Keratin Treatment Compounds

Abstract

Provided herein are compounds and formulations useful for treating keratin in hair and / or skin. In some embodiments, the compounds and formulations provided herein can be used to strengthen hair, for example, by improving the tensile strength and / or improving the elongation rate of hair. TIFF2026502644000041.tif1941

Description

[Technical Field]

[0001] Related Applications This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63 / 481,042, filed January 23, 2023, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] More than 90% of hair's dry weight comprises keratin, which has a high disulfide bond content derived from cysteine ​​amino acids. These disulfide bonds provide stability to the keratin structure. Generally, keratin contains two polypeptide chains twisted together to form a "coiled-coil" structure. The ability of these coiled structures to unwind, even breaking internal hydrogen bonds (H-bonds), allows the α-helical structure to be stretched. Releasing tension typically results in reformation of the hydrogen bonds and recovery of the shape. This, in part, gives hair its characteristic flexibility. However, if the disulfide bonds within hair are damaged or destroyed, hair strands lose their characteristic flexibility and become brittle, prone to tangling and / or fraying. Keratin is also a major component of skin. Damage to keratin's disulfide bonds can cause skin to appear unhealthy, dull, and / or flaky. Maintaining the disulfide bonds in keratin helps keep skin healthy and prevents cracking and splitting.

[0003] One of the major goals of the cosmetics industry is the discovery and development of compounds and formulations for treating keratin in hair and / or skin. Summary of the Invention

[0004] Provided herein are compounds and formulations useful for treating keratin in hair and / or skin. In certain embodiments, the compounds and formulations disclosed herein may be used to strengthen hair, for example, by increasing the tensile strength of hair and / or increasing the elongation rate (or percent elongation) of hair.

[0005] For example, compounds of formula (I) and (II) are described herein: TIFF2026502644000002.tif4394 and cosmetically acceptable salts thereof, wherein G is a bond or a linker. In some embodiments, G is a linker comprised of one or more glycolic acid and / or serine units.

[0006] In certain embodiments, the compound is a compound of formula (Ia) or (II-a): TIFF2026502644000003.tif42110 or a cosmetically acceptable salt thereof, and n is 0 or an integer from 1 to 10 (inclusive).

[0007] In certain embodiments, the compound is a compound of formula (Ib): TIFF2026502644000004.tif1972 or a cosmetically acceptable salt thereof, and m is an integer from 1 to 10.

[0008] In some embodiments, the compound has a molecular weight of 1000 g / mol or less. In some embodiments, the compound has a molecular weight of 500 g / mol or less. In some embodiments, the compound has a length of 90 Å or less. In some embodiments, the compound has a length of 45 Å or less.

[0009] In certain embodiments, the compound is a compound represented by the formula: TIFF2026502644000005.tif1941 or a cosmetically acceptable salt thereof.

[0010] In one embodiment, the compound is Compound (1): TIFF2026502644000006.tif1967 or a cosmetically acceptable salt thereof.

[0011] In certain embodiments, the compound is a compound represented by the formula: TIFF2026502644000007.tif1972 or a cosmetically acceptable salt thereof.

[0012] In certain embodiments, the compound is a compound represented by the formula: TIFF2026502644000008.tif2172 or a cosmetically acceptable salt thereof.

[0013] Also provided herein are formulations (i.e., cosmetically acceptable formulations) comprising a compound provided herein, or a cosmetically acceptable salt thereof, and one or more cosmetically acceptable carriers and / or excipients. In some embodiments, the formulations described herein further comprise one or more organic acids. In some embodiments, the formulations described further comprise one or more amino acids. In other embodiments, the formulations described further comprise one or more alpha hydroxy acids (AHAs) (e.g., glycolic acid). In some embodiments, the formulations described further comprise one or more beta hydroxy acids (BHAs). The present specification also provides examples of organic acids, including amino acids, AHAs, and BHAs. In some embodiments, the formulations are suitable for application to a subject's hair and / or skin. In some embodiments, the formulations are suitable for application to hair.

[0014] The following methods are also provided herein, including, but not limited to: (i) A method comprising applying a compound described herein, or a cosmetically acceptable salt thereof, or a formulation described herein to the hair and / or skin of a subject. In some embodiments, the compound or formulation is applied to the hair. (ii) A method of treating the hair and / or skin of a subject, comprising applying to the hair and / or skin of the subject a compound described herein, or a cosmetically acceptable salt thereof, or a formulation described herein. In some embodiments, the method is a method of treating hair (e.g., by increasing the tensile strength or elongation of hair). (iii) A method of treating keratin in the hair and / or skin of a subject, comprising applying to the hair and / or skin of the subject a compound described herein, or a cosmetically acceptable salt thereof, or a formulation described herein. In some embodiments, the method is a method of treating keratin in hair.

