents of, or purified from the extract may be utilized in any composition as described herein.

[0221] Without wishing to be bound by theory, it is believed the administration of the

[0222] 30 compositions disclosed herein may involve inhibition of a decrease in mitochondrial DNA copy number or concentration, inhibition of a depletion of mitochondrial DNA, inhibition of a PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0223] Docket No. Y20Q8-7007WO degradation of mitochondrial DNA, or a combination of the foregoing. Without wishing to be bound by theory, it is believed the administration of the compositions disclosed herein may involve inducing mitochondrial biogenesis and / or improving mitochondrial function.

[0224] In accordance with certain aspects, administration of the compositions disclosed herein

[0225] 5 may involve an increase in expression of mitochondrial oxidative phosphorylation complexes, an increase in stability of mitochondrial oxidative phosphorylation complexes, and / or an increase in expression of at least one protein selected from PGC-la, TFAM, NRF-1, and COXII.

[0226] In certain aspects, the emblica extract is derived from Emblica officinalis (also known as Phyllanthus emblica, Indian gooseberry, or by its Hindi name Amla). Such an extract from

[0227] 10 Emblica officinalis may be derived from any portion of the plant as desired. For example, the extract may be derived from the stem portion, the fruit portion, or both the stem portion and the fruit portion of Emblica officinalis. In preparing such an extract, the Emblica officinalis may be provided in a powdered from and extracted using chemical solvents known in the art, such as, but not limited to, aqueous ethyl acetate ethanol, and methanol. Other solvents or excipients disclosed herein may be used. In certain exemplary embodiments, the chemical solvent may be methanol.

[0228] In certain aspects, the effective amount of an emblica extract or a compound derived from, constituent of, or purified from and emblica extract is from 1 to 100 mg such as 1 mg, 5, mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg.

[0229] 20 In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a breakdown product of a tannin, wherein the emblica extract is optionally as described above. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is an ellagitannin. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is emblicanin A, emblicanin B, punigluconin,

[0230] 25 pedunculagin, chebulagic acid, gallic acid, chebulic acid, kaempferol, punicalagin, and / or chebulinic acid.

[0231] In certain aspects, the compound is an ellagitannin or a compound having a similarity score of at least 95% with an ellagitannin. Exemplary ellagitannins and compounds having a high similarity score with such ellagitannins are listed in Table 1. Other compounds having a

[0232] 30 high similarity score with ellagitannins are within the scope of the disclosure. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0233] Docket No. Y2008-7007WQ

[0234] Table 1: Ellagitannins and compounds having a high similarity score with ellagitannins PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0235] Docket No. Y2008-7007WQ

[0236] In certain aspects, the compound is chebulinic acid or a compound having a similarity score of at least 95% with chebulinic acid (formula I below). Exemplary compounds having a high similarity score with chebulinic acid are listed in Table 2. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0237] Docket No. Y2008-7007WQ

[0238] Formula I (chebulinic acid):

[0239] 5 Table 2: Compounds having a high similarity score with chebulinic acid. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0240] Docket No. Y2008-7007WQ PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0241] Docket No. Y2008-7007WQ PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0242] Docket No. Y2008-7007WQ PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0243] Docket No. Y2008-7007WQ

[0244] In certain aspects, the compound is chebulagic acid or a compound having a similarity score of at least 95% with chebulagic acid. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0245] Docket No. Y2008-7007WO

[0246] In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O- (C1-C5 alkyl) or O-(Ci-C5 alkenyl) groups. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a benzoic acid substituted with 1 to 3

[0247] 5 hydroxy groups and optionally 1 to 2 O-(Ci-Cs alkyl) or O-(Ci-Cs alkenyl) groups.

[0248] In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a benzene substituted with -CH=CH-(CH2)a-C(0)0H, wherein a is 0

[0249] 10 to 5, and 1 to 3 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0, and 1 to 3 hydroxy groups.

[0250] In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is gallic acid, vanillic acid, chlorogenic acid, caffeic acid, syringic acid, coumaric aid, quercetin, emblicanin A, emblicanin B, punigluconin, pedunculagin, punicafolin, phyllanemblin, kaempferol, ellagic acid, chebulinic acid, chebulagic acid, punicalagin, or a metabolite of any of the foregoing, or a compound having a similarity score of at least 95% with any of the foregoing. In certain aspects, the compound derived from, constituent of, or purified from an emblica extract is ascorbic acid (vitamin C) or citric acid, a metabollite thereof or a

[0251] 20 compound having a similarity score of at least 95% with ascorbic acid (vitamin C) or citric acid.

[0252] In accordance with certain embodiments, the composition may comprise an emblica extract fortified with one or more compound that is a constituent of an emblica extract. The compound constituent of the emblica extract or combination of compounds constituents of the emblica extract may be isolated. The compound constituent of the emblica extract or

[0253] 25 combination of compounds constituents of the emblica extract may be purified, e.g., at least 50% purified, at least 60% purified, at least 70% purified, at least 80% purified, at least 85% purified, at least 90% purified, at least 95% purified, at least 98% purified, at least 99% purified, at least 99.9% purified, at least 99.99% purified, or at least 100% purified.

[0254] In certain aspects, the effective amount of an active agent of the composition, is from 1 to

[0255] 30 100 mg of the, such as 1 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of the compound. In certain embodiments, the preparation may be formulated PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0256] Docket No. Y2008-7007WO to have a concentration of 0.25 to 100 pM of the compound or an active agent of the composition, for example, 0.25 to 0.5 pM, 0.5 to 1 pM, 1 to 2.5 pM, 2.5 to 5 pM45 to 10 pM, 10 to 20 pM, 20 to 50 pM, or 50 to 100 pM of the compound or an active agent of the composition.

[0257] In certain aspects, the fucus extract is derived from Fucus vesiculosus, Fucus serratus,

[0258] 5 Fucus, spiralis, or Fucus guiryi. In certain aspects, the fucus extract is derived from Fucus vesiculosus. Such an extract may be derived from any portion of the algae as desired, hi preparing such an extract, the Fucus vesiculosus, Fucus serratus, Fucus, spiralis, or Fucus guiryi may be provided in a powdered from and extracted using chemical solvents known in the art, such as, but not limited to, aqueous ethyl acetate ethanol, and methanol. Other solvents or

[0259] 10 excipients disclosed herein may be used. In certain exemplary embodiments, the chemical solvent may be methanol.

[0260] In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is a breakdown product of a tannin. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is an ellagitannin. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is fucoidan.

[0261] In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O-(Ci-Cs alkyl) or O-(Ci-Cs alkenyl) groups. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is a benzoic acid substituted with 1 to 3 hydroxy groups and

[0262] 20 optionally 1 to 2 O-(Ci-Cs alkyl) or O-(Ci-Cs alkenyl) groups.

[0263] In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to

[0264] 25 3 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0, and 1 to 3 hydroxy groups.

[0265] In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is gallic acid, vanillic acid, chlorogenic acid, caffeic acid, syringic acid, coumaric aid, or

[0266] 30 a metabolite of any of the foregoing. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0267] Docket No. Y2008-7007WO

[0268] In certain aspects, the active agent in the composition is gallic acid or a compound having a similarity score of at least 95% with gallic acid. In certain aspects, the active agent in the composition is chebulinic acid or a compound having a similarity score of at least 95% with chebulinic acid (see, e.g., Table 2 above). The active agent may be or comprise an ellagitannin or

[0269] 5 a compound having a similarity score of at least 95% with an ellagitannin (see, e.g., Table 1 above). The active agent may be or comprise chebulagic acid or a compound having a similarity score of at least 95% with chebulagic acid. The active agent may be or comprise fucoidan or a compound having a similarity score of at least 95% with fucoidan.

[0270] In accordance with certain embodiments, the composition may comprise a fucus extract

[0271] 10 fortified with one or more compound that is a constituent of a fucus extract. The compound constituent of the fucus extract or combination of compounds constituents of the fucus extract may be isolated. The compound constituent of a fucus extract or combination of compounds constituents of a fucus extract may be purified, e.g., at least 50% purified, at least 60% purified, at least 70% purified, at least 80% purified, at least 85% purified, at least 90% purified, at least 95% purified, at least 98% purified, at least 99% purified, at least 99.9% purified, at least 99.99% purified, or at least 100% purified.

[0272] In certain aspects, the chebula extract is derived from Terminilia chebula, Terminalia arborea, or Lumnitzera racemose. In certain aspects, the chebula extract is derived from Termibnilia chebula. Such an extract may be derived from any portion of the plant as desired. In

[0273] 20 preparing such an extract, the Terminilia chebula, Terminalia arborea, or Lumnitzera racemose may be provided in a powdered from and extracted using chemical solvents known in the art, such as, but not limited to, aqueous ethyl acetate ethanol, and methanol. Other solvents or excipients disclosed herein may be used, In certain exemplary embodiments, the chemical solvent may be methanol.

[0274] 25 In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is a breakdown product of a tannin. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is an ellagitannin. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is chebulinic acid. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is

[0275] 30 chebulagic acid. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is chebulic acid. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0276] Docket No. Y2008-7007WO

[0277] In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O-(Ci-Cs alkyl) or O-(Ci-Cs alkenyl) groups. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is a benzoic acid substituted with 1 to 3 hydroxy groups

[0278] 5 and optionally 1 to 2 O-(Ci-Cs alkyl) or O-(Ci-Cs alkenyl) groups.

[0279] In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from a chebula extract a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1

[0280] 10 to 3 hydroxy groups. In certain aspects, the compound derived from, constituent of, or purified from a fucus extract a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0, and 1 to 3 hydroxy groups.

[0281] In certain aspects, the compound derived from, constituent of, or purified from a chebula extract is chebulinic acid, ellagic acid, gallic acid, tannic acid, punicalagin, chebulagic acid, or a metabolite of any of the foregoing.

[0282] In certain aspects, the compound derived from, constituent of, or purified from a fucus extract is chebulinic acid.

[0283] In certain aspects, the active agent in the composition is chebulinic acid or a compound having a similarity score of at least 95% with chebulinic acid (see, e.g., Table 2 above). The

[0284] 20 active agent may be or comprise an ellagitannin or a compound having a similarity score of at least 95% with an ellagitannin (see, e.g., Table 1 above). The active agent may be or comprise chebulagic acid or a compound having a similarity score of at least 95% with chebulagic acid. The active agent may be or comprise chebulic acid or a compound having a similarity score of at least 95% with chebulic acid.

[0285] 25 In accordance with certain embodiments, the composition may comprise a chebula extract fortified with one or more compound that is a constituent of a chebula extract. The compound constituent of the chebula extract or combination of compounds constituents of the chebula extract may be isolated. The compound constituent of a chebula extract or combination of compounds constituents of a chebula extract may be purified, e.g., at least 50% purified, at

[0286] 30 least 60% purified, at least 70% purified, at least 80% purified, at least 85% purified, at least PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0287] Docket No. Y2008-7007WD

[0288] 90% purified, at least 95% purified, at least 98% purified, at least 99% purified, at least 99.9% purified, at least 99.99% purified, or at least 100% purified.

[0289] The methods, and any of aspects of the foregoing, may comprise administering a composition comprising an effective amount of two or more of an emblica extract or a

[0290] 5 compound constituent of an emblica extract, an effective amount of a fucus extract or a compound constituent of a fucus extract, and an effective amount of a chebula extract or a compound constituent of a chebula extract. In accordance with certain embodiments, the two or more of emblica extract or compound constituent of the emblica extract, the fucus extract or compound constituent of the fucus extract, and the chebula extract or compound constituent of

[0291] 10 the chebula extract may provide synergistic effects in the treatment of the disease or condition.

[0292] The compositions disclosed herein may comprise or be fortified with one or more of: an emblica extract or compound constituent of an emblica extract, a fucus extract or compound constituent of a fucus extract, a chebula extract or a compound constituent of a chebula extract, BAMLET 10, BAMLET 50, ferulic acid, quercetin, urolithin A, pterostilbene, acadesine, embelin, EGCG, eriocitrin, gallic acid, gomsin A, lutein, luteolin, NAD, rutin, zeaxanthin, and melatonin.

[0293] To provide targeted delivery and / or improve skin penetration, the compounds of the disclosure may be formulated in a delivery carrier, for example, a nanoparticle delivery carrier. The delivery carriers disclosed herein may be selected or designed to provide enhanced skin

[0294] 20 penetration, higher stability, site specific targeting, e.g., efficiently deliver cargo inside the mitochondrial matrix, high entrapment efficiency, and / or time-controlled, e.g., delayed or sustained, release of the compounds. Properties of the delivery carrier that may be designed to effectively deliver compounds of the formulation to a target site of a subject include surface chemistry, coating, structure, size, ability to aggregate, and solubility.

[0295] 25 The compounds of the disclosure may be formulated with a functional agent, e.g., mitochondria-targeting agent. For instance, in certain embodiments, the compounds of the disclosure may be conjugated to a functional agent, such as a mitochondria-targeting agent.

[0296] The compounds of the disclosure (whether or not conjugated to a functional agent) may have an average diameter of between about 5 pm and 15 pm, for example, about 9 pm - 12 pm.

[0297] 30 In certain embodiments, methods may include reducing the average particle size of the compounds. The compounds may be reduced to an average diameter 1 nm to 5 pm, for example, PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0298] Docket No. Y2008-7007WO

[0299] 1 nm to 10 nm, 10 nm to 50 nm, 50 nm to 100 nm, 100 nm to 500 nm, 500 nm to 1 pm, 1 pm to

[0300] 2 pm, 2 pm to 3 pm, 3 pm to 4 pm, or 4 pm to 5 gm. In certain embodiments, the composition may have an average diameter of less than 5 gm, for example, less than 4 gm, less than 3 gm, less than 2 pm, or less than 1 gm. In certain embodiments, the average diameter of the

[0301] 5 compounds of the disclosure may be reduced before loading the compounds in a delivery carrier.

[0302] In some embodiments, a composition of the compounds may be granulated through milling, for example, ball milling or jet milling. Ball milling and jet milling may generally produce mostly microparticles with some submicron particles, the average dimensions and ratio of each being a result of the type of milling selected. The method may include a second

[0303] 10 granulation of such a composition. In some embodiments, dry milled particles may be wet milled to produce nanoparticles. Other methods of granulating include using a mortar and pestle and other mechanical devices.

[0304] In some embodiments, the compounds may have an average surface area of 200 - 1000 m2 / g, for example, 200 - 400 m2 / g, 400 - 600 m2 / g, 600-800 m2 / g, or 800 - 1000 m2 / g. In certain embodiments, the compounds may be porous. The compounds may have an average pore volume of 0.5 to 3.0 mL / g, for example, 0.8 to 2.4 mL / g. The compounds may have an average pore diameter of 4 - 50 nm, for example, 4 - 10 nm, 10 - 15 nm, 15 - 20 nm, or 20 - 50 nm.

