Method for reducing wrinkles and crease appearance using small molecule compounds

Abstract

The present invention relates to the field of dermatology and cosmetology, and describes methods for reducing creases and the appearance of wrinkles using small molecule compounds and formulations thereof. These methods and formulations may be used for cosmetic use to reduce the appearance of creases or wrinkles, or for potential therapeutic use to reduce, reverse, or treat creases or wrinkles. Also envisaged are potential therapeutic uses of these compounds for reducing the appearance of creases or wrinkles, or for reducing, reversing or treating creases or wrinkles.

Description

Technical Field

[0001] The present invention relates to methods of reducing the appearance of wrinkles or folds in a person by applying or administering a small molecule compound. Reducing the appearance of wrinkles or folds is desirable for aesthetic and cosmetic purposes, and methods and compositions for reducing the appearance of these wrinkles or folds are commercially attractive to the cosmetic and pharmaceutical industries and chemical manufacturers. Background Art

[0002] The elderly make up an increasing proportion of the global population, and it is expected that by 2030, the population over 65 years old in the United States will account for nearly 40% of the total population (Venkatesh, 2019). According to Chaudhary et al. (2021), by 2050, there will be more than 2 billion people aged 60 years and above. As the global population ages, some predict that the global anti-aging market size (including products, services and devices) will exceed US$270 billion by 2024, and competition among cosmetic brands in this growing anti-aging market is also becoming increasingly fierce (Ferreira, 2020).

[0003] Characteristics 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 decreases and becomes fragmented). With aging, matrix metalloproteinases secreted by skin fibroblasts increase, which leads to a decrease in ECM and collagen fragmentation (Salminen, 2022). According to Saminen et al., changes in the amount of extracellular matrix components "contribute to many of the clinical features seen in aging skin, such as wrinkles and loss of skin elasticity" (2022, pg. 818).

[0004] Venkatesh et al. similarly note that natural aging over time is characterized by clinical changes such as thinning of the skin and the appearance of wrinkles (2019). The dermis of the skin shows a decrease in collagen synthesis and degradation of elastic fibers, and Venkatesh et al. state that "degraded elastic fibers and reduced collagen synthesis are responsible for decreased skin elasticity or sagging, and these changes can lead to the appearance of wrinkles or folds" (2019, pg. 352).

[0005] According to Kim et al., matrix metalloproteinases (MMPs) are the main drivers of skin photoaging, although they reported that MMP2 is the main degrading enzyme and that photoaging is largely induced by aryl hydrocarbon receptor (AhR) activation. They subsequently showed that the use of vitamin B12 and folic acid as aryl hydrocarbon receptor antagonists (inhibition of AhR) improved ultraviolet B (UVB)-induced wrinkle formation (2022). These authors further reported that Kyat2, an enzyme involved in the endogenous production of kynurenic acid and that kynurenic acid is the main endogenous ligand for aryl hydrocarbon receptor stimulation (kynurenic acid is an AhR agonist or AhR activator), has a positive correlation with the messenger RNA (mRNA) expression of MMP2 and MMP11 (2022). Therefore, these data suggest that kynurenic acid, which has been previously reported to upregulate MMP1 and MMP3 (Poormasjedi-Meibod, 2014), may also increase the expression of MMP2 and generally promote the degradation of the extracellular matrix in the skin.

[0006] Given the high prevalence of wrinkles and folds worldwide, new compositions and methods for reducing, reversing, or treating, or otherwise reducing the appearance of wrinkles or folds continue to be of commercial and industrial importance for both medical and cosmetic purposes. SUMMARY OF THE INVENTION

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

[0009] In one embodiment, the present invention contemplates a method of reducing the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0010] In one embodiment, the present invention contemplates a method of treating the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0011] In one embodiment, the present invention contemplates a method of treating wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0012] In one embodiment, the present invention contemplates a method of reversing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0013] In one embodiment, the present invention contemplates a method for preventing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0014] In one embodiment, the present invention contemplates a method of concealing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid.

[0015] In one embodiment, the present invention contemplates a method of treating, reversing, masking 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0016] In one embodiment, the present invention contemplates a method of treating, reversing, masking or reducing the appearance of 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-hydroxy-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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid for use in treating wrinkles or folds. In one embodiment, the compound is kynurenic acid for use in treating wrinkles or folds. In one embodiment, kynurenic acid is an ingredient of a composition formulated for topical administration for treating wrinkles or folds. In one embodiment, the compound is kynurenine for use in treating wrinkles or folds.