[0015] Also provided herein are kits (e.g., hair care kits) containing one or more compounds, cosmetically acceptable salts thereof, or combinations thereof described herein. The kits may include instructions for applying the compounds or combinations to hair. The kits may further include one or more additional compounds or combinations intended for application to hair, e.g., in separate containers.

[0016] Details of certain embodiments of the present disclosure are set forth in the Detailed Description of Certain Embodiments, as set forth below. Other features, objects, and advantages of the present disclosure will become apparent from the definitions, examples, drawings, and claims. [Brief explanation of the drawings]

[0017] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the present disclosure and, together with the description, provide non-limiting examples.

[0018] Figure 1 compares the tensile strength of hair after treatment with Compound (1) with that of a control, which was hair treated with 100% deionized (DI) water. Tensile strength tests using Compound (1) were performed in triplicate (each replicate is represented by a bar). The results show that Compound (1) significantly improves the tensile strength of hair.

[0019] Figure 2 compares the tensile strength of hair after treatment with Compound (1) to glycolic acid. A 2.5 wt% solution of Compound (1) significantly improves hair tensile strength compared to a 2.5 wt% solution of glycolic acid. The control is hair treated with 100% deionized (DI) water.

[0020] Figure 3 compares the elongation rate of hair treated with Compound (1) with that of a control. The control was hair treated with 100% deionized (DI) water. The elongation test using Compound (1) was performed in triplicate (each replicate is represented by a bar). The results demonstrate that Compound (1) improves hair elongation rate.

[0021] Figure 4 compares hair growth rates after treatment with Compound (1) and glycolic acid. A 2.5 wt% solution of Compound (1) significantly improved hair growth rates compared to a 2.5 wt% solution of glycolic acid. The control was hair treated with 100% deionized (DI) water.

[0022] 5A-5B show the effect of immersion time on the tensile strength (FIG. 5A) and elongation (FIG. 5B) of hair. Tests were performed using a 2.5 w / w% solution of Compound (1).

[0023] Detailed Description of Certain Embodiments Provided herein are compounds and formulations useful for treating keratin in hair and / or skin. In some embodiments, the compounds and formulations provided herein can be used to strengthen hair, for example, by increasing the tensile strength and / or elongation of hair.

[0024] compound Provided herein are compounds (e.g., Formulas (I) and (II)), and cosmetically acceptable salts thereof, which contain one or more serine and / or glycolic acid units. "Serine" refers to the amino acid serine, including D-serine, L-serine, or a combination thereof.

[0025] In some embodiments, the compound or cosmetically acceptable salt thereof comprises 1 to 10 glycolic acid units. In some embodiments, the compound or cosmetically acceptable salt thereof comprises 1 to 10 glycolic acid units. In some embodiments, the serine and / or glycolic acid units are linked via ester bonds.

[0026] Provided herein are compounds of formula (I) and (II), and cosmetically acceptable salts thereof, wherein G is a bond or a linker. TIFF2026502644000009.tif4082

[0027] In some embodiments, G is a bond. In some embodiments, G is a linker. In some embodiments, G is a linker consisting of one or more glycolic acid and / or serine units.

[0028] In some embodiments, the glycolic acid unit has the following formula: Represented as TIFF2026502644000010.tif2443. In one embodiment, G is 0 to 10 (inclusive) glycolic acid units. In certain embodiments, the serine unit has the following formula: Represented as TIFF2026502644000011.tif2843. In one embodiment, G comprises 0 to 10 (inclusive) serine units.

[0029] In some embodiments, the compound has formula (Ia) or (II-a): TIFF2026502644000012.tif4089 or a cosmetically acceptable salt thereof, and n is 0 or an integer from 1 to 10 (inclusive).

[0030] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10.

[0031] In one embodiment, the compound has formula (Ib): TIFF2026502644000013.tif2064, or a cosmetically acceptable salt thereof, wherein m is an integer of 1 to 10 (inclusive).

[0032] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10.

[0033] In some embodiments, the compound has a molecular weight of 1000 g / mol or less. In some embodiments, the compound has a molecular weight of 900 g / mol or less. In some embodiments, the compound has a molecular weight of 800 g / mol or less. In some embodiments, the compound has a molecular weight of 700 g / mol or less. In some embodiments, the compound has a molecular weight of 600 g / mol or less. In some embodiments, the compound has a molecular weight of 500 g / mol or less. In some embodiments, the compound has a molecular weight of 400 g / mol or less. In some embodiments, the compound has a molecular weight of 300 g / mol or less. In some embodiments, the compound has a molecular weight of 200 g / mol or less. In some embodiments, the compound has a molecular weight of about 163 g / mol to about 1000 g / mol. In some embodiments, the compound has a molecular weight of about 163 g / mol to about 500 g / mol.