[0305] The methods disclosed herein, for example, the treatment methods, and any aspects of the foregoing, may further comprise one or more of the steps: (i) identifying a subject in need or

[0306] 20 treatment; and (ii) providing a compound of the disclosure or a pharmaceutical composition comprising a compound of the disclosure.

[0307] In any of the foregoing embodiments, and any aspects of the foregoing, when the term “preventing” is used the term may refers to at least a partial inhibition, for example a 10% inhibition, a 20% inhibition, a 30% inhibition, a 40% inhibition, 50% inhibition, a 60%

[0308] 25 inhibition, a 70% inhibition, an 80% inhibition, a 90% inhibition, a 95% inhibition or greater than 95% inhibition.

[0309] In any of the foregoing embodiments, and any aspects of the foregoing, the compound, or pharmaceutically acceptable form thereof, may be administered alone or as a part of a pharmaceutical composition. The pharmaceutical composition may be formulated by combining

[0310] 30 a solution of the compound with a pharmaceutically suitable carrier. The solution of the compound may comprise 1 to 1,000 mg of the compound, for example, 10 to 600 mg, 20 to 500 PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0311] Docket No. Y20Q8-7007WO mg, 30 to 200 mg, 50 to 100 mg, or 1 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1,000 mg of the compound.

[0312] The compound and the pharmaceutically suitable carrier may be combined in a ratio of

[0313] 5 1:5 to 5:1. The pharmaceutical composition may be formulated to have a concentration of 1 to 1,000 mg / ml of the compound, for example, 10 to 600 mg / ml, 20 to 500 mg / ml, 30 to 200 mg / ml, 50 to 100 mg / ml, or 1 mg / ml, 5 mg / ml, 10 mg / ml, 20 mg / ml, 30 mg / ml, 40 mg / ml, 50 mg / ml, 60 mg / ml, 70 mg / ml, 80 mg / ml, 90 mg / ml, 100 mg / ml, 200 mg / ml, 300 mg / ml, 400 mg / ml, 500 mg / ml, 600 mg / ml, 700 mg / ml, 800 mg / ml, 900 mg / ml, or 1,000 mg / ml of the

[0314] 10 compound.

[0315] The pharmaceutical composition may be formulated to have a concentration of 0.01 wt% to 2 wt % of the compound, for example, 0.01 wt%, 0.02 wt%, 0.05 wt%, 0.1 wt%, 0.2 wt%, 0.5 wt%, 1 wt%, or 2 wt% of the compound. The pharmaceutical composition may be formulated to have a concentration of 1 wt% to 5 wt % of the compound, for example, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt% of the compound. The pharmaceutical composition may be formulated to have a concentration of 1-5 wt%, 5-10 wt%, 10-20 wt%, 20- 30 wt%, 30-40 wt%, 40-50 wt%, of the compound or more.

[0316] The pharmaceutical composition may be formulated to have a concentration of 0.25 to 100 pM of the compound, for example, 0.25 pM, 0.5 pM, 1 pM, 2.5 pM, 5 pM, 10 pM, 20 pM,

[0317] 20 50 pM, or 100 pM of the compound. The pharmaceutical composition may be formulated to have a concentration of 50 to 500 pM of the compound, for example, 50 pM, 100 pM5200 pM5300 pM, 400 pMaor 500 pM of the compound.

[0318] The pharmaceutical composition may be formulated to have a concentration of 0.25 to 100 pg / L of the compound, for example, 0.25 pg / L, 0.5 pg / L, 1 pg / L, 2.5 pg / L, 5 pg / L, 10 pg / L,

[0319] 25 20 pg / L, 50 pg / L, or 100 pg / L of the compound. The pharmaceutical composition may be formulated to have a concentration of 50 to 500 pg / L of the compound, for example, 50 pg / L, 100 g / L, 200 g / L, 300 pg / L, 400 pg / L, or 500 pg / L of the compound.

[0320] In any of the foregoing embodiments, and any aspects of the foregoing, the compound, or pharmaceutically acceptable form thereof, may be administered alone or as a part of a cosmetic

[0321] 30 composition. The cosmetic composition may be formulated by combining a solution of the compound with a cosmetically suitable carrier. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0322] Docket No. Y20Q8-7007WO

[0323] In any of the methods, and any aspects of the foregoing, a compound described herein is in the form of a pharmaceutically acceptable salt, solvate, or hydrate. Such a compound may be formulated as a pharmaceutically acceptable salt, e.g., acid addition salt, and complexes thereof. The preparation of such salts can facilitate the pharmacological use by altering the physical

[0324] 5 characteristics of the agent without preventing its physiological effect. Examples of useful alterations in physical properties include, but are not limited to, increasing the solubility to facilitate administering higher concentrations of the compound.

[0325] In any of the methods, and any aspects of the foregoing, a compound or an extract described herein is administered topically, intravenously, intraperitoneally, parenterally,

[0326] 10 intramuscularly, orally or via the respiratory tract. In any of the methods, and any aspects of the foregoing, the compound or the extract is administered topically.

[0327] The compound or an extract described herein may be administered locally, e.g., at a local site of the disease or condition. The compound or an extract described herein may be formulated for local administration, e.g., to a target site of the disease or condition. The compound or an extract described herein may be administered systemically. Systemic administration may be, e.g., topical, intravenous, intraperitoneal, parenteral, intramuscular, oral, or via the respiratory tract. The compound or an extract described herein may be formulated for systemic administration.

[0328] The composition may be formulated for immediate release or extended release. The

[0329] 20 composition may be formulated for controlled or sustained release. For example, the composition may be formulated for sustained release over a period of 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, or more.

[0330] In some aspects, a method may further comprise administering a second amount of the composition to the subject. The second amount may be administered as a second dose of the

[0331] 25 same formulation. The second amount may be administered in another formulation. The second amount may be administered in another formulation by the same route of administration, e.g., a topical solution or oil with a shampoo, conditioner, spray, cream, gel, body wash, soap, or lotion. The second amount may be administered by another route of administration, e.g., each amount may independently be administered topically, parenterally, or enterally.

[0332] 30 In some aspects, a method may further comprise administering a second composition to the subject. The second composition may be a compound that is a constituent of the same extract. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0333] Docket No. Y2008-7007WG

[0334] The second composition may be a compound that is a constituent of another extract. The second composition may be a compound having a similarity score of at least 95% with a compound of the first composition. The second composition may be administered in the same formulation. The second composition may be administered in another formulation.

[0335] 5 The composition may be administered as part of a combination therapy. The method may further comprise administering a second treatment in combination with the composition. The composition may be administered for a period of time prior to initiating the second treatment. The composition may be administered concurrently with the second treatment. The composition may be administered for a period of time subsequent to ceasing the second treatment. The second

[0336] 10 treatment may be administered via an alternate mode of administration. The second treatment may be a cosmetic and / or therapeutic treatment.

[0337] The composition may be administered in combination with a second agent, e.g., cosmetic or therapeutic agent, approved to treat or commonly used to treat the disease or condition or a symptom thereof.

[0338] The composition may be administered in combination with caffeine, B vitamins (e.g., Bl, B2, B3, B5, B6, B8, B9 and / or B 12), vitamin C, iron, magnesium, and / or zinc.

[0339] The composition may be administered in combination with UV-blocking agent, moisturizer, sunscreen, wrinkle cream, retinoid, alpha-hydroxy acid, beta-hydroxy acid, squalene, antioxidant, tretinoin, glycosaminoglycan (GAG), lactic acid, malic acid, citric acid,

[0340] 20 tartaric acid, hydroquinone, kojic acid, L-ascorbic acid, licorice extract, N-acetylglucosamine, niacinamide, squalene, soy, dermal filler or injection, e.g. hyaluronic acid or calcium hydroxylapatite, botulinum toxin, laser resurfacing procedure, ultrasound therapy, chemical peel, e.g. glycolic acid peel, trichloroacetic acid or salicylic acid, or dermabrasion procedure.

[0341] The composition may be administered in combination with an antioxidant. Exemplary

[0342] 25 antioxidants include CoQlO, vitamin C, vitamin E, carotenoids, e.g., beta-carotene, minerals, e.g., selenium and manganese, glutathione, lipoic acid, flavonoids, betaflavonoid, phenols, polyphenols, phytoestrogens, mitoquinol mesylate, and ubiquinone.

[0343] The composition may be administered in combination with an antioxidant, e.g., melatonin, an exfoliator, e.g., salicylic acid or N-acetyl glucosamine, an anti-inflammatory, e.g.,

[0344] 30 curcumin or turmeric extract. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0345] Docket No. Y2008-7007WO

[0346] The fucus compound may be administered in combination with an emblica extract or a compound constituent of an emblica extract. The fucus compound may be administered in combination with a chebula extract or a compound constituent of a chebula extract. The emblica compound may be administered with a fucus extract or a compound constituent of a fucus

[0347] 5 extract. The emblica compound may be administered with a chebula extract or a compound constituent of a chebula extract. In accordance with certain embodiments, the combination of two or more of an emblica compound, a fucus compound, and a chebula compound may provide synergistic effects in the treatment of the disease or condition.

[0348] In accordance with one or more embodiments, an effective amount of the preparation

[0349] 10 may be administered to a face of a subject. In accordance with one or more embodiments, the preparation may be administered to the scalp of the subject. In accordance with one or more embodiments, the preparation may be administered to the body of the subject. For example, the preparation may be applied to one or more of the more of the forehead, eye region, neck, scalp, head, shoulder, arm, hands, leg, underarm, torso, chest, feet, knee, ankle, back, buttock, or genitals of the subject.

[0350] Delivery Carriers

[0351] In accordance with certain aspects, the compositions of the disclosure may be loaded in a drug delivery platform or “delivery carrier” that can be designed with selected physical and

[0352] 20 functional properties. For instance, the composition of the carrier may be designed to provide a desired release profile of the deliverable (i.e., composition or active agent). The delivery carrier may be loaded with an effective amount of the deliverable. In some embodiments, the delivery platform may carry multiple deliverables. Thus, the delivery carriers disclosed herein may be formulated to provide combination therapy.

[0353] 25 The delivery carriers may be incorporated into one or more formulations for administration. The formulations may contain an effective amount of the delivery carrier with a suitable amount of an acceptable vehicle to provide a form proper for administration to a subject. For instance, the vehicle may be selected to produce a formulation suitable for topical, parenteral, enteral, or other modes of administration. The effective amount of the delivery carrier

[0354] 30 may be selected to produce a formulation having a desired concentration of the deliverable or active agent. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0355] Docket No. Y2008-7007WO

[0356] The effective loading amount for each deliverable or the combination of deliverables in the delivery carrier may be 0.1 wt%, 0.1-1 wt%, 1 wt%, 1-5 wt%, 5 wt%, 5-10 wt%, 10 wt%, 10- 20 wt%, 20 wt%, 20-30 wt%, 30 wt%, 30-40 wt%, 40 wt%, 40-50 wt%, 50 wt%, or more. In practice, the loading amount for each deliverable or combination of the deliverables in the

[0357] 5 delivery carrier may be + / - 1-5% of the target or design loading amount. In some embodiments, the effective amount of the delivery carrier in the formulation may be 0.01-1 wt%, 1-2 wt%, 1-5 wt%, 5-10 wt%, 10-20 wt%, 20-30 wt%, 30-40 wt%, 40-50 wt%, 50-60 wt%, 60-70 wt%, 70-80 wt%, 80-90 wt%, or more, or in some instances, as low as 0.001 wt% or less. The effective amount of the delivery earner in the formulation may be selected to produce a formulation

[0358] 10 having a concentration of the deliverable or active agent between 0.25 to 100 pM, for instance, 0.25 pM, 0.5 pM, 1 pM, 2.5 pM, 5 pM, 10 pM, 20 pM, 50 pM, or 100 pM.

[0359] The effective amount of the deliverable may be equal to the loading amount times the concentration of the delivery carrier in the formulation. Thus, in some embodiments, the effective amount of the deliverable is from 0.01 to 45 wt%, for example, 0.01-0.1 wt%, 0.1-1 wt%, 1-5 wt%, 5-10 wt%, 10-15 wt%, 15-20 wt%, 20-25 wt%, 25-30 wt%, 30-35 wt%, 35-40 wt%, or 40-45 wt%.

[0360] The formulation may comprise one or more additional active agents or combination therapies. The additional active agent or combination therapy may be incorporated in a similar delivery carrier or provided independently of the delivery carriers of the disclosure.

[0361] 20 The delivery carrier may be formulated to be a nanoparticle carrier. Exemplary nanoparticle carriers may be dimensioned to have an average size of about 1 to 5000 nm, for example, 1 to 10 nm, 10 to 50 nm, 10 to 100 nm, 50 to 500 nm, 50 to 100 nm, 100 to 500 nm, 500 to 1000 nm, or 1000 nm to 5000 nm, which can be selected based on the target tissue, compound to be delivered, and other properties of the nanomaterial. In some embodiments,

[0362] 25 exemplary nanoparticle carriers may be dimensioned to have an average size of about 100 nm to 200 nm, 200 nm to 300 nm, 250 nm to 350 nm, 300 nm to 400 nm, or 400 nm to 500 nm.

[0363] The delivery carrier may be formulated to be a microparticle carrier. Exemplary microparticle carriers may be dimensioned to have an average size of about 1 to 50 pm, for example, 1 to 5 pm, 5 to 10 pm, 10 to 15 pm, 15 to 20 pm, 20 to 30 pm, 30 to 40 pm, or 40 to

[0364] 30 50 pm, which can be selected based on the target tissue, compound to be delivered, and other properties of the nanomaterial. In some embodiments, exemplary microparticle earners may be PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0365] Docket No. Y2008-7007WO dimensioned to have an average size of about 1 to 2 pm, 2 to 3 pm, 3 to 4 pm, 4 to 5 pm, 5 to 6 pm, 6 to 7 pm, 7 to 8 pm, 8 to 9 pm, or 9 to 10 pm.

[0366] In certain embodiments, the loaded carriers comprise 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100 pg or more of the deliverable per mg of carrier. In certain

[0367] 5 embodiments, the loaded carriers comprise 20-60, 20-40, 25-40, 50-60 pg or more of deliverable per mg of carrier.

[0368] In certain embodiments, the loaded carriers comprise 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100 pg or more of deliverable per mg of carrier per unit time. In certain embodiments, the loaded carriers comprise 20-60, 20-40, 25-40, 50-60 pg or more of deliverable

[0369] 10 per mg of carrier per unit time. In certain embodiment, the unit time is 1- 5, 5-10, 10-15, 15-20, 20-25, 25-30, 30-35, 35-40, 40-45, 45-50, 50-60 secs, 1-2 mins, 2-5 mins, 5-10 mins, 10-30 mins, 30-60 mins, or more.