[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 microneedle therapy with 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 microneedle therapy.

[0019] In another embodiment, the compound is a composition formulated for platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. In yet another embodiment, the compound is a composition formulated for microneedle therapy with platelet-rich plasma or platelet-rich fibrin. In a further embodiment, the compound is administered or applied in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. Platelet-rich plasma or platelet-rich fibrin can be administered in combination with the compound. This combined administration can be performed simultaneously. This combined administration can be performed continuously. Platelet-rich plasma or platelet-rich fibrin can be administered before the compound, and the compound can also be administered before platelet-rich plasma or platelet-rich fibrin.

[0020] In another embodiment, antigen presenting cells (APCs) are presented to a mammal and the compound is administered to the mammal. The antigen presenting cells may be allogeneic or isogenic. The antigen presenting cells may be non-professional antigen presenting cells or professional antigen presenting cells. The antigen presenting cells and the compound may be administered in combination. This combined administration may be simultaneous or sequential. The antigen presenting cells may be administered before the compound, and the compound may also be administered before the antigen presenting cells. The antigen presenting cells may be administered intraperitoneally. The compound may be administered orally. The antigen presenting cells may be selected from one or more of the following: fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, beta cells, and endothelial cells. The antigen presenting cells may be fibroblasts. The mammal may be a human. The mammal may be a human with wrinkles and / or folds. The mammal may be a human with wrinkles and / or folds, and the antigen presenting cells may be fibroblasts. The method may also include administering the compound periodically after the first administration of the antigen presenting cells and the compound. The compound may be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine and 3-hydroxy-DL-kynurenine. Kynurenine may 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, kynurenine butyl ester and kynurenic acid. Kynurenine may be an isomer of kynurenine or an analog thereof.

[0021] In one embodiment, the compound is an ingredient of a composition formulated for oral delivery. In one embodiment, the compound is an ingredient of a product for oral consumption.

[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 for topical use. In one embodiment, the compound accounts for 0.05% to 10% of the weight of the lotion, cream, gel, solution or suspension. In one embodiment, the compound accounts for 0.05% to 6% of the weight of the lotion, cream, gel, solution or suspension. In one embodiment, the compound accounts for 0.05% to 3% of the weight of the lotion, cream, gel, solution or suspension. In one embodiment, the compound accounts for 0.1% to 1% of the weight of the lotion, cream, gel, solution or suspension. In one embodiment, the compound accounts for 0.1% to 0.5% of the weight of the lotion, cream, gel, solution or suspension. In one embodiment, the compound accounts for 0.25% to 0.5% of the 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 in an amount of 0.1% to 1% by weight of a lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present in an amount of 0.1% to 0.5% by weight of a lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present in an amount of 0.5% by weight of a lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present in an amount of 0.25% by weight of a lotion, cream, gel, solution, or suspension. In one embodiment, kynurenic acid is present in an amount of 0.1% by weight of a lotion, cream, gel, solution, or suspension.

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

[0025] In some embodiments, the application, administration or use of the compound is envisioned to be once, twice or three times a day. In some embodiments, the application, administration or use of the compound is envisioned to be once, twice or three times a day, wherein the compound is kynurenine or kynurenic acid. In some embodiments, the application, administration or use is a lotion, cream, gel, solution or suspension containing between 0.1% and 3% kynurenine or kynurenic acid by weight. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Shown are the relative expression of collagen 1 (A) and fibronectin (B) proteins normalized to β-actin in dermal fibroblasts after treatment with kynurenine and kynurenic acid (reproduced from Poormasjedi-Meibod et al. (2014), Figure 1 ).

[0028] Figure 2 Shown is the relative expression of MMP1 protein secreted by dermal fibroblasts normalized to β-actin after treatment with kynurenine and kynurenic acid (reproduced from Poormasjedi-Meibod et al. (2014), Figure 2 ). DETAILED DESCRIPTION OF THE INVENTION

[0030] I. Definition

[0031] Any term not directly defined herein should be understood to have the meaning commonly given in the art to which the invention belongs. Throughout the specification, unless otherwise specified, the following terms should be understood to have the following meanings.

