Nail reinforcement method using a complex Michael addition treatment composition

Abstract

A method for treating a nail plate that is brittle, broken, cracked, or otherwise damaged. The method of the present invention involves applying a prepared composition to the nail using an aqueous organic medium treatment composition containing a Michael mono-adduct or bis-adduct of a complex of a diamine and maleic anhydride, thereby allowing the mono-adduct and / or bis-adduct to penetrate from the surface of the nail plate into its interior region.

Description

[Technical Field]

[0001] Claim of priority This patent application claims the benefit of a continuation-in-part application under PCT application number PCT / US23 / 65266 filed on April 3, 2023, and the benefit of priority to U.S. Provisional Application No. 63 / 578,725 filed on August 25, 2023, the entire disclosure of which is incorporated herein by reference.

[0002] Technical field The present invention relates to a method for treating damaged nail plates using a Michael addition treatment composition. [Background technology]

[0003] Human digital soft tissue functions as one of the primary sensory interactions with the human environment. Therefore, digital soft tissue is highly sensitive to tactile stimuli, heat, cold, and electromagnetic radiation (infrared and UV light), and can be damaged if these are excessive. In digital appendages, the nail plate protects the digital soft tissue and the corresponding internal bone from external forces and impacts that can occur due to heating, freezing, radiation, contact, grasping, holding, walking, and / or standing. For example, when the fingertip strikes a hard object, a human nail absorbs and deflects the impact on the soft tissue and bone. A weak, brittle, cracked, and / or damaged nail plate does not offer this protection, resulting in significant pain from the external force.

[0004] Traditionally, damaged, cracked, or weak nails have been treated with formaldehyde compositions to repair the damage and cracks. Formaldehyde reacts with the proteins in the nail to form imine bonds, hardening the tissue. This treatment does not have a strong odor, kills the associated cells, and often causes allergic reactions. The treatment is the same as that performed by embalming techniques.

[0005] Nevertheless, formaldehyde treatment of cracked and damaged nails is a currently approved FDA treatment. Recently, in an attempt to avoid the undesirable side effects of formaldehyde treatment, other aldehyde formulations have been developed. Citral, remonal / geranial, and citronellal are aldehyde terpenoids that have traditionally been used in trace amounts to create fragrances in perfumes. Recently, citral and citronellal formulations with higher concentrations of this aldehyde have been developed for use in nail strengthening applications. Another challenge associated with formaldehyde is the issue of these longer carbon chain aldehydes.

[0006] Other nail strengthening treatments include iodine, hydrazine, divinylsulfone, and dithiopyridine. Of these, iodine is the active ingredient in some commercially available nail strengtheners, but hydrazine, divinylsulfone, and dithiopyridine are not considered safe alternatives to formaldehyde. Bismaleimide hexane and bismaleimide triethylene glycol are also known agents for treating brittle, frizzy hair. These may also be useful for strengthening nails, because nails and hair contain similar protein families.

[0007] More recently, nail strengthening treatments using non-reactive, non-covalent complexes of diamines and unsaturated dicarboxylic acids (e.g., maleic acid) are described in U.S. Patent Application Publication 2022 / 0257534 and PCT / US2018 / 041408, filed July 10, 2018.

[0008] Therefore, it remains desirable to develop safe, effective, and non-invasive treatments for weak, damaged, and cracked nail plates that provide the strongest possible reinforcement and reshaping of the damaged nail. Another objective is the development of preparations that do not cause discoloration of the human nail plate and can be combined with color components for selectively coloring the nail plate. [Overview of the Initiative]

[0009] The present invention relates to a method for treating weak, brittle, inflexible, cracked, and / or damaged fingernails or toenails, the method for treatment comprising applying a nail strengthening composition to the nail plate of the fingernail or toenail. Embodiments of the treatment method involve applying a treatment composition to the damaged nail plate, which is a combination of an organic medium, an aqueous medium, or an aqueous organic medium and a mono adduct that is 2-(amino)succinic acid having multiple organo groups or siliconyl groups, an ester, an amide, anhydride, or imide, and / or a Michael adduct that is N,N'-bis(2-succinoylhydroxy)- or N,N'-bis(2-succinoyloxyalkyl ester)- or N,N'-bis(2-succinamide)- or N,N'-bis(2-succinoanhydride)- or N,N'-bis(2-succinimide), an α,ω-multiorgano group, or siliconyl group substituted diamine, or any combination thereof.

[0010] Monoadducts and / or bisadducts are prepared by combining an α,β-unsaturated carbonyl compound such as maleic acid or maleic acid diester or maleic acid diamide or maleic anhydride or maleimide with a diamine such as a polyorgano diamine or silicone diamine via a Michael addition reaction. A polyorgano diamine has a primary amino group at its terminus, and the polyorgano portion between the termini is linear or branched, preferably a linear organic chain. Examples of skeletal chains composed of such organic chains include long hydrocarbon chains, heterohydrocarbon chains with multiple nitrogen atoms, oxygen atoms and / or sulfur atoms interposed in the chain, polyamide chains, polyester chains, hydrocarbon chains or heterohydrocarbon chains or polyamide chains or polyester chains having ester groups, amide groups and / or amino groups at the side chains and / or termini, cyclic aliphatic chains, or aromatic chains. Silicone diamines have primary amines at their terminals and / or one or more branched chains, and the interterminal silicone chains may be linear silicone polymer chains composed of dimethylsiloxane moieties and / or block copolymer chains of dimethylsiloxane polymer blocks and polyether, polyester and / or polyamide blocks. Typically, the amine group is configured as an aminoalkyl or aminoalkylenyl-mono-, di-, or tri-iminoalkylenyl group.

[0011] Embodiments of the treatment composition can be prepared according to known procedures using solvent-free or solvent reaction conditions with heat for efficient hydrogen transfer and an optional reaction promoter. The Michael addition reaction product can be isolated and purified to provide a mono-adduct, a bis-adduct, or a combination thereof. An alternative method for preparing the treatment composition has been found to be achieved by forming an alcoholic dispersion or solution of the starting material and allowing the dispersion or solution to stand at room temperature for a long period of time, such as up to 6 to 12 months. The resulting mixture has been found to contain mono-adducts and / or bis-adducts with unreacted starting material. The resulting mixture may be purified to provide mono-adducts and / or bis-adducts, or it may be used as a treatment composition without further purification.

[0012] Embodiments of the treatment composition also include, as a treatment composition for nail strengthening, optionally a diamine starting compound having multiple organo groups or siliconyl groups in combination with a mono-adduct and / or bis-adduct, and further optionally with an α,β-unsaturated carbonyl starting compound. In at least some cases of the Michael addition reaction, small to large amounts of the diamine starting compound remain as components of the treatment composition. The diamine starting material may also have nail strengthening properties. Consequently, in such situations, the diamine remains with the mono-adduct and / or bis-adduct.

[0013] Embodiments of treatment compositions incorporating monoadducts, bisadducts, mixtures thereof, at least one of polyorgano-grouped diamines or siliconyl-grouped diamines, and any combination thereof, are not limited but provide multifunctional use properties including desired aqueous and solubility, desired nail surface penetration, and desirable intermolecular bonding of keratin proteins within the damaged area of ​​a broken and / or cracked nail.

[0014] Acids and / or bases of monoadducts and / or bisadducts, polyorgano diamines or siliconyl diamine salts, and pH control of the medium are further embodiments of these embodiments of the present invention.

[0015] When embodiments of the treatment composition consist of a mono-adduct alone, a bis-adduct alone, or a mixture of a mono-adduct and a bis-adduct, and / or salts thereof, any amount of the mono-adduct or bis-adduct or mixture thereof or salt may be used in the treatment composition up to an amount that brings the mono-adduct or bis-adduct or mixture to weight percentage saturation in an aqueous or aqueous organic medium (e.g., up to about 40-60% by weight, or more, depending on the substituents of the mono-adduct and bis-adduct and the pH of the medium). Examples of the ratio of mono-adduct to bis-adduct in the mixture range from almost undetectable to substantially pure, and include, but are not limited to, cases where the weight percentage ratio of mono-adduct to bis-adduct is 100:1 to 1:100. The treatment composition further comprises monoadduct alone, bisadduct alone, and / or variations in the concentrations thereof, and may contain unreacted starting materials in amounts ranging from small amounts (approximately 0.1% by weight) to large amounts (approximately 85-98% by weight) relative to the amount of monoadduct and / or bisadduct. The unreacted starting materials may include, but are not limited to, the corresponding maleine-based starting materials and the corresponding diamine-based starting materials.

[0016] A preferred embodiment of the Michael addition product comprises a mono-adduct that is 2-(polyorgano amino or siliconyl amino)succinic acid, an ester, an amide, or an imide, which may optionally be mixed with a bis-adduct of the same carbonyl sequence (e.g., acid, ester, amide, or imide). A more preferred embodiment comprises the acid and / or ester of the mono-adduct, optionally mixed with the corresponding bis-adduct. Particularly preferred is the acid or ester of the mono-adduct, especially the acid. Another preferred embodiment is the acid or ester of the bis-adduct, especially the acid.

[0017] When one or both of the mono-adduct and bis-adduct are carboxylic acid embodiments, they possess dual ionization properties of carboxylic acid and amine groups. This dual property results in multiple ionic and neutral forms depending on the acidity or basicity of the treatment composition. These forms are described in the following section on pH control.

[0018] The ester, amide, and imide embodiments of mono-adducts and / or bis-adducts are also ionizable. They also produce a number of ionic and neutral forms depending on the acidity or basicity of the treatment composition, although these forms are less complex than those of adducts with carboxylic acids. These forms of the ester, amide, and imide embodiments are also described in the following section on pH control.

[0019] The aqueous medium, organic medium, or aqueous organic medium may be water, an organic alcohol, or a mixture of water and an alcohol, and each may optionally contain a non-alcoholic organic solvent.

[0020] The treatment composition may optionally contain one or more of the following: film-forming polymer, nail plate penetration enhancer, fatty alcohol, rheology control agent, nonionic surfactant, colorant, and perfume, preferably at least one of the nail plate penetration enhancer, rheology control agent, and nonionic surfactant.

[0021] Embodiments of this method include applying one or more, preferably multiple, fluid preparations, fluid gel preparations, or gel preparations from the constituent embodiments of the composition to a clean, dry nail plate at the concentrations described below. The applied coatings are left on the nail plate in a semi-fluid / gel state for at least 0.5 to 15 minutes, preferably 1 to 10 minutes, before drying. The thus coated nail plate is optionally recoated with a fluid preparation after a period of 10 minutes to 1 hour. One or more coatings may optionally be air-dried by applying low heat.

[0022] The present invention also relates to embodiments of treatment compositions comprising one or more monoadducts, bisadducts, mixtures thereof, and the aforementioned unreacted starting materials and combinations thereof. The treatment compositions do not contain aldehyde components conventionally found in nail strengthening preparations.

[0023] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art.

[0024] As used herein and in the appended claims, the singular forms "a," "an," and "the" include the plural form unless otherwise specified by the context.

[0025] As used herein, the term "about" refers to a numerical value or range, for example, allowing for a degree of variation within 10% or 5% of the stated value or range limit.

[0026] Unless otherwise stated, all percentage compositions are expressed as a weight percentage of the total weight of the composition.

[0027] Unless otherwise specified, all average molecular weights of polymers are weight-average molecular weights.

[0028] In this context, the terms "may" mean "to be able to" and are synonymous with "can" and "is." As used herein, the term "may" does not imply feasibility or possibility.

[0029] "And / or" means both when both or all of the items referred to by these conjunctions are included together, and when each item is included individually and separately from the others. When more than two items are mentioned, the term "and / or" means any combination of these multiple items, as well as all of them and each item individually.

[0030] As used herein, the term “substantially free” means “completely” or “nearly completely.” For example, if a composition is “substantially free” of a certain component, it means that it does not contain that component, or that it contains such a small amount of the component in question that none of the composition’s relevant functional properties are affected. A compound that is “substantially pure” contains only negligible trace amounts of impurities.

[0031] The term "substantial" refers to a significant amount, such as a majority. For example, a mixture of compounds A and B in which A is present in a substantial amount means that A is present in a weight percentage or number of moles greater than the weight percentage or number of moles of B. The term can also mean exceeding a minimum characteristic, such as substantial flow or substantial treatment.

[0032] Throughout this application, the following group of terms is used: 1) preferred, preferably, favorable; 2) more preferred, more favorably, more favorably; 3) particularly preferred, particularly more favorably, particularly favorably; 4) most preferred, most favorably, most favorably; 5) particularly preferred, particularly most favorably, particularly favorably; 6) especially preferred, particularly most favorably, particularly favorably. These groups convey a sense of preference for a group of substituents, structures, parts, components, and compounds. The degree of preference is self-evident from the term itself. Within each group, the synonyms “preferred,” “preferably,” and “favorable” have the same meaning. If a group is described as “preferred” in one sentence and then as “preferably” in another sentence, there is no difference in meaning in the context of this application. Not all six preference categories are used in this application to describe each substituent, formula, subgenus integer symbol, and atomic designation symbol. In some cases, two or three categories are used, and in other cases, five or six categories are used. The degree of preference expressed by these terms is self-evident and internally consistent with respect to the specific series described, with respect to the constituent elements of a series progressing from many to few, each individually named.