[0370] In certain embodiments, the composition of loaded carriers has an average core size of 50-60, 60-70, 70- 80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, 190-200, 200-300, 300-400, 400-500 nm, or more. In certain embodiments, the composition of loaded carriers has an average core size of 70-150 nm.

[0371] In certain embodiments, the composition of loaded carriers may have an average diameter in dry form of 1 nm to 1000 pm, 1 nm to 10 nm, 1 nm to 50 nm, 10 nm to 500 nm, 50 nm to 200 pm, 50 nm to 1 pm, 50 nm to 500 nm, 100 nm to 500 nm, 200 nm to 500 nm, 100 nm

[0372] 20 to 200 nm, 500 nm to 1000 nm, 50 nm to 100 nm, 1 pm to 5 pm, 5 pm to 10 pm, 10 pm to 15 pm, 15 pm to 20 pm, 20 pm to 50 pm, 50 pm to 100 pm, 100 pm to 200 pm, 200 pm to 500 pm, or 500 pm to 1000 pm. In certain embodiments, the composition of loaded carriers may have an average diameter in dry form of less than 500 nm, for example, less than 400 nm, less than 200 nm, or less than 100 nm.

[0373] 25 In certain embodiments, the loaded carriers have a size distribution of 0-5%, 5-10%, 10- 15%, 15-20%, 20-25%, 25-30%, 30-35%, 35-40%, 40-45%, 45-50%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or less than 5%. In certain embodiments, the loaded carriers have a size distribution of less than 1%. In certain embodiments, the loaded carriers have a size distribution of less than 0.1%.

[0374] 30 The loaded carriers may have a size distribution with a span (D90-D10) / (D50) in the range of from 1.0 to 2.5, 1.5 to 2.0, 2.5 to 3.0, or greater than 3.0, where D90 is the diameter at PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0375] Docket No. Y2008-7007WO which 90% of the total particles have a smaller diameter, DIO is the diameter at which 10% of the total particles have a smaller diameter, and D50 is the diameter at which 50% of the total particles have a smaller diameter. In some embodiments, D90 is 5 pm to 30 pm, for example, 5 pm to 15 pm, 15 pm to 25 pm, 25 pm to 30 pm, 9 pm to 12 pm, or 9 pm to 18 pm. In some

[0376] 5 embodiments, D90 is less than 5 pm, for example, less than 4 pm, less than 3 pm, less than 2 pm, or less than 1 pm. In some embodiments, D50 is 5 pm to 15 pm, for example, 9 pm to 12 pm. In some embodiments, D50 is less than 5 pm, for example, less than 4 pm, less than 3 pm, less than 2 pm, or less than 1 pm. D10 may be less than 5 pm, for example, less than 4 pm, less than 3 pm, less than 2 pm, or less than 1 pm.

[0377] 10 While not wishing to be bound by theory, it is believed the delivery carriers disclosed herein have improved permeability as compared to compositions lacking the delivery carriers. Improved permeability may be in the form of skin penetration, crossing the blood brain barrier, cell membrane penetration, and others.

[0378] Exemplary delivery earners may be formed of amorphous silica particles. Silica particle delivery carriers may be produced from hydrogels formed from polymerized silanes, such as tetramethoxy silane (TMOS) or tetraethoxy silane (TEOS). The properties of the hydrogel may be controlled by selecting formation conditions, such as temperature, water to alcohol ratio, and pH of the formation steps. The controllable properties include, for example, polymer size and degree of polymer packing in the hydrogel, which may be used to control the release profile of the

[0379] 20 carriers. Thus, the hydrogel may be formulated to provide immediate release of the deliverable or extended or sustained release of the deliverable.

[0380] Additionally, any of the delivery carriers disclosed herein may comprise, be formed of, and / or be functionalized with one or more of carbon-based nanomaterials, liposomal delivery vehicles, polymeric nanocarriers, micelles, dendrimers, lipophilic cations, solid-lipid

[0381] 25 nanoparticles (SLN), peptide-based nanomaterials, nanostructured lipid carriers (NLC), niosomes, nanoemulsions, metal nanoparticles, nanospheres, polymerosomes, cubosomes, and combinations thereof. Exemplary nanomaterials are described in “Nano therapeutic Approaches to Target Mitochondria in Cancer,” (Mani, 2021) and “Role of Nanotechnology in Cosmeceuticals: A Review of Recent Advances,” (Kaul, 2018), each of which is incorporated

[0382] 30 herein by reference in its entirety for all purposes. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0383] Docket No. Y2008-7007WG

[0384] The delivery carrier may be designed for mitochondrial targeting or specific cell type targeting. Exemplary mitochondrial targeting agents include antibodies, polymeric functional moieties, such as PEG, lipophilic cations, such as triphenylphosphine (TPP), and peptides, such as mitochondrial penetrating peptides (MPP), The delivery carrier may be formed of a targeting

[0385] 5 moiety, for example, encapsulating or conjugated with the compounds disclosed herein, and / or the delivery carrier may be functionalized with a surface targeting moiety.

[0386] Exemplary carbon-based nanomaterials include carbon dots (C-dots or CD), carbon nanotubes (CNT), graphene derivatives, nanodiamonds (ND), quantum dots (QD), and magnetic nanoparticles (MNP). Carbon nanoparticles may be formed into different shapes including, for

[0387] 10 example, spherical, elliptical, tube, horn-shaped, and combinations thereof.

[0388] CNTs are graphene sheets formed into cylindrical tubes. CNTs have demonstrated low toxicity profile, good biocompatibility, and targeted accumulation. CNTs of the disclosure may be single-walled carbon nanotubes (SWCNT) and / or multi-walled carbon nanotubes (MWCNT). SWCNTs have a smaller diameter, in the range of 1 to 10 nm. MWCNTs have a larger diameter, in the range of 2 to 50 nm. CNTs may be functionalized with a targeting sequence. For instance, CNTs may be functionalized to target mitochondria and / or a specific cell type. Graphene derivatives also include two-dimensional carbon allotropes. Graphene derivatives may be designed to exhibit specific physicochemical properties, such as a high surface area and selected multifaceted surface properties. Graphene derivatives may be functionalized, e.g., surface

[0389] 20 functionalized, for targeted delivery to mitochondria and / or a specific cell type. CNTs have been used successfully in hair colorants and cosmetic hair care formulations.

[0390] Nanodiamonds have been shown to provide high affinity to biomolecules, biocompatibility, and non- or low-cytotoxicity. Nanodiamonds, quantum dots, and magnetic nanoparticles may be conjugated with the compounds disclosed herein for targeted delivery.

[0391] 25 Certain MNP may be designed to encapsulate the compounds disclosed herein. QDs are generally formed of a semiconductive core layered by a shell designed to provide selected physical and chemical characteristics. MNPs are formed of a magnetic core, such as an iron oxide material core, and surface coating designed to improve stability and biocompatibility in physiological environments. Thus, MNPs and QDs are highly adaptable for their selected use.

[0392] 30 Liposome based delivery vehicles are typically formed of enclosed spherical vesicles composed of a lipid bilayer with an internal bilayer and internal aqueous core region. The PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0393] Docket No. Y2008-7007WO liposome may have a unilamellar or multilamellar structure. Liposomes may be designed to have a surface chemistry effective for targeted delivery and / or controlled release delivery. For instance, engineered liposomes have shown improved cellular update and accumulation of a delivery compound in the mitochondria. Antioxidants, such as carotenoids, CoQlO, lycopene and

[0394] 5 agents such as vitamin A, E, and K, may be incorporated into liposomes to amplify physical and chemical stability. Liposomes may be formulated with phosphatidylcholine to provide moisturizing properties to skin and hair care products. Vegetable phospholipids and soya phospholipids may be used with topical formulations for their high content of esterified essential fatty acids. For example, when applied with an active agent, the barrier function of the skin is

[0395] 10 increased and water loss is decreased. It has been shown that certain liposomes have an effect on wrinkle reduction, decreasing efflorescence in acne treatment, and increasing skin smoothness.

[0396] Niosomes are vesicles having a bilayer structure composed of self-assembled hydrated nonionic surfactants. Niosomes may have cholesterol incorporated into their lipids or may be free of cholesterol. Niosomes may be formulated as multilamellar or unilamellar structures encapsulating the compounds disclosed herein by a membrane formed when the surfactant macromolecules are organized as a bilayer. Exemplary nonionic surfactants include spans, tweens, brijs, alkyl amides, sorbitan ester, crown ester, polyoxyethylene alkyl ether, and steroid- linked surfactants. Niosomes may encapsulate the compounds disclosed herein, providing prolonged systemic circulation and enhanced penetration into target tissue. Niosomes in cosmetic

[0397] 20 and skin care applications provide skin penetration, increased stability of entrapped ingredients, and improved bioavailability of typically poorly adsorbed compounds. Niosomes may be designed for a target application by controlling the nature and structure of surfactants, membrane composition, and temperature of hydration, which influences size and shape of the particle. Specialized niosomes called proniosomes may be used. Proniosomes are nonionic based

[0398] 25 surfactant vesicles which are hydrated immediately before use to yield aqueous noisome dispersions. To further enhance drug delivery, niosomes and proniosomes may be combined in a formulation.

[0399] Polymeric nanocarriers are generally formed of biodegradable polymers. The polymeric nanocarriers may be reservoir type (nanocapsules in which compounds are dissolved / distributed

[0400] 30 in the core of the polymer), matrix type (nanospheres, in which compounds are entrapped in the polymer matrix), and combinations thereof. Polymeric nanocarriers may offer the benefits of low PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0401] Docket No. Y2008-7007WO toxicity, easy modification (for example, for targeted delivery), high drug loading capacity, small size, good aqueous solubility, and biocompatibility. Exemplary polymeric nanocarriers for mitochondrial targeting include hydrophilic block polymer, such as polyethylene glycol (PEG), poly E-caprolactone (PCL). Other nanoparticles disclosed herein may be modified for

[0402] 5 mitochondrial targeting, such as by including surface hydrophilic block polymers (e.g., PEGylation). Polymerosomes are artificial vesicles formed of self-assembling block copolymer amphiphiles. Polymerosomes typically have a hydrophilic core and lipophilic bilayer. Polymerosomes are highly customizable. Drug encapsulation and release capabilities may be controlled by forming the poly mero some with block copolymers that are biodegradable and / or

[0403] 10 responsive to stimuli. The composition and molecular weight of the polymerosome may be selected to control properties, such as, response to stimuli, membrane thickness, permeability, flexibility, and size (polymerosomes may be designed to have a radius from 50 nm to 5000 nm or more). Polymerosomes provide benefits, such as, improved skin elasticity and skin cell activation energy enhancement.

[0404] Cubosomes are nano structured particles formed from self-assembled liquid crystalline particles of aqueous lipids and surfactants. Cubosomes are formed of a bicontinuous liquid phase, enclosing two separate vesicles of aqueous formulations divided by a surfactant- controlled bilayer in a strongly packed structure. Cubosomes may be designed as a honeycombed structure having more than two separate vesicles. Release of each vesicle may be separately

[0405] 20 controlled. Cubosomes may provide benefits, such as, providing controlled and / or targeted release of the compounds, possessing lipid biodegradability, and having a high internal surface area with different drug-loading modalities.

[0406] Micelles are colloidal aggregates that are generally amphiphilic in nature, having a hydrophilic head and hydrophobic tail. The size and shape of micelle nanoparticles may be

[0407] 25 selected by varying the solution’s isotonic strength, pH, temperature, and the nature of the amphiphilic molecule. Micelles may be utilized to improve uptake of the compounds disclosed herein in mitochondria. For instance, micelle formulations have been found to improve bioavailability of low absorption compounds, prevent mitochondrial swelling (indicating less mitochondrial permeability transition pore (mPTP) opening and prevention of injury), and

[0408] 30 protect cells from nitrosative stress, “Curcumin Micelles Improve Mitochondrial Function in Neuronal PC12 Cells and Brains of NMRI Mice - Impact on Bioavailability” (Hagl, 2015) PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0409] Docket No. Y2008-7007WD

[0410] (incorporated herein by reference in its entirety for all purposes). Micelles may be functionalized with a targeting group, such as mitochondrial targeting TPP, MPP, or PEGyltaion. In some embodiments, micelle nanoparticles may be polymeric micelles.

[0411] Dendrimers are hyperbranched macromolecules which may be formed of sugars, amino

[0412] 5 acids, and / or nucleotides. Dendrimers are generally formed of a central core, repeated branches, and diverse peripheral groups. The peripheral groups may be designed or functionalized for a target application, such as targeted delivery. Benefits of dendrimers include the ability to provide drug encapsulation, high aqueous solubility, high retention time, biodegradability, specificity, low toxicity, and surface modification capabilities that may provide properties such as

[0413] 10 monodispersity, polyvalence, and stability. Dendrimers may be functionalized with a targeting group, such as TPP, MPP, or PEGylation. Dendrimers may be formulated to encapsulate the compound or conjugate to the compound.

[0414] Lipophilic cations are positively charged ions that can penetrate the plasma and mitochondrial membranes. The lipophilic cations tend to accumulate in the mitochondria. Thus, lipophilic cations, such as TPP, dequalinum, and rhodamine 123, may be utilized for mitochondrial-targeted therapeutic delivery. Delocalized lipophilic cations (DLC) have a strong mitochondrial targeting ability to cross the membrane and drive specific aggregation of attached moieties within the mitochondria of the cells. Thus, DLCs may be utilized as nanoparticle carriers and / or as surface modifications for targeted delivery. For instance, the compositions

[0415] 20 disclosed herein may be conjugated to a DLC, such as TPP, or encapsulated in another carrier having a TPP surface functionalization for targeted delivery.

[0416] Solid-lipid nanoparticles are sub-micron colloidal carriers in the range of 50 to 1000 nm, for example 50 to 500 nm or 50 to 100 nm. SLNs are generally formed of physiological lipid disseminated in water or a liquid surfactant solution having an oil-based or lipoidal core. SLNs

[0417] 25 may be prepared from complex glyceride mixtures, purified triglycerides, and waxes having phospholipid hydrophobic chains in the fat matrix. SLNs provide benefits such as small size, large surface area, high drug loading capacity, and the contact of phases at the interface. SLNs may be designed to provide controlled or sustained release of the compound. In cosmetics and pharmaceuticals, SLNs may provide increased penetration of the compounds disclosed herein

[0418] 30 through the skin. SLNs may have ultraviolet (UV) resistant properties, occlusive properties PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0419] Docket No. Y2008-7007WO which can be used to increase skin hydration, and good stability coalescence due to their solid nature, which reduces mobility and leakage of the active molecules.

[0420] Nano structured lipid carriers (NLC) are a form of lipid nanoparticle formed by blending solid lipids with spatially incompatible liquid lipid compositions, forming an amorphous solid.