[0032] Provided herein are a variety of compounds for treating wrinkles or folds, or reducing the appearance of wrinkles or folds. In the context of this specification, the term "wrinkles" refers to fine lines or folds in the skin, which may be referred to colloquially as lines, wrinkles, or furrows. Although there is overlap, in the context of this specification, the term "folds" refers to visible folds in the skin, which are generally deeper and more obvious than wrinkles. Both wrinkles and folds can be static or dynamic, where "dynamic" refers to wrinkles or folds caused by repeated movement of muscles under the skin (and generally becomes more or less obvious as the muscles move); while "static" refers to wrinkles or folds caused by gravity, light damage, or other reasons, which are generally unrelated to muscle movement under the skin.

[0033] In the context of this specification, the term "treatment" may refer to the treatment of existing wrinkles or folds, or to treatment performed before existing wrinkles or folds appear to prevent their development or worsening. The compounds described herein may be used alone or in combination with tracer compounds, liposomes, carbohydrate carriers, polymer carriers, or other agents or excipients known to those skilled in the art. In another embodiment, such compounds may constitute a medicament, wherein such compounds may be present in a pharmacologically effective amount. Since the subject may benefit from the prevention or treatment of existing wrinkles or folds, the compound is suitable for administration to a subject in need. The compound may also include tautomers or stereoisomers.

[0034] As used herein, KA or KynA can be used as an abbreviation for kynurenic acid (CAS#492-27-3), and XA can be used as an abbreviation for xanthurenic acid (CAS#59-00-7). L-kynurenine (CAS#2922-83-0) can be represented as L-Kyn in this article, and D-kynurenine (CAS#13441-51-5) can be represented as D-Kyn. Unless otherwise indicated, kynurenine includes L-Kyn, D-Kyn and their racemic mixtures (wherein the racemic mixture can be represented as DL-Kyn or DL-kynurenine, CAS#343-65-7). The stereochemistry of other amino acids can be similarly represented by D-, L- or DL- to represent their racemic mixtures. Salt forms of the compound are also contemplated, for example, the salt form of kynurenic acid is kynurenic acid sodium salt (CAS#2439-02-3).

[0035] As used herein, the term "drug" refers to a composition that can be administered to a patient or test subject and can produce an effect in the patient or test subject. The effect can be chemical, biological or physical, and the patient or test subject can be a human, or a non-human animal, such as a rodent, a transgenic mouse, a dog, a cat, a cow, a sheep, a horse, a hamster, a guinea pig, a rabbit or a pig. The drug can consist of only an effective chemical entity or can be combined with a pharmaceutically acceptable excipient.

[0036] The term "pharmaceutically acceptable excipient" may include any and all solvents, dispersion media, coatings, antibacterial, antimicrobial or antifungal agents, isotonic agents and absorption delaying agents, etc., which are physiologically compatible. The excipient may be suitable for intravenous, intraperitoneal, intramuscular, subcutaneous, intrathecal, topical or oral administration. The excipient may include a sterile aqueous solution or dispersion for the extemporaneous preparation of a sterile injection solution or dispersion. The use of such media is known in the art to prepare drugs.

[0037] The term "antigen presenting cell (APC)" (also referred to as an auxiliary cell) refers to a cell that displays a foreign antigen bound to the major histocompatibility complex (MHC) on its cell surface. Subsequently, the APC with the antigen bound to the MHC can be recognized by the T cell through the T cell receptors (TCRs). As used herein, APC is intended to cover non-professional APCs (e.g., fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, β cells, endothelial cells) and professional APCs (e.g., dendritic cells, macrophages, B cells, and activated epithelial cells). APC is also intended to cover allogeneic and isogenic cells.

[0038] The compound or composition according to some embodiments can be applied by a variety of known routes, or formulated into a form for application. Examples of methods suitable for applying compounds include oral, intravenous, inhaled, intramuscular, subcutaneous, local, intraperitoneal, rectal or vaginal suppositories, sublingual, etc. The compounds described herein can be applied as sterile aqueous solutions, or can be applied in the form of fat-soluble excipients or other solutions, suspensions, patches, tablets or pastes, depending on the circumstances. For example, in Remington's Pharmaceutical Sciences (19th edition), A. Gennaro edited, 1995, Mack Publishing Company, Easton, Pa., other methods of preparing preparations known in the art can be found.

