EA040937B1 - REDUCING OR PREVENTING HAIR DAMAGE DURING LIGHTENING - Google Patents

Description

Cross-reference to related applications

This application claims priority to U.S. Provisional Application Serial No. 61/994,709, filed May 16, 2014, the disclosure of which is incorporated herein by reference in its entirety.

Technical field

The present invention relates generally to compositions and methods for treating keratin in hair, skin or nails, and in particular to strengthening and/or restoring hair during or after coloring or permanent waving.

State of the art

Hair coloring is now a globally recognized fashion phenomenon. Color changing procedures include coloring, highlighting and lightening hair. Coloring products can be divided into several types, which include permanent, semi-permanent, semi-permanent, and temporary color formulations. Permanent hair color products make up the majority of the market worldwide.

Considerable effort has gone into creating different approaches to hair coloring; this includes oxidation dyes, direct dyes, natural dyes, metallic dyes and reactive dyes. Many hair color formulations, particularly permanent color formulations, use reducing agents to break disulfide bonds in the hair, allowing hair dyes and lightening agents to penetrate deeper into the hair.

In addition, disulfide bonds in the hair are destroyed by the application of reducing agents, for example during permanent waving and hair straightening procedures. Once the disulfide bonds are broken, pressure is applied to the hair to create the final shape (eg, straight, wavy, or curly) and the disulfide bonds are re-formed.

Thioglycolic acid, especially in the form of the ammonium salt, is often used to cleave cysteine-formed disulfide bonds in hair. Sodium bisulfite is another example of a known reducing agent commonly used in various coloring and lightening agents in color changing procedures.

Typically, oxidation to re-form a previously reduced bond is partially achieved when an oxidizing agent, such as hydrogen peroxide, is present in the coloring composition and/or when the hair is exposed to atmospheric oxygen. However, this oxidation step can be too slow and can leave hair frizzy and damaged.

Additionally, hair during the permanent waving procedure is usually treated with a reducing agent followed by treatment with an oxidizing agent. Hydrogen peroxide is optionally added in the second step to return the hair to its previous state. The newly formed disulfide bonds in the treated hair are stressed to maintain the new shape of the hair; thus, they are easily destroyed, which leads after a while to the restoration of the original shape of the hair.

The use of peroxides in the hair shaping process can damage the hair, remove unnatural color from the hair, and/or leave the hair frizzy. In addition, some hidden reduced thiol groups may remain in the hair even after treatment with an oxidizing agent. Peroxide hair reshaping procedures include the following reaction with thiol groups:

KSH +H ₂ O ₂ KSS-K+2 H ₂ O (Reaction I) where K is keratin in hair.

In the event that two K-S-H groups are not available for reaction I to proceed, the following reaction is considered to take place, which leads to hair damage:

KSH + H ₂ O ₂ - K-SO ₂ -OH (Reaction II)

In addition to being the main component of hair, keratin is also the main component of skin and nails. There are a number of different types of keratin, which are generally grouped into soft or hard keratins. Soft keratins are more abundant in the skin, while hard keratins predominate in hair and nails. Specifically, nails are made up of modified keratin similar to that found in hair. Disulfide bonds in the keratin of the nails contribute to their impermeability. Thus, damage to the disulfide bridges present in the keratin of the skin or nails can lead to soreness and/or scaling of the skin or nails, i. maintaining keratin disulphide bridges helps keep skin healthy and prevents brittle and cracking nails.

Significant improvement is needed in the areas of color saturation, color development, accurate initial color consistency, increased washout resistance, and improved hair conditioning when applying color changing procedures. For example, providing accurate initial colors that are retained by the hair for a desired period of time remains an elusive goal. In addition, color-changing compounds cause serious damage to the hair, especially with repeated dyeing procedures. In addition, various routine daily hair activities, such as brushing hair, blow drying hair, and exposure to sunlight, can cause even more damage to hair.

Additionally, similar hair damage can result from permanent waving procedures. Both coloring and permanent waving procedures also need improvement in terms of repairing damage and/or strengthening the hair during or after such reshaping procedures. Additionally, there is a need for improved treatments and methods that can be applied to skin and nails to repair damaged keratin.

There is a need for hair compositions and methods that restore and/or strengthen keratin in hair damaged by coloring and/or perm treatments using restorers.

In addition, there is a need for hair formulations and methods that can eliminate latent reduced thiol groups in hair.

Additionally, there is a need for formulations and treatments that can repair damage to keratin present in skin and hair.

Thus, the present invention provides improved formulations and methods for repairing and/or strengthening damaged hair.

Furthermore, the subject of the present invention are methods of using compositions that restore and/or strengthen the hair after and/or during coloring or permanent waving procedures.

Additionally, the subject of the present invention are compositions and methods of using such compositions to restore and/or strengthen hair after treatment with a reducing agent.

Also a subject of the present invention are compositions and methods of using said compositions that restore and/or strengthen keratin in hair, skin or nails that have been damaged by normal wear and tear or natural aging.

Brief description of the essence of the invention

Compositions, kits and methods for restoring hair damaged during dyeing or permanent waving procedures are disclosed. The formulations have similar beneficial effects when used with various chemical coloring procedures such as lightening, highlighting, tinting, semi-permanent, semi-permanent and permanent coloring. The invention also relates to improved methods for shaping hair, such as permanently waving hair and curling hair into spirals. The compositions can be used every time you wash your hair or daily, once a week, twice a week, once every two weeks, once a month, every other month or less. Preferably the formulations are used once a month to achieve the desired results.

Conventional hair curling, curling or straightening methods use hydrogen peroxide after treatment with a reducing agent. The process generally takes about three days to complete. The methods disclosed herein use active agents for hair restoration; said active agents are washed from the subject's hair on the day of application to the hair. Under the same conditions, such as temperature and humidity, hair treated with the compositions disclosed herein takes a longer time to return to its original state compared to the same hair treated with hydrogen peroxide.