[0421] 5 NLCs may be of the imperfect type, amorphous type, or multiple type. NLC particles typically range in size from 10 nm to 1000 nm. When formulated from biodegradable and physiological lipids, NLCs show very little toxicity. Thus, NLC formulations may provide the benefits of reduced systemic side effects and higher drug loading capacity. NLCs may be designed to have a biphasic drug release pattern. For example, a first compound release profile may be immediate or

[0422] 10 controlled release, and a second compound release profile may be controlled or delayed release. Like SLNs, NLCs may also provide increased penetration of the compounds disclosed herein through the skin, ultraviolet (UV) resistant properties, occlusive properties which can be used to increase skin hydration, and good stability coalescence.

[0423] Nanoemulsions are kinetically and thermodynamically stable dispersions of liquid formed from an oil phase and a water phase in combination with a surfactant. The nanoemulsions disclosed herein may be oil in water, water in oil, or bicontinuous formulations. Properties of nanoemulsions may be designed by controlling method of preparation. Nanoemulsions are typically dispersed phase, comprising small particles or droplets having low oil or water interfacial tension. Nanoemulsions are tupically formed of a lipophilic core surrounded by a

[0424] 20 monomolecular layer of phospholipids. Nanoemulsions provide benefits, such as, low viscosity, high kinetic stability, high interfacial area, high solubilization capacity, and increased rate of absorption. In cosmetic and pharmaceuticals, nanoemulsions may provide rapid penetration and active transport of active ingredients and hydration to the skin. Nanoemulsions may be formulated into foams, creams, sprays, or liquids.

[0425] 25 Certain nanoparticle formulations, such as SLNs, nanoemulsions, liposomes, and niosomes, may be used in moisturizing formulations, providing humectants that retain moisture for a prolonged period of time.

[0426] Metal nanoparticles may be designed to have specific properties and may be shaped as nanospheres, nanoshells, nanoclusters, nanorods, nanostars, nanocubes, branched, and

[0427] 30 nanotriangles. Shape, size, and dielectric properties of metal nanoparticles may have an effect on resonance frequency. Metal nanoparticles may be designed to have high drug loading capacity PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0428] Docket No. Y20Q8-7007WO and effectively penetrate the cell wall by controlling size, surface area, and crystallinity. Benefits of metal nanoparticles include acceleration of blood circulation, anti-inflammatory properties, antiseptic properties, improvising firmness and elasticity of skin, delaying aging, and vitalizing skin metabolism. Exemplary metal nanoparticles are gold, silver, and copper. Such metal

[0429] 5 nanoparticles have been shown to provide strong antifungal and / or antimicrobial properties. Another exemplary metal nanoparticle is titanium dioxide (TiCh), which has been shown to provide protection from ultraviolet (UV) radiation. Metal nanoparticles may be designed to be inert in nature, highly stable, biocompatible, and noncytotoxic. More than one metal may be used to form metal nanocomposites with selected properties.

[0430] 10 Nanospheres are spherical nanoparticles having a core-shell structure. The compounds may be encapsulated, conjugated, dissolved, or otherwise entrapped in the nanoparticle. The nanospheres may be crystalline or amorphous structures. The nanospheres may be biodegradable or nonbiodegradable. Exemplar)' biodegradable biospheres include gelatin, modified starch, and albumin nanospheres. One exemplary nonbiodegradable nanosphere is polylactic acid. In cosmetics and pharmaceuticals, nanospheres may be used to deliver the compounds disclosed herein into a deep layer of the skin more precisely and efficiently. Nanospheres have been shown to provide protection against actinic aging.

[0431] Peptide-based nanomaterials are biomolecules made up of several amino acids linked by peptide bond. Peptides may generally provide rapid clearance in the kidney due to enzymatic

[0432] 20 degradation. Peptide nanomaterials may provide several benefits including targeting and accumulating capacity, small size, ease of production and customizability, and biocompatibility. Certain peptide nanomaterials may be designed to self-assemble into distinct shapes and sizes in response to environmental factors, such as temperature, pH, ionic strength, or molecular interaction between the host and peptide. Peptide nanoparticles may also be functionalized for

[0433] 25 targeted delivery. Functionalized peptides have been found to exhibit improved targetability and enhanced efficacy.

[0434] One exemplary peptide nanomaterial with mitochondrial-targeting ability is mitochondrial penetrating peptides (MPP). MPPs are cell penetrating peptides which can efficiently penetrate mitochondrial double membranes. MPPs are generally designed or selected

[0435] 30 to be positively charged peptides. Due to the strongly negative charge of mitochondrial membranes, positively charged peptides are capable of penetrating mitochondria. MPPs are PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0436] Docket No. Y2008-7007WO described in more detail in “Mitochondrial targeted strategies and their application for cancer and other diseases treatment,” (Li, 2020), incorporated herein by reference in its entirety for all purposes. Thus, MPPs may be utilized as nanoparticle carriers and / or as surface modifications for targeted delivery. For instance, the compositions disclosed herein may be conjugated to an

[0437] 5 MPP or encapsulated in another carrier having an MPP surface functionalization for targeted delivery.

[0438] Dosage and Administration

[0439] In accordance with the methods, the compounds of the disclosure are administered to the

[0440] 10 subject (or are contacted with cells of the subject) in an effective amount.

[0441] In certain embodiments, therapeutically the effective amount of a compound of the disclosure ranges from about 0.05 mg / kg / day to about 50 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 40 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 30 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 20 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 10 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 8 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 6 mg / kg / day. In certain embodiments, the effective amount

[0442] 20 ranges from about 0.05 mg / kg / day to about 4 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 3 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 2 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 1 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 0.8

[0443] 25 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 0.6 mg / kg / day. In certain embodiments, the effective amount ranges from about 0.05 mg / kg / day to about 0.4 mg / kg / day. In certain embodiment, the amounts per day described above are administered according to a course of treatment and may be administered in a single dose or in more than 1 dose per day. The amounts per day described above may be administered

[0444] 30 according to a course of treatment and administered in one dose (q.d.) or two doses each day PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0445] Docket No. Y2008-7007WO

[0446] (b.i.d.), wherein the amount of the compound of the disclosure in each dose need not be the same.

[0447] In certain embodiments, each dose is administered according to a course of treatment. As used herein, the term “dose” refers to an amount of a compound of the disclosure administered at

[0448] 5 a given time point according to a course of treatment. For example, if a course of treatment for a compound of the disclosure is b.i.d (2 times / administrations per day) for 7 days, the two administrations on each of days 1-7 would each comprise administering a dose of a compound of the disclosure (for 2 doses each day). In certain embodiments, a dose is administered q.d. (1 time / administration per day) according to a course of treatment. In certain embodiments, a dose

[0449] 10 is administered b.i.d. according to a course of treatment. In certain embodiments, a dose is administered t.i.d. (three times / administrations per day) according to a course of treatment.

[0450] When 2 or more doses are administered on a given day according to a course of treatment, each dose administered according to the course of treatment may contain the same amount of a compound of the disclosure or one or more of doses administered according to the course of treatment may contain a greater or lesser amount of a compound of the disclosure as compared to another dose administered according to the course of treatment. For example, if a course of treatment for a compound of the disclosure is b.i.d for 7 days, the first dose administered on day 1 may contain a first amount (i.e., 2 mg / kg) and the second dose administered on day 1 may contain a second amount (i.e., 0.5 mg / kg). As another example, if a

[0451] 20 course of treatment for a compound of the disclosure is b.i.d for 7 days, the first dose administered on day 1 may contain a first amount (i.e., 2 mg / kg), the second dose administered on day 1 may contain a second amount (i.e., 0.5 mg / kg), the two doses administered on each of days 2-4 may contain the second amount, and the two doses administered on each of days 5-7 may contain a third amount (i.e., 1 mg / kg).

[0452] 25 A dose may be further divided into a sub-dose. Any given dose may be delivered in a single unit dose form or more than one unit dose form. For example, a dose when given by IV administration may be provided as a single IV infusion (i.e., a single 5 mg / kg IV infusion) or as two or more IV infusions administered one after the other (i.e., two 2.5 mg / kg IV infusions). Further, a sub-dose might be, for example, a number of discrete loosely spaced administrations,

[0453] 30 such as multiple inhalations from an insufflator, by application of a plurality of drops into the eye, or multiple tablets for oral administration. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0454] Docket No. Y2008-7007WO

[0455] In certain embodiments, more than one dose of a compound of the disclosure is administered during a course of treatment. Therefore, in the methods described herein, the methods may comprise the administration of multiple doses during the course of treatment. In certain embodiments, the course of treatment may range from months to years. In certain

[0456] 5 embodiments, the course of treatment may range from 2 days to 1 month, from 2 days to 3 weeks, from 2 days to 2 weeks, or from 2 days to 1 week. In certain embodiments, the course of treatment may range from 1 year to 20 years or longer. In certain embodiments, a dose is delivered at least 1 time per day (i.e., 1 to 3 times) during the course of treatment. In certain embodiments, a dose is not administered every day during the course of treatment (for example,

[0457] 10 a dose is be administered at least 1 timer per day every other day, every third day, every week, or ever}' month during the course of treatment). Furthermore, the amount of a compound of the disclosure in each dose need not be the same as discussed above. In certain embodiments, of the foregoing, one or more doses, or all of the doses, contain an effective amount of a compound of the disclosure.

[0458] In one embodiment, a course of treatment may comprise administering at least one dose as a loading dose and at least one dose as a maintenance dose, wherein the loading dose contains a greater amount of a compound of the disclosure as compared to the maintenance dose (such as, but not limited to, 2 to 10 times higher). In one aspect of this embodiment, the loading dose is administered initially, either as a single administration or more than one administration, followed

[0459] 20 by administration of one or more maintenance doses through the remaining course of treatment. For example, for a course of treatment that is q.d. every week for 10 years, a loading dose of 3 mg / kg may be administered as the first dose on week 1 of the course of treatment, followed by maintenance doses of 0.5 mg / kg every week for the remainder of the course of treatment. Furthermore, a loading dose may be given as a dose that is not the first dose administered during

[0460] 25 a course of treatment. For example, a loading dose may be administered as the first dose on week and as a dose on one or more additional weeks (for example, weeks 10 and 20).

[0461] In one embodiment, a course of treatment may comprise administering a first dose formulated in a first composition and administering at least one second or subsequent dose formulated in a second composition. The first composition and the second composition may be

[0462] 30 the same formulation. The first composition and the second composition may be different formulations. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0463] Docket No. Y20Q8-7007WO

[0464] The compositions may be formulated to have 0.1 wt% to 5.0 wt% of the active agent, for example, 0.5 wt% to 3.0 wt%, 0.5 wt% to 2.0 wt%, or 0.5 wt% to 1.0 wt% of the active agent. Certain exemplary compositions may have 0.1 wt%, 0.5 wt%, 1.0 wt%, 1.5 wt%, 2.0 wt%, 2.5 wt%, 3.0 wt%, 3.5 wt%, 4.0 wt%, 4.5 wt%, or 5.0 wt% of the active agent.

[0465] 5

[0466] Pharmaceutical, Cosmetic, and / or Dietary Compositions

[0467] Pharmaceutical compositions are provided that comprise an amount, e.g., an effective amount, of a compound of the disclosure. In one embodiment, such pharmaceutical compositions contain a therapeutically effective amount of a compound of the disclosure. In addition, other

[0468] 10 active agents may be included in such pharmaceutical compositions. Additional active agents to be included may be selected based on the disease or condition to be treated.

[0469] The pharmaceutical compositions disclosed may comprise one or more compound of the disclosure, alone or in combination with additional active agents, in combination with a pharmaceutically acceptable carrier and / or excipient and / or in combination with a cosmetically acceptable carrier and / or excipient. Such pharmaceutical compositions may be used in the manufacture of a medicament for use in the methods described herein. The compounds of the disclosure are useful in both free form and in the pharmaceutically acceptable forms, such as pharmaceutically acceptable salts.

[0470] The pharmaceutically acceptable carriers and / or excipients and / or cosmetically

[0471] 20 acceptable carriers and / or excipients are well-known to those who are skilled in the art. The choice of carrier and / or excipient will be determined in part by the particular compound(s), as well as by the particular method used to administer the compound composition. Accordingly, there is a wide variety of suitable formulations of the composition of the disclosure. The following methods and excipients are merely exemplary and are in no way limiting. Suitable

[0472] 25 carriers and excipients include solvents such as water, alcohol, and propylene glycol, solid absorbants and diluents, surface active agents, suspending agent, tableting binders, lubricants, flavors, and coloring agents. The pharmaceutically and / or cosmetically acceptable carriers can include polymers and polymer matrices. Examples of acceptable carriers include carboxymethyl cellulose, crystalline cellulose, glycerin, gum arabic, lactose, magnesium stearate, methyl

[0473] 30 cellulose, powders, saline, sodium alginate, sucrose, starch, talc and water, among others. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0474] Docket No. Y2008-7007WG

[0475] Typically, the acceptable carrier is chemically inert to the active agents in the composition and has no detrimental side effects or toxicity under the conditions of use.

[0476] Surfactants such as, for example, detergents, are also suitable for use in the formulations. Specific examples of surfactants include polyvinylpyrrolidone, polyvinyl alcohols, copolymers

[0477] 5 of vinyl acetate and of vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol or polyoxyethylenated esters of sorbitan; lecithin or sodium carboxymethylcellulose; or acrylic derivatives, such as methacrylates and others, anionic surfactants, such as alkaline stearates, in particular sodium, potassium or ammonium stearate; calcium stearate or triethanolamine stearate; alkyl sulfates, in particular sodium lauryl sufate and

[0478] 10 sodium cetyl sulfate; sodium dodecylbenzenesulphonate or sodium dioctyl sulphosuccinate; or fatty acids, in particular those derived from coconut oil, cationic surfactants, such as water- soluble quaternary ammonium salts of formula N+R'R"R'"R""Y-, in which the R radicals are identical or different optionally hydroxylated hydrocarbon radicals and Y- is an anion of a strong acid, such as halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is one of the cationic surfactants which can be used, amine salts of formula N+R'R"R"', in which the R radicals are identical or different optionally hydroxylated hydrocarbon radicals; octadecylamine hydrochloride is one of the cationic surfactants which can be used, non-ionic surfactants, such as optionally polyoxyethylenated esters of sorbitan, in particular Polysorbate 80, or polyoxyethylenated alkyl ethers; polyethylene glycol stearate, polyoxyethylenated derivatives of

[0479] 20 castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids or copolymers of ethylene oxide and of propylene oxide, amphoteric surfactants, such as substituted lauryl compounds of betaine.

