Methods of using small molecule chemical compounds to reduce the appearance of wrinkles and lines - Patents.com

Abstract

The present invention relates to the fields of dermatology and cosmetology and describes methods of using small molecule chemical compounds and their formulations to reduce the appearance of wrinkles and lines.These methods and formulations are contemplated for cosmetic use to reduce the appearance of wrinkles or lines, or for potential therapeutic use to reduce, restore, or treat wrinkles or lines.The use of these compounds to reduce the appearance of wrinkles or lines, or for potential therapeutic use to reduce, restore, or treat wrinkles or lines, is also contemplated.

Description

[Technical Field]

[0001] The present invention relates to methods for reducing the appearance of wrinkles or lines in humans by applying or administering small molecule chemical compounds. Reducing the appearance of wrinkles or lines is desirable for aesthetic and cosmetic purposes, and methods and compositions for reducing their appearance would be commercially desirable to the cosmetic and pharmaceutical industries, as well as to chemical manufacturers. [Background technology]

[0002] Elderly people are making up an increasingly large proportion of the world's population, and it is predicted that people over 65 years of age will account for nearly 40% of the US population by 2030 (Non-Patent Document 1). According to Non-Patent Document 2, by 2050, more than 2 billion people in the world will be over 60 years of age. As the world's population ages, the size of the global anti-aging market (including products, services, and devices) is predicted to exceed 270 billion US dollars by 2024, and competition among cosmetic brands to meet this growing anti-aging market is intensifying (Non-Patent Document 3).

[0003] Characteristic features of skin aging include histological changes such as thinning of the skin due to atrophy of the epidermal cell layer and a decrease in extracellular matrix (ECM) components in the dermis (e.g., collagen loss and collagen fragmentation). This ECM loss and collagen fragmentation are caused by increased secretion of matrix metalloproteinases by skin fibroblasts with aging (Non-Patent Document 4). According to Salminen et al., changes in the amount of ECM components "result in many of the clinical features seen in aging skin, such as wrinkles and decreased skin elasticity" (2022, p. 818).

[0004] Venkatesh et al. (2019) also state that chronological aging is characterized by clinical changes such as skin thinning and wrinkles. The dermis of the skin shows a decrease in collagen synthesis and degradation of elastic fibers, and Venkatesh et al. state that "degradation of elastic fibers and decreased collagen synthesis cause a decrease in skin elasticity, i.e., skin ptosis, and these changes contribute to wrinkles, i.e., creases" (2019, p. 352).

[0005] Kim et al. reported that MMPs are the primary promoters of photoaging in the skin, with MMP2 being the primary degradative enzyme, and that photoaging is primarily induced by activation of the aryl hydrocarbon receptor (AhR). Kim et al. subsequently demonstrated that aryl hydrocarbon receptor antagonism (AhR inhibition) using vitamin B12 and folic acid improved UVB-induced wrinkle formation (2022). Kim et al. further reported that Kyat2 expression, an enzyme involved in the endogenous production of kynurenic acid, is the primary endogenous ligand for AhR stimulation (kynurenic acid is an AhR agonist or activator), and that it was positively correlated with the mRNA expression of MMP2 and MMP11 (2022). Therefore, these data suggest that kynurenic acid, previously reported to upregulate MMP1 and MMP3 (Non-Patent Document 5), also increases MMP2 expression, contributing to ECM degradation in the skin in general.

[0006] Given the high prevalence of wrinkles and creases worldwide, new compositions and methods for reducing, repairing, or treating wrinkles or creases, or for reducing the appearance of wrinkles or creases, continue to attract commercial and industrial interest for both medical and cosmetic purposes. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Venkatesh, 2019 [Non-patent document 2] Chaudhary et al. (2020) [Non-patent document 3] Ferreira, 2020 [Non-patent document 4] Salminen, 2022 [Non-Patent Document 5] Poormasjedi-Meibod, 2014 Summary of the Invention

[0008] The present invention relates to compositions and methods for reducing or diminishing the appearance of wrinkles or lines in humans by applying or administering small molecule chemical compounds.Reducing the appearance of wrinkles and lines, or treatments to reduce wrinkles and lines, is desirable for cosmetic, aesthetic and medical reasons.

[0009] In one embodiment, the invention contemplates a method of reducing the appearance of wrinkles or lines comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0010] In one embodiment, the invention contemplates a method of treating the appearance of wrinkles or wrinkles comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0011] In one embodiment, the invention contemplates a method of treating wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0012] In one embodiment, the present invention contemplates a method of reducing wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0013] In one embodiment, the invention contemplates a method of preventing wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0014] In one embodiment, the invention contemplates a method of concealing wrinkles or blemishes comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0015] In one embodiment, the invention contemplates a method of treating, ameliorating, concealing, or reducing the appearance of wrinkles comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0016] In one embodiment, the invention contemplates a method of treating, ameliorating, concealing, or reducing the appearance of wrinkles comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0017] In one embodiment, the present invention contemplates a compound selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid for use in treating wrinkles or creases. In one embodiment, the compound is kynurenic acid for use in treating wrinkles or creases. In one embodiment, the kynurenic acid is a component of a composition formulated for topical administration for use in treating wrinkles or creases. In one embodiment, the compound is kynurenine for use in treating wrinkles or creases.