The compositions disclosed in the present description contain one or more polyfunctional compounds. The polyfunctional compound contains at least one ionizable functional group capable of forming ionic bonds, and the polyfunctional compound additionally contains at least one functional group capable of forming a covalent bond with the thiol group. In some embodiments of the invention polyfunctional compounds contain at least two ionizable groups. Optionally, the composition is applied simultaneously with the procedure for dyeing or permanently waving the hair. Alternatively, the composition can be applied after a hair coloring or permanent waving procedure or on damaged hair. For example, the formulations can be applied within one week of treatment and/or damage to the hair, preferably within three days, more preferably within two days, most preferably immediately after application of the color or perm.

Detailed Description of the Invention

I. Definitions.

The term hair refers to one or more strands of hair, as well as the natural components of hair, such as fat produced in the body. In addition, hair refers to untreated hair or treated hair, such as hair that has been contacted with perm or hair straightening formulations.

Pharmaceutically acceptable and cosmetically acceptable are used interchangeably and denote those compounds, materials and/or formulations which are, within the scope of the medical diagnosis, suitable for use in contact with tissues of human beings and animals without

- 2 040937 excessive toxicity, irritation, allergic reaction or other problems or complications, commensurate with a reasonable benefit/risk ratio. More specifically, pharmaceutically acceptable means a material, compound, or formulation suitable for use in contact with the skin, scalp, or hair. Pharmaceutically acceptable materials are known to those of ordinary skill in the art.

Shampoo as used herein generally refers to a liquid or semi-solid composition applied to the hair that contains a detergent or soap for washing the hair.

Conditioner, as used herein, generally refers to a composition (eg, liquid, cream, lotion, gel, semi-solid formulation) applied to the hair to soften the hair, smooth the hair, and/or change the shine of the hair.

Analogue and derivative are used interchangeably herein and refer to a compound containing the same nucleus as the parent compound but differing from the parent compound in the order of the bonds, the absence or presence of one or more atoms and/or groups of atoms, or a combination thereof. The derivative may differ from the parent compound, for example, in one or more substituents present on the nucleus, which may include one or more atoms, functional groups, or substructures. In general, a derivative may be formed, at least theoretically, from the parent compound by chemical and/or physical means.

An electrophilic group or an electrophilic moiety is used interchangeably and refers to one or more functional groups or moieties that have an affinity for or attract electrons.

Nucleophilic group or nucleophilic fragment are used interchangeably and refer to one or more functional groups or fragments rich in electrons and capable of reacting with electrophilic groups.

The Michael acceptor in the present description is a kind of electrophilic groups or fragments that take part in nucleophilic addition reactions. The Michael acceptor may be or may contain an α,β-unsaturated carbonyl-containing group or moiety, such as a ketone. Other Michael acceptors include pi bonds such as double or triple bonds conjugated to another pi bond that contains electron withdrawing groups such as nitro groups, nitrile groups and carboxyl groups.

Carboxylic acid in the present description means the group-COOH. Unless otherwise indicated, the term carboxylic acid encompasses both the free acid and the carboxylate salt.

Alkyl as used herein means a radical of saturated or unsaturated aliphatic groups, including straight chain alkyl, alkenyl or alkynyl groups, branched alkyl, alkenyl or alkynyl groups, cycloalkyl, cycloalkenyl or cycloalkynyl (alicyclic) groups, alkyl-substituted cycloalkyl, cycloalkenyl or cycloalkynyl groups. groups, as well as alkyl, alkenyl or alkynyl groups substituted by cycloalkyl. Unless otherwise noted, straight or branched alkyl has 30 or fewer carbon atoms in the skeleton (e.g., C1-C30 for straight chain, _C3 - _C30 for branched chain), more preferably 20 or fewer carbon atoms, more preferably 12 or less carbon atoms, and most preferably 8 or less carbon atoms. In some embodiments, the chain contains 1-6 carbon atoms. In addition, preferred cycloalkyls contain from 3 to 10 carbon atoms in the ring structure and more preferably contain 5, 6 or 7 carbon atoms in the ring structure. The ranges suggested above include all values between the minimum value and the maximum value.

The term alkyl includes both unsubstituted alkyls and substituted alkyls, the latter of which denotes alkyl moieties containing one or more substituents replacing hydrogen on one or more carbon atoms of the hydrocarbon skeleton. Such substituents include, but are not limited to, halogen, hydroxyl, carbonyl (such as carboxyl, alkoxycarbonyl, formyl, or acyl), thiocarbonyl (such as a thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety.

Unless otherwise stated, lower alkyl as used herein refers to an alkyl group as defined above but having one to ten carbon atoms, more preferably one to six carbon atoms in the skeletal structure. In addition, lower alkenyl and lower alkynyl have a similar chain length. Preferred alkyl groups are lower alkyls.

Additionally, alkyl groups may contain one or more heteroatoms within the carbon skeleton. Examples include oxygen, nitrogen, sulfur, and combinations thereof. In certain embodiments of the invention, the alkyl group contains from one to four heteroatoms.

Alkenyl and alkynyl as used herein refer to unsaturated aliphatic groups containing one or more double or triple bonds of similar length (eg C ₂ -C ₃₀ ) and an optional substitution on the alkyl groups described above. Aryl as used herein refers to 5-, 6- and 7-membered aromatic rings. The ring may be a carbocyclic, heterocyclic, fused carbocyclic, fused heterocyclic, bicarbocyclic or biheterocyclic ring system, optionally substituted as described above for alkyl. In a broad sense, Ar in the present description includes 5-, 6- and 7-membered aromatic groups with one ring, which may contain from zero to four heteroatoms. Examples include, but are not limited to, benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. In addition, aryl groups containing heteroatoms in the ring structure may be referred to as heteroaryl, arylheterocycles, or heteroaromatic. The aromatic ring may be substituted at one or more ring positions with such substituents as set forth above, e.g. halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxy, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate , carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic fragments, --CF ₃ and --CN. Additionally, the term Ar includes polycyclic ring systems containing two or more cyclic rings, in which two or more carbon atoms are shared by two adjacent rings (rings are fused rings), where at least one of the rings is aromatic, for example, other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocycles, or both rings are aromatic.