[0480] Exemplary pharmaceutically acceptable carriers and / or excipients and / or cosmetically acceptable carriers and / or excipients include water, silica, glycerin, dimethicone, butylene

[0481] 25 glycol, pentylene glycol, ethoxydiglycol, polyacrylate- 13, pentapeptide-34 trifluoroacetate, polyisobutene, lysolecithin, sclerotium gum, pullulan, polysorbate 20, diethylhexyl syringylidenemalonate, caprylyl glycol, glyceryl stearate, PEG- 100 stearate, cetearyl alcohol, butyrospermum parkii (shea) butter, acetyl tetrapeptide-2, betaine, melanin, tocopheryl acetate, tocopherol, hydroxyacetophenone, caprylic / capric triglyceride, batyl alcohol, C12-15 alkyl

[0482] 30 benzoate, panthenol, ceteareth-20, xanthan gum, ethylhexylglycerin, disodium EDTA, propanediol, caprylyl glycol, potassium sorbate, sorbic acid, and phenoxyethanol. The PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0483] Docket No. Y2008-7007WO compounds of the disclosure and pharmaceutical compositions containing such compounds as described in the instant disclosure can be administered by any conventional method available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in combination with additional therapeutic agents.

[0484] 5 In one embodiment, the compounds of the disclosure are administered in an effective amount, whether alone or as a part of a pharmaceutical composition. The effective amount and the dosage administered will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration, the age, health and weight of the recipient; the severity and stage of the disease

[0485] 10 state or condition; the kind of concurrent treatment; the frequency of treatment; and the effect desired.

[0486] The total amount of the compound administered will also be determined by the route, timing and frequency of administration as well as the existence, nature, and extent of any adverse side effects that might accompany the administration of the compound and the desired physiological effect. It will be appreciated by one skilled in the art that various conditions or disease states, in particular chronic conditions or disease states, may require prolonged treatment involving multiple administrations.

[0487] In these pharmaceutical or cosmetic compositions, the compound(s) of the disclosure will ordinarily be present in an amount of about 0.5-95% weight based on the total weight of the

[0488] 20 composition, or about 0.1-99.9% weight based on the total weight of the composition. Multiple dosage forms may be administered as part of a single treatment.

[0489] The active agent can be administered enterally in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as milk, elixirs, syrups and suspensions. It can also be administered parenterally, in sterile liquid dosage forms. The compound(s) of the

[0490] 25 disclosure can also be administered intranasally (nose drops) or by inhalation via the pulmonary system, such as by propellant based metered dose inhalers or dry powders inhalation devices. Other dosage forms include topical administration, such as administration transdermally, via patch mechanism or ointment.

[0491] Formulations suitable for enteral or oral administration may be liquid solutions, such as

[0492] 30 an effective amount of the compound(s) dissolved in diluents, such as milk, water, saline, buffered solutions, infant formula, other suitable carriers, or combinations thereof. Formulations PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0493] Docket No. Y2008-7007WO suitable for enteral or oral administration of the compounds of the disclosure are known in the art as exemplified by: Shaji, et al., Indian J Pharm Sci. 2008 May-Jun; 70(3): 269-277; Bruno, et al., Ther Deliv. 2013 Nov; 4(11): 1443-1467; Ibrahim, et al., DARU Journal of Pharmaceutical Sciences, 2020, 28, 403-416. The compound(s) can then be mixed to the diluent just prior to

[0494] 5 administration. In an alternate embodiment, formulations suitable for enteral or oral administration may be capsules, sachets, tablets, lozenges, and troches. In each embodiment, the formulation may contain a predetermined amount of the compound(s) of the disclosure, as solids or granules, powders, suspensions and suitable emulsions. Liquid formulations may include diluents, such as water and alcohols, for example, ethanol, benzyl alcohol, propylene glycol,

[0495] 10 glycerin, and the polyethylene alcohols, either with or without the addition of an acceptable surfactant, suspending agent, or emulsifying agent. Capsule forms can be of the ordinary hard- or soft-shelled gelatin type containing, for example, surfactants, lubricants, and inert fillers, such as lactose, sucrose, calcium phosphate, and com starch. Tablet forms can include one or more of the following: lactose, sucrose, mannitol, corn starch, potato starch, alginic acid, microcrystalline cellulose, acacia, gelatin, guar gum, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, calcium stearate, zinc stearate, stearic acid, and other excipients, colorants, diluents, buffering agents, disintegrating agents, moistening agents, preservatives, flavoring agents, and pharmacologically compatible carriers.

[0496] Lozenge forms can comprise the active ingredient in a flavor, usually sucrose and acacia

[0497] 20 or tragacanth, as well as pastilles comprising the active ingredient in an inert base, such as gelatin and glycerin, or sucrose and acadia, emulsions, and gels containing, in addition to the active ingredient, such carriers as are known in the art.

[0498] Formulations suitable for parenteral administration include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain anti-oxidants, buffers, bacteriostats, and

[0499] 25 solutes that render the formulation isotonic with the blood of the patient, and aqueous and nonaqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. The compound(s) can be administered in a physiologically acceptable diluent in an acceptable carrier, such as a sterile liquid or mixture of liquids, including water, saline, aqueous dextrose and related sugar solutions, an alcohol, such as ethanol,

[0500] 30 isopropanol, or hexadecyl alcohol, glycols, such as propylene glycol or polyethylene glycol such as poly(ethyleneglycol) 400, glycerol ketals, such as 2,2-dimethyl-l,3-dioxolane-4-methanol, PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0501] Docket No. Y20Q8-7007WO ethers, an oil, a fatty acid, a fatty acid ester or glyceride, or an acetylated fatty acid glyceride with or without the addition of an acceptable surfactant, such as a soap or a detergent, suspending agent, such as pectin, carbomers, methylcellulose, hydroxypropylmethylcellulose, or carboxymethylcellulose, or emulsifying agents and other pharmaceutical adjuvants.

[0502] 5 Oils, which can be used in parenteral formulations include petroleum, animal, vegetable, or synthetic oils. Specific examples of oils include peanut, soybean, sesame, cottonseed, corn, olive, petrolatum, and mineral. Suitable fatty acids for use in parenteral formulations include oleic acid, stearic acid, and isostearic acid. Ethyl oleate and isopropyl myristate are examples of suitable fatty acid esters. Suitable soaps for use in parenteral formulations include fatty alkali

[0503] 10 metal, ammonium, and triethanolamine salts, and suitable detergents include (a) cationic detergents such as, for example, dimethyldialkylammonium halides, and alkylpyridinium halides, (b) anionic detergents such as, for example, alkyl, aryl, and olefin sulfonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates, (c) nonionic detergents such as, for example, fatty amine oxides, fatty acid alkanolamides, and polyoxyethylene polypropylene copolymers, (d) amphoteric detergents such as, for example, alkyl .beta.-aminopropionates, and 2-alkylimidazoline quaternary ammonium salts, and (e) mixtures thereof.

[0504] The parenteral formulations typically contain from about 0.5% to about 50% by weight of the compound(s) in solution. Suitable preservatives and buffers can be used in such formulations. In order to minimize or eliminate irritation at the site of injection, such compositions may

[0505] 20 contain one or more nonionic surfactants having a hydrophile-lipophile balance (HLB) of from about 12 to about 17. The quantity of surfactant in such formulations ranges from about 5% to about 15% by weight. Suitable surfactants include polyethylene sorbitan fatty acid esters, such as sorbitan monooleate and the high molecular weight adducts of ethylene oxide with a hydrophobic base, formed by the condensation of propylene oxide with propylene glycol.

[0506] 25 The compound(s) of the disclosure can be formulated into aerosol formulations to be administered via nasal or pulmonary inhalation. These aerosol formulations can be placed into pressurized acceptable propellants, such as dichlorodifluoromethane, propane, and nitrogen. Such aerosol formulations may be administered by metered dose inhalers. They also may be formulated as pharmaceuticals for non-pressured preparations, such as in a nebulizer or an

[0507] 30 atomizer. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0508] Docket No. Y2008-7007WD

[0509] The compound(s) of the disclosure, alone or in combination with other suitable components, may be administered in an aqueous solution as a nasal or pulmonary spray and may be dispensed in spray form by a variety of methods known to those skilled in the art. Systems for dispensing liquids as a nasal spray are disclosed in U.S. Pat. No. 4,511,069. The formulations

[0510] 5 may be presented in multi-dose containers, for example in the sealed dispensing system disclosed in U.S. Pat. No. 4,511,069. Additional aerosol delivery forms may include, e.g., compressed air-, jet-, ultrasonic-, and piezoelectric nebulizers, which deliver the active agent dissolved or suspended in a pharmaceutical solvent, e.g., water, ethanol, or a mixture thereof.

[0511] Nasal and pulmonary solutions of the disclosure may typically comprise the drug or drug

[0512] 10 to be delivered, optionally formulated with a surface-active agent, such as a nonionic surfactant (e.g., polysorbate-80), and one or more buffers. In some embodiments, the nasal spray solution further comprises a propellant. The pH of the nasal spray solution is optionally between about pH 3.0 and 6.0, or 4.5 + / - 0.5. Suitable buffers for use within these compositions are as described above or as otherwise known in the art. Other components may be added to enhance or maintain chemical stability, including preservatives, surfactants, dispersants, or gases. Suitable preservatives include, but are not limited to, phenol, methyl paraben, paraben, m-cresol, thiomersal, chlorobutanol, benzylalkonimum chloride, and the like. Suitable surfactants include, but are not limited to, oleic acid, sorbitan trioleate, polysorbates, lecithin, phosphatidyl cholines, and various long chain diglycerides and phospholipids. Suitable dispersants include, but are not

[0513] 20 limited to, ethylenediaminetetraacetic acid, and the like. Suitable gases include, but are not limited to, nitrogen, helium, chlorofluorocarbons (CFCs), hydrofluorocarbons (HFCs), carbon dioxide, air, and the like.

[0514] Within alternate embodiments, nasal and pulmonary formulations are administered as dry powder formulations comprising the active agent in a dry, usually lyophilized, form of an

[0515] 25 appropriate particle size, or within an appropriate particle size range, for intranasal delivery. Minimum particle size appropriate for deposition within the nasal or pulmonary passages is often about 0.5 pm. mass median equivalent aerodynamic diameter (MMEAD), commonly about 1 pm MMEAD, and more typically about 2 pm MMEAD. Maximum particle size appropriate for deposition within the nasal passages is often about 10 pm MMEAD, commonly about 8 pm

[0516] 30 MMEAD, and more typically about 4 pm MMEAD. Intranasally and pulmonaryly respirable powders within these size ranges can be produced by a variety of conventional techniques, such PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0517] Docket No. Y2008-7007WO as jet milling, spray drying, solvent precipitation, supercritical fluid condensation, and the like. These dry powders of appropriate MMEAD can be administered to a patient via a conventional dry powder inhaler (DPI), which relies on the patient's breath, upon pulmonary or nasal inhalation, to disperse the power into an aerosolized amount. Alternatively, the dry powder may

[0518] 5 be administered via air-assisted devices that use an external power source to disperse the powder into an aerosolized amount, e.g., a piston pump.

[0519] To formulate compositions for nasal or pulmonary delivery, the active agent can be combined with various pharmaceutically and / or cosmetically acceptable additives, as well as a base or carrier for dispersion of the active agent(s). Desired additives include, but are not limited

[0520] 10 to, pH control agents, such as arginine, sodium hydroxide, glycine, hydrochloric acid, citric acid, etc. In addition, local anesthetics (e.g., benzyl alcohol), isotonizing agents (e.g., sodium chloride, mannitol, sorbitol), adsorption inhibitors (e.g., Tween 80), solubility enhancing agents (e.g., cyclodextrins and derivatives thereof), stabilizers (e.g., serum albumin), and reducing agents (e.g., glutathione) can be included. When the composition for nasal or pulmonary delivery is a liquid, the tonicity of the formulation, as measured with reference to the tonicity of 0.9% (w / v) physiological saline solution taken as unity, is typically adjusted to a value at which no substantial, irreversible tissue damage will be induced in the nasal mucosa at the site of administration. Generally, the tonicity of the solution is adjusted to a value of about 1 / 3 to 3, more typically 1 / 2 to 2, and most often 3 / 4 to 1.7.

[0521] 20 The compound(s) of the disclosure may be dispersed in a base or vehicle, which may comprise a hydrophilic compound having a capacity to disperse the active agent and any desired additives. The base may be selected from a wide range of suitable carriers, including but not limited to, copolymers of polycarboxylic acids or salts thereof, carboxylic anhydrides (e.g., maleic anhydride) with other monomers (e.g., methyl (meth)acrylate, acrylic acid, etc.),

[0522] 25 hydrophilic vinyl polymers such as polyvinyl acetate, polyvinyl alcohol, polyvinylpyrrolidone, cellulose derivatives such as hydroxymethylcellulose, hydroxypropylcellulose, etc., and natural polymers such as chitosan, collagen, sodium alginate, gelatin, hyaluronic acid, and nontoxic metal salts thereof. Often, a biodegradable polymer is selected as a base or carrier, for example, polylactic acid, poly(lactic acid-glycolic acid) copolymer, polyhydroxybutyric acid,

[0523] 30 poly(hydroxybutyric acid-glycolic acid) copolymer and mixtures thereof. Alternatively or additionally, synthetic fatty acid esters such as polyglycerin fatty acid esters, sucrose fatty acid PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0524] Docket No. Y2008-7007WD esters, etc. can be employed as carriers. Hydrophilic polymers and other carriers can be used alone or in combination, and enhanced structural integrity can be imparted to the carrier by partial crystallization, ionic bonding, crosslinking and the like. The carrier can be provided in a variety of forms, including, fluid or viscous solutions, gels, pastes, powders, microspheres and

[0525] 5 films for direct application to the nasal mucosa. The use of a selected carrier in this context may result in promotion of absorption of the active agent.

[0526] The compounds of the disclosure may be formulated in a delivery carrier. The delivery systems disclosed herein may offer benefits in mitochondria-targeted delivery and improving the therapeutic ability of the compounds. For instance, nanoparticle formulations have been shown

[0527] 10 to effectively transport drug molecules in their original form, solubilize hydrophobic drug molecules, enhance half-life of molecules, and decrease side effects and immunogenicity attributable to the molecules. The delivery carriers disclosed herein may be selected or designed to provide enhanced skin penetration, higher stability, site specific targeting, e.g., efficiently deliver cargo inside the mitochondrial matrix, high entrapment efficiency, and / or time- controlled, e.g., delayed or sustained, release of the compounds. Properties of the delivery carrier that may be designed to effectively deliver compounds of the formulation to a target site of a subject include surface chemistry, coating, structure, size, ability to aggregate, and solubility.

[0528] The formulations disclosed herein may comprise one or more skin penetration enhancer. Generally, small and moderately lipophilic molecules are likely to penetrate the skin barrier.