[0039] The dosage of the composition or compound of some embodiments described herein can vary according to the route of administration (oral, injection, microneedle, topical, etc.) and the form of administration (solution, controlled release, etc.) of the composition or compound. It is within the capabilities of those skilled in the art to determine the appropriate dosage. As used herein, the "effective amount", "therapeutically effective amount" or "pharmacologically effective amount" of a drug refers to the presence of a drug at such a concentration to produce therapeutic levels of drug delivery during drug use. This may depend on the delivery method, dosage duration, age, weight, general health, sex and diet of the subject receiving the drug. As used herein, "effective amount" refers to the amount required to produce the necessary results. For example, the effective amount of a therapeutic agent is the level of disease symptoms for which the therapeutic agent administered is effectively treated, cured or alleviated. Methods for determining an effective amount are known in the art.

[0040] 2. Biology

[0041] As the skin ages, it undergoes biological and physical changes, and as more people live longer, the number of elderly and very old people increases. Longer life expectancy means more exposure to external factors that exacerbate the age-related changes seen in the skin (Venkatesh, 2019). Changes during 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., less collagen and collagen becomes fragmented). With age, the secretion of matrix metalloproteinases by skin fibroblasts increases, which leads to a decrease in the extracellular matrix and fragmentation of collagen (Salminen, 2022). According to Saminen et al., changes in the amount of extracellular matrix components "contribute to many of the clinical features seen in aged skin, such as wrinkles and loss of skin elasticity" (2022, pg. 818) (2022, pg. 818).

[0042] Venkatesh et al. similarly note that natural aging over time is characterized by clinical changes such as thinning of the skin and the appearance of wrinkles (2019). The dermis of the skin shows a decrease in collagen synthesis and degradation of elastic fibers, and Venkatesh et al. state that "degraded elastic fibers and reduced collagen synthesis are responsible for decreased skin elasticity or sagging, and these changes can lead to the appearance of wrinkles or folds" (2019, pg. 352).

[0043] Although it is not necessary to understand the mechanism of the invention and without being bound by any particular theory, kynurenine and other kynurenine pathway metabolites, including kynurenic acid, have been previously described for use in treating fibroproliferative diseases, namely hypertrophic scars and keloids (US9737523B2). Fibroproliferative diseases 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 (US Pat. No. '523 B2). Figure 2and Figure 3), and down-regulated the expression of collagen 1 and fibronectin in dermal fibroblasts (Figures 10 and 16 of the '523 patent). The results of dermal fibroblasts were confirmed in a rabbit ear hypertrophic scar model using topical application to the skin, showing that kynurenine reduced collagen and increased MMP-1 relative to the control (Figure 13 of the '523 patent). This combination of upregulating known matrix degrading enzymes (i.e., MMP-1 and MMP-3) and simultaneously downregulating collagen 1 shown in the '523 patent effectively reversed hypertrophic scars in animal models and effectively reversed hypertrophic keloids in the skin of human subjects (BirchBioMed Inc., 2021). However, these data contradict the use of kynurenine (including kynurenic acid) for the treatment of wrinkles and folds. Venkatesh et al. note that "degraded elastic fibers and reduced collagen synthesis are responsible for decreased skin elasticity or skin sagging, and these changes can lead to the development of wrinkles or folds" (2019, pg. 352), while Saminen et al. note that a reduction in the number of extracellular matrix components "leads to many of the clinical features seen in aging skin, such as wrinkles and loss of skin elasticity" (2022, pg. 818). As shown in the '523 patent, upregulating known matrix-degrading enzymes (i.e., MMP-1 and MMP-3) and simultaneously downregulating collagen 1 in the skin will accelerate the net loss of skin matrix and is expected to exacerbate the formation of wrinkles and folds. In short, one skilled in the art would reasonably expect that increasing catabolic enzymes (i.e., MMP-1 and MMP-3) and decreasing matrix anabolic proteins (collagen 1) would exacerbate wrinkles or folds.