[0018] In one embodiment, the compound is a component of a composition formulated for injection and is administered by injection. In one embodiment, the injection is subcutaneous, intradermal, or intramuscular. In another embodiment, the compound is a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. In yet another embodiment, the compound is a component of a composition formulated for microneedling using PRP or PRF. In a further embodiment, the compound is administered or applied in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy or microneedling.

[0019] In another embodiment, the compound is a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. In yet another embodiment, the compound is a component of a composition formulated for microneedling using PRP or PRF. In a further embodiment, the compound is administered or applied in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. PRP or PRF can be co-administered with the compound. Co-administration can be simultaneous. Co-administration can be sequential. PRP or PRF can be administered before the compound. The compound can be administered before PRP or PRF.

[0020] In another embodiment, antigen presenting cells (APCs) are provided to the mammal and the compound is administered to the mammal. The APCs can be allogeneic. The APCs can be syngeneic. The APCs can be non-professional APCs. The APCs can be professional APCs. The APCs and the compound can be co-administered. The co-administration can be simultaneous. The co-administration can be sequential. The APCs can be administered before the compound. The compound can be administered before the APCs. The APCs can be administered intraperitoneally. The compound can be administered orally. The APCs can be selected from one or more of the following: fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, beta cells, and endothelial cells. The APCs can be fibroblasts. The mammal can be a human. The mammal can be a human with wrinkled skin and / or wrinkles. The mammal can be a human with wrinkled skin and / or wrinkles, and the APCs can be fibroblasts. The method can further include administering the compound periodically after an initial administration of the APCs and the compound. The compound can be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine, and 3-hydroxy-DL-kynurenine. Kynurenine can be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, kynurenine, butyl ester, and kynurenic acid. Kynurenine can be an isomer of kynurenine or an analog thereof.

[0021] In one embodiment, the compound is a component of a composition formulated for oral delivery, hi one embodiment, the compound is an ingredient in a product intended for oral ingestion.

[0022] In one embodiment, the compound is a component of a composition formulated for topical delivery. In one embodiment, the compound is a component of a composition formulated for topical application. In one embodiment, the compound is a component of a lotion, cream, gel, solution, or suspension intended for topical use. In one embodiment, the compound is 0.05-10% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is 0.05-6% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is 0.05-3% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is 0.1-1% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is 0.1-0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is 0.25-0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, the compound is kynurenic acid. In one embodiment, the compound is kynurenine.

[0023] In one embodiment, kynurenic acid is present at 0.1 to 1% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present at 0.1 to 0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present at 0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present at 0.25% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present at 0.1% by weight of the lotion, cream, gel, solution, or suspension.

[0024] In one embodiment, kynurenine is present at 0.1 to 1% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenine is present at 0.1 to 0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenine is present at 0.5% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenine is present at 0.25% by weight of the lotion, cream, gel, solution, or suspension. In one embodiment, kynurenine is present at 0.1% by weight of the lotion, cream, gel, solution, or suspension.

[0025] In some embodiments, application, administration, or use of the compound is considered to be once, twice, or three times daily. In some embodiments, application, administration, or use of the compound is considered to be once, twice, or three times daily, and the compound is kynurenine or kynurenic acid. In some embodiments, application, administration, or use is application, administration, or use of a lotion, cream, gel, solution, or suspension containing 0.1 to 3% by weight of kynurenine or kynurenic acid. [Brief explanation of the drawings]

[0026] [Figure 1] Figure 1 shows the relative expression of collagen 1 (A) and fibronectin (B) proteins in dermal fibroblasts normalized to β-actin after treatment with kynurenine and kynurenic acid (adapted from Poormasjedi-Meibod et al. (2014), Figure 1). [Figure 2] Figure 2 shows the relative expression of MMP1 protein secreted by skin fibroblasts normalized to β-actin after treatment with kynurenine and kynurenic acid (adapted from Poormasjedi-Meibod et al. (2014), Figure 2). DETAILED DESCRIPTION OF THE INVENTION

[0027] I. Definition Any terms not directly defined herein shall be understood to have the meaning commonly associated with them as understood in the art of the invention. As used throughout this specification, the following terms shall be understood to have the following meanings unless otherwise indicated:

[0028] Provided herein are a number of compounds for use in treating wrinkles or creases, or for reducing the appearance of wrinkles or creases.In the present context, the term rhytids refers to the fine lines or folds of skin, and may be colloquially referred to as lines, wrinkles, or furrows.Although there is some overlap, in the present context, the term wrinkles refers to the visible folds of skin, and are generally deeper and more prominent than wrinkles.Both wrinkles and creases can be static or dynamic, where dynamic refers to wrinkles or creases that arise from repeated muscle movements under the skin (often becoming more or less visible due to muscle movements), and static refers to wrinkles or creases that arise due to gravity, photodamage, or other causes, and are generally unrelated to the movement of underlying muscles.