[0529] 20 Other compounds may require a suitable skin penetration enhancer to penetrate the barrier by either diminishing the barrier properties of the skin or actively driving movement of compounds across the skin with the input of external energy. Skin penetration enhancers are described in “Penetration Enhancement of Topical Formulations,” (Ng, 2018) and “Transdermal Deliver}' Systems in Cosmetics,” (Kim, 2020), each of which is incorporated herein by reference in its

[0530] 25 entirety for all purposes.

[0531] The delivery carriers disclosed herein may provide skin penetration enhancement for the compounds. The formulations disclosed herein may additionally or alternatively contain one or more chemical or physical skin penetration enhancers. Exemplary chemical skin penetration enhancers include alcohols, such as, ethanol and glycol, sulfoxides, such as, dimethyl sulfoxide,

[0532] 30 laurocapram, pyrrolidones, dimethyl isosorbide, isopropyl myristate, propylene glycol, oleic acid, eucalyptol, water / aqua (hydration), surfactants, urea, fatty acids, fatty alcohols, and PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0533] Docket No. Y2008-7007WO terpenes and / or terpenoids. Exemplary physical skin penetration enhancers include rollers, scrapers, scrubbers, exfoliators, microdermabrasion needles, iontophoresis devices, electroporation devices, ultrasound devices, such as sonophoresis, thermal ablation, magnetophoresis, photomechanical waves, electron beam irradiation, and low light therapy

[0534] 5 devices, such as light emitting diode (LED) sources. Two or more skin penetration enhancers may be used in the formulation synergistically.

[0535] Chemical skin penetration enhancers may be included in dermatological, transdermal, cosmetic, and pharmaceutical products to enhance the dermal absorption of drug compounds. Chemical enhancers may enable or improve solubility, penetration, and / or absorption of the

[0536] 10 compounds disclosed herein. Exemplary chemical enhancers are described below.

[0537] Water (aqua) generally increases fluidity of the composition, providing higher permeability. Additionally, water hydrates the skin barrier, altering skin lipids and / or proteins for improved permeation. Hydrating compounds, such as glycerol and urea, may promote transdermal permeation by facilitating hydration of the stratum corneum and forming hydrophilic diffusion channels within the barrier.

[0538] Alcohol solvents, such as ethanol and propylene glycol, may provide penetration enhancement by increasing fluidity of the compound and also act as good solvents. Degree of permeation may be selected by controlling alkyl chain length of fatty alcohols.

[0539] Surfactants generally solubilize lipophilic agents, including active ingredients of the

[0540] 20 formulation as well as lipids within the stratum corneum. Thus, surfactants may enhance skin permeability by partitioning into the epithelial cell membranes and disrupting the packing of membrane lipids, forming structural defects that reduce membrane integrity. The effect of the surfactant on skin permeation may be designed by selecting concentration and type of surfactant. The surfactant may be anionic, cationic, or nonionic. Anionic surfactants may be selected for

[0541] 25 skin or hair applications because they interact with keratin and lipids. Cationic surfactants may be selected for skin applications because they interact with skin proteins via poler interactions. Non-ionic surfactants are generally less irritating to the skin and have better tolerability.

[0542] Fatty acids may increase percutaneous drug absorption. Long-chain fatty acids, which are carboxylic acids with typically long, unbranched aliphatic tails, have been demonstrated to

[0543] 30 increase percutaneous drug absorption as an effect of alkyl chain length. Low molecular weight alkanols may act as solubilizers to enhance the solubility of the compound in the fatty matric of PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0544] Docket No. Y2008-7007WO the stratum comeum. Polyunsaturated fatty acids, such as linoleic, alpha- linoleic, and arachidonic acids, may enhance the skin permeation. One exemplary fatty acid chemical penetration enhancer is oleic acid. Oleic acid provides increased fluidity and reduced resistance toward the permeation of molecules.

[0545] 5 Terpenes are hydrocarbons commonly found in plant extracts. Terpenoids are terpenes containing additional functional groups. One group of terpenes that may provide penetration enhancement are oxygen-containing terpenes. Exemplary oxygen containing terpenes include menthol, thymol, carvacrol, menthone, and cineole. Such terpenes may enhance penetration in a similar mechanism as alcohols. However, terpenes may be considered natural products. Benefits

[0546] 10 of terpenes include high percutaneous ability with minimal irritancy and toxicity.

[0547] The compounds of the disclosure may be formulated with a functional agent, e.g., mitochondria-targeting agent. For instance, in certain embodiments, the compounds of the disclosure may be linked with a functional agent, such as a mitochondria-targeting agent. Exemplary mitochondrial targeting agents include antibodies, polymeric functional moieties, such as PEG, lipophilic cations, such as triphenylphosphine (TPP), and peptides such as mitochondrial targeting peptides (MPP).

[0548] The compounds of the disclosure may be formulated with a pharmaceutically and / or cosmetically acceptable vehicle. The pharmaceutically and / or cosmetically acceptable vehicle may be formulated for topical, parenteral, or enteral administration. The vehicle may comprise

[0549] 20 substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc. For solid compositions, conventional nontoxic pharmaceutically and / or cosmetically acceptable carriers can be used which include, for

[0550] 25 example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, magnesium carbonate, and the like.

[0551] Compositions of the disclosure can also be formulated as a solution, microemulsion, foam, or other ordered structure suitable for high concentration of active ingredients. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, glycols, diols,

[0552] 30 glycerin, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. In some embodiments, the carrier may be free of water. In PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0553] Docket No. Y20Q8-7007WO some embodiments, the carrier may be free of alcohols, e.g., ethanol. Proper fluidity for solutions can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of a desired particle size in the case of dispersible formulations, and by the use of surfactants.

[0554] In certain exemplary embodiments, viscosifiers may be incorporated, such as xanthan,

[0555] 5 cellulosics, or guar, to produce an end viscosity in the range of 1000 - 2000 cps. The selected viscosity will have an effect on aesthetics upon application of the formulation.

[0556] The pH of the formulation may be controlled to be substantially neutral, for example, between 6-8, 6-7, or 6.5-7. In general, the delivery carriers disclosed herein may cause a pH shift of the formulation once combined with vehicle. Thus, pH may be monitored during and after

[0557] 10 combination of any delivery carriers with a vehicle.

[0558] The compositions, e.g., delivery carriers, disclosed herein may be designed to provide time-controlled release, e.g., immediate release, extended release, or slow or sustained release of the deliverable. The formulations disclosed herein may additionally or alternatively be formulated for time-controlled release. In certain embodiments, compound(s) and compositions of the disclosure are administered in a time-release formulation, for example in a composition which includes a slow release polymer. Such compositions can be prepared with carriers that will protect against rapid release, for example a controlled release vehicle such as a polymer, microencapsulated delivery system or bioadhesive gel. Prolonged delivery, in various compositions of the invention can be brought about by including in the composition agents that

[0559] 20 delay absorption, for example, aluminum monosterate hydrogels and gelatin. When controlled release formulations is desired, controlled release binders suitable for use in accordance with the invention include any biocompatible controlled-release material which is inert to the active agent and which is capable of incorporating the biologically active agent. Numerous such materials are known in the art.

[0560] 25 Formulations suitable for topical administration include solutions, oils, creams, emulsions, foams, and gels containing, in addition to the active ingredient, such carriers as are known in the art. Topical formulations may be pharmaceutical or cosmetic formulations. In some embodiments, the compound is formulated as a shampoo, conditioner, spray, cream, gel, balm, body wash, soap, lotion, or make-up.

[0561] 30 The compounds of the disclosure and compositions of the disclosure can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and can be stored in a PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0562] Docket No. Y2008-7007WD freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid excipient, for example, water, for injections, immediately prior to use. Suitable unit doses, i.e., effective amounts, may be determined during clinical trials designed appropriately for each of the conditions for which administration of a chosen compound is indicated and will, of course, vary

[0563] 5 depending on the desired clinical endpoint. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules, and tablets. The requirements for effective pharmaceutically acceptable carriers for injectable compositions are well known to those of ordinary skill in the art. See Pharmaceutics and Pharmacy Practice, J.B. Lippincott Co., Philadelphia, Pa., Banker and Chalmers, Eds., 238-250 (1982) and ASHP Handbook on

[0564] 10 Injectable Drugs, Toissel, 4thed., 622-630 (1986).

[0565] Additionally, formulations suitable for rectal administration may be presented as suppositories by mixing with a variety of bases such as emulsifying bases or water-soluble bases. Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulas containing, in addition to the active ingredient, such carriers as are known in the art to be appropriate.

[0566] The compositions disclosed herein may be associated with a variety of natural products, and examples of such products are set out below. The compositions disclosed herein may be formulated as a natural product. The compositions disclosed herein may be administered in combination with a natural product. The compositions disclosed herein may be incorporated in a

[0567] 20 natural product. These natural products may be comprised of formulations or compositions disclosed throughout this disclosure.

[0568] Natural products may be or comprise products for commercial purposes, and may refer to dietary supplements, and foods, e.g., food, food supplements, medical food, food additive, nutraceutical, or drink, produced from natural sources. Natural products may have

[0569] 25 pharmacological or biological activity that may be of therapeutic benefit, e.g., in treating disease or conditions. Natural products may be included in traditional medicines, treatments for cosmetological purposes, cosmetics, and spa treatments. A natural product referred to herein may comprise any one or more of the components described as a natural product to be incorporated into a composition or formulation comprising one or more other components, e.g., excipients.

[0570] 30 The preparation or formulation referred to as a natural product may comprise a natural product defined herein and one or more additional components or ingredients. Any of the compositions, PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0571] Docket No. Y20Q8-7007WO preparations, or formulations discussed throughout this disclosure may be or comprise one or more natural products.

[0572] One skilled in the art will appreciate that suitable methods of administering a compound of the disclosure to a patient are available, and, although more than one route can be used to

[0573] 5 administer a particular compound, a particular route can provide a more immediate and more effective reaction than another route.

[0574] The compositions or formulations disclosed herein may be provided in an end-use container. The end-use container may be a single use container or a multi-use container. The end-use container may comprise an air-tight seal or be configured to be hermetically sealed. In

[0575] 10 some embodiments, the end-use container may also comprise an oxygen absorber. In some embodiments, the end-use container may comprise or be formed of a light- shielding material. For instance, the end-use container may comprise or be formed of a light- shielding polymer or composite material. The material may be selected to provide temperature control or reduce a degree of temperature fluctuations within the sealed end-use container.

[0576] The compositions or formulations disposed in an end-use container may comprise storage instructions. In some embodiments, the compositions or formulations disposed in an end-use container may comprise instructions to store the container at a temperature of 2-8 °C. The compositions or formulations disposed in an end-use container may comprise an indication of an expiration date. In some embodiments, the indication of the expiration date may be at 1 month, at

[0577] 20 2 months, at 3 months, at 4 months, at 5 months, at 6 months, at 12 months, at 18 months, or at 24 months from a packaging date of the end-use container.

[0578] Examples

[0579] The function and advantages of these and other embodiments can be better understood

[0580] 25 from the following examples. These examples are intended to be illustrative in nature and are not considered to be limiting the scope of the invention.

[0581] Example 1: Delivery Carrier Encapsulation of Emblica Extract and Isolated Chebulinic Acid

[0582] 30 Emblica extract (Y100), encapsulated emblica extract (Y100), isolated chebulinic acid, and encapsulated isolated chebulinic acid formulations were tested in vitro for induced PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0583] Docket No. Y2008-7007WO expression of mitochondrial biogenesis regulatory proteins including mitochondrial complex IV subunit 2 (COXII), mitochondrial transcript factor A (TFAM) at timepoints of 6, 12, 18, and 24 hours post-administration.

[0584] Formulations of varying concentrations were tested, including 10 pM, encapsulated 0.25

[0585] 5 pM, encapsulated 0.5 pM, and encapsulated 1.0 pM. The test formulations were compared to DMSO, ciprofloxacin, blank carriers, and untreated vehicle controls. The results are presented in the graphs of FIGS. 1A-1D (COXII) and 2A-2D (TFAM). The x-axis legend of the graphs of FIGS. 1A-1D and 2A-2D is as follows:

[0586] U: Untreated

[0587] 10 D: DMSO

[0588] C: Ciprofloxacin

[0589] Y: YlOO-S-O

[0590] 1: Chebulinic Acid 10 pM

[0591] B: Blank Delivery Carriers

[0592] 2: Encapsulated Chebulinic Acid 0.25 pM

[0593] 3: Encapsulated Chebulinic Acid 0.5 pM

[0594] 4: Encapsulated Chebulinic Acid 1 pM

[0595] 5: Encapsulated YlOO-S-O 4.38xl04% (v / v)

[0596] As shown in the graphs of FIGS. 1A-1D and 2A-2D, the greater effect was shown by the

[0597] 20 encapsulated compositions.

[0598] Encapsulated emblica extract formulations at varying delivery carrier loading concentration were also tested, including 0.01%, 0.05%, 0.10%, 0.20%, 50 pg / L, 100 pg / L, 200 pg / L, and 400 pg / L. The samples were tested for induced expression of COXII at 6 hours postadministration. The test formulations were compared to DMSO, ciprofloxacin, blank delivery

[0599] 25 carriers, and untreated vehicle controls. The results are presented in the graphs of FIGS. 3A-3B. As shown in the graphs of FIGS. 3A-3B, the greater effect was shown by encapsulated compositions, generally proportionately with increasing compound loading concentration.

[0600] Formulations having varying sizes of delivery carriers were also tested, including 4.4 pm, 7.7 pm, 9.4 pm, 11.7 pm, and 95 pm. The varying formulations also included octyl-doped

[0601] 30 delivery carriers and undoped delivery carriers, as well as powder loaded and oil loaded delivery carriers. The samples were tested for induced expression of COXII and TFAM at 6, 12, 24, and PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0602] Docket No. Y2008-7007WO

[0603] 48 hours post-administration. The results are presented in the graphs of FIGS. 4A-4D (COXII), FIGS. 5A-5D (TFAM), and FIGS. 6A-6D (COXII). In the graphs, the x-axis legend is as follows:

[0604] A: Y100 (emblica extract) powder loaded (40% LF; mean particle size = 11.6 pm)

[0605] 5 B: Y100 (emblica extract) oil loaded (42% LF; mean particle size = 9.4 pm)

[0606] C: undoped blank (mean particle size = 7.7 pm)

[0607] D: large size octyl-doped blank (mean particle size = 95 pm)

[0608] E: small size octyl-doped blank (mean particle size = 4.4 pm)

[0609] As shown in the graphs of FIGS. 4A-4D, FIGS. 5A-5D, and FIGS. 6A-6D, the greater

[0610] 10 effect was generally observed as a result of smaller particles.