Alkylaryl as used herein means an alkyl group substituted with an aryl group (eg an aromatic or heteroaromatic group).

Heterocycle or heterocyclic as used herein means a cyclic radical attached via a ring carbon or nitrogen atom of a monocyclic or bicyclic ring system containing 3 to 10 ring atoms, and preferably 5 to 6 ring atoms, which contains carbon atoms and one to four heteroatoms, each of which is selected from non-peroxide oxygen, sulfur and N(Y), where Y is absent or represents H, O, (C1_ ₄ )alkyl, phenyl or benzyl, and optionally contains one or more double or triple bonds and optionally substituted with one or more substituents. In addition, the term heterocycle includes substituted and unsubstituted heteroaryl rings. Примеры гетероциклических колец включают, но не ограничиваясь этим, бензимидазолил, бензофуранил, бензотиофуранил, бензотиофенил, бензоксазолил, бензоксазолинил, бензтиазолил, бензтриазолил, бензтетразолил, бензизоксазолил, бензизотиазолил, бензимидазолинил, карбазолил, 4aH-карбазолил, карболинил, хроманил, хроменил, циннолинил, декагидрохинолинил, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanil, imidazolidinyl, imidazolinyl, imidazolyl, N-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3Nindolyl, isatinyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1, 3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxatinil, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pipe ridonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrazolinyl, quinazolinyl, quinazolinyl, quinazolinyl quinolisinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1, 3,4thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl and xanthenyl.

Heteroaryl in the present description means a monocyclic aromatic ring containing five or six ring atoms, which contains carbon atoms and 1, 2, 3 or 4 heteroatoms, each of which is selected from non-peroxide oxygen, sulfur and N(Y), where Y is absent or is H, O, (C ₁ -C ₈ )alkyl, phenyl or benzyl. Non-limiting examples of heteroaryl groups include furyl, imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide), thienyl, pyrimidinyl (or its Noxide), indolyl, isoquinolyl (or N-oxide thereof), quinolyl (or N-oxide thereof), and the like. The term heteroaryl may include orthofused bicyclic heterocycle radicals of about eight to ten ring atoms derived from it, especially a benzo derivative or a derivative obtained by condensing a propylene, trimethylene or tetramethylene diradical with it. Examples of heteroaryl include, but are not limited to, furyl, imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl (or its N-oxide), thienyl, pyrimidinyl (or its N- oxide), indolyl, isoquinolyl (or N-oxide thereof), quinolyl (or N-oxide thereof), and the like.

Halogen in the present description means fluorine, chlorine, bromine or iodine.

- 4 040937

The term substituted in the present description means all valid substituents of the compounds described in the present description. In the broadest sense, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Illustrative examples of substituents include, but are not limited to, halogens, hydroxyl groups, or any other organic groups containing any number of carbon atoms, preferably 1-14 carbon atoms, and optionally containing one or more heteroatoms such as oxygen, sulfur, or nitrogen, grouped into unbranched, branched or cyclic structural formats. Representative substituents include alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, C ₃ -C ₂₀ cyclic, substituted C ₃ -C 2o cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide and polypeptide groups.

Heteroatoms, such as nitrogen, may contain hydrogen substituents and/or any valid substituents of the organic compounds described herein that satisfy the valency of the heteroatoms. It is to be understood that substitution or substituted includes the implicit condition that such substitution is in accordance with the allowable valency of the substituted atom and substituent, and that the substitution results in the formation of a stable compound, i.e. a compound that does not undergo spontaneous transformation such as reorganization, cyclization, elimination, and the like.

The polymer in the present description means a molecule containing more than 10 monomer fragments.

Water-soluble in the present description generally means that at least 50, 75, 100, 125, 150, 200, 225 or 250 g is dissolved in 1 liter of water at 25°C.

II. Compositions.

The compositions and methods disclosed herein are directed to the treatment of keratin in hair, skin or nails. In one embodiment of the invention, the methods are related to straightening and/or restoring hair after a coloring procedure or after or during a permanent waving procedure. Additionally, the compositions can reduce or prevent hair damage during hair coloring and/or lightening processes.

A. Compositions.

The compositions contain one or more polyfunctional compounds (also referred to herein as active agents).

The active agents may be combined with one or more pharmaceutically acceptable carriers and/or excipients which are considered safe and effective on human hair and/or human scalp and which can be applied to the subject's hair without causing undesirable biological side effects such as stinging. , itching and/or redness or similar adverse reactions. In addition, the formulations may contain an excipient that provides the formulations with a neutral pH or a pH value ranging from about pH 3 to about pH 12, preferably from pH 5 to pH 8.

The active agent is typically present in an amount ranging from about 0.01% to about 50% by weight of the composition, preferably from about 1% to about 25% by weight of the composition, more preferably from about 1% to about 15% by weight, most preferably from about 1 to about 10 wt.%. Typically, the active agent may be present in an amount ranging from about 0.5% to about 3% by weight of the formulation, or from about 1% to about 3% by weight of the formulation.

The active agent is stable in aqueous solution for a period of at least 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 months or longer at a pH of 6 to 8 and a temperature of approximately 25-30°C, preferably around 25°C. Stable as used herein with respect to shelf life means that at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the compound remains unchanged over the specified period.

a) active agents.

The active agent is a polyfunctional compound that may contain ionizable functional groups capable of forming ionic bonds and functional groups capable of forming a covalent bond with a thiol. Suitable ionizable functional groups include, but are not limited to, acidic groups such as carboxylic acids, sulfonic acids, phosphonic acids, and basic groups such as amines. Suitable functional groups capable of forming a covalent bond with a thiol include, but are not limited to

- 5 040937 notably, Michael acceptors, alkyl halides or sulfonate esters.