[0034] In some embodiments, the length of the compound is 90 Å or less. As used herein, the "length" of a compound refers to the total distance between the two ends of the longest linear chain of atoms of the compound. In some embodiments, the length of the compound is 80 Å or less, 70 Å or less, 60 Å or less, 50 Å or less, 45 Å or less, 40 Å or less, 30 Å or less, 20 Å or less, 10 Å or less, or 5 Å or less. In some embodiments, the length of the compound is from about 3 Å to about 90 Å. In some embodiments, the length of the compound is from about 3 Å to about 45 Å.

[0035] In certain embodiments, the compound has the following formula: TIFF2026502644000014.tif1941, or a cosmetically acceptable salt thereof.

[0036] In one embodiment, the compound is Compound (1): TIFF2026502644000015.tif1941 Compound (1) or a cosmetically acceptable salt thereof.

[0037] In certain embodiments, the compound has the following formula: TIFF2026502644000016.tif1941, or a cosmetically acceptable salt thereof.

[0038] In certain embodiments, the compound has the following formula: TIFF2026502644000017.tif1972, or a cosmetically acceptable salt thereof.

[0039] In certain embodiments, the compound has the following formula: TIFF2026502644000018.tif2172, or a cosmetically acceptable salt thereof.

[0040] In certain embodiments, the compound has the following formula: TIFF2026502644000019.tif2172, or a cosmetically acceptable salt thereof.

[0041] As used herein, "compound," "a compound," or "the compound" refers to any compound described herein (including those belonging to formula (1) or (II), or any of the classes thereunder, and any species described herein), or a cosmetically acceptable salt thereof.

[0042] The term "salt" refers to any and all salts, including cosmetically acceptable salts. Salts include ionic compounds resulting from the neutralization reaction of an acid and a base. A salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions), and is electrically neutral (has no net charge). Salts of the compounds of the present disclosure include those derived from inorganic and organic acids and bases.

[0043] A "cosmetically acceptable salt" refers to a salt that is suitable for use in contact with human or other animal tissues (hair, skin, nails, etc.) without undue toxicity, irritation, allergic reaction, etc., and that is commensurate with a reasonable benefit / risk ratio. Cosmetically acceptable salts include those derived from suitable inorganic and organic acids and bases. Examples of cosmetically acceptable non-toxic acid addition salts are amino salts formed from inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric, and perchloric acids, or organic acids such as acetic, oxalic, maleic, tartaric, citric, succinic, or malonic acid, or by using other known methods such as ion exchange. Other cosmetically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfite, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, and 2-hydroxyethanesulfonate. Cosmetically acceptable salts derived from appropriate bases include salts of alkali metals, alkaline earth metals, ammonium, and N-methyl-N ... + (C 1-4 Alkyl)4 -Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Cosmetically acceptable salts also include non-toxic ammonium, quaternary ammonium, and amine cations, formed where appropriate with counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkylsulfonates, and arylsulfonates.

[0044] Compounds that have the same molecular formula but differ in the type or sequence of bonding of their atoms or the arrangement of their atoms in space are called "isomers." Isomers that differ in the arrangement of their atoms in space are called "stereoisomers." Stereoisomers that are not mirror images of one another are called "diastereomers," and stereoisomers that are non-superimposable mirror images of each other are called "enantiomers." A mixture of compounds containing equal proportions of enantiomers is called a "racemic mixture."

[0045] The compounds described herein may have one or more asymmetric centers and may exist in various stereoisomeric forms, e.g., enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers, or geometric isomers, or may be in the form of mixtures of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid column chromatography (HPLC) and chiral salt formation and crystallization, or preferred isomers can be prepared by asymmetric synthesis.

[0046] The compounds provided herein can include L-serine units, D-serine units, or a combination of both. For example, compounds of the formula: Any relevant part of TIFF2026502644000020.tif2843 can be independently TIFF2026502644000021.tif3043 (L-serine) or TIFF2026502644000022.tif2843 (D-serine).

[0047] Cosmetic formulations Provided herein are formulations comprising a compound described herein (e.g., a compound of Formula (I) or (II)) or a cosmetically acceptable salt thereof, and one or more cosmetically acceptable carriers and / or excipients (or additives).

[0048] In some embodiments, the formulations described herein further comprise one or more organic acids, wherein the one or more organic acids are independently selected from amino acids, alpha hydroxy acids (AHAs), and beta hydroxy acids (BHAs). In some embodiments, the formulation comprises an amino acid selected from serine, tyrosine, and aspartic acid. In some embodiments, the formulation comprises an alpha hydroxy acid (AHA) selected from glycolic acid, lactic acid, citric acid, tartaric acid, malic acid, mandelic acid, alpha-hydroxyoctanoic acid, alpha-hydroxydecanoic acid, and alpha-hydroxybutyric acid. In some embodiments, the formulation comprises glycolic acid. In some embodiments, the formulation comprises a beta hydroxy acid (BHA) selected from salicylic acid or beta-hydroxybutyric acid. In some embodiments, the formulation comprises maleic acid.