[0044] Although it is not necessary to understand the mechanism of the invention and not to be bound by any particular theory, Kim et al. reported that aryl hydrocarbon receptor activation is an important factor in wrinkle formation, and AhR antagonists (inhibition) such as vitamin B12 and folic acid help reduce UVB-induced wrinkle formation in animal models (Kim, 2022). Kim's data also showed that the enzyme that produces kynurenic acid (Kyat2) is positively correlated with the production of MMPs in the skin (Kim, 2022). Of note, kynurenine and kynurenic acid are known AhR agonists (activators) that inhibit collagen production in the skin (such as Figure 1 ) and increase the production of MMPs (as Figure 2Thus, the studies by Kim and Poormasjedi-Meibod together suggest that kynurenine or kynurenic acid would be expected to be detrimental to the dissipation, treatment, or reduction of the appearance of wrinkles or folds. Wrinkles and folds are caused by a deficiency in the extracellular matrix and an excess of MMPs, both of which are expected to be exacerbated or worsened by kynurenine, kynurenic acid, or other AhR agonists (AhR activators), according to the studies by Kim and Poormasjedi-Meibod.

[0045] 3. Compound Usage and Preparation

[0046] In one embodiment, the present invention contemplates a method of reducing the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0047] In one embodiment, the present invention contemplates a method of treating the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

[0048] In one embodiment, the present invention contemplates a method of treating wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0049] In one embodiment, the present invention contemplates a method of reversing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0050] In one embodiment, the present invention contemplates a method for preventing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0051] In one embodiment, the present invention contemplates a method of concealing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid.

[0052] In one embodiment, the present invention contemplates a method for preventing wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0053] In one embodiment, the present invention contemplates a method of treating, reversing, concealing or reducing the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid.

[0054] In one embodiment, the present invention contemplates 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid for use in treating wrinkles or folds.

[0055] In one embodiment, the present invention contemplates 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid for use in reducing the appearance of wrinkles or folds.

[0056] 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid for use in treating wrinkles or folds. In one embodiment, kynurenic acid is used to treat wrinkles or folds. In one embodiment, the compound is kynurenic acid for use in treating wrinkles or folds. In one embodiment, kynurenic acid is a component of a composition formulated for topical application for treating wrinkles or folds. In one embodiment, kynurenic acid is a component of a composition formulated for topical application for concealing wrinkles or folds. In one embodiment, kynurenic acid is an ingredient of a composition formulated for topical administration as a cosmetic treatment for wrinkles or folds. In one embodiment, kynurenic acid is an ingredient of a composition formulated for topical administration as a cosmetic product for reducing the appearance of wrinkles or folds. In one embodiment, the compound is kynurenine, for use in the treatment of wrinkles or folds.

[0057] In one embodiment, the compound is a component of a composition formulated for injection and is administered by injection. In one embodiment, the injection method is subcutaneous injection, intradermal injection or intramuscular injection. 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 another embodiment, the compound is a component of a composition formulated for microneedle treatment with platelet-rich plasma or platelet-rich fibrin. In a further embodiment, the compound is administered or applied in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy. Platelet-rich plasma or platelet-rich fibrin can be administered in combination with the compound. This combined administration can be performed simultaneously or continuously. Platelet-rich plasma or platelet-rich fibrin can be administered before the compound. The compound can also be administered before platelet-rich plasma or platelet-rich fibrin.

[0058] In another embodiment, antigen presenting cells (APCs) are presented to a mammal and the compound is administered to the mammal. The antigen presenting cells may be allogeneic or isogenic. The antigen presenting cells may be non-professional antigen presenting cells or professional antigen presenting cells. The antigen presenting cells and the compound may be administered in combination. This combined administration may be simultaneous or sequential. The antigen presenting cells may be administered before the compound. The compound may also be administered before the antigen presenting cells. The antigen presenting cells may be administered intraperitoneally. The compound may be administered orally. The antigen presenting cells may be selected from one or more of the following: fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, beta cells, and endothelial cells. The antigen presenting cells may be fibroblasts. The mammal may be a human. The mammal may be a human with wrinkles and / or folds. The mammal may be a human with wrinkles and / or folds, and the antigen presenting cells may be fibroblasts. The method may also include administering the compound periodically after the first administration of the antigen presenting cells and the compound. The compound may be selected from one or more of DL-kynurenine, L-kynurenine, D-kynurenine and 3-hydroxy-DL-kynurenine. Kynurenine may 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, kynurenine butyl ester and kynurenic acid. Kynurenine may be an isomer of kynurenine or an analog thereof.

[0059] In one embodiment, the compound is an ingredient of a composition formulated for oral delivery. In one embodiment, the compound is an ingredient of a product for oral consumption.