[0029] In the context of this specification, the term "treatment" may refer to the treatment of existing wrinkles or wrinkles, or alternatively, to treatment administered before existing wrinkles or wrinkles to prevent their occurrence or progression. The compounds described herein may be used alone or may be combined or used in combination with tracer compounds, liposomes, carbohydrate carriers, polymer carriers, or other agents or additives, as will be apparent to those skilled in the art. In alternative embodiments, such compounds may constitute a drug, in which case such compounds may be present in a pharmacologically effective amount. The compounds may be suitable for administration to a subject in need thereof, in that the subject may benefit from the prevention or treatment of existing wrinkles or wrinkles. The compounds may include tautomers or stereoisomers.

[0030] As used herein, KA or KynA may be used as an abbreviation for kynurenic acid (CAS No. 492-27-3), and XA may be used as an abbreviation for xanthurenic acid (CAS No. 59-00-7). L-kynurenine (CAS No. 2922-83-0) may be referred to herein as L-Kyn, and D-kynurenine (CAS No. 13441-51-5) may be referred to herein as D-Kyn. Unless otherwise specified, kynurenine includes L-Kyn, D-Kyn, and their racemic mixtures (wherein the racemic mixture may be referred to as DL-Kyn or DL-kynurenine, CAS No. 343-65-7). The stereochemistry of other amino acids may similarly be designated as D-, L-, or DL- to refer to their racemic mixtures. Salt forms of the compounds are also contemplated, for example, the salt form of kynurenic acid is kynurenic acid sodium salt (CAS number 2439-02-3).

[0031] The term "drug," as used herein, refers to a composition that can be administered to a patient or subject and that can produce an effect on the patient or subject. The effect can be chemical, biological, or physical, and the patient or subject can be a human or a non-human animal, such as a rodent or transgenic mouse, or a dog, cat, cow, sheep, horse, hamster, guinea pig, rabbit, or pig. A drug can consist of an active chemical substance alone or in combination with a pharmaceutically acceptable excipient.

[0032] The term "pharmaceutically acceptable excipient" may include any and all physiologically compatible solvents, dispersion media, coatings, antibacterial, antimicrobial or antifungal agents, isotonic and absorption delaying agents, and the like. The excipients may be suitable for intravenous, intraperitoneal, intramuscular, subcutaneous, intrathecal, topical, or oral administration. The excipients may include sterile aqueous solutions or dispersions for the extemporaneous preparation of sterile injectable solutions or dispersions. The use of such vehicles in the preparation of pharmaceuticals is well known in the art.

[0033] The term "antigen-presenting cell (APC)" (also known as accessory cell) refers to a cell that presents a foreign antigen bound to the major histocompatibility complex (MHC) on its cell surface. The APC with the antigen bound to the MHC can then be recognized by a T cell via a T cell receptor (TCR). As used herein, APC is intended to encompass both non-professional APCs (e.g., fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, beta cells, endothelial cells) and professional APCs (e.g., dendritic cells, macrophages, B cells, and activated epithelial cells). APC is also intended to encompass both allogeneic and syngeneic cells.

[0034] The compounds or compositions according to some embodiments can be administered or formulated for administration by any of a variety of known routes. Examples of methods that may be suitable for administering the compounds include oral, intravenous, inhalation, intramuscular, subcutaneous, topical, intraperitoneal, rectal or vaginal suppository, sublingual, etc. The compounds described herein may be administered as a sterile aqueous solution, or in the form of a lipid-soluble excipient, or another appropriate solution, suspension, patch, tablet, or paste. Other methods known in the art for making formulations are described, for example, in "Remington's Pharmaceutical Sciences," (1999). th edition), ed. A. Gennaro, 1995, Mack Publishing Company, Easton, Pa.

[0035] The dosage of the compositions or compounds of some embodiments described herein may vary depending on the route of administration (oral, injection, microneedling, topical, etc.) and the form in which the composition or compound is administered (solution, controlled release, etc.). Determining the appropriate dosage is within the capabilities of one of ordinary skill in the art. As used herein, an "effective amount," "therapeutically effective amount," or "pharmacologically effective amount" of a drug refers to the amount of drug present at a concentration that results in a therapeutic level of the drug being delivered over the period of drug use. This may depend on the mode of delivery, the duration of administration, and the age, weight, general health, sex, and diet of the subject receiving the drug. As used herein, an "effective amount" refers to the amount required to produce the desired result. For example, an effective amount of a therapeutic agent is a level effective in treating, curing, or alleviating the symptoms of the disease for which the therapeutic agent is administered. Methods for determining effective amounts are known in the art.