[0049] In certain embodiments, the formulation is suitable for application to the hair and / or skin of a subject. In preferred embodiments, the formulation is suitable for application to hair. The terms "formulation" and "composition" are used interchangeably.

[0050] Formulations containing the compounds described herein can be formulated and prepared according to principles generally known in the cosmetic and personal care product arts.

[0051] Formulations suitable for application to a subject's hair and / or skin may be in the form of shampoos, conditioners, creams, lotions, pastes, gels, sprays, mousses, or other solutions or suspensions. Cosmetically acceptable carriers and / or excipients (or additives) include, but are not limited to, solvents, surfactants, conditioners, emollients, humectants, penetrating agents, foaming agents, thickeners, emulsifiers, dispersing agents, diluents, lubricants, propellants, sequestering or chelating agents, preservatives, buffers, antioxidants, vitamins, lipids, proteins, amino acids, oils, waxes, extracts, colorants or dyes, opacifiers, and fragrances. Other cosmetically acceptable additives may also be included.

[0052] As described herein, in some embodiments, the formulation includes one or more organic acids, in some embodiments, the one or more organic acids are independently selected from alpha hydroxy acids (AHAs), beta hydroxy acids (BHAs), and amino acids.

[0053] In some embodiments, the formulation includes one or more AHAs. Non-limiting examples of AHAs include glycolic acid, lactic acid, citric acid, tartaric acid, malic acid, mandelic acid, α-hydroxyoctanoic acid, α-hydroxydecanoic acid, and α-hydroxybutyric acid. In some embodiments, the formulation includes glycolic acid.

[0054] In some embodiments, the formulation includes one or more BHAs. Non-limiting examples of BHAs include salicylic acid and beta-hydroxybutyric acid.

[0055] In certain embodiments, the formulation comprises one or more amino acids, non-limiting examples of which include serine, tyrosine, and aspartic acid.

[0056] In certain embodiments, the formulation includes maleic acid.

[0057] The present specification also provides kits (e.g., hair care kits) containing one or more compounds, cosmetically acceptable salts thereof, or formulations thereof described herein. The kits may include instructions for applying the compounds or formulations to hair. The kits may further include one or more additional cosmetically acceptable compounds or formulations intended for application to hair, e.g., in separate container(s).

[0058] "Cosmetically acceptable" refers to materials that are suitable for use in contact with human and animal tissue (e.g., hair, skin, nails) and that are not associated with undue toxicity, irritation, allergic reactions, or other problems or complications, in light of a reasonable benefit / risk ratio. More specifically, cosmetically acceptable can refer to materials that are suitable for use in contact with the skin, scalp, and / or human hair. Cosmetically acceptable materials are known to those skilled in the art.

[0059] Hair and skin treatment method The compounds and formulations described herein can be used to treat keratin, and therefore can be used to treat hair and / or skin. "Keratin" refers to α-keratin, an important structural protein found in the hair, nails, and outer layer of skin of vertebrates, including humans. Keratin (α-keratin) comprises a single protein strand wound in an α-helix, which can further twist into a superhelical rope, which can further coil (a "coiled-coil" structure). In addition to intramolecular and intermolecular hydrogen bonds (H-bonds), a distinctive feature of keratin is the relatively large number of disulfide bonds derived from cysteine ​​amino acids. These disulfide bridges provide additional strength and rigidity. If the disulfide bonds of keratin are broken, the protein can lose its strength and rigidity.

[0060] Without being bound by any particular theory, treating keratin with the compounds or formulations described herein promotes cross-linking of adjacent keratin protein strands by repairing broken disulfide bonds and / or hydrogen bonds, thereby repairing and / or stabilizing the secondary structure of keratin. Treating keratin in hair and / or skin results in hair and / or skin with improved physical and / or cosmetic properties.

[0061] Provided herein are methods that include applying to the hair and / or skin of a subject a compound described herein, or a cosmetically acceptable salt thereof, or a formulation thereof. In some embodiments, the compound, cosmetically acceptable salt, or formulation is applied to the hair.

[0062] Provided herein are methods of treating the hair and / or skin of a subject, comprising applying to the hair and / or skin of a subject a compound described herein, or a cosmetically acceptable salt thereof, or a combination thereof. In some embodiments, the method is a method of treating the hair of a subject.

[0063] In some embodiments, the method of the present disclosure is a method of strengthening hair in a subject. As used herein, "strengthening" refers to increasing a material's resistance to breakage or physical damage. Thus, "strengthening hair" refers to increasing hair's resistance to breakage or physical damage. "Tensile strength" refers to a material's resistance to breaking under tension. The tensile strength of hair can be measured by the tensile strength test described herein.

[0064] In some embodiments, hair tensile strength is increased by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% compared to a control. In some embodiments, hair tensile strength is increased by about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% compared to a control. In some embodiments, hair tensile strength is improved by about 10% to about 50% compared to a control. A "control" may be a formulation or carrier that does not contain a compound described herein or a cosmetically acceptable salt thereof.