[0060] In one embodiment, the compound is an ingredient of a composition formulated for topical delivery. In one embodiment, the compound is an ingredient of a composition formulated for topical application. In one embodiment, the compound is an ingredient of a lotion, cream, gel, solution, or suspension for topical use.

[0061] In some embodiments, it is contemplated that the application, administration or use of the compound is one to five times per day. In some embodiments, it is contemplated that the application, administration or use of the compound is once, twice or three times per day. In some embodiments, it is contemplated that the application, administration or use of the compound is topical.

[0062] In one embodiment, the compound is selected from 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid, and is a component of a composition formulated for topical use or topical application.

[0063] In one embodiment, the compound is selected from 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-hydroxy-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.

[0064] In one embodiment, the compound is selected from 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid, and is formulated with one or more other pharmaceutical compositions, wherein the pharmaceutical composition includes a retinoid or a retinoid-like compound (e.g., tretoin, adapalene, tazarotene).

[0065] In one embodiment, the compound is selected from 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid, and is formulated with one or more over-the-counter drugs, wherein the over-the-counter drugs are covered in the FDA over-the-counter drug (OTC) monograph. Non-limiting examples of the over-the-counter drugs 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, Peru balsam, shark liver oil and tannic acid.

[0066] In one embodiment, the compound is kynurenic acid and is present at 0.1% to 1% by weight of the 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 the composition for topical use or topical application. In one embodiment, the compound is kynurenic acid and is present at 0.5% by weight of the 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 the composition for topical use or topical application for reducing the appearance of wrinkles or folds. In one embodiment, the compound is kynurenic acid and is present at 0.1% to 2% by weight of the composition for use as a cosmetic product to reduce the appearance of wrinkles or folds.

[0067] In one embodiment, the present invention contemplates the use of kynurenic acid in the manufacture of a cosmetic or pharmaceutical product for reducing the appearance of wrinkles or folds. In one embodiment, the present invention contemplates a topical formulation containing trace amounts to 2% by weight of kynurenine, kynurenic acid, or xanthuric acid; and the use of the formulation for reducing the appearance of wrinkles or folds. In one embodiment, the present invention contemplates a topical formulation containing trace amounts to 2% by weight of kynurenine, kynurenic acid, or xanthuric acid; and the formulation is used to reduce the appearance of wrinkles or folds. In one embodiment, the present invention contemplates a topical formulation containing 0.1% to 0.75% by weight of kynurenine, kynurenic acid, or xanthuric acid; and the formulation is used to reduce the appearance of wrinkles or folds. In one embodiment, the present invention contemplates a topical formulation containing 0.25% to 0.5% by weight of kynurenine, kynurenic acid, or xanthuric acid; and the formulation is used to reduce the appearance of wrinkles or folds. In one embodiment, the present invention contemplates a topical formulation comprising 0.1% to 0.75% by weight of kynurenic acid; and the formulation is used to reduce the appearance of wrinkles or folds. 4. Embodiment

[0068] A. Topical preparations

[0069] I. The topical cream is prepared as follows: Kynurenic acid is dissolved in 1M NaOH phosphate buffer solution, the pH is adjusted to 5.5 at room temperature, and then the KynA solution is added to the dermatological composite matrix (GlaxalBase TM, WellSpring, Ontario, Canada), and filled into polyethylene bottles after adjusting the pH to 6. Topical creams of kynurenic acid at 0.15%, 0.25%, 0.4%, and 0.5% were prepared by weight percentage (Papp et al., 2018).

[0070] II. Other compounded creams are known in the art, such as VersaPro Cream Base (Product No. 2529, MEDISCA Pharmaceutique Inc., Richmond, BC, Canada). Using VersaPro Cream Base, dry kynurenic acid powder was manually mixed into the cream (using a mortar and pestle) at 0.5% final weight.

[0071] III. Moisturizing cream containing kynurenic acid

[0072] The 0.5% kynurenic acid moisturizing cream is made of the following ingredients by weight: water, petrolatum, cetearyl alcohol, light mineral oil, ceteareth-20, TroyCare TM EPP37, sodium dihydrogen phosphate dihydrate, kynurenic acid, sodium hydroxide, hydrochloric acid, sodium chloride and disodium hydrogen phosphate dihydrate. The kynurenic acid moisturizing cream 0.25% by weight is composed of the same ingredients (water, petrolatum, cetearyl alcohol, light mineral oil, ceteareth-20, TroyCare TM EPP37, sodium dihydrogen phosphate dihydrate, kynurenic acid, sodium hydroxide, hydrochloric acid, sodium chloride and disodium hydrogen phosphate dihydrate), wherein the amount of kynurenic acid is reduced to 0.25% of the final weight of the product.