[0036] II. Biology Skin undergoes both biological and physical changes with aging, but more people are living longer, leading to an increase in the number of elderly and geriatric individuals. Longer life expectancies mean increased exposure to exogenous factors that exacerbate age-related changes observed in the skin (Venkatesh, 2019). Skin aging includes histological changes such as thinning of the skin due to atrophy of the epidermal cell layer and a decrease in extracellular matrix (ECM) components in the dermis (e.g., collagen loss and collagen fragmentation). This ECM loss and collagen fragmentation are attributed to increased secretion of matrix metalloproteinases by dermal fibroblasts during aging (Salminen, 2022). According to Salminen et al., changes in the amount of ECM components "result in many of the clinical features seen in aging skin, such as wrinkles and decreased skin elasticity" (2022, p. 818).

[0037] Venkatesh et al. (2019) also state that chronological aging is characterized by clinical changes such as skin thinning and wrinkles. The dermis of the skin shows a decrease in collagen synthesis and degradation of elastic fibers, and Venkatesh et al. state that "degradation of elastic fibers and decreased collagen synthesis cause a decrease in skin elasticity, i.e., skin ptosis, and these changes contribute to wrinkles, i.e., creases" (2019, p. 352).

[0038] Although it is not necessary to understand the mechanism of an invention and we are not bound by any particular theory, the use of kynurenine and other kynurenine pathway metabolites, including kynurenic acid, has previously been described for the treatment of fibroproliferative disorders, namely hypertrophic scars and keloids (U.S. Patent No. 9,737,523). Fibroproliferative disorders are characterized by excessive accumulation of extracellular matrix, and kynurenine (including kynurenic acid) has been shown to increase the expression of MMP-1 and MMP-3 enzymes in dermal fibroblasts (Figures 2 and 3 of U.S. Patent No. 9,737,523, respectively) and downregulate the expression of collagen 1 and fibronectin by dermal fibroblasts (Figures 10 and 16 of U.S. Patent No. 9,737,523, respectively). Topical application to skin tissue using a rabbit ear hypertrophic scar model confirmed the results with dermal fibroblasts, demonstrating that kynurenine reduced collagen and increased MMP-1 compared to controls (U.S. Patent No. 9,737,523, Figure 13). As shown in U.S. Patent No. 9,737,523, the combination of upregulation of known matrix-degrading enzymes (i.e., MMP-1 and MMP-3) and simultaneous downregulation of collagen 1 effectively reverses hypertrophic scars in animal models and hypertrophic keloid scars in the skin of human subjects (BirchBioMed Inc., 2021). However, these data suggest a shift away from the use of kynurenines, including kynurenic acid, in the treatment of wrinkles and aging. Venkatesh et al. state that "degradation of elastic fibers and decreased collagen synthesis are responsible for decreased skin elasticity, i.e., skin ptosis, and these changes contribute to wrinkles and aging" (2019, p. 352), and Salminen et al. state that a decrease in the amount of ECM components "results in many of the clinical features seen in aging skin, such as wrinkles and decreased skin elasticity" (2022, p. 818). As shown in U.S. Pat. No. 9,737,523, upregulating known matrix-degrading enzymes (i.e., MMP-1 and MMP-3) while simultaneously downregulating dermal collagen 1 is expected to promote net loss of dermal matrix and enhance the formation of wrinkles and creases.Briefly, one of skill in the art would reasonably expect that an increase in catabolic enzymes (i.e., MMP-1 and MMP-3) and a decrease in matrix anabolic proteins (collagen 1) would exacerbate wrinkles or creases.

[0039] While it is not necessary to understand the mechanism of the invention and we are not bound by any particular theory, Kim et al. report that activation of the aryl hydrocarbon receptor (AhR) is an important contributor to wrinkle formation and that AhR antagonists, such as vitamin B12 and folic acid, help reduce UVB-induced wrinkle formation in animal models (Kim, 2022). Kim's data also show that the enzyme that produces kynurenic acid (Kyat2) positively correlates with MMP production in the skin (Kim, 2022). Of note, kynurenine and kynurenic acid are known AhR agonists, suppressing collagen production in the skin (Figure 1) and increasing MMP production (Figure 2) (Poormasjedi-Meibod, 2014). Therefore, Kim and Poormasjedi-Meibod together suggest that kynurenine or kynurenic acid would be expected to be problematic in attempting to eliminate, treat, or reduce the appearance of wrinkles or creases. Wrinkles and creases result from a lack of ECM and excess MMPs, and it would be predicted based on Kim and Poormasjedi-Meibod that both of these features would be exacerbated or aggravated by kynurenine, kynurenic acid, or other AhR agonists (activators).