[0065] In some embodiments, the percent elongation of hair is improved. "Elongation" refers to the percentage increase in hair length when hair is stretched. In some embodiments, hair elongation is increased by at least 1%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% compared to a control. In some embodiments, the percent elongation of hair is increased by about 1%, about 2%, about 5%, about 10%, about 15%, or about 20% compared to a control. In some embodiments, the percent elongation of hair is increased by about 1% to about 10% compared to a control. A "control" may be a formulation or carrier that does not contain a compound described herein or a cosmetically acceptable salt thereof.

[0066] Provided herein are methods for treating keratin in a subject's hair and / or skin, comprising applying to the subject's hair and / or skin a compound described herein, or a cosmetically acceptable salt thereof, or a combination thereof. In some embodiments, the method is a method for treating keratin in a subject's hair. In some embodiments, the method includes repairing and / or stabilizing the secondary structure of the keratin.

[0067] As used herein, the terms "applying," "application," and the like, when used in the context of the methods described herein, refer to physically contacting a compound or formulation described herein with a subject. For example, "applying" a compound or formulation described herein to a subject's hair refers to physically contacting the compound or formulation with the subject's hair, e.g., topically, for any period of time.

[0068] As used herein, "subject" refers to a human or non-human mammal of any gender or age group. In certain embodiments, the subject is a human.

[0069] As used herein, "treatment," "treat," "treating," and the like refer to improving one or more cosmetic and / or physical properties of what is being treated. For example, "treating hair" refers to improving one or more cosmetic and / or physical properties of hair. Physical properties of hair include, but are not limited to, tensile strength, extensibility (extension potential), softness, and elasticity. Cosmetic properties of hair include, but are not limited to, shine, texture, and overall aesthetic appearance. Similarly, "treating skin" refers to improving one or more cosmetic or physical properties of skin. Similarly, "treating keratin" refers to improving one or more physical properties of keratin, for example, repairing and / or stabilizing the secondary structure of keratin.

[0070] Example In order that the present disclosure may be more fully understood, the following examples are set forth, which are provided to illustrate the compounds, formulations, and methods provided herein, and should not be construed as in any way limiting the scope thereof.

[0071] Example 1: Compound synthesis and characterization Compound (1) Compound (1) shown below: TIFF2026502644000023.tif1961 can be prepared by esterification of serine with glycolic acid.

[0072] For example, compound (1) was synthesized by N,N'-dicyclohexylcarbodiimide (DCC) coupling followed by HCl gas-solid deprotection according to the following general procedure, which afforded measurable yields of compound (1) with quantifiable purity.

[0073] General Procedure A stirred solution of a carboxylic acid (protected serine) in an anhydrous organic solvent is charged to a glass reactor. To this solution, 4-dimethylaminopyridine (DMAP) and a stoichiometric amount of an alcohol (protected glycolic acid) are added. A stoichiometric amount of DCC is added to the reaction mixture at 0°C, followed by stirring for 5 minutes at 0°C and then for 3 hours or more at ambient temperature. After the reaction is complete, the precipitated by-product is removed by filtration. The organic filtrate is washed twice in a separatory funnel with 0.5 N HCl, then with saturated NaHCO3 solution, and then dried over Na2SO4. The Na2SO4 is removed by filtration, and the remaining solvent is removed by evaporation to give the solid intermediate product.

[0074] For a dual-chamber reactor, the solid intermediate product is loaded into the first chamber (A) and the chloride salt is loaded into the second chamber (B). Under a closed system, the organic acid is injected into chamber B. Both chambers are stirred for at least one hour. After a sufficient time, the system pressure is released and chamber B is vented. Additional chloride salt is loaded into chamber B, the acid is injected, and the system is allowed to react. This process is repeated a total of six times. The product remaining in chamber A is compound (1) (10 mmol), as confirmed by NMR and HR-MS.

[0075] The physical property data of compound (1) are shown below. 1 H NMR (400MHz, DMSO-d6) δ8.62(br, 3H), 5.55(br, 1H), 4.71(d, 2H), 4.19(t, 1H), 3.84(s, 2H) 13 C NMR (600MHz, DMSO-d6) δ168.4, 167.8, 61.8, 59.5, 54.2 HR-MS(ES + ): m / z 164, 100% (M) + ;165, 6% (M+H) + ;327, 15% (M+MH) +

[0076] Example 2: Tensile strength of hair General Method Hair tensile strength can be measured according to the following general method: The "test compound" may be any compound described herein. 1. Collect about 3 hair strands from the hair bundle, 2. Clamp both ends of a single hair strand and hold it taut. 3. Place a ruler over the hair strand and cut it into 2.75cm pieces. 4. Repeat steps 2-3 until 30 segments are created. 5. Prepare a solution of deionized water and a specific concentration (w / w%) of a test compound (e.g., Compound (1)) in a 50 mL beaker. 6. Soak hair in the solution for the desired time, then remove and allow to dry for 30 minutes. 7. Using a precision balance with four decimal places, weigh all the hairs together and calculate the average value. 8. Insert the hair into the digital force gauge. 9. Pull the two clamps apart until the hair separates into two separate pieces, and 10. Record the maximum force required to break the hair and the length traveled by the digital force gauge.