The active agent may have the following formula I:

(B)—Z—(A) HP η

Formula I where Z is a linker or none, each of m and n is an integer independently selected from 0-6, provided that m+n is at least 2, B is a functional group capable of forming a covalent bond with thiol, and A is an ionizable functional group. In some embodiments, the ionizable group A may be independently selected from the group consisting of -COOH, -SO3H, -PO3H2 and -N(R ¹ )2; where R ¹ is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted or substituted with one or more substituents. In some other embodiments, the ionizable group A may be an ionic group such as -N ⁺ (R1) ₃ . In some preferred embodiments of the invention, each R ¹ is independently selected from a methyl, ethyl, or isopropyl group.

Examples of active agents according to formula I may contain, as group B, thiol reactive functional groups, for example as illustrated by the following fragments:

R ^R ,.

where R is independently selected from hydrogen, C1-6 alkyl, aryl, or an ionizable functional group; Z' is oxygen (O), NH or absent; and G is carbon (C) and g is 1, or G is sulfur (S) and g is 2.

Linker Z, if present, may be or may contain an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group. One or more carbon atoms in the alkyl, alkenyl, cycloalkyl, cycloalkenyl and aryl groups can be replaced by a heteroatom to form, for example, an ether or alkylamine containing linker.

Linker Z may optionally be substituted with one or more substituents, which may be the same or different, including hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl , carboxylic acid (-COOH), -C(O)R1, -C(O)OR ¹ , carboxylate (-COO-), primary amides (for example, -CONH2), secondary amides (for example, -CONHR _n ), C (O)NR1R ² , -NR1R ² , -NR^O^R ² , -NR1C(O)R ² , -S(O^R ² , -SR ¹ And -S(O)2NR ¹ R ² , sulfinyl group (for example, -SOR1) and a sulfonyl group (for example, -SOOR1); where each of R ¹ and R ² independently can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl; and each of R ¹ and R ² is optionally and independently substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halo or alk hydroxy or aryloxy, aryl optionally substituted with one or more of halogen or alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or oxo or alkyl optionally substituted with hydroxyl, cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more of halogen or alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl.

In some preferred embodiments of the invention, the linker Z is a C _1-10 alkyl group, which may be unsubstituted or contain one or more oxo, hydroxyl, carboxyl, amido, or amino substituents. Preferably the linker Z is a C _1-4 alkyl group. The alkyl group may be straight or branched. In addition, the alkyl group may be interrupted one or more times by a heteroatom selected from oxygen, sulfur and nitrogen. An example of such dicarboxylic acids containing an intermediate heteroatom is thiodipropionic acid. In other embodiments of the invention, the alkyl groups may contain one or more double or triple bonds.

In some embodiments of the invention, the active agent of formula I has one of the following structures:

- 6 040937 or is a simple salt of these structures. In some other embodiments of the invention, the active agent may have the following formula II:

Formula II where Z is a linker or none, each of m and n is an integer independently selected from 0-6, provided that m+n is at least 2, B is a functional group capable of forming a covalent bond with a nucleophile such as, but not limited to, a thiol or amine group, A is an ionizable functional group as defined above, and C contains an ionic group and a functional group that is also capable of forming a covalent bond with a nucleophile, such as but not limited to this, a thiol or amine group whose charge is opposite to that of the ionizable group A. The C group is ionically bonded (indicated by a dotted line) to the A group. In an ionic group, C o is an integer value independently selected from 0-6, such that the sum of the charges of the group C and the ionizable group A is zero. In some embodiments, the ionizable group A may be independently selected from the group consisting of -COOH, -SO3H, PO ₃ H ₂ and -N(R ¹ )2; where R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl groups; wherein each R ¹ is independently unsubstituted or substituted with one or more substituents. In some other embodiments, the ionizable group A may be an ionic group such as -N ⁺ (R ¹ )3. In some preferred embodiments of the invention, each R ¹ is independently selected from a methyl, ethyl, or isopropyl group.

Examples of active agents according to formula I may contain, as group B, thiol reactive functional groups, for example as illustrated by the following fragments:

where R is independently selected from hydrogen, C _1-6 alkyl, aryl, or an ionizable functional group; Z' is oxygen (O), NH or absent; and G is carbon (C) and g is 1, or G is sulfur (S) and g is 2.

Linker Z, if present, may be or may contain an alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group. One or more carbon atoms in the alkyl, alkenyl, cycloalkyl, cycloalkenyl and aryl groups may be replaced by a heteroatom, to form, for example, an ether or alkylamine containing linker.

Linker Z may optionally be substituted with one or more substituents, which may be the same or different, including hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl , carboxylic acid (-COOH), -C(O)R1, -C(O)OR ¹ , carboxylate (-COO-), primary amides (eg -CONH2), secondary amides (eg -CONHR ¹ ), - C(O)NR1R ² , -NR ¹ R ² , -NR1S(O)2R ² , -NR1C(O)R ² , -S(O)2R ² , -SR ¹ And -S(O)2NR1R ² , sulfinyl a group (eg -SOR1) and a sulfonyl group (eg -SOOR ¹ ); where each of R ¹ and R ² independently may represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroaryl; wherein each of R ¹ and R ² is optionally and independently substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halo or alkoxy or aryloxy, aryl optionally substituted with one or more of halogen or alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or oxo or alkyl optionally substituted with hydroxyl, cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more of halogen or alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl.