[0033] Throughout this specification, the expressions “embodiment,” “one embodiment,” “preferred embodiment,” “more preferred embodiment,” or “most preferred embodiment” mean any one or more features of the present invention and may be used in relation to different elements of the present invention. Certain features, structures, and / or characteristics described in relation to a particular embodiment may not be the same as other features, structures, or characteristics of other embodiments of the present invention. Thus, while the expressions “in one embodiment,” “in a particular embodiment,” or “in a preferred embodiment” appear in various places throughout this specification, they do not necessarily all refer to the same embodiment, but may refer to different embodiments of the present invention. Furthermore, features, structures, or characteristics in one or more embodiments may be arbitrarily and appropriately combined, as will be apparent to those skilled in the art from this disclosure. Some embodiments described herein include some features included in other embodiments, but not others. As will be understood to those skilled in the art, combinations of features of different embodiments are within the scope of the subject matter and are intended to form different embodiments. For example, in the appended claims, any combination of the claimed embodiments may be used.

[0034] The term "film-forming agent" refers to a fully formed polymer, such as poly(meth)acrylate, polyester, polyamide, polyurethane, cellulosic ether or ester, or shellac, which forms a continuous film or layer when a film-forming agent in an organic or aqueous medium is coated onto a substrate and dried to remove the medium. Film-forming agents typically do not undergo substantial crosslinking or other chemical reactions after their deposition as a film.

[0035] The term "surfactant" refers to amphoteric, nonionic, anionic, or cationic compounds that possess lipophilic and hydrophilic properties, thereby capable of solubilizing lipophilic substances in hydrophilic and / or aqueous media.

[0036] The term "rheology modifier" refers to a rheology modifier that thickens a otherwise freely flowing liquid composition. This modification allows the composition to flow when applied by spray, brush, or other coating methods, but remains static when at rest. Such agents are typically classified as thixotropic agents. Examples include polyvinyl alcohol, polyethylene glycol, vegetable rubber, laponite, and hydrocarbon waxes.

[0037] The term "alcohol" refers to a monool, diol, triol, or polyol that can solubilize other components of a composition. Alcohols include methanol, ethanol, propanol, butanol, ethylene glycol (ethylenediol), glycerin (glycerol), propylenediol or diethylene glycol, dipropylene glycol, and glycim (methoxylated ethylene glycol). Preferred alcohols include, but are not limited to, methanol, ethanol, propanol, ethylene glycol, propylene glycol, and glycerin.

[0038] The term "penetrating agent" refers to organic compounds that facilitate the penetration of organic solids through the dermis and / or stratum corneum of the nail plate. Examples include dimethyl sulfoxide, lauryl sulfate, dimethylformamide, glycerol, and azon.

[0039] The term "gel" refers to a liquid in a three-dimensional network that forms at least semi-solid consistency in a static, resting state. This gel possesses sufficient rheological controllability and / or density in a resting state and maintains the continuous integrity of the liquid gel as a coating or layer on a flat or curved surface. The gel properties of a liquid mean that while the liquid does not spontaneously flow from the coated surface, it can be easily removed by mechanical force, for example, by wiping with a cloth or tissue paper. According to the present invention, the treatment composition may be a gel when it contains a rheological control agent.

[0040] The term "fluidity" refers to a liquid that flows when in contact with mechanical means such as a brush, sponge, or other applicator, like water or a water-based latex paint.

[0041] The terms "gel" and "fluidity," taken together, mean that a liquid possessing these properties is thixotropic.

[0042] As used in this invention, the term alkylenyl refers to a linear C2-C6 hydrocarbon chain having open valencies at both ends. One example is hexylenyl, of the formula -(CH2)6-.

[0043] The term "nail plate" refers to the fingernails of human fingers and toenails of human feet. [Modes for carrying out the invention]

[0044] This invention provides a method for preventing and / or treating a painful and difficult-to-heal condition of the human nail plate. Weak, brittle, and / or inflexible nails are prone to cracking, breaking, fracturing, and / or splitting that reaches the soft tissue nail bed. When this occurs, the person may suffer unbearable pain. The treatment according to the present invention relieves pain and aids in the healing of the nail plate.

[0045] Composition components At least part of the treatment aspect of the present invention is achieved by applying an embodiment of the treatment composition of the present invention to the damaged nail plate.

[0046] Embodiments of the first treatment composition include Michael monoadducts which are 2-(amino)succinic acid having multiple organo groups or siliconyl groups), esters, amides, anhydrides or imides, or any combination thereof.

[0047] Embodiments of the second treatment composition include Michael bis-adducts which are diamines having N,N'-bis(2-succinoylhydroxy)-, N,N'-bis(2-succinoyloxyalkylester)-, N,N'-bis(2-succinamide)-, N,N'-bis(2-succinoanhydride)-, or N,N'-bis(2-succinimide)-1,ω-polyorgano groups or siliconyl groups, or any combination thereof.

[0048] Embodiments of the third treatment composition include a mixture of Michael's monoadduct and Michael's bisadduct in any weight ratio, indicated by the phrase "monoadduct and / or bisadduct".

[0049] Embodiments of the fourth treatment composition include combinations of one or more of the first, second and / or third embodiments with compounds used to produce embodiments of Michael addition products, which include, but are not limited to, starting material residues such as unprotonated diamines, diamine salts, salts of unsaturated carboxylate compounds, amides formed between diamines and unsaturated carboxylate compounds, and similar non-Michael addition compounds formed by diamines and unsaturated carboxylate compounds, as well as unreacted starting materials such as diamines and unsaturated carboxyl compounds.

[0050] Embodiments of the mono-adduct include carboxylic acid compounds having a polyorgano-substituted amino group at the α-position of formula VI and / or compounds having a polyorgano-substituted amino group at the α-position of formulas IXA and IXB.

[0051] Embodiments of the bis-adduct include bis-α-aminopolycarboxylic acid compounds of formula VII or bis-α-amino polyorganocarboxyl compounds of formulas XIA and XIB.

[0052] Embodiments of siliconyl monoadducts include monoadducts having a siloxane chain of formula XIIIA and monoadducts having a branched siloxane chain of formula XIIIB.

[0053] Embodiments of siliconyl bis adducts having siloxane chains include bis adducts having siloxane chains of formula XIVA or bis adducts having branched siloxane chains of formula XIVB. TIFF2026530604000001.tif35170 Formula VI Monoadculation TIFF2026530604000002.tif34170 Formula VII bis-adductor TIFF2026530604000003.tif35170 Mono-adductor of type IXA TIFF2026530604000004.tif34170 formula IXB Monoadculation TIFF2026530604000005.tif36170FormulaXIA bis-adductor TIFF2026530604000006.tif36170 formula XIB bis-adductor TIFF2026530604000007.tif35170 Formula XIIIA Monoadducts containing siloxane chains TIFF2026530604000008.tif43170 Formula XIIIB Monoadduct having branched siloxane chains TIFF2026530604000009.tif36170 formula XIVA Bis adducts having siloxane chains TIFF2026530604000010.tif43170 formula XIVB Bis adducts having branched siloxane chains

[0054] For formulas VI, VII, IXA, IXB, XIA, XIB, XIIIA, XIIIB, XIVA, and XIVB, each designation symbol l, l', m, m', n, n', k, o, p, q, r, s, u, u', and v, and the substituents X, X', W, Z, E, E', and G are defined to provide the following: 1) l, l', m, m', n and n' may each independently be zero or an integer from 1 to 100. The sum of l, l', m, m', n and n' may be at least 2 and at most 100, preferably at most 50, more preferably at most 30, even more preferably at most 20, and the individual sum is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15. 2) The designated symbols o and r may each independently be zero or an integer from 1 to 4. 3) The designated symbol s may be an integer from 1 to 4. 4) Both X and X 1 may be -OH, -OR 2 or -NHR 3 . 5) W and Z may each independently be O, S or NR 6 . 6) R 2 is C1-C4 linear alkyl. 7) R 3 is H or C1-C4 linear alkyl. 8) R 4 and R 5 may each individually and separately be hydrogen or C1-C10 alkyl, and said C1-C10 alkyl may be substituted with one or more selected from the group consisting of C1-C4 alkyl groups, C1-C4 alkoxy groups, C1-C4 alkylthio (alkthio) groups, C1-C4 alkyl substituted with -CO2-C1-C4 alkyl groups, C1-C4 alkyl substituted with -CONH-C1-C4 alkyl groups, C1-C4 alkyl substituted with -SO2-C1-C4 alkyl groups, and C1-C4 alkyl substituted with -SO2-NH-C1-C4 alkyl groups. 9) R 6 may be hydrogen or a C1-C20 linear or branched alkyl group. 10) Both X and X 1 may be -OH, -OR 2 or -NHR 3 , wherein R 2 and R 3 are defined as given for formulas VI and VII. 11) E may be cyclopentyl, cyclohexyl, C1-C4 mono, di, or trialkylcyclohexyl, phenyl or C1-C4 alkylphenyl, C6-C10 aryl having one or two rings or C1-C4 mono or multialkylC6-C10 aryl having one or two rings, pyridinyl, 1,3,5-triazinyl, or 1,3,5-triazine substituted with alkyl or phenyl. 12) E' may be cyclopentyl or cyclohexyl, C1-C4 mono, di, or trialkylcyclohexyl, phenyl, or C1-C4 alkylphenyl. 13) G is -(CH2) k It can be -, -SO2-, or -NH-. 14) k can be an integer from 1 to 10. 15) p, p', and q can each be zero or 1 independently. 16) u, u', and v can each be an integer, independently of any other, ranging from zero to 50, preferably from 1 to 20, more preferably from 1 to 10, and most preferably from 1 to 5. 17)R 9 is hydrogen or -(CH2) k - It is possible. 18)R 10 This can be hydrogen or a C1-C6 alkyl group.

[0055] Alternatively, with respect to equations VI, VII, IX, and XI, X and X 1 These, along with their corresponding carbonyl groups, are anhydrous of the formula -OC-O-CO- or -OC-NR 3 It can form a -CO- imide.

[0056] Preferred embodiments of the mono-adduct and / or bis-adduct are carboxylic acid embodiments and alkyl ester embodiments. More preferred embodiments are carboxylic acid embodiments and methyl ester embodiments of the mono-adduct and / or bis-adduct. Particularly preferred embodiments are carboxylic acid embodiments of the mono-adduct and / or bis-adduct. Most preferred embodiments are carboxylic acid embodiments of the mono-adduct, and mixtures of mono-adducts and carboxylic acid bis-adducts, wherein the weight ratio of the mono-adduct to the bis-adduct in the mixture is in the range of 100:1 to 2:1, preferably 50:1 to 5:1, and more preferably 50:1 to 20:1. Optionally, these preferred, more preferred, and most preferred forms of Michael addition products are not necessarily required, but the starting material residue and / or unreacted starting material, including the starting diamine and the unsaturated carboxylic acid compound, may be present in an amount of 0.1% to 95% by weight, preferably 0.1% to 75% by weight, more preferably 1% to 50% by weight, particularly more preferably 1% to 30% by weight, and most preferably 1% to 25% by weight, relative to the total amount of the mono-adduct and / or bis-adduct and the starting material residue and / or unreacted starting material. The exemplary concentrations of the starting material residue and / or unreacted starting material may be in a range encompassing the minimum to maximum mass percent in each of the aforementioned ranges in 1% by weight increments, for example, from 1% to 25% by weight in 1% by weight increments.

[0057] The concentration of mono-adducts and / or bis-adducts in the treatment composition, with or without starting material residue and / or unreacted starting material, may be at least 0.2 weight percent, preferably 0.2 weight percent to about 40 weight percent, more preferably about 0.2 weight percent to about 25 weight percent, most preferably about 0.2 weight percent to about 20 weight percent, and most preferably about 0.2 weight percent to about 6.5 weight percent to about 15 weight percent or 0.2 weight percent to about 6 weight percent to 10 weight percent. Exemplary concentrations include 1.5% by weight, 2.0% by weight, 2.5% by weight, 3.0% by weight, 3.5% by weight, 4.0% by weight, 4.5% by weight, 5.0% by weight, 5.5% by weight, 6.0% by weight, 6.5% by weight, 7.0% by weight, 7.5% by weight, 8.0% by weight, 8.5% by weight, 9.0% by weight, 9.5% by weight, 10.0% by weight, and all 0.1% by weight intervals between these exemplary concentrations. The weight percentages are relative to the total weight of the composition containing the optional component.

[0058] The above-described embodiments of mono-adducts and / or bis-adducts, as well as any starting material residues and unreacted starting materials, may have ionized and neutral electron configurations depending on the pH of the medium. These modifications produce molecules of these embodiments having forms such as uncharged neutral, amphoteric, free amine, cationic, and anionic forms (both variable-charge embodiments). These forms of mono-adducts and / or bis-adducts, as well as optionally selected starting material residues and unreacted starting materials, constitute variants of their mixtures depending on the pH of the medium. The generation of these forms is described in the pH control section.