[0611] Formulations having a similar size of delivery carriers, including octyl-doped and undoped carriers were also tested. The samples were tested for induced expression of COXII and TFAM at 6, 12, 24, and 48 hours post-administration. The results are presented in the graphs of FIGS. 7A-7D (COXII), and FIGS. 8A-8D (TFAM). In the graphs of FIGS. 7A-7D and FIGS. 8A-8D, the x-axis legend is as follows:

[0612] U: Untreated

[0613] D: DMSO

[0614] C: Ciprofloxacin

[0615] B: Blank Undoped

[0616] 20 0: Blank Octyl-Doped

[0617] 5: YlOO-S-O 0.005%

[0618] 1: YlOO-S-O 0.01%

[0619] 2: YlOO-S-O 0.02%

[0620] As shown in the data presented in FIGS. 7A-7D and FIGS. 8A-8D, octyl-doped carriers

[0621] 25 showed a greater expression than their undoped counterparts.

[0622] Overall, the data show that induction of mitochondrial biogenesis depends on delivery carrier load concentration and the size of delivery carriers. Differences in delivery carrier preparation (between octyl-doped and undoped) and load have an effect on mitochondrial biogenesis induction.

[0623] 30 PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0624] Docket No. Y2008-7007WQ

[0625] Example 2: Safety Study of Isolated Chebulinic Acid Loaded Delivery Carriers

[0626] A human repeat insult patch test (HRIPT) study was performed to determine skin irritation and sensitization of encapsulated 1.0% isolated chebulinic acid after repeated application to the skin of human subjects. In the study, 54 participants (42 female and 12 male,

[0627] 5 aged 18 to 64 years old) topically applied the test product in two phases: phase I included 9 inductions and phase II included 2 challenges. No adverse reactions of any kind were reported during the study. Accordingly, the encapsulated 1.0% isolated chebulinic acid test formulation was shown to be safe and well tolerated for human topical application.

[0628] 10 Example 3: In vitro Studies for Induced Mitochondrial Biogenesis

[0629] Several test compositions were administered in vitro to HEK293 cells, primary adult dermal fibroblast cells, or primary adult epidermal keratinocyte cells in various dosing schemes. Cells were harvested at 6 hours, 12 hours, 24 hours, or 48 hours after administration of the test compound. Harvested cells were tested for COXII expression and TFAM expression for induced

[0630] 15 mitochondrial biogenesis. The test and control compounds are listed in Table 3 below.

[0631] Table 3: Test and Control Compounds for In vitro Studies PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0632] Docket No. Y2008-7007WQ

[0633] Various Dosages of Chebulinic Acid Administered to HEK293 Cells

[0634] Chebulinic acid formulations having concentrations of 2.5 pM, 5 |aM, 10 pM, 20 pM, 50 M, or 100 M were administered to HEK293 cells in vitro. COXII and TFAM expression

[0635] 5 increased after administration of the 2.5 pM concentration formulation at 6 hours (n=l) (4.73%, 3.90%, respectively) and 12 hours (n= 1 ) (9.02%, 20.07%, respectively). COXII and TFAM expression increased after administration of the 5 pM concentration formulation at 12 hours (n=4) (2.95%, 0.63%, respectively) and 48 hours (n=l) (10.91%, 23.99%, respectively). TFAM expression also increased after administration of the 5 pM concentration formulation at 6 hours

[0636] 10 (n=3) (11.15%). COXII and TFAM expression increased after administration of the 10 pM concentration formulation at 6 hours (n=4) (1.94%, 7.92%, respectively), 12 hours (n=4) (2.76%, 4.88%, respectively), and 48 hours (n=l) (9.42%, 24.41%, respectively). COXII and TFAM expression increased after administration of the 20 pM concentration formulation at 12 hours (n=2) (11.46%, 5.48%, respectively). COXII and TFAM expression increased after

[0637] 15 administration of the 50 pM concentration formulation at 6 hours (n=2) (13.63%, 15.55%, respectively) and 12 hours (n=l) (1.91%, 3.48%, respectively). TFAM expression also increased after administration of the 50 pM concentration formulation at 48 hours (n=l) (29.36%). COXII PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0638] Docket No. Y2008-7007WO and TFAM expression increased after administration of the 100 pM concentration formulation at 6 hours (n= 1 ) (12.42%, 24.75%, respectively). TFAM expression also increased after administration of the 100 pM concentration formulation at 12 hours (n=l ) (5.14%). COXII expression also increased after administration of the 100 pM concentration formulation at 24

[0639] 5 hours (n= 1 ) (11.36%).

[0640] Chebulinic Acid Administered to Primary Adult Dermal Fibroblast Cells or Primary Adult Epidermal Keratinocyte Cells

[0641] Chebulinic acid formulations having concentrations of 1 pM, 5 pM, or 10 pM were administered to primary adult dermal fibroblast cells or primary adult epidermal keratinocyte cells in vitro. TFAM expression increased in primary adult epidermal keratinocyte cells at 6 hours after administration (n=2) at all concentrations tested (1 pM, 5 pM, or 10 pM) by 19.34%, 19.53%, and 30.87%, respectively.

[0642] 15 Chebulinic Acid Combination Formulations Administered to HEK293 Cells

[0643] Formulations having chebulinic acid (10 pM) alone or chebulinic acid (10 pM) with chebulagic acid (10 pM), gallic acid (50 pM), or kaempferol (10 pM) were administered to HEK293 cells in vitro. TFAM and COXII expression increased in the chebulinic acid with gallic acid samples (n=3) at 6 hours after administration by 21.77% and 0.07%, respectively. TFAM and COXII expression also increased in the chebulinic acid alone samples (n=6) at 12 hours after administration by 4.02% and 14.90%, respectively.

[0644] Sequential Doses of Chebulinic Acid Administered to HEK293 Cells

[0645] Sequential doses of chebulinic acid (10 pM) were administered to HEK293 cells in vitro.

[0646] 25 The cells received one, two, three, or four doses of chebulinic acid prior to harvesting, according to the dosing scheme summarized in Table 4 below.

[0647] Table 4: Dosing Scheme for Sequential Dosing In vitro HEK293 Cells Study PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0648] Docket No. Y2008-7007WO

[0649] COXII expression increased by 45% in the two-dose group. TFAM expression increased by 18%, 2.5%, and 24% in the two-dose, three-dose, and four-dose groups, respectively. Accordingly, sequential doses of chebulinic acid may increase mitochondrial biogenesis

[0650] 5 induction in cells.

[0651] Chebulinic Acid in Delivery Carriers (10% Load Factor) Administered to HEK293 Cells

[0652] Chebulinic acid loaded in deliver}' carriers at a 10% load factor was administered to HEK293 cells in vitro at concentrations of 0.25 pM, 0.5 pM, or 1 pM. COXII and TFAM expression increased after administration of the 0.25 pM concentration formulation at 12 hours (n=5) (40.66%, 9.28%, respectively) and at 24 hours (n=5) (3.67%, 4.55%, respectively). COXII and TFAM expression increased after administration of the 0.5 pM concentration formulation at all timepoints tested, namely at 6 hours (n=5) (14.95%, 5.21%, respectively), at 12 hours (n=5) (39.21%, 10.48%, respectively), and at 24 hours (n=5) (4.50%, 6.21%, respectively). COXII and

[0653] 15 TFAM expression increased after administration of the 1 pM concentration formulation at 24 hours (n=5) (16.60%, 18.27%, respectively). COXII expression also increased after administration of the 1 pM concentration formulation at 6 hours (n=5) (6.51%) and 12 hours (n=5) (21.41%).

[0654] The 0.25 pM, 0.5 pM, and 1 pM concentration formulations were also tested at 18 hours. TFAM expression increased after administration of the 0.25 pM concentration formulation (n=l) (6.16%), COXII and TFAM expression increased after administration of the 0.5 pM concentration formulation (n=l) (25.08%, 37.98%, respectively), and COXII and TFAM expression increased after administration of the 1 pM concentration formulation (n=l) (57.73%, 45.66%, respectively).

[0655] 25

[0656] Chebulinic Acid in Delivery Carriers (10% Load Factor) Administered to HEK293 cells, Primary Adult Dermal Fibroblast Cells, or Primary Adult Epidermal Keratinocyte Cells PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0657] Docket No. Y2008-7007WO

[0658] Chebulinic acid loaded in deliver}' carriers at a 10% load factor was administered to HEK293 cells, primary adult fibroblast cells, or primary adult epidermal keratinocyte cells in vitro at concentrations of 1 pM, 5 pM, or 10 pM.

[0659] COXII and TFAM expression increased in the HEK293 cells after administration of the 1

[0660] 5 pM concentration formulation at 6 hours (n=l) (3.38%, 11.23%, respectively) and 12 hours (n=l) (51.47%, 62.39%, respectively). COXII and TFAM expression increased in the HEK293 cells after administration of the 5 pM concentration formulation at 12 hours (n=l) (35.67%, 42.13%, respectively). TFAM expression also increased in the HEK293 cells after administration of the 5 pM concentration formulation at 6 hours (n=l) (2.69%). COXII and TFAM expression

[0661] 10 increased in the HEK293 cells after administration of the 10 pM concentration formulation at 12 hours (n=l) (24.84%, 40.34%, respectively). COXII expression also increased in the HEK293 cells after administration of the 10 pM concentration formulation at 48 hours (n=l) (4.50%).

[0662] COXII expression increased in the primary adult fibroblast cells after administration of all concentrations (1 pM, 5 pM, or 10 pM) at all timepoints (6 hr, 12 hr, 24 hr, 48 hr) (n=2). The results are presented in Table 5 below. TFAM expression also increased in the primary adult fibroblast cells after administration of the 5 pM concentration formulation at 24 hours (11.21%).

[0663] COXII expression increased in the primary adult epidermal keratinocyte cells after administration of all concentrations (1 pM, 5 pM, or 10 pM) at all timepoints (6 hr, 12 hr, 24 hr, 48 hr), except the 10 pM concentration formulation at 24 hours after administration. The results

[0664] 20 are presented in Table 5 below.

[0665] Table 5: Expression Increase of COXII in Primary Adult Fibroblast Cells or Primary Adult Epidermal Keratinocyte Cells PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0666] Docket No. Y2008-7007WQ

[0667] Various Load Factors of Chebulinic Acid in Delivery Carriers Administered to HEK293 Cells Chebulinic acid loaded in deliver}' carriers at a 10% load factor, 20% load factor, or 30% load factor was administered to HEK293 cells in vitro at concentrations of 1 |aM or 5 pM.

[0668] 5 TFAM expression increased after administration of the 5 pM concentration formulation at all load factors (10%, 20%, 30%) at 6 hours after administration (n=l) (3.21%, 5.60%, 16.14%).

[0669] High Load Factor (30% ) Chebulinic Acid in Delivery Carriers Administered to HEK293 Cells Chebulinic acid loaded in deliver}' carriers at a 30% load factor was administered to

[0670] 10 HEK293 cells in vitro at concentrations of 0.25 pM, 0.5 pM, 1 pM, or 20 pM. COXII expression increased after administration of all concentrations (0.25 pM, 0.5 pM, 1 pM, and 20 pM) at all timepoints (6 hr, 12 hr, 24 hr), except the 20 pM concentration formulation at 6 hours after administration. COXII expression increase was especially noticeable at low concentrations, 1 pM or less. TFAM expression also increased after administration of the 0.25 pM and 0.5 pM

[0671] 15 concentration formulations at 12 hours (n=l) (12.49% and 1.36%, respectively). The results are presented in Table 6 below. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0672] Docket No. Y2008-7007WQ

[0673] Table 6: Expression Increase of COXII in HEK293 Cells

[0674] As shown in the data presented above, different dosages of the test formulation, with and without delivery carriers, showed increased expression of mitochondrial biogenesis proteins

[0675] 5 COXII and TEAM.

[0676] Example 4: Differentially Expressed Gene Analysis of 3 Participants

[0677] Three individuals were topically administered Y 100 cream (chebulinic acid). Subjects 1 and 3 were older than subject 2. RNA sequencing was performed on the three participants before 10 and after use of the Y100 cream. The results are presented in Tables 7-8 and FIGS. 9 through

[0678] 14C. Notably, administration of the Y100 cream upregulated many keratin genes.

[0679] FIG. 9 shows a heatmap of gene expression. The heatmap depicts similarities and differences in the 3 samples. Samples 1 and 3 are age matched, as shown by the gene expression clustering on top of the dendrogram. Samples 1 and 3 show more similitude.

[0680] 15 FIG. 10 is a Venn diagram showing gene expression from each sample. As shown in FIG.

[0681] 10, there were 14 genes that showed regulated expression across all three samples. Table 7 lists the common 14 genes, each of which was either upregulated or downregulated. Although the 14 PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0682] Docket No. Y2008-7007WQ genes were common for all 3 samples, the direction of regulation (up or down) is opposite for sample 2, from the younger participant.

[0683] Table 7: Common Genes Across Samples and Fold Change

[0684] Accordingly, administration of Y100 was effective to alter, e.g., upregulate or downregulate, AQP5, ARGHGAP115-SCG5 (e.g., ARGHGAP115, SCG5), AWAT2, DNER, AIF3CL, KRT19, KRT8, KRT81, S100A7, SPDEF, STAC2, THRSP, TMEM139, PADI2. Additional information on these genes is listed in Table 8 below.

[0685] Table 8: Genes Altered by Administration of Y100 PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0686] Docket No. Y2008-7007WQ PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0687] Docket No. Y2008-7007WQ

[0688] Two genes, DNER and THRSP, were tested for differences on sun exposed and nonexposed skin expression. The results are presented in the graphs of FIGS. 11A-1 IB.

[0689] The graphs of FIGS. 12A-12C, 13A-13C, and 14A-14C show biological roles of the

[0690] 5 differentially expressed genes as a whole (gene set enrichments) from subject 1 (FIGS. 12A- 12C), subject 3 (FIGS. 13A-13C), and subject 2 (FIGS. 14A-14C), respectively.

[0691] In vitro analysis of collagen gene COL1A1

[0692] Collagen gene COL1A1 expression as a result of the administration of Y100 (chebulinic

[0693] 10 acid) was also tested in vitro. The results are shown in the graphs of FIG. 15A-15C. As shown in FIGS. 15A-15C, Y100 had a significant upregulation of the collagen gene, COL1A1.

[0694] Furthermore, Y100 outperformed retinol in upregulation of COL1A1 at 6 hours, 12 hours, and 24 hours after administration.

[0695] 15 Administration of Y 100 is believed to improve mitochondrial function in subjects.

[0696] Specifically, administration of Y100 is believed to protect skin from dryness; reduce oxidative stress; target pigmentation; prevent inflammation (anti-inflammatory); boost collagen PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0697] Docket No. Y2008-7007WO production; and increase ATP (“energy”) levels, providing more energy to skin cells to perform necessary functions.