- 7 040937

In some preferred embodiments of the invention, the linker Z is a C ₁ - ₁₀ alkyl group, which may be unsubstituted or contain one or more substituents oxo, hydroxyl, carboxyl, amido or amino. Preferably the linker Z is a C _1-4 alkyl group. The alkyl group may be straight or branched. In addition, the alkyl group may be interrupted one or more times by a heteroatom selected from oxygen, sulfur and nitrogen. An example of such dicarboxylic acids containing an intermediate heteroatom is thiodipropionic acid. In other embodiments of the invention, the alkyl groups may contain one or more double or triple bonds.

Group C is an ionic group ionically bonded to an ionizable group A and contains at least one reactive thiol selected from Michael acceptor, succinimidyl-containing group, maleimide-containing group, azlactone, benzoxazinone derivative, vinyl sulfone, vinyl sulfoximine, vinyl sulfonate, vinyl phosphonate, benzoxazinone, isocyanate, epoxide, electrophilic leaving group, electrophilic thiol acceptor, acrylic or acrylate group, methacrylic or methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, fumarate group, itaconate group, vinyl ether group, allyl ether group , an allyl ester group, a vinyl ester group, a sulfonate group, a phosphonate group, a sulfoxide group, a sulfonamide group, a sulfinimide group, a sulfinamide group, a sulfonimide group, or a sulfonimide group.

In some embodiments of the invention, the active agent of formula II has one of the following structures:

b) Excipients.

The formulations typically contain one or more cosmetically acceptable excipients. Cosmetically acceptable excipients include, but are not limited to, preservatives, antioxidants, chelating agents, sunscreens, vitamins, dyes, hair coloring agents, proteins, amino acids, natural extracts such as plant extracts, humectants, fragrances, fragrances, liquid oils. , emollients, lubricating agents, solid oils, penetrants, thickeners, viscosity modifiers, polymers, resins, hair fixers, film formers, surfactants, detergents, emulsifiers, opacifiers, volatiles, propellants, liquid bases, carriers, salts , pH adjusting agents (eg, citric acid), neutralizing agents, buffers, hair conditioning agents, antistatic agents, anti-frizz agents, anti-dandruff agents, absorbents, and combinations thereof.

The compositions usually contain at least two cosmetically acceptable excipients. In some forms, the formulations contain an active agent, water, and optionally a preservative and/or flavor.

The hair treatment composition may be in any suitable physical form. Suitable forms include, but are not limited to, low to moderate viscosity liquids, lotions, milks, mousses, sprays, gels, creams, shampoos, conditioners, and the like. Suitable excipients, such as those listed above, are included in or omitted from the hair care formulation, depending on the form of the formulation (eg hair spray, cream, conditioner or shampoo).

The pharmaceutical excipient is typically present in an amount ranging from about 10% to about 99.99% by weight of the formulation, preferably from about 40% to about 99% by weight, more preferably from about 80% to about 99% by weight.

i) Surfactants.

Surfactants are surfactants capable of reducing the surface tension of water and allowing the hair formulation to penetrate through or onto the skin or hair. In addition, surfactants include detergents and soaps. Surfactants can be amphoteric, anionic or cationic. Suitable surfactants that can be used in the formulation include, but are not limited to, 3-aminopropane sulfonic acid, almond amide _, almond amidopropyl betaine, almond amidopropylamine oxide, aluminum hydrogenated tallow glutamate, aluminum lanolate, aminoethyl sulfate, aminopropyl laurylglutamine, C _12-15 ammonium alkyl sulfate, ammonium C ₁₂ - ₁₅ pareth sulfate, ammonium C _12-16 alkyl sulfate, ammonium C _9-10 perfluoroalkylsulfonate, ammonium caprylet sulfate, ammonium caprylet-3 sulfate, ammonium monoglyceride sulfate, ammonium sulfate, ammonium isothianate, ammonium cocoyl sarcosinate diammonium polyammonium cumene cumene , ammonium dodecyl

- 8 040937 benzenesulfonate, ammonium isostearate, ammonium laureth sulfate, ammonium laureth-12 sulfate, ammonium laureth-5 sulfate, ammonium laureth-6 carboxylate, ammonium laureth-7 sulfate, ammonium laureth-8 carboxylate, ammonium laureth-9 sulfate, ammonium cosine sulfate аммония лаурилсульфат, аммония лаурилсульфосукцинат, аммония миретсульфат, аммония миристилсульфат, аммония ноноксинол-30 сульфат, аммония ноноксинол-4 сульфат, аммония олеат, аммония пальмоядерный сульфат, аммония полиакрилат, аммония стеарат, аммония таллат, аммония ксиленсульфонат, аммония ксиленсульфонат, ampизостеароил желатин/кератин аминокислота/лизин гидроксипропилтримониум хлорид, amp-изостеароил гидролизованный коллаген, ПЭГ-6 эфиры масла абрикосовых косточек, абрикосовый амид, абрикосовый амидопропилбетаин, арахидет-20, авокадамид, авокадамидопропилбетаин, бабассуамид, бабассуамидопропилбетаин, бабассуамидопропиламина оксид, бегеналкония хлорид, бегенамид, бегенамид, бегенамидопропилбетаин, behenamine oxide, sodium l aureth sulfate, sodium lauryl sulfate, polyoxyether lauryl alcohol or ceteareth-20, or combinations thereof.

Suitable anionic surfactants include, but are not limited to, those containing carboxylate, sulfonate and sulfate ions. Examples of anionic surfactants include sodium, potassium, ammonium salts of long chain alkyl sulfonates and alkylaryl sulfonates such as sodium dodecylbenzenesulfonate; dialkyl sodium sulfosuccinates such as sodium dodecylbenzenesulfonate; dialkyl sodium sulfosuccinates such as sodium bis(2-ethylthioxyl)sulfosuccinate; and alkyl sulfates such as sodium lauryl sulfate. Cationic surfactants include, but are not limited to, quaternary ammonium compounds such as benzalkonium chloride, benzalkonium chloride, cetrimonium bromide, stearyldimethylbenzylammonium chloride, polyoxyethylene, and coconut amine. Examples of non-ionic surfactants include ethylene glycol monostearate, propylene glycol myristate, glyceryl monostearate, glyceryl stearate, polyglyceryl-4-oleate, sorbitan acylation, sucrose acylation, PEG-150 laurate, PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbates, polyoxyethylene octylphenyl ether, PEG-1000 cetyl ether, polyoxyethylene tridecyl ether, polypropylene glycol butyl ether, Poloxamer® 401, stearoyl monoisopropanolamide, and polyoxyethylene hydrogenated tallow amide. Examples of amphoteric surfactants include sodium N-dodecyl-β-alanine, sodium N-lauryl-v-iminodipropionate, myristoamphoacetate, lauryl betaine, and lauryl sulphobetaine.