[0059] These embodiments of mono-adducts and bis-adducts, as well as optional starting material residues and unreacted starting materials, include: a) Embodiments comprising at least a portion of monoadducts and / or bisadducts, and an optional starting material residue and unreacted starting material having a carboxylic acid, wherein the carboxylic acid and amine are in a non-ionized state and a non-protonated state, respectively, and at least a portion provides an uncharged neutral embodiment; b) Embodiments comprising at least a portion of monoadducts and / or bisadducts, as well as optional starting material residues and unreacted starting materials and a carboxylic acid, wherein the carboxylic acid protonates the amine, resulting in an electrostatic balance between the anion of the carboxylate group and the cation of the ammonium group, thereby providing at least a portion of a net-chargeless zwitterionic form; c) Embodiments comprising at least a portion of mono-adducts and / or bis-adducts having ester, amide, or imide groups, as well as optional starting material residues and unreacted starting materials having unneutralized free amine groups, and providing at least a portion of the free amine form; d) Embodiments comprising at least a portion of monoadducts and / or bisadducts, and optionally selected starting material residues and unreacted starting materials having neutralized carboxylic acids as anionic groups, wherein at least a portion provides an anionic embodiment; and e) An embodiment comprising at least a portion of a mono-adduct and / or bis-adduct, and optionally selected starting material residue and unreacted starting material, wherein these have a carboxylic acid group, an ester group, an amide group or an imide group, and their amine groups are neutralized as cationic groups, thereby providing a cationic embodiment in at least a portion of the embodiment.

[0060] These electronic forms (i.e., uncharged neutral embodiments, amphoteric embodiments, free amine embodiments, anionic embodiments, and cationic embodiments) exist in multiple forms in the total amount of mono-adducts and / or bis-adducts present. The multiple forms present can be balanced so as to change from one form to another, or so as to adjust the portion of the multiple forms present by adjusting the pH of the medium of the treatment composition. As described in the pH control section, these forms constitute the pH control portion of the mono-adducts and / or bis-adducts, as well as optional starting material residues and unreacted starting materials. The total amount of mono-adducts and / or bis-adducts, as well as optional starting material residues and unreacted starting materials, can constitute these multiple portions, and as a result, one form may exist together with other complementary forms, and furthermore, the amount and identity of portions of these forms may vary depending on the pH control provided by the medium.

[0061] Preparation of monoadductors and / or bisadductors Embodiments of monoadduct and / or bisadduct carboxylic acids can be prepared by Michael addition synthesis of a starting material comprising a polyorgano diamine of formulas V, VIIIA, and VIIIB, a siliconyl diamine of formulas XIIA and XIIB, and an unsaturated carboxyl compound of formula IV (e.g., a malein compound). H2N-(CH2) l- (W-CH2) l’ -(CHR 4 ) m -(CH2) m’ -(Z-CHR 5 ) n -(CH2) n’ -NH2 Formula V H2N-(CH2) o -E-[(G) p -E'-] q -(CH2) r -NH2 Formula VIIIA H2N-(CH2) o -(CH(R 9 NH2)R10 ) p -[(G) p’ -E'-] q -(CH2) r -NH2 Formula VIIIB H2N-(CH2) s -(Me2SiO) u -(Me2SiO) u’ -(CH2) r -NH2 Formula XIIA H2N-(CH2) s -(Me2SiO) u -[MeSiO(SiMe2O) v -SiMe3)](Me2SiO) u’ -(CH2) r -NH2 Formula XIIB X-OC-HC=CH-CO-X Formula IV

[0062] The designation symbols for formula V are l, l', m, m', n, n', k, o, p, p', q, r, s, u, u', v and r, and the substituents W, Z, R 4 , R 5 E, E', and G are as described above for formulas VI, VII, IXA, IXB, XIA, XIB, XIIIA, XIIIB, XIVA, and XIVB.

[0063] The substituents specified as X in formula IV are all -OH or -OR. 2 or -NHR 3 It is possible. Substituent R 2 It is a C1-C4 linear alkyl group. Substituent R 3 is either hydrogen or a C1-C4 linear alkyl. In summary, these definitions of X are maleic acid, maleic acid dialkyl esters, maleamide (R) 3 The present invention provides an N,N'-dialkylmaleamide (where H is the alkyl group) or an N,N'-dialkylmaleamide (where both alkyl groups are C1-C4 linear alkyl groups).

[0064] Alternatively, the malein compound of formula IV can have substituents X and X bonded together with their respective CO groups to form an anhydride of formula -C=OOC=O- or -C=O-NR. 3 It may also form an imide -C=O-, where R 3 This is the same as that specified for amides. This alternative example provides formula IV as maleic anhydride, or as maleimide, where N may be substituted with a C1-C4 alkyl group.

[0065] As a starting material, formula IV has the same X substituent at both positions. Both are hydroxyl, alkoxy, or alcamides. When formula IV reacts with a diamine to form the addition product of formula I and / or formula II, the X in X-OC- adjacent to the unsaturated carbon residue to which the amine nitrogen is bonded is X 1 This is the result.

[0066] Exemplary classes of polyorgano-containing diamines and siliconyl-containing diamines include, but are not limited to, linear aliphatic diamines, alicyclic diamines, aromatic diamines, polyether diamines, polyimines, polyamide diamines, amide diamines, silicone diamines, and diaminosilanes. Preferably, these exemplary classes of diamines are soluble in ethanol or water, have a preferred molecular weight of about 100 Da to about 5000 Da, a preferred molecular weight of up to about 500 Da, have a melting point of less than about 42°C, are more preferably liquid in STP, and the amine group forming the reactive diamine moiety is a primary amine.

[0067] Species of these exemplary classes of diamines include, but are not limited to, diethylenetriamine, dipropylenetriamine, tetraethylenepentaamine, laurylaminedipropylenediamine, trimethylhexamethylenediamine, propylene oxidetriamine, e.g., EC310 or EC311 produced by BASF, methylenedianiline, m-xylenediamine, p-phenylenediamine, o-phenylenediamine, diaminophenylsulfone, 4,4'diaminobiphenyl, benzoguanamine, and isophorone. Diamines, e.g., Vestaminpacm produced by Evonik or Epikure 3300 produced by Momentive, methyldiaminocyclohexane, 4,4'-diaminodicyclohexylmethane, diaminocyclohexane, 3,3'dimethyl-4,4'-diamino-cyclohexylmethane, 1,8-diamino-p-menthane, 1,3-bis(aminomethyl)cyclohexane, serotonin, polyoxypropylenediamines, e.g., Jeffamine produced by Huntsman This includes D-230, D400 T403 and similar Jeffamines, or Baxxodur EC302 or CE301 manufactured by BASF, 4,9-dioxadodecane-1,12-diamine, poly(propylene oxide triamine), Versamidamidoamine by Gabriel Performance Produces, Genamid 490amidoamine by BASF, bis-aminopropyl dimethicone, aminopropyl dimethicone, amodimethicone, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, and N-(2-aminoethyl)-3-aminopropyltrimethoxysilane.

[0068] In Michael addition synthesis, when maleic anhydride is involved, the reaction conditions are aqueous, and / or acidic or basic work-up is performed, the anhydride group opens to form a carboxylic acid group. Embodiments of the anhydride can be synthesized from maleic anhydride in an aprotic organic medium and isolated by non-aqueous chromatography, but subsequent preparation of treatment compositions in aqueous or aqueous organic mediums and adjustment of pH inevitably hydrolyze the anhydride. For these reasons, embodiments of the anhydride and the carboxylic acid can be considered at least substantially equivalent in use.

[0069] Embodiments of mono-adduct and / or bis-adduct esters, amides, and imides are shown in formula IV, with the corresponding starting material, alkanediamine and alkyl maleate, N,N'-bis-(R 3 ) Maleamide or NR 3 -It can be prepared by Michael addition synthesis using maleimide. Alternatively, embodiments of monoadducts and / or bisadducts esters, amides and imides include monoadducts and / or bisadducts containing X as a carboxylic acid, for example, J March, Advanced Organic Chemistry, 4 th It can be prepared by converting to the corresponding ester, amide, or imide embodiment according to the carboxylic acid conversion described in Ed. Wiley Interscience Publication, Jon Wiley & Sons New York, 1992.

[0070] The molar ratios of the diamine and maleic acid in the starting materials correspond to the molar ratios between residues of these two starting materials as adducts of formulas VI, VII, IXA, IXB, XIA, XIB, XIIIA, XIIIB, XIVA, and XIVB. When a mono-adduct is formed, the molar ratio of the diamine of formula V, VIIIA, VIIIB, XIIA, or XIIB to the maleic acid compound of formula IV is at least 2, preferably greater than 2, and includes values ​​in 1 / 10 molar ratio increments from 2 to 3 or 4. When a bis-adduct is formed, the molar ratio of the maleic acid compound (formula IV) to the diamine of formula V, VIIIA, VIIIB, XIIA, or XIIB is at least 2, preferably greater than 2 (the inverse of the molar ratio for forming a mono-adduct). The molar ratio is calculated by determining how many times a single diamine of formula V, VIIIA, VIIIB, XIIA, or XIIB and VIII react with the maleic acid starting material of formula IV. When a bis-adduct is formed, two malee molecules (formula IV) react with one diamine molecule (formulas V, VIIIA, VIIIB, XIA, or XIB) due to the presence of two primary amine groups for each diamine molecule and one conjugate ethylene group for each malee molecule. When a mono-adduct is formed, one diamine molecule reacts with one malee molecule once. Since each diamine molecule has a secondary primary amine, their molar ratios ensure that the primary combination produced is either a mono-adduct or a bis-adduct. As with any addition reaction, both are possible, but the preference of the mono-adduct over the bis-adduct is largely controlled by the molar ratio of the starting materials. Using more than 2 molar amounts of diamine for the formation of a mono-adduct, or more than 2 molar amounts of the malee compound for the formation of a bis-adduct, increases the preference for either the mono-adduct or the bis-adduct, respectively. In each case, excess unreacted starting materials may be removed during the workup of the reaction mixture or may be left as part of the composition for treatment.

[0071] Experimental procedures for the preparation of monoadducts and bisadducts may be followed according to those outlined in U.S. Patents 3,158,635, 5,846,925 and 6,465,690, which are incorporated herein by reference.

[0072] medium The liquid medium of the treatment composition is aqueous, organic, or an aqueous organic liquid mixture. The organic solvent of the organic medium or aqueous organic medium may be an alcohol alone, or in combination with a non-alcohol selected from ketones, esters, acetates, dimethyl isosorbide, DMSO, DMF, THF, or any mixture or combination thereof.

[0073] The alcohol may be a monoalcohol, a polyalcohol, or a mixture of such alcohols. Preferably, the alcohol component is a combination of one or more monoalcohols, or a polyol, such as methanol, ethanol, or propanol, or a polyol, such as glycerol, ethylene glycol, or propylene glycol. Any mixture of any combination of monoalcohols and polyalcohols may be used.

[0074] Non-alcohols selected from ketones, esters, acetates, dimethyl isosorbide, DMSO, DMF, and THF are water-soluble and alcohol-soluble. The ketone may be acetone or methyl ethyl ketone or a mixture thereof. The non-alcohol can be combined with one or more of the above alcohols to form the organic portion of an organic medium or an aqueous organic medium. The volume ratio of non-alcohol to alcohol may be about 1:100 to 1:10, preferably 1:50 to 1:20. Preferably, the non-alcohol is not included in the organic portion of the organic medium and aqueous organic medium.

[0075] The concentration of the organic liquid component in the aqueous organic medium may be in the range of about 1 weight percent to about 100 weight percent, or the volume-to-volume ratio of the organic liquid to water may be in the range of 1:50 to 2:1, preferably about 1:50 to about 1:2. The remainder is water for the aqueous organic medium, and it is all water for the aqueous medium.

[0076] pH control of treatment compositions pH control of the treatment composition controls, at least in part, the ability of the mono-adduct and / or bis-adduct to penetrate or permeate the inner portion of the nail plate, thereby reinforcing the nail plate. Any penetration of the nail plate can be achieved by all embodiments of the mono-adduct and / or bis-adduct in a pH range from highly acidic, such as about 1.5 or 2, to highly basic, such as about 10 or 11.5. The preferred pH range is about 2 to about 11, more preferably about 2.5 to about 10.5. The varying degrees of penetration within these pH ranges depend, at least in part, on the acidic, basic, or amphoteric nature of the mono-adduct and / or bis-adduct.

[0077] The permeation of organic compounds into the nail plate has been widely studied. See, for example, S. Murdan et.al., Skin Pharmacol. Physiol., 2011;24(4):175-81; S Baswan, et.al., Mycoses 2017 May;60(5)285-295 Pub Med Central PMC5383514 and D. Mertin et al, J. Pharm. Pharmocol., 1997,49,30-34(1996).

[0078] These authors explain that the permeability of organic compounds in the nail plate depends, at least in part, on their hydrophobic / hydrophilic properties, and, if the organic compounds are acidic or basic, also on the pH of the medium in which they are contained. While at least some permeability of acidic and basic organic compounds occurs over a very wide pH range, controlling the pH to provide more molecules of compounds with nonionic and non-dissociative properties allows for more effective transport into the nail plate. See S. Baswan, page 7, cited above.