[0073] B. Topical use of kynurenic acid (0.5%, by weight) to reduce the appearance of wrinkles and folds (female)

[0074] A female in her 60s with typical facial wrinkles and folds applied a topical cream containing 0.5% kynurenic acid twice daily, approximately 3 mg of kynurenic acid per application, at an application rate of approximately 60 micrograms per square centimeter. Initial skin effects were tracked by visual inspection of the application site. Over a period of approximately two months, the subject reported a significant reduction in the appearance and visibility of her wrinkles and folds. The subject also stated that others noticed an improvement in the appearance of her wrinkles and folds after she began using the kynurenic acid cream.

[0075] C. Topical use of kynurenic acid (0.5%, by weight) to reduce the appearance of wrinkles and folds (males)

[0076] A male approximately 70 years of age with facial wrinkles and folds self-reported applying a topical cream containing 0.5% kynurenic acid once daily for 4 months, with approximately 3 mg of kynurenic acid applied at a rate of approximately 80 micrograms per square centimeter. Initial skin effects were tracked by visual inspection of the application site. The user reported that his wrinkles and folds became less noticeable and appeared to have improved after two months. The subject also stated that others noticed a reduction in the visibility of his wrinkles and folds.

[0077] D. Topical use of kynurenine for the treatment of hypertrophic scars (it is envisioned that it could be used to treat wrinkles and folds)

[0078] A 0.05% by weight topical kynurenine cream is described in the literature for in vivo treatment of hypertrophic scars (Li et al., 2014; Poormasjedi-Meibod et al., 2014), and the cream preparation and topical application methods are expressly incorporated herein by reference. The 0.05% by weight topical kynurenine cream can be used for topical treatment of wrinkles and folds.

[0079] E. Clinical classification of wrinkles and folds

[0080] There are many classification schemes for wrinkles and folds described in the art, examples of which include: Glogau classification: mild (few wrinkles, little to no makeup required), moderate (early wrinkles, sallow complexion, minimal makeup required), severe (persistent wrinkles, skin discoloration with telangiectasia and actinic keratosis, makeup often required), very severe (severe wrinkles and furrows, actinic keratosis, makeup often required but difficult to conceal aging changes). Another example is the Fitzpatrick facial wrinkle classification (commonly used for perioral and periorbital areas): Grade I (fine lines), Grade II (fine to moderately deep wrinkles, moderate number of wrinkles), Grade III (fine to deep wrinkles, dense wrinkles, possibly with redundant skin folds). Another example is the modified Fitzpatrick classification (0-3 scale): Grade 0 (no wrinkles, no visible wrinkles, continuous skin lines), Grade 3 (deep wrinkles, deep and furrowed wrinkles, wrinkle depth greater than 3 mm).

[0081] References

[0082] Chaudhary,M.,Khan,A.,&Gupta,M.(2020). Skin ageing: Pathophysiology and current market treatment approaches. Current Aging Science, 13(1), 22-30.

[0083] Eldin,R.M.S.,Nassar,A.A.,&Awad,H.Updated Management of ForeheadWrinkles:An Overview.European Journal of Molecular&Clinical Medicine,8(03),2021.

[0084] Ferreira,M.S., M.C.,Sousa-Lobo,J.M.,&Almeida,I.F.(2020).Trending anti-aging peptides.Cosmetics,7(4),91.

[0085] Kim,D.J.,Iwasaki,A.,Chien,A.L.,&Kang,S.(2022).UVB-mediated DNA damageinduces matrix metalloproteinases to promote photoaging in an AhR-and SP1-dependent manner.JCI insight,7(9).

[0086] Li,Y.,Kilani,R.T.,Rahmani-Neishaboor,E.,Jalili,R.B.,&Ghahary,A.(2014).Kynurenine increases matrix metalloproteinase-1and-3expression incultured dermal fibroblasts and improves scarring in vivo.Journal ofInvestigative Dermatology,134(3),643-650.