[0698] Example 5: In Vitro Wound Healing Assays

[0699] 5 A series of scratch assays on human epidermal keratinocytes (HaCaT cells) was performed. An untreated control sample was compared against a series of treatments: DMSO, Ciprofloxacin, LY294002 (50 pM), Allantoin (50 pg / ml) and Y100 (chebulinic acid) (1 pM). The percent of wound closure after a predetermined period of time subsequent to administration was evaluated. Y100 exhibited superior results in terms of wound closure in comparison to the control and all

[0700] 10 other treatments. This included superior performance over Allantoin which is the current premier standard in terms of natural healing aids. The data is graphically presented in FIG. 16A and related assay images are presented in FIG. 16B.

[0701] Example 6: In Vivo Wound Healing

[0702] Y 100 (chebulinic acid; encapsulated) was applied to a facial stab wound of a subject over the course of a couple of weeks. The facial stab wound exhibited significant scarring prior to treatment. It was demonstrated that Y 100 was able to help with wound and scar healing. The scar was virtually gone after the couple of weeks of Y100 administration. Before and after photos are presented in FIGS. 17A and 17B.

[0703] 20

[0704] Example 7: Particle Size Distribution

[0705] Silica particle delivery carriers were manufactured as disclosed herein. The particle size distribution for several exemplary compositions of silica particle carriers is summarized below.

[0706] 25 Composition 1

[0707] • D90 = 12 pm

[0708] • D10 = 1 pm

[0709] • D50 - 5 pm

[0710] • Particle size distribution = 2.2

[0711] 30 PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0712] Docket No. Y2008-7007WO

[0713] Composition 2

[0714] • D90 = l 8 u m

[0715] • DIO = 2 pm

[0716] • D50 = 5 pm

[0717] 5 • Particle size distribution = 3.3

[0718] Composition 3

[0719] • D90 = 30 pm

[0720] • DIO = 5 pm

[0721] • D50 = 12 pm

[0722] • Particle size distribution = 2.08

[0723] Table 9B: Properties of Exemplary Compositions of Silica Particle Delivery Carriers

[0724] 15 The phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. As used herein, the term “plurality” refers to two or more items or components. The terms “comprising,” “including,” “carrying,” “having,” “containing,” and “involving,” whether in the written description or the claims and the like, are open-ended terms, i.e., to mean “including but not limited to.” Thus, the use of such terms is meant to encompass the items listed thereafter, and equivalents thereof, as well as additional items. Only the transitional phrases “consisting of’ and “consisting essentially of,” are closed or semi-closed transitional phrases, respectively, with respect to the claims. Use of ordinal terms such as “first,” “second,” “third,” and the like in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in

[0725] 25 which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements. PCT / US25 / 48097 26 September 2025 (26.09.2025)

[0726] Docket No. Y2008-7007WQ

[0727] Having thus described several aspects of at least one embodiment, it is to be appreciated various alterations, modifications, and improvements will readily occur to those skilled in the art. Any feature described in any embodiment may be included in or substituted for any feature of any other embodiment. Such alterations, modifications, and improvements are intended to be

[0728] 5 part of this disclosure and are intended to be within the scope of the invention. Accordingly, the foregoing description and drawings are by way of example only.

[0729] Those skilled in the art should appreciate that the parameters and configurations described herein are exemplary and that actual parameters and / or configurations will depend on the specific application in which the disclosed methods and materials are used. Those skilled in 10 the art should also recognize or be able to ascertain, using no more than routine experimentation, equivalents to the specific embodiments disclosed.

Claims

Docket No. Y2008-7007WGCLAIMS1. A method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof.

2. A method of treating or diminishing appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof.

3. The method of any of the preceding claims, wherein the emblica extract is derived from Emblica officinalis.

4. The method of any of the preceding claims, wherein the compound constituent of the emblica extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O- (C1-C5 alkyl) or O-(Ci-Cs alkenyl) groups, or a pharmaceutically acceptable form thereof, or a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups, or a pharmaceutically acceptable form thereof, or a combination of the foregoing.

5. The method of any of the preceding claims, wherein the compound constituent of the emblica extract is gallic acid, vanillic acid, chlorogenic acid, caffeic acid, syringic acid, coumaric acid, quercetin, , emblicanin A, emblicanin B, punigluconin, pedunculagin, punicafolin, phyllancmblin, kaempferol, ellagic acid, chcbulinic acid, chcbulagic acid, punicalagin, a metabolite of any of the foregoing, a compound having a similarity score of at least 95% with any of the foregoing, or a pharmaceutically acceptable form of any of the foregoing.

6. A method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fucusDocket No. Y2008-7007WG extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.

7. A method of treating or diminishing appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fucus extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.

8. The method of any of the preceding claims, wherein the fucus extract is derived from Fucus vesiculosus, Fucus serratus, Fucus, spiralis, or Fucus guiryi.

9. The method of any of the preceding claims, wherein the compound constituent of the fucus extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O- (C1-C5 alkyl) or O-(Ci-Cs alkenyl) groups, or a pharmaceutically acceptable form thereof, or a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups, or a pharmaceutically acceptable form thereof, or a combination of the foregoing.

10. The method of any of the preceding claims, wherein the compound constituent of the fucus extract is gallic acid, vanillic acid, chlorogenic acid, caffeic acid, syringic acid, coumaric acid, quercetin, fucoidan, punigluconin, pedunculagin, punicafolin, phyllanemblin, kaempferol, ellagic acid, chebulinic acid, chebulagic acid, punicalagin, a metabolite of any of the foregoing, a compound having a similarity score of at least 95 % with any of the foregoing, or a pharmaceutically acceptable form of any of the foregoing.

11. A method of treating a wound or promoting wound healing in a subject, the method comprising administering to the subject a composition comprising an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.Docket No. Y2008-7007WG12. A method of treating or diminishing appearance of a scar or scarring in a subject, the method comprising administering to the subject a composition comprising an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof, or one or more compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.

13. The method of any of the preceding claims, wherein the chebula extract is derived from Terminilia chebula, Terminalia arborea, or Lumnitzera racemose.

14. The method of any of the preceding claims, wherein the compound constituent of the chebula extract is a benzoic acid substituted with 1 to 5 hydroxy groups and optionally 1 to 3 O- (C1-C5 alkyl) or O-(Ci-Cs alkenyl) groups, or a pharmaceutically acceptable form thereof, or a benzene substituted with -CH=CH-(CH2)a-C(O)OH, wherein a is 0 to 5, and 1 to 5 hydroxy groups, or a pharmaceutically acceptable form thereof, or a combination of the foregoing.

15. The method of any of the preceding claims, wherein the compound constituent of the chebula extract is gallic acid, vanillic acid, chlorogenic acid, caffeic acid, syringic acid, coumaric acid, quercetin, tannic acid, punigluconin, pedunculagin, punicafolin, phyllanemblin, kaempferol, ellagic acid, chebulinic acid, chebulagic acid, punicalagin, a metabolite of any of the foregoing, a compound having a similarity score of at least 95% with any of the foregoing, or a pharmaceutically acceptable form of any of the foregoing.

16. The method of any of the preceding claims, wherein the composition comprises two or more of: an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or a compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof; an effective amount of a fucus extract, or a pharmaceutically acceptable form thereof, or a compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof; andDocket No. Y2008-7007WG an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof, or a compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.

17. The method of any of the preceding claims, wherein the method comprises administering to the subject two or more of: an effective amount of an emblica extract, or a pharmaceutically acceptable form thereof, or a compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof; and an effective amount of a fucus extract, or a pharmaceutically acceptable form thereof, or a compound constituent of contained a fucus extract or having a similarity score of at least 95% with a compound constituent of an fucus extract, or a pharmaceutically acceptable form thereof; and an effective amount of a chebula extract, or a pharmaceutically acceptable form thereof, or a compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.

18. The method of any of the preceding claims, further comprising administering to the subject a second or subsequent amount of the emblica extract, or a pharmaceutically acceptable form thereof, or a compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof.

19. The method of any of the preceding claims, further comprising administering to the subject a second or subsequent amount of the fucus extract, or a pharmaceutically acceptable form thereof, or a compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.Docket No. Y2008-7007WG20. The method of any of the preceding claims, further comprising administering to the subject a second or subsequent amount of the chcbula extract, or a pharmaceutically acceptable form thereof, or a compound constituent of a chebula extract or having a similarity score of at least 95% with a compound constituent of a chebula extract, or a pharmaceutically acceptable form thereof.

21. The method of any of the preceding claims, wherein the second or subsequent amount is administered as a second dose of the same formulation.

22. The method of any of the preceding claims, wherein the second or subsequent amount is administered in another formulation.

23. The method of any of the preceding claims, wherein the composition is fortified with one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract, or a pharmaceutically acceptable form thereof.

24. The method of any of the preceding claims, wherein the composition is fortified with one or more compound constituent of a fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract, or a pharmaceutically acceptable form thereof.

25. The method of any of the preceding claims, wherein the one or more compound constituent of an emblica extract or having a similarity score of at least 95% with a compound constituent of an emblica extract is purified, e.g., at least 80% purified, at least 85% purified, at least 90% purified, at least 95% purified, at least 98% purified, at least 99% purified, at least 99.9% purified, at least 99.99% purified, or at least 99.999% purified.

26. The method of any of the preceding claims, wherein the one or more compound constituent of the fucus extract or having a similarity score of at least 95% with a compound constituent of a fucus extract is purified, e.g., at least 80% purified, at least 85% purified, at leastDocket No. Y2008-7007WG90% purified, at least 95% purified, at least 98% purified, at least 99% purified, at least 99.9% purified, at least 99.99% purified, or at least 99.999% purified.

27. The method of any of the preceding claims, wherein the effective amount is a therapeutically effective amount.

28. The method of any of the preceding claims, wherein treating or promoting involves inducing mitochondrial biogenesis and / or improving mitochondrial function.

29. The method of any of the preceding claims, wherein the effective amount or therapeutically effective amount is sufficient to induce mitochondrial biogenesis.

30. The method of any of the preceding claims, wherein administration increases expression of at least one protein selected from PGC-la, TFAM, NRF-1, and COX II.

31. The method of any of the preceding claims, wherein the composition is administered topically.

32. The method of any of the preceding claims, wherein the composition is administered parenterally, e.g., intravenously, intraperitoneally, or intramuscularly.

33. The method of any of the preceding claims, wherein the composition is administered enterally.

34. The method of any of the preceding claims, wherein the composition is formulated as a topical solution, oil, cream, emulsion, or gel.

35. The method of any of the preceding claims, wherein the composition is formulated as a shampoo, conditioner, spray, cream, gel, balm, body wash, soap, lotion, or make-up.Docket No. Y2008-7007WG36. The method of any of the preceding claims, wherein the composition is formulated as a parenteral liquid solution.

37. The method of any of the preceding claims, wherein the composition is formulated as an enteral capsule or tablet, or dietary supplement or food, e.g., food, food supplement, medical food, food additive, nutraceutical, or drink.

38. The method of any of the preceding claims, wherein the composition is administered locally.

39. The method of any of the preceding claims, wherein the composition is administered systemically.

40. The method of any of the preceding claims, wherein the composition is formulated for immediate release.

41. The method of any of the preceding claims, wherein the composition is formulated for extended release, e.g., controlled or sustained release.

42. The method of any of the preceding claims, wherein the composition comprises a nanoparticle-based delivery carrier.

43. The method of any of the preceding claims, wherein the composition comprises a skin penetration enhancer or is administered in combination with a skin penetration enhancer, e.g., a chemical skin penetration enhancer or a physical skin penetration enhancer.

44. The method of any of the preceding claims, wherein the composition comprises a mitochondria-targeting agent or a delivery carrier functionalized with a mitochondria-targeting agent.Docket No. Y2008-7007WG45. The method of any of the preceding claims, wherein the wound is associated with mitochondrial dysfunction.

46. The method of any of the preceding claims, wherein the compound constituent of an emblica extract was derived from, purified from, or isolated from the emblica extract.

47. The method of any of the preceding claims, wherein the compound constituent of an emblica extract was derived from, purified from, or isolated from a source other than the emblica extract.

48. The method of any of the preceding claims, wherein the compound constituent of an emblica extract was synthesized.

49. The method of any of the preceding claims, wherein the compound constituent of a fucus extract was derived from, purified from, or isolated from the fucus extract.

50. The method of any of the preceding claims, wherein the compound constituent of a fucus extract was derived from, purified from, or isolated from a source other than the fucus extract.

51. The method of any of the preceding claims, wherein the compound constituent of a fucus extract was synthesized.

52. The method of any of the preceding claims, wherein the compound constituent of a chebula extract was derived from, purified from, or isolated from the chebula extract.

53. The method of any of the preceding claims, wherein the compound constituent of a chebula extract was derived from, purified from, or isolated from a source other than the chebula extract.

54. The method of any of the preceding claims, wherein the compound constituent of a chebula extract was synthesized.Docket No. Y2008-7007WG55. The method of any of the preceding claims, wherein the wound is an open wound.

56. The method of any of the preceding claims, wherein the open wound is a penetrating wound such as a cut, scrape, bruise, or scratch, a puncture wound, a surgical wound, an environmental wound (e.g. thermal, chemical or electric bum), a bite (e.g. animal), a sting or a high velocity wound (e.g. gunshot wound).

57. The method of any of the preceding claims, wherein the open wound is a blunt force trauma wound such as an abrasion, laceration, puncture or skin tear (abulsion).

58. The method of any of the preceding claims, wherein the wound is a closed wound.

59. The method of any of the preceding claims, wherein the closed wound is a contusion, a blister, a seroma, a hematoma or a crush injury.

60. The method of any of the preceding claims, wherein the wound is an ulcer, e.g. a pressure ulcer, a venous ulcer, an arterial ulcer, a diabetic ulcer or a neuropathic ulcer.

61. The method of any of the preceding claims, wherein the scar or scarring is a fine line, surface line, pitted hole, abnormal overgrowth of tissue or deep furrow.

62. The method of any of the preceding claims, wherein the scar or scarring is associated with a sunburn, bed sore, wound, inflammatory lesion, or burn.

63. The method of any of the preceding claims wherein treating the wound or promoting wound healing addresses one or more symptoms or side effects of the wound, e.g. scarring, pain, swelling, bleeding, soreness, redness, oozing, pus or infection.

64. The method of any of the preceding claims, wherein a desired degree of wound closure and / or scar diminishment is achieved.Docket No. Y2008-7007WG65. The method of any of the preceding claims, wherein the composition is administered in connection with a second wound or scar treatment protocol.

66. The method of any of the preceding claims, wherein the composition is applied to a wound dressing (e.g. bandage) which, in turn, is applied to a wound or a scar.

67. A wound dressing (e.g. bandage) imbued with any of the compositions described herein.

68. A kit, comprising: a wound dressing (e.g. bandage); and a source of any of the compositions as described herein.

Images