[0079] For example, Mertin discloses that benzoic acid produces a permeability coefficient of 78.6 at pH 2, but this coefficient decreases to 8.29 at pH 7.4. This pH-variable effect can be understood when considering the pKa of benzoic acid. pKa is the dissociation constant when half of the benzoic acid molecule dissociates (i.e., benzoate anions) and the other half does not dissociate (i.e., benzoic acid). At this point, the pH is the same, and for benzoic acid, the pH is 4.2. Therefore, at this pH, only half of the benzoic acid molecule is nonionic and in an undissociated state. Lowering the pH to 2, as Mertin did, yields almost completely undissociated benzoic acid. In other words, almost all of the benzoic acid molecules at this pH are electrically neutral. Therefore, these authors show that benzoic acid can penetrate the nail plate across a pH range from very acidic to basic, but the amount of benzoic acid that penetrates the nail plate relative to the total amount dissolved in the carrier medium (water) is the undissociated portion. This undissociated portion depends on the pH of the medium and the pKa of the compound. As a result, these studies of the nail plate permeability coefficient of organic acids show that permeability increases as the undissociated portion of the organic acid increases. This relationship depends on the pH of the medium and the pKa of the organic acid. The same is true for organic bases.

[0080] These scientific studies explain that while the penetration of acidic or basic organic molecules into the nail plate can occur over a wide pH range, the number of molecules that can penetrate depends on the control of the pH of the medium containing the acidic or basic organic compound. By controlling the pH relative to the acidic or basic nature of the organic compound, it is possible to increase or decrease the number of organic compound molecules that remain in an undissociated form, thereby enabling them to penetrate into the nail plate.

[0081] According to these scientific studies, the pH of the treatment composition medium according to the present invention affects the number of mono-adduct and / or bis-adduct molecules, as well as the optional starting material residues and unreacted starting materials that penetrate the nail plate and result in nail reinforcement. A pH range from highly acidic to highly basic allows at least some penetration of these mono-adduct and / or bis-adduct molecules, but there will be a "sweet spot pH" that maximizes the number of mono-adduct and / or bis-adduct molecules, as well as the optional starting material residues and unreacted starting materials that can penetrate the nail plate.

[0082] The corresponding pH behavior of monoadducts and / or bisadducts containing carboxylic acids differs from that of benzoic acid or organic amines because the adducts contain both carboxylic acid and amine groups. Similar to amino acids, these adducts are amphoteric, with an equilibrium existing between the carboxylic acid and amine groups. In low pH media, the carboxylic acid group of the adduct is almost completely undissociated or deionized, while at this low pH, the amine group is almost completely protonated. As the pH increases, the opposite begins to occur, resulting in a predominant presence of carboxylate anions and free amine groups at higher pH levels. Therefore, changes in pH control the distribution of monoadducts and / or bisadducts with different combinations of carboxylic acid, carboxylate, protonated amine, and free amine groups. A specific pH range exists between highly acidic and highly basic conditions, where the distribution of adduct molecules results in the highest number of undissociated molecules. This is the "sweet spot" pH range where the number of these adduct molecules with non-ionized carboxylic acid and free amine groups is highest. In other words, the proportion of these molecules present in undissociated form, depending on the pH, follows a Gaussian curve. This Gaussian curve also indicates the degree of resulting nail reinforcement by the mono-adduct and / or bis-adduct embodiments having a carboxylic acid group, depending on the pH. While some penetration and reinforcement occurs throughout this pH range, this "sweet spot" pH range achieves the greatest penetration of undissociated molecules and the strongest nail reinforcement.

[0083] In general, these studies show that, in order to provide a reinforcing effect for treatment compositions containing embodiments of mono-adducts and / or bis-adducts having carboxylic acids, media having a pH range from highly acidic pH of 1 or 2 to neutral pH of 6.5 to 7.5 and highly basic pH of 10.5 to 11 are suitable, preferably media having a pH in the range of about 2 to about 10, more preferably about 2 to about 7, and particularly more preferably about 2.5 to about 5. These studies also show that the sweet spot for embodiments of mono-adducts and / or bis-adducts having carboxylic acid groups can be estimated by the isoelectric points of the amino acids aspartic acid and glutamic acid. Similar to the mono-adducts and / or bis-adducts, these amino acids have two carboxylic acid groups and one amine group. The isoelectric points of these amino acids are averaged at about pH 3. Therefore, a pH range from highly acidic to highly basic for the treatment composition is suitable for nail reinforcement of monoadducts and / or bisadducts having carboxylic acids, but the "sweet spot" pH range is about 2 to about 5, preferably about 2.5 to 3.5.

[0084] The mono-adducts and / or bis-adducts (hereinafter, embodiments of amine mono-adducts and / or bis-adducts) and the optional starting material residues and unreacted starting materials have different "sweet spots" than those of the mono-adducts and / or bis-adducts having carboxylic acid groups. Because they only have protonable amine groups, their "sweet spots" are determined by the basicity of the amine group. While embodiments of amine mono-adducts and / or bis-adducts also exhibit claw reinforcement over a wide pH range, the strongest claw reinforcement is likely in this "sweet spot." The "sweet spot" is determined, at least partially, by the basic pH that provides the unprotonated forms of these amine adducts, i.e., the free amine embodiments. Mertin found that at least some permeation of pyridine occurred at pH 2, but the high permeation coefficient of pyridine was obtained at pH 7.4. Considering the conjugate acid pKa of pyridine (5.25), Mertin's basic pH findings indicate that the pH "sweet spot" of the amine is higher than the conjugate acid pKa of the amine.

[0085] Embodiments of amine monoadducts and / or bisadducts may have a pH sweet spot higher than 5.25, since the pKa of the presumed conjugate acid is at least somewhat higher than the pKa of pyridine conjugate acid (5.25). However, very basic pH levels, such as above 11.5, can cause cleavage of the ester, amide, or imide group and damage the nail plate. See B.Chiego, et al., J.Investigatory Dermatology, 5(2)95-103 (1942).

[0086] Therefore, at least some permeability and, consequently at least some nail reinforcement, can be obtained from the amine adducts and / or bis adducts, as well as optional starting material residues and unreacted starting materials, across the acidic to basic pH range of the medium. Quantitatively, this pH range may be about 2 to about 11. The “sweet spot” pH in the treatment compositions of the free amine mono adducts and / or bis adducts, as well as optional starting material residues and unreacted starting materials, that provides a stronger nail reinforcement effect, is in the range of about 6 to about 10.5, preferably about 7.5 to about 10, and more preferably about 7.8 to about 9.5.

[0087] Chemicals for pH control With respect to the electronic forms of monoadducts and / or bisadducts having a carboxylic acid group, pH adjustment can be performed by adding an acid to the medium of the treatment composition. Suitable acids include hydrochloric acid, sulfuric acid, acetic acid, and / or sodium bisulfate or potassium bisulfate, as well as combinations with acidic buffer systems such as citrate buffer and / or maleate buffer.

[0088] With respect to the electronic forms of carboxylate esters, imide or amide groups, and mono and / or bis adducts having optional starting material residues and unreacted starting materials, pH adjustment can be performed by adding a base to the medium of the treatment composition. Suitable bases include sodium hydroxide or potassium hydroxide, bicarbonates or carbonates, borates, ammonia, organic amines and / or their buffer systems.

[0089] Selective components of the treatment composition Optional components of the treatment composition include one or more of the following: film-forming agents, nonionic surfactants, fatty alcohols, rheology control agents, penetrating agents, perfumes, preservatives, and alternative diamines. While some combinations of these optional components may be included in the composition, optional components that complex with, occlude, absorb, adsorb, form electrostatic complexes with, and / or entangle with mono-adducts and / or bis-adducts, or that may inhibit or delay the ability of mono-adducts and / or bis-adducts to penetrate into the nail plate, as well as optional components that significantly alter the pH of the medium, should be minimized or avoided.

[0090] The film-forming agent of the composition is a fully formed, non-reactive polymer. The film-forming agent may be a poly(meth)acrylate, polyester, polyamide, polyurethane, cellulosic ether or ester, or shellac, which forms a continuous film or layer when the film-forming agent in an organic medium, an organic aqueous medium, and / or an aqueous medium is coated onto a substrate and dried to remove the medium. The polyester may be a polymer of hydroxycarboxylic acid or a polymer of diol and dicarboxylic acid. The polyamide may be a polymer of aminocarboxylic acid or a polymer of diamine and diacid. The polyurethane may be a polymer of diol and diisocyanate.

[0091] Exemplary film-forming agents include polymethyl or ethyl (meth)acrylate, copolymers of methyl or ethyl (meth)acrylate with styrene or vinyl methoxide, styrene / acrylate / ammonium acrylate copolymers, vinyl copolymers, such as polyvinyl butyral or polyvinyl chloride, polylactide, polyglycolide, copolymers of lactide and glycolide, copolymers of C4-C6 alkylenediol and C4-C6 alkylenyl dicarboxylic acid, adipic acid / neopentyl glycol / trimellitic anhydride copolymer, and C4-C6 alkylenediol. These include polyamides of amines and C4-C6 alkylenyl dicarboxylic acids, polyurethanes of C4-C6 alkylenyl diols and C4-C6 alkylenyl diisocyanates or 1,4-diisocyanatobenzene, methyl, ethyl and / or propyl cellulose, cellulose acetate, cellulose propionate, nitrocellulose, cellulose acetate butyrate, cellulose butyrate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, hydroxypropylmethylcellulose, and similar cellulose esters and ethers. These film-forming polymers do not contain side chains or terminal groups that would make the polymer susceptible to crosslinking by actinic (UV) irradiation.

[0092] Film-forming polymers form polymer chain networks and entanglements, which aggregate and / or solidify into a solid, continuous coating on the fingernails. This three-dimensional physical structure begins to form while the film-forming polymer is in a solution or dispersion state in the medium. Therefore, the film-forming polymer can delay and / or inhibit the delivery of mono-adducts and / or bis-adducts to and through the surface of the nail plate. The polarity and lipophilicity of the film-forming polymer may also tend to affect the permeability coefficient of mono-adducts and / or bis-adducts to the nail plate. After the film-forming polymer has condensed and / or solidified, the resulting coating may be resistant to the penetration of further treatment compositions into the nail plate surface. Therefore, it is preferable to begin treatment of fingernails with a treatment composition that does not contain film-forming polymers. Multiple treatments with a treatment composition that does not contain film-forming polymers are preferred. A final treatment with a treatment composition containing film-forming polymers may be preferred because the resulting lacquer and / or enamel coating seals the nail plate surface, thereby avoiding or limiting the unintended removal of mono-adducts and / or bis-adducts from the nail plate surface.

[0093] The concentration of the film-forming agent optionally included in the components of the treatment composition according to the present invention may be in the range of about 0.1% to about 20% by weight, preferably about 0.1% to about 10% by weight, more preferably about 0.2% to about 5 to 8% by weight, and particularly more preferably about 0.2% to about 3 or 4% by weight.

[0094] Surfactants are surfactants that reduce the surface tension of water, allowing aqueous or aqueous organic media to contain water-insoluble components. The term surfactant can include nonionic, amphoteric, anionic, and cationic surfactants, but nonionic surfactants are the most suitable for incorporation into treatment compositions. Charged surfactants, such as anionic, cationic, and amphoteric surfactants, can affect the permeability coefficients of mono-adducts and / or bis-adducts.

[0095] The preparation may contain multiple nonionic surfactants. Examples of nonionic surfactants include sucrose acetate / isobutyrate, ethylene glycol monostearate, propylene glycol myristate, glyceryl monostearate, glyceryl stearate, polyglyceryl-4-oleate, sorbitan acylate, sucrose acylate, PEG-150 laurate, PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbate, polyoxyethylene octylphenyl ether, PEG-1000 cetyl ether, polyoxyethylene tridecyl ether, polypropylene glycol butyl ether, Poloxamer.RTM.401, stearoyl monoisopropanolamide, polyoxyethylene hydrogenated tallowamide, polyoxyether or ceteareth-20 of lauryl alcohol, and / or combinations thereof.

[0096] Nonionic surfactants may be included in the composition in a weight percentage of about 0.1% to about 10% by weight, preferably about 0.1% to about 5% by weight, and more preferably about 0.1% to about 2% by weight, relative to the total weight of the composition.

[0097] The rheological agent controls the viscosity of the composition, preferably making it flowable under pressure and gel-like in a steady state (at rest). That is, the rheological agent also possesses thixotropy. Preferably, the rheological control imparts thixotropy to the composition so that it flows under the force applied during application by spraying, brushing, or other methods, while having sufficient viscosity to prevent flow in a static state.

[0098] The rheological agents useful in this composition are polyols with medium molecular weights. These polymers, including polyglycols, polyethers, polyols, polyamides, polyurethanes, polyesters, and block copolymers, have medium to high intrinsic viscosity and contribute to rheological control to achieve the aforementioned fluidity / gel properties of this composition. Exemplary components include polyethylene glycol and polypropylene glycol with about 10 to about 1000 units or more, polyethers of butylene oxide and / or pentylene oxide with about 20 to 1000 units or more, polyesters such as polylactides, polyglycols and their copolymers, polyurethanes formed from C4-C6 alkyl diisocyanates and C4-C6 alkyldiols, and block copolymers of such polyesters or polyurethanes with polyethylene glycol and / or polypropylene glycol, which also function as useful rheological control agents in this composition. These agents may have an average molecular weight in the range of 200 Da to about 10 kDa, preferably 300 Da to about 5 kDa, and more preferably about 400 Da to about 2 kDa.