More than one surfactant may be included in the formulation.

Surfactants are optionally included in the composition in an amount ranging from about 0.1 to about 15 wt.% in the composition, preferably from about 1 to about 10 wt.% in the composition.

ii) Softening agents.

Emollient means a material that protects against moisture or irritation, softens, soothes, coats, lubricates, moisturizes, protects and/or disinfects the skin. Suitable emollients for use in formulations include, but are not limited to, a silicone compound (e.g. dimethicone, cyclomethicone, dimethicone copolyol or a mixture of cyclopentasiloxane and a dimethicone/vinyl dimethicone cross-linked polymer, cyclopentasiloxane polysilicon), polyols such as sorbitol, glycerol, propylene glycol , ethylene glycol, polyethylene glycol, caprylyl glycol, polypropylene glycol, 1,3-butanediol, hexylene glycol, isoprene glycol, xylitol; ethylhexyl palmitate; a triglyceride such as caprylic/capric triglyceride; and a fatty acid ester such as cetearyl isononanoate or cetyl palmitate. In a particular embodiment, the emollient is dimethicone, amidodimethicone, dimethiconol, cyclopentasiloxane, PEG-7 potassium dimethicone panthenyl phosphate, or combinations thereof. The composition may include more than one emollient agent.

The softening agent is optionally included in the composition in an amount ranging from about 0.5 to about 15 wt.% of the composition, preferably from about 1 to about 10 wt.% of the composition.

iii) Emulsifiers.

Additionally, the composition may contain one or more emulsifiers. Suitable emulsifiers include, but are not limited to, unsaturated ester-styrene sulfonate monomer copolymers, cetearyl alcohol, glyceryl ether, polyoxyethylene glycol cetearyl alcohol ether, stearic acid, polysorbate-20, ceteareth-20, lecithin, glycol stearate, polysorbate-60, polysorbate- 80 or combinations thereof. More than one emulsifier may be included in the formulation.

The emulsifier is optionally included in the composition in an amount ranging from about 0.05 to 15 wt.% in the composition, preferably from about 0.1 to 10 wt.% in the composition.

iv) Preservatives.

The composition may include one or more preservatives.

Suitable preservatives include, but are not limited to, glycerol-containing compounds (e.g., glycerol or ethylhexylglycerol or phenoxyethanol), benzyl alcohol, parabens (methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, etc.), sodium benzoate, ethylenediaminetetraacetic acid (EDTA) , potassium sorbate and/or grapefruit seed extract, or a combination thereof

- 9 040937 More than one preservative may be included in the formulation. Other preservatives known in the cosmetic industry include salicylic acid, DMDM hydantoin, formaldehyde, chlorphenism, triclosan, imidazolidinyl urea, diazolidinyl urea, sorbic acid, methylisothiazolinone, sodium dehydroacetate, dehydroacetic acid, quaternium-15, stearalkonium chloride, zinc pyrithione, sodium meta-bisulfite, 2-bromo-2-nitropropane, chlorhexidine bigluconate, polyaminopropyl biguanide, benzalkonium chloride, sodium sulfite, sodium salicylate, citric acid, neem oil, essential oils (various), lactic acid and vitamin E (tocopherol).

The preservative is optionally included in the composition in an amount ranging from about 0.1 to about 5 wt.% in the composition, preferably from about 0.3 to about 3 wt.% in the composition. Preferably, the compositions do not contain parabens.

v) Conditioning agents.

The composition may include one or more conditioning agents. Suitable conditioning agents include, but are not limited to, silicone-based agents (e.g., quaternium-8 silicone), panthenol, wheat and/or soy protein hydrolyzate, amino acids (e.g., wheat amino acids), rice bran wax, meadowfoam seed oil, mango seed oil, grape seed oil, jojoba seed oil, sweet almond oil, hydroxyethyl behenamidopropyldimonium chloride, aloe leaf extract, aloe vera leaf juice, phytantriol, panthenol, retinyl palmitate, behentrimonium methosulfate, cyclopentasiloxane, quaternium-91, stearamidopropyl dimethylamine, and combinations thereof.

Conditioning(s) agent(s) optionally included in the composition in an amount ranging from about 0.1 to about 5 wt.% in the composition, preferably from about 0.3 to about 3 wt.% in the composition.

vi) Thinners.

The diluent in the present description means the substance(s) with which the active agent is diluted. Water is the preferred diluent. The composition usually contains more than 1 wt.% water, preferably more than 5 wt.% water, more preferably more than 50 wt.% water, and most preferably more than 80 wt.% water. Alcohols, such as ethyl alcohol and isopropyl alcohol, can be used at low concentrations (about 0.5 wt.% in the composition) to enhance penetration into the hair and/or reduce odor.

vii) Viscosity modification agents.

The compositions may contain one or more viscosity modifying agents, such as viscosity increasing agents. Classes of such agents include, but are not limited to, viscous liquids such as polyethylene glycol, semi-synthetic polymers such as semi-synthetic cellulose derivatives, synthetic polymers such as carbomers, poloxamers and polyethyleneimines (e.g. PEI-10), natural polymers such as gum , tragacanth, alginates (e.g. sodium alginate), carrageenan, vegetable gums such as xanthan gum, liquid paraffin, waxes, bulk colloids such as bentonite, colloidal silicon dioxide and microcrystalline cellulose, surface active agents such as PPG-2 hydroxyethyl coco/isostearamide, emulsifiers such as disteareth-75 IPDI, and salts such as sodium chloride, and combinations thereof.

viii) Antioxidants.