[0077] Control experiments can be performed according to the procedures described above, for example, by omitting the test compound from the solution or by substituting a comparative compound (eg, glycolic acid) for the test compound.

[0078] result As shown in Figure 1, Compound (1) significantly increases hair tensile strength compared to the control (control is hair treated with 100% deionized water (DI)). As shown in Figure 2, Compound (1) significantly increases hair tensile strength compared to glycolic acid. Table 1 below shows the tensile strength (gram force / denier (gf / denier)) after treatment with the control (100% deionized water), 2.5 wt% glycolic acid, 1 wt% Compound (1), and 2.5 wt% Compound (1). Notably, the 2.5 wt% Compound (1) solution increased tensile strength by 43.9% compared to the control. [Table 1]

[0079] Example 3: Hair elongation (or lengthening) Compound (1) increases hair elongation. Figure 3 shows the hair elongation rate after treatment with Compound (1) compared to a control. Figure 4 shows the hair elongation rate after treatment with Compound (1) compared to glycolic acid. Table 2 below shows the increase in elongation rate (%) after treatment with a control (100% deionized (DI) water), 2.5 wt.% glycolic acid, 1 wt.% Compound (1), and 2.5 wt.% Compound (1). [Table 2]

[0080] Example 4: Formulations containing a combination of Compound (1) and glycolic acid A combination formulation (Formulation 1) containing Compound (1) and glycolic acid was tested as an aqueous mixture. Formulation 1 contained Compound (1) and glycolic acid in a 1:1 ratio (by weight). To prepare Formulation 1, a mixture containing 50 wt% Compound (1) and 50 wt% glycolic acid (crystal) was prepared (Mixture A). Mixture A was diluted with deionized (DI) water (aqua) to a concentration of 5 wt%.

[0081] Formula 1 was analyzed independently to determine whether it increased the elongation at breaking stress of bleached hair compared to both the control solution and the glycolic acid solution. The glycolic acid solution was a 5 wt% glycolic acid solution in DI water. The control was DI water alone. The resulting data are shown in Table 3 below. [Table 3]

[0082] Other combinations are possible. For example, the glycolic acid portion of Formulation 1 may be substituted with or combined with one or more organic acids selected from the following: lactic acid, citric acid, malic acid, maleic acid, tartaric acid, mandelic acid, salicylic acid, and hydroxybutyric acid. Also, for example, the glycolic acid portion of Formulation 1 may be substituted with or combined with one or more of the following amino acids: serine, tyrosine, and aspartic acid.