[0087] Papp,A.,Hartwell,R.,Evans,M.,&Ghahary,A.(2018).The Safety andTolerability of Topically Delivered Kynurenic Acid in Humans.A Phase1Randomized Double-Blind Clinical Trial.J Pharm Sci,107(6),1572-1576.doi:10.1016 / j.xphs.2018.01.023.

[0088] Poormasjedi-Meibod,M.S.,Hartwell,R.,Taghi Kilani,R.,&Ghahary,A.(2014).Anti-scarring properties of different tryptophan derivatives.PloS one,9(3),e91955.

[0089] Salminen,A.,Kaarniranta,K.,&Kauppinen,A.(2022).Photoaging:UVradiation-induced inflammation and immunosuppression accelerate the agingprocess in the skin.Inflammation Research,1-15.

[0090] Tran,H.M.,Yang,C.Y.,Wu,T.H.,&Yen,F.L.(2022).Liposomes EncapsulatingMorin:Investigation of Physicochemical Properties,Dermal AbsorptionImprovement and Anti-Aging Activity in PM-Induced Keratinocytes.Antioxidants,11(6),1183.

[0091] Venkatesh,S.,Maymone,M.B.,&Vashi,N.A.(2019).Aging in skin ofcolor.Clinics in dermatology,37(4),351-357.

[0092] All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety, as if each were individually incorporated by reference. In the event of a conflict, the present specification, including definitions, will control.

[0093] The present invention has been described with reference to certain preferred embodiments, but it should be understood that it can be embodied in other specific forms or variations without departing from its specific or essential characteristics. Therefore, the above embodiments should be considered in all aspects as illustrative and not restrictive, and the scope of the present invention is defined by the appended claims rather than the foregoing description.

Claims

1. 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid and kynurenic acid for use in treating wrinkles or folds.

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

3. The compound for use according to claim 1, which is selected from kynurenine and kynurenic acid, for treating wrinkles or folds.

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

5. The compound for use according to claim 3, wherein the compound is kynurenine.

6. The compound for use according to claim 1, wherein the compound 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. The compound for use according to claim 6, wherein the compound is kynurenic acid and the composition is formulated to contain 0.5% by weight of kynurenic acid.

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

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

11. The compound for use according to claim 6, wherein the administration or application is topical administration or application to skin having wrinkles or folds.

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

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

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

15. The compound for use according to claim 6, wherein the administration or application is topical administration to the skin with wrinkles or folds and is administered or applied in combination with antigen presenting cells (APC).

16. Use of a compound according to claim 1 selected from kynurenine and kynurenic acid for treating wrinkles or folds.

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

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

19. The use of a compound according to claim 1, wherein the compound is administered or applied as a component of a composition formulated for topical use.

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

21. The use of a compound according to claim 19, wherein the compound is kynurenic acid and the composition is formulated to contain 0.5% by weight of kynurenic acid.

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

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

24. The use of a compound according to claim 19, wherein the administration or application is topical administration to skin having wrinkles or folds.

25. The use of a compound according to claim 1, wherein the compound is administered as a component of a composition formulated for injectable use.

26. The use of a compound according to claim 1, 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. The use of a compound according to claim 24, wherein the administration or application is topical administration to wrinkled or folded skin in combination with platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

28. The use of a compound according to claim 24, wherein the administration or application is topical administration to the skin having wrinkles or folds, and is combined with the administration or application of antigen presenting cells (APCs).

29. A method of reducing the appearance of wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthurenic acid, and kynurenic acid.

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

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

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

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

35. The method of claim 30, wherein the administering or applying is topical administration to wrinkled or folded skin.

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

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

39. The method of claim 30, wherein the administration or application is topical administration or application to wrinkled or folded skin and is combined with the administration or application of antigen presenting cells (APCs).

40. A method for treating wrinkles or folds 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-hydroxy-kynurenine, 4-chloro-DL-kynurenine, xanthuric acid and kynurenic acid.

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

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

44. 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. The method of claim 41, wherein the administration or application is topical administration or application to wrinkled or folded skin and is combined with administration or application of platelet-rich plasma (PRP) therapy or platelet-rich fibrin (PRF) therapy.

46. ​​The method of claim 41, wherein the administration or application is topical administration or application to wrinkled or folded skin and is combined with the administration or application of antigen presenting cells (APCs).

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

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

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

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