[0040] III. Methods of Use and Formulations of the Compounds In one embodiment, the invention contemplates a method of reducing the appearance of wrinkles or lines comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0041] In one embodiment, the invention contemplates a method of treating the appearance of wrinkles or wrinkles comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0042] In one embodiment, the invention contemplates a method of treating wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0043] In one embodiment, the present invention contemplates a method of reducing wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0044] In one embodiment, the invention contemplates a method of preventing wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0045] In one embodiment, the invention contemplates a method of concealing wrinkles or blemishes comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0046] In one embodiment, the invention contemplates a method of preventing wrinkles or creases comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0047] In one embodiment, the invention contemplates a method of treating, ameliorating, concealing, or reducing the appearance of wrinkles or lines comprising administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0048] In one embodiment, the present invention contemplates a small molecule compound selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid for the treatment of wrinkles or creases.

[0049] In one embodiment, the present invention contemplates a small molecule compound selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid for reducing the appearance of wrinkles or creases.

[0050] In one embodiment, the present invention contemplates a compound for use in treating wrinkles or creases selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid. In one embodiment, kynurenic acid is used in treating wrinkles or creases. In one embodiment, the compound is kynurenic acid for use in treating wrinkles or creases. In one embodiment, kynurenic acid is a component of a composition formulated for topical administration for use in treating wrinkles or creases. In one embodiment, kynurenic acid is a component of a composition formulated for topical administration for use in concealing wrinkles or lines. In one embodiment, kynurenic acid is a component of a composition formulated for topical administration used as a cosmetic treatment for wrinkles or lines. In one embodiment, kynurenic acid is a component of a composition formulated for topical administration used as a cosmetic to reduce the appearance of wrinkles or lines. In one embodiment, the compound is kynurenine for use in treating wrinkles or lines. In one embodiment, the compound is kynurenine for use in treating wrinkles or lines.

[0051] In one embodiment, the compound is a component of a composition formulated for injection and is administered by injection. In one embodiment, the injection is subcutaneous, intradermal, or intramuscular. In another embodiment, the compound is a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. In yet another embodiment, the compound is a component of a composition formulated for microneedling using PRP or PRF. In a further embodiment, the compound is administered or applied in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy or microneedling. PRP or PRF can be co-administered with the compound. Co-administration can be simultaneous. Co-administration can be sequential. PRP or PRF can be administered before the compound. The compound can be administered before PRP or PRF.

[0052] In another embodiment, antigen presenting cells (APCs) are provided to the mammal and the compound is administered to the mammal. The APCs can be allogeneic. The APCs can be syngeneic. The APCs can be non-professional APCs. The APCs can be professional APCs. The APCs and the compound can be co-administered. The co-administration can be simultaneous. The co-administration can be sequential. The APCs can be administered before the compound. The compound can be administered before the APCs. The APCs can be administered intraperitoneally. The compound can be administered orally. The APCs can be selected from one or more of the following: fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, beta cells, and endothelial cells. The APCs can be fibroblasts. The mammal can be a human. The mammal can be a human with wrinkled skin and / or wrinkles. The mammal can be a human with wrinkled skin and / or wrinkles, and the APCs can be fibroblasts. The method can further include administering the compound periodically after an initial administration of the APCs and the compound. The compound can be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine, and 3-hydroxy-DL-kynurenine. Kynurenine can be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, kynurenine, butyl ester, and kynurenic acid. Kynurenine can be an isomer of kynurenine or an analog thereof.

[0053] In one embodiment, the compound is a component of a composition formulated for oral delivery, hi one embodiment, the compound is an ingredient in a product intended for oral ingestion.

[0054] In one embodiment, the compound is a component of a composition formulated for topical delivery. In one embodiment, the compound is a component of a composition formulated for topical application. In one embodiment, the compound is a component of a lotion, cream, gel, solution, or suspension for topical use.

[0055] In some embodiments, application, administration, or use of the compound is considered to be 1 to 5 times daily. In some embodiments, application, administration, or use of the compound is considered to be 1, 2, or 3 times daily. In some embodiments, application, administration, or use is considered to be topical.

[0056] In one embodiment, the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid, and is a component of a composition formulated for topical use or application.

[0057] In one embodiment, the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid, and is a component of a composition formulated as a cream, gel, lotion, foam, suspension, or ointment.

[0058] In one embodiment, the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid, and is formulated with one or more additional pharmaceutical compositions, wherein the pharmaceutical composition comprises a retinoid or retinoid-like compound (e.g., tretoin, adapalene, tazolotene).

[0059] In one embodiment, the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid, and is formulated with one or more additional non-prescription drugs, wherein the non-prescription drug is covered by an FDA OTC monograph. Non-limiting examples of such non-prescription agents include salicylic acid, benzoyl peroxide, allantoin, cocoa butter, dimethicone, glycerin, petrolatum, live yeast cell derivative (LYCD), zinc stearate, zinc acetate, zinc carbonate, zinc oxide, mineral oil, resorcinol, valsarum perum, shark liver oil, and tannic acid.