[0083] Additional Embodiments Additional embodiments are provided, as illustrated by the following numbered embodiments: Embodiment 1 A compound of formula (I) or (II), or a cosmetically acceptable salt thereof, wherein G is a bond or a linker: TIFF2026502644000027.tif3692Embodiment 2 The compound of embodiment 1, or a cosmetically acceptable salt thereof, wherein G is a linker consisting of one or more glycolic acid and / or serine units. Embodiment 3 The compound of embodiment 1 or 2, wherein the compound is a compound of formula (Ia) or (II-a), or a cosmetically acceptable salt thereof, wherein n is 0 or an integer from 1 to 10, inclusive: TIFF2026502644000028.tif39100Embodiment 4 The compound of embodiment 1 or 2, wherein the compound is of formula (Ib), or a cosmetically acceptable salt thereof, wherein m is an integer from 1 to 10, inclusive: TIFF2026502644000029.tif1967Embodiment 5 The compound of any one of embodiments 1 to 4, or a cosmetically acceptable salt thereof, wherein the molecular weight of the compound is 1000 g / mol or less. Embodiment 6 The compound of any one of embodiments 1 to 5, or a cosmetically acceptable salt thereof, wherein the molecular weight of the compound is 500 g / mol or less. Embodiment 7 The compound of any one of embodiments 1 to 6, or a cosmetically acceptable salt thereof, wherein the compound has a length of 90 Å or less. Embodiment 8 The compound of any one of embodiments 1 to 7, or a cosmetically acceptable salt thereof, wherein the compound has a length of 45 Å or less. Embodiment 9. The compound of embodiment 1, having the formula: TIFF2026502644000030.tif1841Embodiment 10: The compound of embodiment 7, having the formula: TIFF2026502644000031.tif1841Embodiment 11: The compound of embodiment 7, having the formula: TIFF2026502644000032.tif1872Embodiment 12: The compound of embodiment 11, having the formula: TIFF2026502644000033.tif2172Embodiment 13 A formulation comprising a compound of any one of embodiments 1 to 12, or a cosmetically acceptable salt thereof, and one or more cosmetically acceptable carriers and / or excipients. Embodiment 14 The formulation of embodiment 13, wherein the formulation further comprises an organic acid. Embodiment 15 The formulation of embodiment 14, wherein the organic acid is an amino acid. Embodiment 16 The formulation of embodiment 15, wherein the amino acids are selected from serine, tyrosine, and aspartic acid. Embodiment 17 The formulation of embodiment 14, wherein the organic acid is an alpha hydroxy acid (AHA). Embodiment 18 The formulation of embodiment 17, wherein the AHA is selected from glycolic acid, lactic acid, citric acid, tartaric acid, malic acid, mandelic acid, alpha-hydroxyoctanoic acid, alpha-hydroxydecanoic acid, and alpha-hydroxybutyric acid. Embodiment 19 The formulation of embodiment 17 or 18, wherein the AHA is glycolic acid. Embodiment 20 The formulation of embodiment 14, wherein the organic acid is a beta hydroxy acid (BHA). Embodiment 21 The formulation of Embodiment 20, wherein the BHA is selected from salicylic acid and beta-hydroxybutyric acid. Embodiment 22 The formulation of any one of embodiments 13-21, wherein the formulation further comprises maleic acid. Embodiment 23 The formulation of any one of embodiments 13-22, wherein the formulation is suitable for application to the hair or skin of a subject. Embodiment 24 The formulation of embodiment 23, wherein the formulation is suitable for application to hair. Embodiment 25. A method comprising applying a compound of any one of embodiments 1-12, or a cosmetically acceptable salt thereof, or a formulation of any one of embodiments 13-24 to the hair and / or skin of a subject. Embodiment 26 The method of embodiment 25, wherein the compound, cosmetically acceptable salt thereof, or formulation is applied to hair. Embodiment 27. A method of treating the hair and / or skin of a subject, comprising applying to the hair and / or skin of a subject a compound of any one of embodiments 1-12, or a cosmetically acceptable salt thereof, or a formulation of any one of embodiments 13-24. Embodiment 28 The method of embodiment 27, wherein the hair of the subject is treated. Embodiment 29 The method of embodiment 27 or 28, wherein the method is a method of strengthening hair in a subject. Embodiment 30 The method of embodiment 28 or 29, wherein the tensile strength of the hair is increased by at least 10% relative to the control. Embodiment 31 The method of embodiments 28-30, wherein the hair growth rate is increased by at least 5% relative to the control. Embodiment 32. A method of treating keratin in hair and / or skin comprising applying a compound of any one of embodiments 1-12, or a cosmetically acceptable salt thereof, or a formulation of any one of embodiments 13-24 to the hair and / or skin of a subject. Embodiment 33 The method of embodiment 32, wherein the method treats keratin in the hair of the subject. Embodiment 34 The method of embodiment 32 or 33, wherein the method repairs and / or stabilizes the secondary structure of keratin.

[0084] Equivalents and Scope In the claims, articles such as "a," "an," and "the" may mean one or more unless otherwise indicated or clear from the context. A claim or description including "or" between one or more group members is considered to be sufficient if one, more than one, or all of the group members are present in, used in, or otherwise relevant to a given product or process, unless otherwise indicated or clear from the context. The disclosure includes embodiments in which exactly one member of a group is present in, used in, or otherwise relevant to a given product or process. The disclosure includes embodiments in which more than one, or all of the group members are present in, used in, or otherwise relevant to a given product or process.

[0085] Furthermore, the disclosure includes all variations, combinations, and permutations that introduce limitations, elements, statements, and explanations from one or more enumerated claims into other claims. For example, any claim that is dependent on another claim may be modified to include one or more limitations found in any other claim that is dependent on the same base claim. When elements are presented as lists, for example in Markush format, each subgroup of elements is also disclosed, and any element may be removed from the group.

[0086] In general, when the present disclosure, or aspects of the present disclosure, are referred to as comprising certain elements and / or features, it should be understood that certain embodiments of the present disclosure or aspects of the present disclosure consist of, or consist essentially of, such elements and / or features. For the sake of brevity, these embodiments are not described verbatim or specifically herein. It should also be noted that the terms "comprising" and "containing" are intended to be open and permit the inclusion of additional elements or steps.

[0087] When ranges are expressed, the endpoints are included. Furthermore, unless otherwise indicated or apparent from the context and the understanding of one of ordinary skill in the art, values ​​expressed as ranges are understood to be able to take any specific value or subrange within the ranges set forth in various embodiments of this disclosure, to one-tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0088] This application may refer to issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. In the event of a conflict between any incorporated reference and this specification, this specification shall control. Additionally, any certain embodiments of the present disclosure that fall within the prior art may be expressly excluded from any one or more claims. Because such embodiments are deemed known to those of skill in the art, they may be excluded even if the exclusion is not expressly set forth herein. Any certain embodiments of the present disclosure may be excluded from any claim for any reason, whether or not related to the existence of prior art.