[0099] The concentration of the rheological agent may be in the range of about 0.01% to about 3% by weight, preferably about 0.01% to about 2% by weight, more preferably about 0.01% to about 1% by weight, and particularly up to about 0.5% or 0.2% or 0.1% by weight.

[0100] Clay, silica, starch, rubber, and their derivatives can act as thixotropic agents, but preferably they can be modified to avoid and / or minimize the absorption or occlusion of monoadducts and / or bisadducts. Therefore, clay, starch, silica, rubber, and their derivatives modified with organic materials, such as those provided by laponite, can be useful in providing treatment modes for compositions.

[0101] The fatty alcohol functions as an emulsifier and / or anti-aggregating and / or smoothing agent to promote a substantially uniform flow of the composition when applied to the nail. The fatty alcohol may be a linear or slightly branched alkyl monoalcohol of C8 to C36, preferably a fatty alcohol of C16 to C20, or a fatty alcohol of this configuration covalently bonded as an ether to polyethylene glycol or polypropylene glycol having 5 to 20 glycol groups. The concentration of the fatty alcohol may range from about 0.01% to about 2% by weight, preferably about 0.01% to about 1% by weight, more preferably about 0.01% to about 0.5% by weight, and particularly up to about 0.3% or 0.2% or 0.1% by weight.

[0102] Penetrating agents facilitate the transport or delivery of other agents through the nail plate surface into the nail plate. These agents are known and include dimethyl sulfoxide (DMSO), dimethylformamide (DMF), lauryl sulfate, glycerin, dodecyl azacycloheptan-2-one (Azone), N-methylpyrrolidone, diethylene glycol and tetraethylene glycol, lauric acid, myristic acid or capric acid, and terpenoids such as citral, menthol, camphor and hydroxylimonene, as well as mixtures thereof. In addition, diesters and triesters with low to medium molecular weights from 200 Da to about 1 kDa, preferably 500 Da, such as trimethylpentanyl diisobutyrate or acetyl tributyl citrate or acetyl tripropyl ascorbate or dihexyl succinate, can enable the penetration of mono-adducts and / or bis-adducts. The lipophilic and semi-polar properties of these esters contribute to the plasticization of the nail plate, thereby facilitating the penetration and permeation of monoadducts and / or adducts. The concentration of the penetrating agent may be in the range of about 0.001% to about 2% by weight, preferably about 0.005% to about 1% by weight, and more preferably about 0.01% to about 0.1% by weight.

[0103] Fragrances such as cinnamon, cascarilla, safflower, rose, jasmine, mimosa, narcissus, cassia, citrus, apple, strawberry, cherry, lavender, patchouli, sage, violet, rosemary, myrrh, benzoin, pine, fir amber, copal, and related aromatic esters and aromatic terpenes are useful as optional components in this composition. The concentration of the perfume may be in the range of about 0.01% to about 1% by weight, preferably about 0.01% to about 0.5% by weight, and more preferably about 0.01% to about 0.1% by weight, based on the total weight of the composition.

[0104] Preservatives such as alkylparabens, phenoxyethanol, benzoic acid, germabens, DMDM ​​hydantoin, and diazolidinyl urea are useful as optional components in this composition. The concentration of the preservative may be in the range of about 0.001% to about 1% by weight, preferably about 0.001% to about 0.05% by weight, and more preferably about 0.001% to about 0.01% by weight, based on the total weight of the composition.

[0105] Pigment-soluble dyes and colorants containing metal oxides are also useful as optional components in this composition.

[0106] The treatment compositions according to the present invention may include any combination of optional components, but the inclusion of any aspect of these optional components that inhibits, delays, or alters the ability of the mono-adducts and / or bis-adducts to penetrate and permeate the nail plate by forming complexes with them, occluding them, absorbing them, adsorbing them, or otherwise intertwining with them should be minimized and / or avoided. Optional components that enable increased penetration of the nail plate, such as penetrating agents, are preferred optional components. Nonionic surfactants in minimum to low to moderate concentrations are also preferred optional components due to their ability to promote a homogeneous single-phase composition and to bring the nail plate closer to the permeation and penetration of the mono-adducts and / or bis-adducts.

[0107] Application method The treatment composition of the present invention comprises an aqueous medium or an aqueous organic medium, which provides a composition in a liquid state that flows freely at least under pressure. The medium, combined with a rheology control agent, can optionally provide a composition that is fluid under all conditions, such as a gel, which is thick and viscous under all conditions, or a composition that may be fluid under pressure, such as brushing, but is thick and viscous when standing, i.e., thixotropic.

[0108] In an embodiment of a composition that is free-flowing and does not contain rheology control agents, the composition can be delivered to the nail plate by immersing the nail plate in the free-flowing liquid composition. In this embodiment, the nail plate is preferably left immersed in the liquid composition for a sufficient time to allow the mono-adduct and / or bis-adduct to penetrate into the nail plate.

[0109] To promote the healing properties of a composition when the nail plate cannot be immersed in it, the coating of the composition on the nail plate is maintained in place as a gel by including a rheology control agent. The rheology control agent maintains an appropriate coating density on the substrate so that at least the mono-adducts and / or bis-adducts of the coating, which are in a viscous, static state, can effectively penetrate the surface of the nail plate. When the rheology control agent enables at least some of the gel properties of the composition, the viscosity of the composition is preferably controlled so that the composition as a gel can be slightly spread by brushing or the like when applied to the nail plate.

[0110] Rheological control of the treatment composition reduces or prevents the natural flow of the composition once it is coated onto the nail plate. While rheological control allows for the formation of a continuous, fluid coating on the nail plate when applied, it also allows the coating to maintain its integrity and remain in place once it covers the nail plate. This property allows the coating to maintain contact with the nail plate for a sufficient amount of time to allow the complex to penetrate into the internal regions of the nail plate.

[0111] The treatment composition of the present invention is allowed to dry slowly on the nail, thereby enabling the mono-adduct and / or bis-adduct to penetrate the surface of the nail plate and into the internal region of the nail plate. This penetration allows the mono-adduct and / or bis-adduct to come into contact with the damaged and / or torn portions of the nail plate beneath the nail plate surface. This contact is thought to repair, at least partially, the broken peptide bonds between the internal region of the nail plate and the underlying nail bed, thereby treating the damaged and / or torn nail.

[0112] An exemplary method of the present invention involves applying a prepared composition to the nail for a sufficient time to allow the mono-adduct and / or bis-adduct to penetrate through the nail surface into the interior of the nail. Penetration also preferably delivers the mono-adduct and / or bis-adduct to the contact surfaces between the nail plates. Preferably, multiple applications of the treatment composition to the nail can be achieved by 2 to 20 applications, preferably 3 to 10 applications, more preferably at least 4 applications, with optionally selected drying periods between applications.

[0113] Only combinations of the medium and mono-adducts and / or bis-adducts enable this delivery to the interior and contact surface of the nail plate; however, delivery can be facilitated by penetrating agents, nonionic surfactants, and fatty alcohols. Any, all, or any combination of these components may be used to facilitate delivery.

[0114] Embodiments of this method include immersion and / or coating as described above. In the immersion method, the nail plate is immersed for a sufficient amount of time in a free-flowing treatment composition to allow delivery of mono-adducts and / or bis-adducts to the interior and contact surfaces of the nail plate.

[0115] In the coating method, the treatment composition is applied to the nail plate by painting, sponge brushing, spraying, or other methods. In this case, the treatment composition is preferably prepared as a fluid gel so that when applied it will produce a continuous and complete coating on the nail plate substantially uniformly, but will remain stationary after application so as not to run off the nail plate.

[0116] For immersion and coating, the treatment composition moistened with the medium is kept in contact with the nail plate for a sufficient time to allow the complex to penetrate into the nail plate and, preferably, to remain in contact with the nail. Typical wet contact times range from 2 minutes to several hours.

[0117] After sufficient time has been achieved for contact and penetration, the "moist" composition may optionally be dried by air-drying techniques using moderately forced air, such as from a hairdryer or heated air gun. If a film-forming agent is present, the drying action will establish a film or dry coating of the film-forming agent on the surface of the nail.

[0118] The penetration of mono-adducts and / or bis-adducts, as well as optional starting material residues and unreacted starting materials, is primarily achieved during the "wet" stage of application of the treatment composition. However, the subsequent "drying" stage of the treatment composition also allows for the penetration of mono-adducts and / or bis-adducts, as well as optional starting material residues and unreacted starting materials, particularly if one or more fatty alcohols, penetrating agents, and / or surfactants are present, at least to some extent. By including a film-forming agent that produces a varnish or enamel coating on the nail after the drying step, the penetration in the "drying" stage may be delayed at least partially due to at least partial occlusion of mono-adducts and / or bis-adducts by the varnish and / or enamel.

[0119] The coating can be removed from the nail plate after sufficient time has elapsed, allowing the nail to regenerate into a continuous, natural nail plate. In some cases, the coating wears away naturally as the nail plate regrows. If early removal is desired, the coating can be removed by solvent and polishing. Film-forming agent coatings can also be removed by solvent removal.

[0120] Functional properties of nail-like adducts The reinforcement and adduct formation tests described below demonstrate that Michael adducts provide superior nail reinforcement compared to the use of diamines alone. Michael adducts include those having simple diamines as described in the applicant's PCT application WO / US23 / 65266 (the disclosure of which is incorporated herein by reference) and those having complex diamines as described herein. The use of complex organic diamines in adducts, in contrast to simple alkyl diamines, and the inclusion of optional residues and unreacted starting materials, are thought to enable the use of higher concentrations of adducts in the medium and better treatment of nail brittleness, breakage, and damage. The water solubility of complex organic diamine adducts and the corresponding unreacted diamines is influenced by the type and number of hydrophilic groups in the complex organic diamine moiety in the adduct and unreacted starting materials. While the chemical, electronic, polar, and hydrophilic / hydrophobic factors governing nail penetration are complex, the interaction of these functions with mono and bis adducts having complex organic diamine moieties is thought to result in significant improvements in the treatment of poor nail conditions.

[0121] Preparation of adducts Michael adducts are prepared by one of three methods: the boiling water technique; the boiling aqueous alcohol technique with optional pH control from neutral to alkaline; and the "standing" solvent-free or alcohol technique with optional pH control from neutral to alkaline.

[0122] Using the boiling water technique, carboxylic acid monoadducts can be prepared according to the procedure outlined in DE848045. This disclosure is incorporated herein by reference. One equivalent of maleic anhydride in distilled water is heated to about 100°C, and then two equivalents of isophorone diamine, diaminocyclohexane, or bis(3-aminopropyl)diethylene glycol are added, and the reaction mixture can be stirred at about 100°C for 24 hours. Then, about two equivalents of barium hydroxide are added, and heating is continued for 48 hours. The hydroxide treatment hydrolyzes the anhydride groups to carboxylate groups. The reaction mixture can be cooled to produce a barium salt precipitate, which can be filtered and repeatedly washed with distilled water. This acid post-treatment converts the barium salt precipitate to barium sulfate, dissolving the monoadduct as a carboxylic acid monoadduct (along with a small amount of bisadduct). The suspension can be filtered, and the filtrate can be concentrated under reduced pressure to produce the carboxylic acid monoadduct as a sulfate. Purification by precipitation from a water / methanol solution and concentration of the filtrate under reduced pressure can yield the purified carboxylic acid monoadduct as a sulfate.

[0123] Methyl ester monoadducts can be prepared similarly, or by esterifying carboxylic acid monoadducts.

[0124] Using the alcohol technique or the alcohol technique at a neutral to alkaline pH, the methyl ester monoadduct can be prepared by forming a solution in which 1 molar equivalent of dimethyl maleate is contained in a solvent system of methanol, ethanol, propanol, butanol and / or monoglycime and / or diethylene glycol monomethyl ether, preferably methanol, optionally adding 1% to 3% by weight of water, and heating this solution to near boiling point as described in the procedures of U.S. Patents No. 3,158,635, 5846,925 and 6465,690. A solution containing 2 molar equivalents of isophorone diamine, diaminocyclohexane, or bis(3-aminopropyl)diethylene glycol can be added to the same solvent system, and the solution can be maintained near boiling point for at least one day. In addition, the conditions of the alcohol technique can be adjusted to neutral or slightly alkaline (up to about pH 9 or 10). The reaction mixture can then be cooled and subjected to chromatography to obtain the dimethyl ester monoadduct.

[0125] The bis-adduct can be similarly prepared by changing the molar equivalent ratio of dimethyl maleate to the diamine from 1:2 to 2:1. Molar excess dimethyl maleate promotes Michael addition to each amine group of diaminohexane, separating the dimethyl maleate molecule.

[0126] Alternatively, the mono-adduct and bis-adduct carboxylic acid embodiments can be converted to methyl ester embodiments by methylation of the carboxylic acid group with azomethane or methyl iodide.

[0127] Michael addition products are also formed using the "standing" technique. Starting materials in a calculated maleic acid-to-diamine ratio to provide a mono-adduct or bis-adduct, or to produce a mono-adduct / bis-adduct mixture containing excess unreacted diamine, are dissolved in a water-free alcoholic solvent or a base-containing alcoholic solvent with an operating pH of 6 to 9, and allowed to stand in a sealed flask under ambient conditions for up to 6 to 12 months.