[0060] In one embodiment, the compound is kynurenic acid and is present at 0.1% to 1% by weight of a composition for topical use or topical application. In one embodiment, the compound is kynurenic acid and is present at 0.25% to 0.5% by weight of a composition for topical use or topical application. In one embodiment, the compound is kynurenic acid and is present at 0.5% by weight of a composition for topical use or topical application. In one embodiment, the compound is kynurenic acid and is present at 0.5% by weight of a lotion. In one embodiment, the compound is kynurenic acid and is present at 0.5% by weight of a cream. In one embodiment, the compound is kynurenic acid and is present at 0.1% to 2% by weight of a composition for topical use or topical application used to reduce the appearance of wrinkles or fine lines. In one embodiment, the compound is kynurenic acid and is present at 0.1% to 2% by weight of a composition used as a cosmetic to reduce the appearance of wrinkles or fine lines.

[0061] In one embodiment, the present invention contemplates the use of kynurenic acid in the manufacture of a cosmetic or pharmaceutical product to reduce the appearance of wrinkles or wrinkles. In one embodiment, the present invention contemplates topical formulations containing trace amounts to 2% by weight of kynurenine, kynurenic acid, or xanthurenic acid, and the use of such formulations to reduce the appearance of wrinkles or wrinkles. In one embodiment, the present invention contemplates topical formulations containing trace amounts to 2% by weight of kynurenine, kynurenic acid, or xanthurenic acid, and the use of such formulations to reduce the appearance of wrinkles or wrinkles. In one embodiment, the present invention contemplates topical formulations containing 0.1 to 0.75% by weight of kynurenine, kynurenic acid, or xanthurenic acid, and the use of such formulations to reduce the appearance of wrinkles or wrinkles. In one embodiment, the present invention contemplates topical formulations containing 0.25 to 0.5% by weight of kynurenine, kynurenic acid, or xanthurenic acid, and the use of such formulations to reduce the appearance of wrinkles or wrinkles. In one embodiment, the present invention contemplates a topical formulation containing 0.1 to 0.75% by weight of kynurenic acid, and said formulation being used to reduce the appearance of wrinkles or creases. [Example]

[0062] IV. Working Examples A. Formulations for topical use I. A topical cream was prepared as follows: Kynurenic acid was diluted to 1M (1000 mol / m 3 After solubilization in a phosphate-buffered solution of NaOH, the pH was adjusted to 5.5 at room temperature. This KynA solution was then added to a dermatological formulation base (Glaxal Base™, WellSpring, Ont., Canada) with constant mixing, and the pH was adjusted to 6 before packaging in a poly bottle. Topical creams were made with 0.15%, 0.25%, 0.4%, and 0.5% kynurenic acid by weight (Papp et al., 2018).

[0063] II. Other compounded creams are known in the art, one example is VersaPro™ Cream Base (Product No. 2529, MEDISCA Pharmaceutique Inc., Richmond, BC, Canada). Using VersaPro™ Cream Base, dry kynurenic acid powder was hand-mixed into a cream using a mortar and pestle to a final mass of 0.5%.

[0064] III. Moisturizing cream containing kynurenic acid A 0.5% by weight kynurenic acid moisturizing cream was made by combining water, petrolatum, cetearyl alcohol, light mineral oil, ceteareth-20, TroyCare™ EPP37, sodium dihydrogen phosphate dihydrate, kynurenic acid, sodium hydroxide, hydrochloric acid, sodium chloride, and disodium hydrogen phosphate dihydrate. A 0.25% by weight kynurenic acid moisturizing cream was made by combining the same ingredients (water, petrolatum, cetearyl alcohol, light mineral oil, ceteareth-20, TroyCare™ EPP37, sodium dihydrogen phosphate dihydrate, kynurenic acid, sodium hydroxide, hydrochloric acid, sodium chloride, and disodium hydrogen phosphate dihydrate), but the amount of kynurenic acid was reduced to 0.25% of the final product weight.

[0065] B. Use of topical kynurenic acid (0.5% by weight) to reduce the appearance of wrinkles and creases (female).

[0066] A woman in her 60s with typical facial wrinkles and creases applied a topical cream containing 0.5% kynurenic acid by weight twice daily at a rate of approximately 3 mg of kynurenic acid per application and approximately 60 micrograms per square centimeter. Initial dermatological effects can be tracked by visual inspection of the area. Over approximately two months, the subject reported a noticeable and significant reduction in the appearance and visibility of the wrinkles and creases. The subject also reported that after starting to apply the kynurenic acid cream, others commented that the appearance of the wrinkles and creases had been reduced.

[0067] C. Use of topical kynurenic acid (0.5% by weight) to reduce the appearance of wrinkles and creases (male).

[0068] An approximately 70-year-old man with facial wrinkles and lines reported applying a topical cream containing 0.5% kynurenic acid by weight once daily for four months, at a dose of approximately 3 mg of kynurenic acid per application and a rate of approximately 80 micrograms per square centimeter per application. Initial dermatological effects can be tracked by visual inspection of the area. The user reported that after two months, the wrinkles and lines appeared less visible, less noticeable, and were gradually disappearing. The subject also reported that others commented that the user's wrinkles and lines appeared less visible and less noticeable.