The composition may contain one or more antioxidants. Examples include, but are not limited to, tocopherols, butylated hydroxytoluene (BHT), ascorbic acid, Camellia sinensis leaf extract, ascorbyl palmitate, magnesium ascorbyl phosphate, carotenoids, resveratrol, triethylcitrate, arbutin, kojic acid, tetrahexidecilascorbate, superoxide dismutase, zinc, sodium metabisulfite, lycopene , ubiquinone and combinations thereof.

ix) Opacifiers.

The composition may contain one or more opacifiers. Opacifiers are added to formulations to make them opaque. Suitable opacifying agents include, but are not limited to, distearate glycol and ethoxylated fatty alcohols.

c) Composition forms.

i) Sprays.

The composition may be in the form of a spray. Sprays typically contain an active agent and a cosmetically acceptable carrier. In some embodiments of the invention, the carrier is water or a mixture of water and alcohol. The spray formulation optionally contains an antioxidant, sunscreen, vitamin, protein, peptide, plant extract, moisturizer, oil, emollient, lubricant, thickener, hair conditioning agent, polymer, and/or surfactant. Preferably the spray formulation contains a preservative. In some embodiments of the invention, the composition contains a flavoring agent. In some embodiments of the invention, the composition contains a surfactant. In some embodiments of the invention, the composition contains water, flavor, preservative and active agent. In some embodiments of the invention, the composition contains water, flavor, preservative and active agent. In some embodiments of the invention, the composition contains water, a preservative, a flavor, an active agent, and an antistatic agent. In some embodiments of the invention, the composition contains water, preservative, flavor,

- 10 040937 active agent and hair conditioning agent. In some embodiments of the invention, the composition contains water, preservative, flavor, active agent and surfactant.

Hair spray formulations can be dispensed from containers which are equipped with aerosol or spray dispensers. Such dispensers are known in the art and commercially available from various manufacturers.

propellant.

If the hairspray composition is sprayed from a sealed aerosol can, a propellant may be used to push the composition out of the can. Suitable propellants include, but are not limited to, a liquefiable gas or a halogenated propellant. Examples of suitable propellants include dimethyl ether and hydrocarbon propellants such as propane, nbutane, isobutane, CFCs (chlorofluorocarbons), and CFC replacement propellants. The propellants can be used singly or in a mixture.

The amount of propellant may vary from about 10% to about 60% by weight of the composition. The propellant may be separated from the hair restorative composition, for example in a two-compartment container. Other suitable aerosol dispensers are characterized by the use of compressed air as the propellant, with which the dispenser can be filled before use, by means of a pump or equivalent device. In addition, conventional non-aerosol dispensers in the form of a spray, i.e. spray guns can be used to apply the composition to the hair.

ii) Air conditioners.

The composition may be in the form of a conditioner. The conditioner usually contains the active agent in a suitable carrier. Additionally, the conditioner may contain cationic polymers derived from polysaccharides, for example, cationic cellulose derivatives, cationic starch derivatives, cationic guar gum derivatives and cationic locust bean gum derivatives, synthetic cationic polymers, mixtures or combinations of these agents. The composition may contain other synthetic or natural polymers or polymers derived from biological processes, which are functionalized, if appropriate, for example, cationic or neutral groups. Such polymers may have a stabilizing or reinforcing effect on the composition and/or conditioning effect (deposition on the surface of the skin or hair).

The active agent may be formulated at any suitable concentration. Typical concentrations of the active agent in the conditioner range from small amounts, such as about 0.01 wt.%, preferably at least 0.1 wt.%, to large amounts, such as up to 50 wt.%. Preferably, the conditioner contains the active agent at a concentration ranging from 0.1 to 5% by weight, more preferably from 0.1 to 3% by weight. Although higher concentrations of the active agent could be present in the conditioner, they are generally not necessary to achieve the desired results.

iii) Shampoos.

The hair restoration composition may be in the form of a shampoo. The shampoo usually contains the active agent in a suitable carrier. The active agent may be formulated at any suitable concentration. Typical concentrations of the active agent in a shampoo range from small amounts, such as about 0.01 wt.%, preferably at least 0.1 wt.%, to large amounts, such as up to 50 wt.%. Preferably the shampoo contains the active agent at a concentration ranging from 0.1 to 5% by weight, more preferably from 0.1 to 3% by weight. Although higher concentrations of the active agent could be present in the shampoo, in general they are not necessary in order to achieve the desired results.

Additionally, the shampoo may contain from about 0.5% to about 20% by weight of a surfactant. Surfactants used in shampoo compositions are known in the art and are disclosed in, for example, US Pat. No. 6,706,258 to Gallagher et al. and US Pat. No. 7,598,213 to Geary et al.

iv) Creams, lotions, gels and polishes.

The composition for restoring hair, skin or nails may be in the form of a cream, lotion, gel or polish. The cream, lotion, gel, or polish composition usually contains the active agent in a suitable carrier. The active agent may be formulated at any suitable concentration. Typical concentrations of the active agent in a cream, lotion, gel or polish composition range from small amounts, such as about 0.01 wt.%, preferably at least 0.1 wt.%, to large amounts, such as up to 50 wt.% . Preferably the cream or lotion contains the active agent at a concentration ranging from 0.1 to 5% by weight, more preferably from 0.1 to 3% by weight. Although higher concentrations of the active agent could be present in a cream or lotion, they are generally not necessary in order to achieve the desired results.