[0128] Using an accelerated "settlement" technique, the alcohol solution or the manipulated pH alcohol solution is heated at a temperature of 40°C to 60°C, preferably up to 50°C, for an intermediate period of 1 to 2 months at the start of the process.

[0129] At the end of either the static or accelerated static technique, the alcohol solution can be subjected to chromatography to isolate the Michael addition product or to remove only unreacted maleic acid, or it can be used as a treatment composition without further purification. Preferably, the removal of maleic acid and the use of the resulting alcohol solution may be as a treatment composition. Liquid chromatography-mass spectrometry of the contents of the static alcohol solution (without base) shows that 0.5% to 10% by weight of combined mono- and bis-adducts are produced, depending on whether intermediate heating of the solution is provided. Using the basic alcohol accelerated technique, the combined mono- and bis-adducts can be higher, such as 10% to 50-70% by weight, where weight % is relative to the total amount of mono- / bis-adducts and unreacted starting materials and reaction residues.

[0130] Preparation of treatment composition Treatment compositions for application to the nail plate can be prepared by combining mono-adducts and / or bis-adducts and / or adducts with optional starting material residues and unreacted starting materials in an aqueous or organic aqueous medium. Embodiments of carboxylic acid mono-adducts and / or bis-adducts can be appropriately prepared as strong reinforcing treatment compositions by adjusting the pH of the aqueous or organic aqueous medium so that these carboxylic acid embodiments can be presented as electrically neutral amphoteric forms. While appropriate treatment compositions can be obtained with pH ranges from highly acidic to highly basic, pH adjustments may be made to obtain the most appropriate treatment composition by setting the pH of the aqueous or organic aqueous medium to approximately 2 to 5, preferably 2.5 to 3.5. This adjustment can be achieved by combining a neutralized embodiment of the carboxylic acid mono-adduct and / or bis-adduct with a medium to provide an appropriate pH, or by combining an embodiment of the carboxylic acid mono-adduct and / or bis-adduct in a non-neutralized form with a medium already adjusted to have a pH of approximately 2.5 to 3.5 by adding an acid and an optional acid buffer. A treatment composition that provides at least some degree of reinforcing effect on nails can be provided using a medium having a pH of 2 to 10, but a stronger reinforcing effect can be provided by adjusting the pH of the medium to 2.5 to 3.5.

[0131] These embodiments, comprising methyl ester monoadducts and / or bisadducts, as well as optional starting material residues and unreacted starting materials, can be appropriately prepared in an aqueous or organic aqueous medium at a pH of 2 to 11 and can provide at least a certain nail-reinforcing effect. By adjusting the pH of the medium to a basic pH of 6 to 10, preferably 7.5 to 9.5, the treatment composition comprising methyl ester monoadducts and / or bisadducts, as well as optional starting material residues and unreacted starting materials, can provide a stronger reinforcing effect. This pH adjustment can be achieved by using a base such as sodium hydroxide, preferably in combination with a basic buffer. The basic pH may be in the range of about 8.9 to 9.5.

[0132] The medium before pH adjustment may be distilled water, or it may be an organic aqueous medium containing methanol, ethanol, or isopropanol, or a mixture thereof, in an amount of 50 volume percent or less, preferably 30 volume percent or less, more preferably 20 volume percent or less.

[0133] Nail reinforcement test Nail reinforcement tests assess the ability of mono-adductors and / or scis-adductors to reinforce the nail plate. These tests determine the ability of a point probe to puncture or otherwise break a human nail under increasing pressure conditions. Human nails are obtained as nail fragments from naturally grown nails. The resulting multiple nail fragments have an average cross-sectional size of 0.41–0.43 mm, a length of approximately 5 mm, and a width of approximately 8–9 mm.

[0134] The nail fragments may optionally be washed by immersion in isopropanol containing ethyl acetate to remove any residual nail varnish, then rinsed with water, and subsequently coated with a sample of the adductor test solution and dried. The nail fragments coated with the sample thus prepared can be placed in a custom holder of the texture intensity determination device. The holder unit clamps the entire coated nail fragment onto a metal base, securing it so that the underside of the coated nail fragment is in contact with the metal base. A needle probe, fixed to an automatic piston driven by the device, can be positioned at the top of the coated nail fragment and resting in a position where the needle tip is just touching the surface of the coated nail fragment. The device can be activated, and the needle probe can begin to press against the coated nail fragment under digitally controlled increasing pressure. The pressure at the time the coated nail fragment is punctured by the needle probe can be recorded as the hardness of the coated nail.

[0135] Protocol for determining nail strength The operating protocol for the TA.XTplus Connect texture analyzer manufactured by Texture Technologies Corp. (Hamilton, Massachusetts, USA) used to conduct the puncture tests followed the procedures provided by Texture Technologies, and was operated in accordance with the software program for performing variable-control needle puncture tests. This operating program for controlled pressure puncture tests on the TA.XTplus (Texture Technologies Corp.) analyzer was developed by Exponent Software (Stable Micro Systems, Ltd.). Nail hardness was evaluated as the maximum load measured throughout the puncture tests. The percentage difference between the hardness of the treated nail and the hardness of the control nail was used to determine the effectiveness of the embodiment of the nail treatment composition according to the present invention.

[0136] Preparation of treatment composition aliquots Exemplary aliquots of the treatment composition having mono-adduct mixtures of different concentrations can be prepared for performing a nail puncture test using a nail piece coated with the treatment composition according to the present invention.

[0137] Preparation of nail fragments The base material for the nail fragments can be collected by cutting off the free ends of the nails of each of the volunteer's five fingers as individual fragments.

[0138] After cutting each nail fragment into two halves, they may be washed with a dust-free wipe impregnated with isopropanol to remove surface residue. These halves may be paired and dried overnight under ambient conditions. One of the paired halves may be coated with the treatment composition according to the present invention according to the procedure described below. The other half may be kept uncoated and used as an untreated puncture test specimen for comparison, thereby allowing for accurate determination of the degree of reinforcement effect of the treatment composition.

[0139] Reinforcement effect and generation of adducts Table 1 shows the results of comparing the reinforcing effects of any diamine alone (e.g., hexanediamine) and maleic acid alone with any Michael mono-adduct (e.g., a purified mono-adduct of hexanediamine and maleic acid). Table 1 Comparison of Michaelbis adducts and heximethylenediamines TIFF2026530604000011.tif36170

[0140] The reinforcing effect of the static Michael adduct prepared by the static procedure is evaluated using maleic acid (MA) and hexamethylenediamine (HMDA) in anhydrous ethanol or in 95% ethanol held at ambient temperature for 6 months. A second static sample is prepared by combining the same starting materials and solvent, holding the mixture at 45°C for 2 months, and then holding it at ambient temperature for 4 months. The graph shows that approximately 0.5% by weight of the combined adduct is produced by aging at ambient temperature for 6 months, and approximately 10% by weight of the combined adduct is produced by aging at 45°C for 2 months followed by further aging at ambient temperature for 4 months.

[0141] The yield of combined adducts by the standing procedure can be further increased by holding the mixture at a high temperature of approximately 45°C to 55°C for 6 months. Furthermore, the yield of combined adducts by the standing procedure can be increased by providing a pH of the mixture of approximately 5 to 9, preferably 5.5 to 8. By controlling the pH, at least a portion of the diamine is deprotonated, thereby promoting nucleophilic Michael addition. However, maintaining a high pH of 10 or 11 or higher tends to convert the entire maleic acid to its salt form, and the resulting divalent anionic nature of the maleate form reduces the efficiency of Michael addition.

[0142] Table 2 shows a graph illustrating the formation of adducts in an alcohol mixture of starting materials that was left standing at ambient temperature for 6 months. Table 2 Determination of monoadduct formation by the "static" method TIFF2026530604000012.tif96170

[0143] Monoadducts, bisadducts, diamines, and maleic acid combinations are prepared by combining pure maleic acid and diamine in the desired weight ratio in a sealed container such as a reaction flask, dissolving the maleic acid in the diamine, and forming a liquid solution or dispersion (hereinafter referred to as the mixture). The mixture is allowed to stand at ambient temperature for at least 2 months to a maximum of 6 months.

[0144] The weight percentage of combined adducts in a standing mixture can be increased by allowing the mixture to stand at high temperatures, such as 40°C to 60°C, for the aforementioned period. At high temperatures, the amount of combined adducts may range from approximately 40% to 70% of the total weight of the mixture.

[0145] The weight percentage of the combined adduct in a standing mixture can also be increased by adding a solvent, such as an aqueous alcohol containing 85-95% ethanol in water, and a base, such as sodium hydroxide or potassium hydroxide, to adjust the pH to approximately 9-11. By adding the solvent and base, the amount of the combined adduct can increase from approximately 30 to 80 weight percent of the total weight of the mixture.

[0146] Depending on the molar ratio of diamine to maleic acid, the remaining molar amount of diamine will be equal to or less than the remaining molar amount of maleic acid. In particular, when the molar ratio of maleic acid to diamine is 2 or greater, Michael addition mainly forms bis-adducts. Therefore, this type of high molar ratio reduces the remaining molar amount of diamine more than expected when Michael addition is incomplete.

[0147] Following the static mixing technique described above, an ethanol mixture of diamine and maleic acid (3.34% by weight, 0.0288 mol) and the following diamine were prepared: a) Hexamethylenediamine (1.16% by weight, 0.01 mole); b) Isophorone diamine (2.43%, 0.0143 mol); c) Bis(3-aminopropyl)diethylene glycol (3.76% by weight, 0.0171 mol).

[0148] The molar amounts of maleic acid and diamine provided slightly more than 2 moles of maleic acid per mole of diamine (hexanediamine and isophoronediamine), and slightly less than 2 moles of maleic acid per mole of diamine (bis(3-aminopropyl)diethylene glycol). As described above, using these molar amounts and a standing procedure of 6 months at ambient temperature, essentially, the first two diamines (a and b) all produced bis adducts, while the third diamine (c) produced a mixture of a small amount of mono adduct and a larger amount of bis adduct.

[0149] The resulting standing mixture was also found to contain unreacted maleic acid and diamine, as well as Michael addition mixtures. Overall, the relative molar concentration of the bis and mono adducts to the total molar amount of maleic acid and diamine used as starting materials was approximately 20% ± 5%, as determined by LC-MS studies of the mixture.

[0150] These mixtures (a, b, and c) were used as treatment compositions in the nail reinforcement procedure described above. Treatment was performed twice daily for 6 days. The designation "n" indicates the number of nail fragments treated for 6 days. The results are summarized in Table 3. Since the puncture tests were performed using nail fragments obtained from human nails that were not standardized and uniform in thickness, tensile strength, and biochemical composition, the results provided in Table 1 differ from those in Table 3 C1 as a result of the characteristics of these different individual human fingernails. However, the results in Table 3 C1-C3 are directly comparable because the same human nail fragment aliquots were used for all three examples C1-C3. Table 3 Example C1, n=20 TIFF2026530604000013.tif24170 Example C2, n=10 TIFF2026530604000014.tif24170 Example C3, n=9 (one sample lost during treatment) TIFF2026530604000015.tif28170

[0151] The increase in average nail hardness of complex diamines compared to alkyl diamines demonstrates that the use of complex diamines, which have their contribution to the lipophilicity of the mixture, improves the nail-hardening ability of the mixture. This improvement also demonstrates that purified mono and bis adducts of complex diamines show improved nail-hardening ability.

[0152] Description of the Embodiment The following descriptions illustrate embodiments of the present invention in accordance with the preceding description and experimental details. These descriptions provide further disclosure of these embodiments, features, and parameters and may serve as claims of the present invention.