[0069] D. Use of topical kynurenine for hypertrophic scars, with potential use in treating wrinkles and rhytidylcholine.

[0070] A 0.05% by weight topical kynurenine cream has been described in the literature for use in treating hypertrophic scars in vivo (Li et al., 2014; Poormasjedi-Meibod et al., 2014), and the cream's manufacturing method and topical application are incorporated by reference. This 0.05% by weight topical kynurenine cream can be applied topically to treat wrinkles and creases.

[0071] E. Clinical Classification of Wrinkles and Rhytiform Wrinkles Classification schemes for wrinkles and creases have been described in the art, examples of which are listed below: Glogau's classification scheme of mild (few wrinkles, little or no makeup needed for coverage), moderate (early wrinkles, pale complexion, little makeup needed), severe (persistent wrinkles, skin discoloration with vascular damage and actinic keratoses, frequent use of makeup), and severe (severe wrinkles and grooves, actinic keratoses, frequent use of makeup but may not be able to hide age-related changes). Another example is the Fitzpatrick classification of facial skin lines, typically used to refer to the area around the mouth and eyes, as Class I (fine wrinkles), Class II (fine to moderately deep wrinkles and a moderate number of skin grooves), and Class III (fine to deep wrinkles, numerous skin grooves, and sometimes overlapping folds). A further example is the modified Fitzpatrick classification, ranging from 0 (no wrinkles, no visible wrinkles, continuous skin grooves) to 3 (deep wrinkles, deep furrow-like wrinkles, wrinkle depth greater than 3 mm).

[0072] References Chaudhary, M., Khan, A., & Gupta, M. (2020). Skin aging: Pathophysiology and current market treatment approaches. Current Aging Science, 13(1), 22-30. Eldin, RMS, Nassar, AA, & Awad, H. Updated Management of Forehead Wrinkles: An Overview. European Journal of Molecular & Clinical Medicine, 8(03), 2021. Ferreira, MS, Magalhaes, MC, Sousa-Lobo, JM, & Almeida, IF (2020). Trending anti-aging peptides. Cosmetics, 7(4), 91. Kim, D. J., Iwasaki, A., Chien, A. L., & Kang, S. (2022). UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR-and SP1-dependent manner. JCI insight, 7(9). Li, Y., Kilani, R. T., Rahmani-Neishaboor, E., Jalili, R. B., & Ghahary, A. (2014). Kynurenine increases matrix metalloproteinase-1 and-3 expression in cultured dermal fibroblasts and improves scarring in vivo. Journal of Investigative Dermatology, 134(3), 643-650. Papp, A., Hartwell, R., Evans, M., & Ghahary, A. (2018). The Safety and Tolerability of Topically Delivered Kynurenic Acid in Humans. A Phase 1 Randomized Double-Blind Clinical Trial. J Pharm Sci, 107(6), 1572-1576. doi:10.1016 / j.xphs.2018.01.023. Poormasjedi-Meibod, M. S., Hartwell, R., Taghi Kilani, R., & Ghahary, A. (2014). Anti-scarring properties of different tryptophan derivatives. PloS one, 9(3), e91955. Salminen, A., Kaarniranta, K., & Kauppinen, A. (2022). Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin. Inflammation Research, 1-15. Tran, HM, Yang, CY, Wu, TH, & Yen, FL (2022). Liposomes Encapsulating Morin: Investigation of Physicochemical Properties, Dermal Absorption Improvement and Anti-Aging Activity in PM-Induced Keratinocytes. Antioxidants, 11(6), 1183. Venkatesh, S., Maymone, MB, & Vashi, NA (2019). Aging in skin of color. Clinics in dermatology, 37(4), 351-357. All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety to the same extent as if each were individually incorporated by reference. In case of conflict, the present specification, including definitions, will control.

[0073] While the present invention has been described with reference to certain preferred embodiments, it is to be understood that the invention may be embodied in other specific forms or variations thereof without departing from its special or essential characteristics. The foregoing embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description.

Claims

1. 1. A compound for use in treating wrinkles or onset of aging, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

2. 2. The compound for use according to claim 1, which is kynurenic acid.

3. 2. A compound for use according to claim 1, selected from the group consisting of kynurenine and kynurenic acid, for the treatment of wrinkles or blemishes.

4. 4. The compound for use according to claim 3, which is kynurenic acid.

5. 4. The compound for use according to claim 3, which is kynurenine.

6. 10. The compound for use according to claim 1, which is administered or applied as a component of a composition formulated for topical use.

7. The compound for use according to claim 6, wherein the composition is formulated as a cream.

8. 7. The compound for use according to claim 6, wherein the compound is kynurenic acid and the composition is formulated as 0.5% kynurenic acid by weight.