[0089] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the certain embodiments described herein. The scope of the embodiments described herein is not intended to be limited to the above description, but rather is as set forth in the appended claims. Those skilled in the art will appreciate that various changes and modifications to the description can be made without departing from the concept or scope of the present disclosure, as defined in the following claims.

Claims

1. Formula (I) or (II): wherein G is a bond or a linker. or a cosmetically acceptable salt thereof.

2. 2. The compound of claim 1, or a cosmetically acceptable salt thereof, wherein G is a linker consisting of one or more glycolic acid and / or serine units.

3. The compound has formula (I-a) or (II-a): (wherein n is 0 or an integer from 1 to 10) 3. The compound according to claim 1 or 2, which is a compound of the formula: or a cosmetically acceptable salt thereof.

4. The compound has formula (I-b): (wherein m is an integer from 1 to 10) 3. The compound according to claim 1 or 2, which is a compound of the formula: or a cosmetically acceptable salt thereof.

5. 5. The compound of any one of claims 1 to 4, or a cosmetically acceptable salt thereof, wherein the compound has a molecular weight of less than 1000 g / mol.

6. 6. A compound or a cosmetically acceptable salt thereof according to any one of claims 1 to 5, wherein the compound has a molecular weight of less than or equal to 500 g / mol.

7. 7. The compound or cosmetically acceptable salt thereof according to any one of claims 1 to 6, wherein the length of the compound is 90 Å or less.

8. 8. The compound or cosmetically acceptable salt thereof according to any one of claims 1 to 7, wherein the length of the compound is 45 Å or less.

9. The compound has the following formula:

2. The compound of claim 1, wherein the compound is:

10. The compound has the following formula:

8. The compound of claim 7, wherein the compound is:

11. The compound has the following formula:

8. The compound of claim 7, wherein the compound is:

12. The compound has the formula:

12. The compound of claim 11, wherein:

13. A formulation comprising a compound according to any one of claims 1 to 12 or a cosmetically acceptable salt thereof, and one or more cosmetically acceptable carriers and / or excipients.

14. 14. The formulation of claim 13 further comprising an organic acid.

15. 15. The formulation of claim 14, wherein the organic acid is an amino acid.

16. 16. The formulation of claim 15, wherein the amino acid is selected from serine, tyrosine, and aspartic acid.

17. 15. The formulation of claim 14, wherein the organic acid is an alpha hydroxy acid (AHA).

18. 18. The formulation of claim 17, wherein the AHA is selected from glycolic acid, lactic acid, citric acid, tartaric acid, malic acid, mandelic acid, alpha-hydroxyoctanoic acid, alpha-hydroxydecanoic acid, and alpha-hydroxybutyric acid.

19. 19. The formulation of claim 17 or 18, wherein the AHA is glycolic acid.

20. 15. The formulation of claim 14, wherein the organic acid is a beta hydroxy acid (BHA).

21. 21. The formulation of claim 20, wherein the BHA is selected from salicylic acid and beta-hydroxybutyric acid.

22. The formulation of any one of claims 13 to 21, further comprising maleic acid.

23. A formulation according to any one of claims 13 to 22, suitable for application to the hair and / or skin of a subject.

24. 24. A formulation according to claim 23 suitable for application to hair.

25. 25. A method comprising applying a compound according to any one of claims 1 to 12, or a cosmetically acceptable salt thereof, or a formulation according to any one of claims 13 to 24, to the hair and / or skin of a subject.

26. 26. The method of claim 25, wherein the compound, a cosmetically acceptable salt or formulation thereof is applied to the hair.

27. 25. A method of treating the hair and / or skin of a subject, comprising applying to the hair and / or skin of a subject a compound or a cosmetically acceptable salt thereof according to any one of claims 1 to 12, or a formulation according to any one of claims 13 to 24.

28. 28. The method of claim 27, wherein the method is a method of treating hair of a subject.

29. 29. The method of claim 27 or 28, which is a method for strengthening hair in a subject.

30. 30. The method of claim 28 or 29, wherein the tensile strength of the hair is increased by at least 10% relative to the control.

31. 31. The method of any one of claims 28 to 30, wherein the hair growth rate is increased by at least 5% compared to a control.

32. 25. A method of treating keratin in the hair and / or skin of a subject, the method comprising applying a compound according to any one of claims 1 to 12 or a cosmetically acceptable salt thereof, or a formulation according to any one of claims 13 to 24 to the hair and / or skin of the subject.

33. 33. The method of claim 32, wherein the method is a method for treating keratin in the hair of a subject.

34. 34. The method of claim 32 or 33, comprising repairing and / or stabilizing the secondary structure of keratin.

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