[0153] Required information 1. A method for treating a damaged nail plate, comprising applying a treatment composition to the damaged nail plate, wherein the treatment composition comprises one or more mono adducts from formulas VI, IXA, IXB, XIIIA, and XIIIB and / or their amines and / or carboxyl salts; or one or more bis adducts from formulas VII, XIA, XIB, XIVA, and XIVB and / or their carboxyl salts; or a mixture of one or more mono adducts from formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIA and XIVA, or formulas XIIIB and XIVB, and their bis adducts and / or their amines and / or carboxyl salts; TIFF2026530604000016.tif35170 formula VI monoadduct having a diamine moiety TIFF2026530604000017.tif34170 Formula VII Bis adduct having a diamine moiety TIFF2026530604000018.tif35170 Formula IX-A monoadduct having a diamine moiety TIFF2026530604000019.tif34170 Formula IX-B monoadduct having a diamine moiety TIFF2026530604000020.tif36170 Formula XI-A Bis adduct having a diamine moiety TIFF2026530604000021.tif36170 Formula XI-B Bis adduct having a diamine moiety TIFF2026530604000022.tif35170 Formula XIIIA Monoadduct having a siloxanediamine moiety TIFF2026530604000023.tif43170 Formula XIIIB Monoadduct having a branched siloxanediamine moiety TIFF2026530604000024.tif36170 Formula XIV A Bis-adduct having a siloxanediamine moiety TIFF2026530604000025.tif43170 Formula XIV B Bis adduct having a branched siloxanediamine moiety [In the formula, The indicator symbols k, l, l', m, m', n, n', o, p, q, r, and s, and the substituents X, X', W, Z, E, E', and G are defined as follows: 1) l, l', m, m', n, and n' can each be an integer from zero to 100, and the sum of l, l', m, m', n, and n' can be at least 2 and at most 100, preferably at most 50, more preferably at most 30, and even more preferably at most 20, and the individual sums are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, or 15. 2) X and X 1 Both are -OH, -OR 2 or -NHR 3 It is possible. 3) W and Z are independently O, S, or NR 6 It is possible. 4) R 2 It is a C1-C4 linear alkyl group. 5) R 3 It is a H, C1-C4 linear alkyl group. 6)R 4 and R 5 Each of these can be hydrogen or a C1-C10 alkyl group, and the C1-C10 alkyl group may be substituted with one or more of the following: a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 alkylthio (alkthio) group, a C1-C4 alkyl group substituted with a -CO2-C1-C4 alkyl group, a C1-C4 alkyl group substituted with a -CONH-C1-C4 alkyl group, a C1-C4 alkyl group substituted with a -SO2-C1-C4 alkyl group, and a C1-C4 alkyl group substituted with a -SO2-NH-C1-C4 alkyl group. 7) R 6 This can be hydrogen or a C1-C20 linear or branched alkyl group. 8) E may be cyclopentyl, cyclohexyl, C1-C4 mono, di, or trialkylcyclohexyl, phenyl or C1-C4 alkylphenyl, C6-C10 aryl having one or two rings or C1-C4 mono or multialkylC6-C10 aryl having one or two rings, pyridinyl, 1,3,5-triazinyl, or 1,3,5-triazine substituted with alkyl or phenyl. 9) E' may be cyclopentyl or cyclohexyl, C1-C4 mono, di, or trialkylcyclohexyl, phenyl, or C1-C4 alkylphenyl. 10) G is -(CH2) k It can be -, -SO2-, or -NH. 11) k can be an integer from 1 to 10. 12) o and r can each be zero or an integer from 1 to 4, independently of each other. 13) p, p', and q can each be zero or 1 independently. 14) s can be an integer from 1 to 4. 15) u, u', and v can each be an integer, independently of any other, ranging from zero to 50, preferably from 1 to 20, more preferably from 1 to 10, and most preferably from 1 to 5. 16)R 9 is hydrogen or -(CH2) k - It is possible. 17)R 10 This can be hydrogen or a C1-C6 alkyl group, and the concentration of any one of the mono-adducts, bis-adducts, or mixtures is at least 0.2% by weight of the total weight of the composition. A method comprising an organic medium, an aqueous medium, or an aqueous organic medium in combination with the above. 2.X and X 1 However, both are OH, or X and X 1 The method described in item 1, wherein both are anhydrous -CO-O-CO-. 3.X and X 1 However, both are OH, as described in item 2. 4.X and X 1 However, both are -OR 2 And R 2 The method according to item 1, wherein the methyl or ethyl, preferably methyl, is used. 5. The method described in any one of items 1 to 4, comprising substantially only one or more monoadducts from formula VI, IXA, IXB, XIIIA, or XIIIB. 6. The method described in item 5, which includes only mono-adductors. 7. The method described in any one of items 1 to 4, substantially comprising only one or more bis adducts from formula VII, XIA, XIB, XIVA, or XIVB. 8. The method described in item 7, comprising only bis-adductors. 9. The method described in any one of claims 1 to 4, substantially comprising only a mixture of a mono-adduct and a bis-adduct from one or more mono-adducts of formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIA and XIVA, or formulas XIIB and XIVB. 10. The method described in item 9, comprising only the mixture. 11. The method according to claims 9 and 10, wherein the weight percentage of the bis adduct present in the mixture is about 40 mole percent or less, preferably about 20 mole percent or less, more preferably about 10 mole percent or less, particularly more preferably about 5 mole percent or less, and most preferably about 1 to 2 mole percent or less, relative to the total weight of the mixture. 12. The method according to any one of claims 1 to 11, wherein the composition contains, in an organic medium or an aqueous or aqueous organic medium, one or more mono-adducts of formula VI, IXA, IXB, XIIIA, or XIIIB, or one or more bis-adducts of formula VII, XIA, XIB, XIVA, or XIVB, or a mixture of one or more mono-adducts of formula VI and VII, or formula IXA and XIA, or formula IXB and XIB, or formula XIIIA and XIVA, or formula XIIIB and XIVB, in an amount of about 0.2% to about 20% by weight, preferably about 0.5% to about 15% by weight, more preferably about 0.5% to about 10% by weight, and most preferably about 0.5% to about 6.5% by weight, based on the total weight of the composition. 13. The method according to any one of claims 1 to 6, wherein only one or more mono-adducts of formula VI, IXA, IXB, XIIIA, or XIIIB are substantially present, and their concentration in an organic medium, aqueous medium, or aqueous organic medium is about 1.5% to about 10% by weight. 14. The method according to any one of claims 1 to 13, wherein mono-adducts and / or bis-adducts having X and X' as OH groups include amine-neutralized forms as salts of hydrochloric acid, sulfuric acid, nitric acid and / or phosphoric acid, and carboxyl-neutralized forms as salts of alkali metals or ammonia bases. 15. One mono-adduct of formula VI, IXA, IXB, XIIIA, or XIIIB and / or one bis-adduct of formula VII, XIA, XIB, XIVA, or XIVB is X and X 1The method according to any one of claims 1 to 14, wherein the OH group is present, and the pH of the medium is about 1 to about 11, preferably about 2 to about 10, more preferably about 2 to about 7, particularly more preferably about 2 to about 5, and most preferably about 2.5 to about 3.5. 16. The method according to any one of claims 1 to 15, wherein the mono-adduct of any one of formulas VI, IXA, IXB, XIIIA, or XIIIB and / or the bis-adduct of any one of formulas VII, XIA, XIB, XIVA, or XIVB is a methyl ester, and the pH of the medium is about 2 to about 11, preferably about 4 to about 10.5, more preferably about 6 to about 10, particularly more preferably about 7.5 to about 10, and most preferably about 7.8 to about 9.5. 17. The method described in any one of items 1 to 16, wherein the medium is an aqueous medium. 18. The method according to any one of items 1 to 17, wherein the medium is an organic medium or an aqueous organic medium, and the organic component is an alcohol selected from one or more C1-C4 monoalcohols, C2-C4 dialcohols, or C3-C4 trialcohols, or a combination of an alcohol and a non-alcohol selected from one or more ketones, esters, acetates, dimethyl isosorbide, DMSO, DMF, or THF. 19. The method according to claim 18, wherein the aqueous organic medium is an aqueous alcohol, preferably an aqueous ethanol medium. 20. The method according to item 18 or 19, wherein the volume % (v%) of the organic component in the aqueous organic medium is in the range of about 2v% to about 50v%, preferably about 2v% to about 25v%, and more preferably about 2v% to about 10v%, relative to the total volume of the medium. 21. The method according to any one of claims 1 to 20, wherein the mono-adduct and / or bis-adduct is in the form of a non-neutralized and / or amphoteric ion, the medium is an aqueous organic medium in which the organic compound does not exceed 50% by volume, preferably 25% by volume, and the organic compound is an alcohol in which the non-alcohol does not exceed 2% by volume, preferably 1% by volume, relative to the total volume of the organic compound. 22. The method according to any one of claims 1 to 21, wherein the treatment composition further comprises at least one of a film-forming polymer, a fatty alcohol, a rheology agent, a nonionic surfactant, a penetration agent, a perfume, a preservative, a coloring agent, or any combination thereof. 23. The method according to claim 22, comprising a rheology agent and a penetration agent. 24. The method according to claim 22, comprising a rheology agent, a penetration agent, a nonionic surfactant, and an optional film-forming polymer selected from (meth)acrylate polymers, (meth)acrylate-vinyl copolymers, ester polymers, amide polymers, vinyl or olefin polymers, urethane polymers or cellulosic polymers. 25. A method for treating a damaged nail plate according to any one of claims 1 to 24, wherein the treatment composition further comprises at least a diamine having one or more of V, VIIA, VIIIB, XIIA, XIIB, the diamine corresponds to the diamine moiety of a mono-adduct or bis-adduct or a mixture thereof, and the treatment composition optionally further comprises a corresponding unsaturated carboxyl compound starting material of formula IV:[] H2N-(CH2) l- (W-CH2) l’ -(CHR 4 ) m -(CH2) m’ -(Z-CHR 5 ) n -(CH2) n’ -NH2 Formula V H2N-(CH2) o -E-[(G) p -E’-] q -(CH2) r -NH2 Formula VIIA H2N-(CH2) o -(CH(R 9 NH2) R 10 ) p -[(G) p’ -E’-] q -(CH2) r -NH2 Formula VIIIB H2N-(CH2) s -(Me2SiO) u -(Me2SiO) u’ -(CH2) r -NH2 Formula XIIA H2N-(CH2) s -(Me2SiO) u -[MeSiO(SiMe2O) v -SiMe3)](Me2SiO) u’ -(CH2) r -NH2 Formula XIIB X-OC-HC=CH-CO-X; Formula IV In the formula, the indicator symbols k, l, l', m, m', n, n', o, p, q, r and s, and the substituents X, X', W, Z, E, E' and G are defined in item 1, or There are two X molecules, and these two X molecules, together with their CO groups, form an anhydrous or -C=O-NR molecule of the formula -C=OOC=O-. 3 A method for forming an imide with -C=O. 26. The method according to claim 25, wherein a mixture of mono-adducts and bis-adducts is present together with one or more corresponding diamines of formulas V, VIIIA, VIIIB, XIIA, and XIIB, and an optional unsaturated carboxyl compound of formula IV. 27. The method according to claim 25 or 26, wherein the molar ratio of one or more diamines from formulas V, VIIIA, VIIIB, XIIA, and / or XIIB to the corresponding mono-adduct or the corresponding bis-adduct or a mixture of the corresponding mono-adduct and the bis-adduct is at least 1:1. 28. The method described in item 27, wherein the molar ratio is at least 2:1. 29. The method described in item 27, wherein the molar ratio is at least 3:1. 30. The method described in item 27, wherein the molar ratio is approximately 1:1 to approximately 3:1. 31. The method according to claim 25, wherein the weight percentage of one or more diamines from formulas V, VIIIA, VIIIB, XIIA, and XIIB, and an optional unsaturated carboxyl compound of formula IV is about 95% by weight or less of the weight of the corresponding mono-adduct, the corresponding bis-adduct, or a mixture of the corresponding mono-adduct and bis-adduct. 32. The method according to item 31, wherein the amount by weight is about 50% by weight or less, preferably about 25% by weight or less, and more preferably about 10% by weight or less. 33. The method according to any one of claims 25 to 32, wherein the treatment composition is manipulated before being applied to the damaged nail plate to remove any diamine of formula V, VIIIA, VIIIB, XIIA, or XIIB and an unsaturated carboxyl compound of formula IV. 34. The method according to description 33, wherein the treatment composition is manipulated before being applied to the damaged nail plate to separate the bis-adduct, separate the mono-adduct, separate the diamine, separate the unsaturated carboxyl compound, and the mono-adduct and / or bis-adduct and / or mixture thereof are included in the treatment composition applied to the damaged nail. 35. The method according to item 34, wherein the isolated bis-adduct, isolated mono-adduct, and isolated diamine are isolated and purified. 36. A method for treating a damaged nail plate according to any one of items 1 to 35, comprising applying the treatment composition to the damaged nail once or more times. 37. The method according to any one of items 1 to 36, wherein the treatment composition is applied at least once with a brush, sponge, felt or cloth. 38. The method according to description 36 or 37, wherein the composition is applied to the nail at least four times. 39. The method according to description 38, wherein the treatment composition used for final coating further comprises a film-forming polymer. 40. Use of the treatment composition according to any one of claims 1 to 39 as a treatment for damaged nails. 41. A treatment composition comprising a combination of one or more mono adducts from formulas VI, IXA, IXB, XIIIA, and XIIIB as described in item 1 and / or their amines and / or carboxyl salts; or one or more bis adducts from formulas VII, XIA, XIB, XIVA, and XIVB as described in item 1 and / or their carboxyl salts; or a mixture of one or more mono adducts and bis adducts from formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIA and XIVA, or formulas XIIIB and XIVB as described in item 1 and / or their amines and / or carboxyl salts; or a combination of a mono adduct or bis adduct or a mixture thereof with at least one or more diamines having formulas V, VIIIA, VIIIB, XIIA, and XIIB as described in item 25, wherein the diamine corresponds to the diamine portion of the mono adduct or bis adduct or a mixture thereof, and optionally to the corresponding unsaturated carboxyl compound starting material of formula IV.

[0154] Summary The inventions, examples, and results described and claimed herein may include attributes and embodiments that are not limited to those presented, described, or referred to herein.

[0155] All patents, publications, scientific papers, websites, and other documents and official materials described herein represent the state of the art for those skilled in the art to which the present invention pertains, and each such cited document and material is incorporated herein by reference to the same extent as if it were incorporated verbatim in its entirety and explicitly stated herein. The right to physically incorporate all or part of any material and information contained herein in such patents, publications, scientific papers, websites, electronically available information, textbooks, or other cited documents or materials is reserved.

[0156] The written description of this patent application includes all of the claims. All claims, including the original claims, are incorporated by reference in their entirety into the description portion of this specification, and the right to physically incorporate all or part of such claims into the description portion of this specification or any other portion of this application is reserved. Therefore, in no case should it be construed that the patent fails to meet the description requirements with respect to a claim, for example, because the exact wording of a claim is not included verbatim in the description portion of the patent specification.