9. 7. The compound for use according to claim 6, wherein the compound is kynurenine and the composition is formulated as 0.05% kynurenine by weight.

10. 7. The compound for use according to claim 6, wherein said administration or application is once or twice daily.

11. 7. The compound for use according to claim 6, wherein said administration or application is topical to wrinkled or wrinkled skin.

12. 10. The compound for use according to claim 1, administered as a component of a composition formulated for use by injection.

13. 10. The compound for use according to claim 1, administered as a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

14. 7. The compound for use according to claim 6, wherein the administration or application is topical to wrinkled or wrinkled skin in combination with the administration or application of platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

15. 7. The compound for use according to claim 6, wherein said administration or application is topical to wrinkled or wrinkled skin in combination with the administration or application of antigen presenting cells (APCs).

16. 10. The use of a compound according to claim 1 selected from the group consisting of kynurenine and kynurenic acid for the treatment of wrinkles or blemishes.

17. 17. The use of the compound according to claim 16, wherein the compound is kynurenic acid.

18. 17. The use of a compound according to claim 16, wherein the compound is kynurenine.

19. 17. The use of a compound according to claim 16, wherein the compound is administered or applied as a component of a composition formulated for topical use.

20. 20. The use of a compound according to claim 19, wherein the composition is formulated as a cream.

21. 20. The use of the compound of claim 19, wherein the compound is kynurenic acid and the composition is formulated as 0.5% kynurenic acid by weight.

22. 20. The use of a compound according to claim 19, wherein the compound is kynurenine and the composition is formulated as 0.05% kynurenine by weight.

23. 20. The use of a compound according to claim 19, wherein said administration or application is once or twice daily.

24. 20. The use of a compound according to claim 19, wherein said administration or application is topical to wrinkled or wrinkled skin.

25. 17. The use of a compound according to claim 16, wherein the compound is administered as a component of a composition formulated for use by injection.

26. 17. The use of the compound of claim 16, wherein the compound is administered as a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

27. 25. The use of the compound according to claim 24, wherein the administration or application is topical to wrinkled or wrinkled skin in combination with the administration or application of platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

28. 25. The use of a compound according to claim 24, wherein said administration or application is topical to wrinkled or wrinkled skin in combination with administration or application of antigen presenting cells (APCs).

29. 1. A method of reducing the appearance of wrinkles or lines, comprising the step of administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

30. 30. The method of claim 29, wherein the small molecule compound is administered or applied as a component of a composition formulated for topical use.

31. 31. The method of claim 30, wherein the composition is formulated as a cream.

32. 31. The method of claim 30, wherein the compound is kynurenic acid and the composition is formulated as 0.5% kynurenic acid by weight.

33. 31. The method of claim 30, wherein the compound is kynurenine and the composition is formulated as 0.05% kynurenine by weight.

34. 31. The method of claim 30, wherein the administering or applying step is once or twice daily.

35. 31. The method of claim 30, wherein said administering or applying step is topical to wrinkled or wrinkled skin.

36. 30. The method of claim 29, wherein the small molecule compound is administered as a component of a composition formulated for injectable use.

37. 30. The method of claim 29, wherein the small molecule compound is a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

38. 31. The method of claim 30, wherein the administering or applying step is topical to wrinkled or wrinkled skin in combination with the administration or application of platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

39. 31. The method of claim 30, wherein the administering or applying step is topical to wrinkled or wrinkled skin in combination with administering or applying antigen presenting cells (APCs).

40. 1. A method of treating wrinkles or blemishes, comprising the step of administering or applying a small molecule compound, wherein the compound is selected from the group consisting of DL-kynurenine, L-kynurenine, D-kynurenine, 3-hydroxy-DL-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxy-D-kynurenine, 5-hydroxy-DL-kynurenine, 5-hydroxy-L-kynurenine, 5-hydroxy-D-kynurenine, N'-formyl-kynurenine, N-acetyl-3-OH-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

41. 41. The method of claim 40, wherein the small molecule compound is administered or applied as a component of a composition formulated for topical use.

42. 42. The method of claim 41, wherein the composition is formulated as a cream.

43. 41. The method of claim 40, wherein the small molecule compound is administered as a component of a composition formulated for injectable use.

44. 41. The method of claim 40, wherein the small molecule compound is a component of a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

45. 42. The method of claim 41, wherein the administering or applying step is topical to wrinkled or wrinkled skin in combination with the administration or application of platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

46. 42. The method of claim 41, wherein the administering or applying step is topical to wrinkled or wrinkled skin in combination with administering or applying antigen presenting cells (APCs).

47. 42. The method of claim 41, wherein the compound is kynurenic acid and the composition is formulated as 0.5% kynurenic acid by weight.

48. 42. The method of claim 41, wherein the compound is kynurenine and the composition is formulated as 0.05% kynurenine by weight.

49. 42. The method of claim 41, wherein the administering or applying step is once or twice daily.

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