[0157] Although the present invention has been described in conjunction with its detailed description, the above description is intended to illustrate the invention and not to limit its scope, which is defined by the scope of the appended claims. Therefore, it will be understood from the foregoing that certain non-limiting embodiments of the present invention have been described herein for illustrative purposes, but that various modifications can be made without departing from the scope of the invention. Other aspects, advantages and modifications are included in the following claims, and the present invention is not limited except by the appended claims.

Claims

1. A method for treating a damaged nail plate, comprising applying a treatment composition to the nail plate, wherein the treatment composition comprises one or more mono adducts from formulas VI, IXA, IXB, XIIIIA, and XIIIIB and / or their amines and / or carboxyl salts; or one or more bis adducts from formulas VII, XIA, XIB, XIVA, and XIVB and / or their carboxyl salts; or a mixture of one or more mono adducts and bis adducts from formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIIA and XIVA, or formulas XIIIIB and XIVB, and / or their amines and / or carboxyl salts, in an organic medium, aqueous medium, or aqueous organic medium: Formula VI monoadduct having a diamine moiety Formula VII Bis adduct having a diamine moiety Formula IX-A monoadduct having a diamine moiety Formula IX-B monoadduct having a diamine moiety Formula XI-A Bis adduct having a diamine moiety Formula XI-B Bis adduct having a diamine moiety Formula XIIIA Monoadduct having a siloxanediamine moiety Formula XIIIB Monoadduct having a branched siloxanediamine moiety Formula XIV A Bis-adduct having a siloxanediamine moiety Formula XIV B Bis adduct having a branched siloxanediamine moiety [In the formula, The indicator symbols k, l, l', m, m', n, n', o, p, q, r, and s, and the substituents X, X', W, Z, E, E', and G are defined as follows: 1) l, l', m, m', n, and n' can each be an integer from zero to 100, and the sum of l, l', m, m', n, and n' can be at least 2 and at most 100, preferably at most 50, more preferably at most 30, and even more preferably at most 20, and the individual sums can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, or 15. 2) X and X １ Both are -OH and -OR ２ or -NHR ３ It could be, 3) W and Z are each independently O, S, or NR ６ It could be, 4) R ２ It is a C1-C4 linear alkyl group, 5) R ３ It is an H, C1-C4 linear alkyl group, 6) R ４ and R ５ each individually and separately, can be hydrogen or C1-C10 alkyl, wherein the C1-C10 alkyl can be substituted by one or more selected from the group consisting of C1-C4 alkyl groups, C1-C4 alkoxy groups, C1-C4 alkylthio (alkthio) groups, C1-C4 alkyl substituted by -CO ２ -C1-C4 alkyl groups, C1-C4 alkyl substituted by -CONH-C1-C4 alkyl groups, C1-C4 alkyl substituted by -SO ２ -C1-C4 alkyl groups, and C1-C4 alkyl substituted by -SO ２ -NH-C1-C4 alkyl groups. 7) R ６ This can be hydrogen or a C1-C20 linear or branched alkyl group. 8) E may be cyclopentyl, cyclohexyl, C1-C4 mono, di or trialkylcyclohexyl, phenyl or C1-C4 alkylphenyl, C6-C10 aryl having one or two rings or C1-C4 mono or multialkylC6-C10 aryl having one or two rings, pyridinyl, 1,3,5-triazinyl, or 1,3,5-triazine substituted with alkyl or phenyl. 9) E' may be cyclopentyl or cyclohexyl, C1-C4 mono, di, or trialkylcyclohexyl, phenyl, or C1-C4 alkylphenyl. 10) G is - (CH ２ ) ｋ -, -SO ２ -, - It could be NH, 11) k can be an integer from 1 to 10, 12) o and r can each be zero or an integer from 1 to 4, independently. 13) p, p', and q can each be zero or one independently. 14) s can be an integer from 1 to 4, 15) u, u', and v can each be independently zero, or an integer from 1 to 50, preferably 1 to 20, more preferably 1 to 10, and most preferably 1 to 5. 16) R ９ is hydrogen or -(CH ２ ) ｋ - It could be, 17) R １０ This can be hydrogen or a C1-C6 alkyl group. Methods that include...

2. The treatment composition further comprises one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to the diamine portion of one or more mono-adducts from formulas VI, IXA, IXB, XIIIIA, and XIIIIB; or one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to the diamine portion of any one or more bis-adducts from formulas VII, XIA, XIB, XIVA, and XIVB; or one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to the diamine portion of a mixture of mono-adducts and bis-adducts from any one or more mono-adducts from formulas VI and VII or formulas IXA and XIA or formulas IXB and XIB or formulas XIIIIA and XIVA or formulas XIIIIB and XIVB; optionally further comprising an unsaturated carboxyl compound of formula IV: H ２ N-(CH ２ ) ｌ－ (W-CH ２ ) ｌ’ -(CHR ４ ) ｍ -(CH ２ ) ｍ’ -(Z-CHR ５ ) ｎ -(CH ２ ) ｎ’ -NH ２ Formula V H ２ N-(CH ２ ) ｏ -E-[(G) ｐ -E’-] ｑ -(CH ２ ) ｒ -NH ２ Formula VIIIA H ２ N-(CH ２ ) ｏ -(CH(R ９ NH ２ )R １０ ) ｐ -[(G) ｐ’ -E’-] ｑ -(CH ２ ) ｒ -NH ２ Formula VIIIB H ２ N-(CH ２ ) ｓ -(Me ２ SiO) ｕ -(Me ２ SiO) ｕ’ -(CH ２ ) ｒ -NH ２ Formula XIIA H ２ N-(CH ２ ) ｓ -(Me ２ SiO) ｕ -[MeSiO(SiMe) ２ O) ｖ -SiMe ３ )](Me ２ SiO) ｕ’ -(CH ２ ) ｒ -NH ２ Formula XIIB X-OC-HC=CH-CO-X; Formula IV The method according to claim 1, wherein the indicator symbols k, l, l', m, m', n, n', o, p, q, r, and s, and the substituents X, X', W, Z, E, E', and G are defined as described in claim 1.

3. The method according to claim 2, wherein the treatment composition comprises only one or more monoadducts from formulas VI, IXA, IXB, XIIIIA, or XIIIIB in combination with one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to one or more diamine moieties of the monoadduct.

4. The method according to claim 2, wherein the treatment composition comprises only one or more bis-adducts from formulas VII, XIA, XIB, XIVA, or XIVB in combination with one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to one or more diamine portions of the bis-adduct.

5. The method according to claim 2, wherein the treatment composition comprises only a mixture of mono-adducts and bis-adducts from one or more mono-adducts of formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIIA and XIVA, or formulas XIIIIB and XIVB, in combination with one or more diamines from formulas V, VIIIIA, VIIIIB, XIIA, and XIIB corresponding to one or more diamine portions of the mixture.

6. The method according to any one of claims 2, 3, 4, or 5, wherein the treatment composition is manipulated before being applied to the damaged nail plate to remove one or more diamines from formulas V, VIIIA, VIIIB, XIIA, and XIIB.

7. The method according to any one of claims 1 to 6, wherein the concentration of the mono-adduct or bis-adduct or mixture thereof in the organic medium or aqueous medium or aqueous organic medium is about 0.2% to about 20% by weight, preferably about 0.5% to about 15% by weight, more preferably about 0.5% to about 10% by weight, most preferably about 0.5% to about 6.5% by weight, or at least 0.2% by weight, relative to the total weight of the composition.

8. The method according to any one of claims 2 to 5, wherein the concentration of a mono-adduct or bis-adduct or mixture thereof combined with a diamine in an organic medium, an aqueous medium, or an aqueous organic medium is about 0.2% to about 20% by weight, preferably about 0.5% to about 15% by weight, more preferably about 0.5% to about 10% by weight, most preferably about 0.5% to about 6.5% by weight, or at least 0.2% by weight, relative to the total weight of the composition.

9. The treatment composition comprises one or more mono-adducts from formulas VI, IXA, IXB, XIIIA, and XIIIB; or one or more bis-adduct compounds from formulas VII, XIA, XIB, XIVA, and XIVB; or a mixture of one or more mono-adducts and bis-adducts from formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIA and XIVA, or formulas XIIIB and XIVB, and X and X １ The method according to any one of claims 1 to 8, wherein is OH, and the medium has a pH of about 1 to about 11, preferably about 2 to about 10, more preferably about 2 to about 7, particularly more preferably about 2 to about 5, most preferably about 2.5 to about 3.

5.

10. The method according to any one of claims 1 to 9, wherein the medium is an aqueous medium or an aqueous organic medium, and the organic component is an alcohol selected from one or more C1-C4 monoalcohols, C2-C4 dialcohols, or C3-C4 trialcohols, and is optionally combined with a nonalcohol selected from one or more ketones, esters, acetates, dimethyl isosorbide, DMSO, DMF, THF, or any combination thereof.

11. The method according to claim 10, wherein the volume % (v%) of the organic component in the aqueous organic medium is in the range of about 2 v% to about 95 v%, preferably about 2 v% to about 50 v%, more preferably about 2 v% to about 25 v%, and most preferably about 2 v% to about 10 v%.

12. The method according to any one of claims 1 to 11, wherein the treatment composition further comprises at least one of a film-forming polymer, a fatty alcohol, a rheological agent, a nonionic surfactant, a penetrating agent, a perfume, a preservative, a colorant, or any combination thereof.

13. The method according to any one of claims 1 to 12, wherein the treatment composition further comprises at least a rheological agent and a penetrating agent.

14. The method according to claim 12, wherein the film-forming polymer is selected from (meth)acrylate polymers, (meth)acrylate-vinyl copolymers, ester polymers, amide polymers, vinyl or olefin polymers, urethane polymers, or cellulosic polymers.

15. A treatment composition is prepared by a Michael addition reaction carried out in an organic medium, an aqueous medium, or an aqueous organic medium using one of the diamines of formulas V, VIIIIA, VIIIIB, XIIA, XIIB, and XIIB and an unsaturated carboxyl compound of formula IV to form one or more Michael addition products: H ２ N-(CH ２ ) ｌ－ (W-CH ２ ) ｌ’ -(CHR ４ ) ｍ -(CH ２ ) ｍ’ -(Z-CHR ５ ) ｎ -(CH ２ ) ｎ’ -NH ２ Formula V H ２ N-(CH ２ ) ｏ -E-[(G) ｐ -E’-] ｑ -(CH ２ ) ｒ -NH ２ Formula VIIIA H ２ N-(CH ２ ) ｏ -(CH(R ９ NH ２ )R １０ ) ｐ -[(G) ｐ’ -E’-] ｑ -(CH ２ ) ｒ -NH ２ Formula VIIIB H ２ N-(CH ２ ) ｓ -(Me ２ SiO) ｕ -(Me ２ SiO) ｕ’ -(CH ２ ) ｒ -NH ２ Formula XIIA H ２ N-(CH ２ ) ｓ -(Me ２ SiO) ｕ -[MeSiO(SiMe) ２ O) ｖ -SiMe ３ )](Me ２ SiO) ｕ’ -(CH ２ ) ｒ -NH ２ Formula XIIB X-OC-HC=CH-CO-X; Formula IV In the formula, the designation symbols k, l, l', m, m', n, n', o, p, q, r and s and the substituents X, X', W, Z, E, E' and G are as defined in claim 1; there are two X's, and the two X's together with their CO groups form an anhydride of the formula -C=O-O-C=O- or -C=O-NR ３ It forms an imide of -C=O-; and in the formation of one or more Michael addition products, the X-OC- adjacent to the unsaturated carbon residue to which the amine nitrogen is bound is X １ Next; One or more Michael addition products, a) A monoadduct of any one of the following formulas: VI, IXA, IXB, XIIIA, or XIIIB; or b) A bis-adductor of any one of the following formulas: VII, XIA, XIB, XIVA, or XIVB; or c) A mixture of mono-adducts and bis-adducts of formulas VI and VII, or formulas IXA and XIA, or formulas IXB and XIB, or formulas XIIIA and XIVA, or formulas XIIIB and XIVB. Includes or The treatment composition comprises a mono-adduct that is a Michael addition product a), a bis-adduct that is a Michael addition product b), or a mixture that is a Michael addition product c), combined with one unreacted diamine from formulas V, VIIIA, VIIIB, XIIA, and XIIB corresponding to one or more diamine moieties of the mono-adduct, bis-adduct, or mixture, and an unreacted unsaturated carboxyl compound. The method according to any one of claims 1 to 14.

16. The method according to claim 15, wherein the Michael addition product is isolated and purified to remove unreacted diamine and unreacted unsaturated carboxyl compounds.

17. A method for treating a damaged nail, comprising applying the treatment composition according to any one of claims 1 to 16 to the damaged nail once or more times.

18. The method according to claim 17, wherein the composition is applied to the nail at least four times.

19. The method according to claim 17, wherein the composition comprises at least one or more of a rheological agent, a penetrating agent, a fatty alcohol, a colorant, and a nonionic surfactant, or any combination thereof, and optionally, the composition used as the final coating further comprises a film-forming polymer.

20. Use of the method according to any one of claims 1 to 19 as a treatment for a damaged nail.

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