Additionally, the composition, depending on the application, may contain an oil, a hair conditioning agent and/or a thickener. The cream, lotion, gel, or polish may further contain a fragrance, plant extract, and/or surfactant. Cream, lotion, gel, or polish may be packaged in a tube, tube, bottle, or other suitable

- 11 040937 container.

v) Liquid formulations of the active agent.

In some embodiments, the invention provides a liquid composition of the active agent, which at the time of use is mixed with a second composition, such as a composition for coloring or highlighting. In such embodiments, the active agent liquid formulation may contain any suitable concentration of the active agent in a suitable carrier, usually a diluent, such as described above. The concentration of the active agent is appropriate to give the mixture a suitable final volume and provide a final concentration of the active agent.

For example, the active agent liquid formulation may contain an active agent concentration ranging from about 5% to about 50% by weight or more. In a preferred embodiment of the invention, the active agent liquid formulation contains about 20% by weight of the active agent.

For highlighting purposes, a sufficient volume of the active agent liquid formulation is mixed with a sufficient volume of the highlighting formulation prior to use to obtain a highlighting mixture containing the desired concentration of the active agent. Typical concentrations of active agent in the highlighting mixture range from small amounts, such as at least about 0.01 wt.%, preferably at least 0.1 wt.%, to large amounts, such as up to 50 wt.%. Preferably the highlighting mixture contains the active agent at a concentration ranging from 0.1 to 5% by weight, more preferably from 0.1 to 3% by weight. Although higher concentrations of active agent could be present in the highlighting mixture, they are generally not necessary in order to achieve the desired results.

III. Application methods.

A. Treatment of hair with coloring agents.

a) Applying a coloring composition to the hair.

The coloring composition is generally applied to the hair of an individual in accordance with conventional hair coloring procedures that are known to those skilled in the art. Typically, a hair coloring treatment involves two complementary processes: application of a bleaching agent to lighten the natural hair pigment and/or other artificial pigments that are present in the hair, and diffusion of the dye precursors into the hair, followed by coupling reactions that result in the formation of within hair shaft chromophores that are too large to diffuse out of the hair. The lightening composition typically contains a lightening agent to lighten the hair and generate free thiol groups. The hair coloring composition may be a highlighting composition, for example, formed by mixing bleach powder and a developer. More complex colors may include multiple precursors and multiple coupling agents involving multiple reactions.

Dye precursors may contain multiple ingredients, each with a different function. The first ingredient is usually an alkalizing agent (usually ammonia and/or an ammonia substitute such as monoethanolamine [MEA]). The alkalizing agent performs a number of functions in the hair coloring process, including swelling of the hair fibers to aid in the diffusion of dye precursors. Dye percursors generally include p-diamines and p-aminophenols. Precursors are oxidized to active intermediates after they enter the hair shaft. The intermediates then react with the color components to form wash-resistant dyes. More specifically, the intermediates, in the presence of an oxidizing agent, combine with another dye intermediate molecule having oxidizing properties to form a large condensed ring colored compound within the hair shaft. The precursor intermediate must penetrate the hair shaft before the coupling reaction because the fused ring product is too large to penetrate the hair shaft. Color components modify the color formed during the oxidation of precursor compounds. The main difference between partially permanent and permanent products is the alkalizing agent and peroxide concentration. In the case of partially permanent colorants, the cuticle does not swell as much, making the penetration of the colorant less effective compared to permanent color products.

Some color formulations use a reducing agent, such as sodium bisulfate, to break disulfide bonds in the hair, allowing hair dyes to penetrate deeper into the hair. Specifically, the method includes reducing some of the disulfide bonds formed by cystine in the hair shafts to thiol groups to break the hydrogen bonds. The restoration process modifies the chemical and cosmetic characteristics of the hair, which is undesirable.

The hair coloring process may be followed by a shampoo and conditioner treatment, a neutralizing rinse, or an acid-balanced shampoo containing, in addition to cationic or amphoteric surfactants, cationic emollients and quaternary polymers. Alternatively, the hair coloring process may be followed by application of the active agent formulations described herein prior to shampooing.

- 12 040937 and/or air conditioning.

b) Applying the active agent formulation to the hair.

The active agent formulation can be applied simultaneously with the hair coloring formulation or after the hair coloring formulation is applied. For example, an active agent formulation can be mixed with a hair coloring agent, and a mixture containing both the active agent and the hair coloring agent can be applied to the hair.

Alternatively, after dyeing the hair, the active agent formulation or formulation is applied to the hair. Although the active agent is usually applied on the same day as the staining procedure, it can be applied later, for example, within 1-2 weeks after treatment with the reducing agent. Generally, a sufficient amount of the active agent formulation (or a mixture of the active agent formulation and the hair coloring formulation) is applied to saturate the hair. The active agent may be applied to the hair once, or the application of the active agent may be repeated one or more times. Generally, enough of the active agent formulation is applied each time to saturate the hair. The volume of the active agent formulation for each application to the hair may be from about 1 to about 100 ml per individual, depending on the length and volume of their hair. In some embodiments, application of the active agent may be repeated immediately (eg, within 10-15 seconds) or approximately 1, 5, 7.5, 10, 12.5, 15, 17.5, or 20 minutes after the first application.

The active agent can be rinsed from the hair and shampooed immediately after application, for example within 10, 15, 25, 30, 45 or 60 seconds or 2, 3, 4 or 5 minutes after application. Alternatively, the active agent may be washed from the hair within about 30 minutes after application, preferably from about 5 to about 20 minutes, more preferably about 10 minutes after application of the active agent to the hair, depending on the type of hair.

When the active agent formulation is combined with a hair coloring agent and applied to the hair as a mixture, the mixture remains on the hair for as long as necessary for the hair coloring procedure. Typically, the mixture is applied for approximately 10 minutes. The mixture is removed from the hair in accordance with standard hair color procedures, such as rinsing and shampooing, approximately 10 minutes after application of the mixture.

The composition of the active agent is washed off from the hair after its application. After the final application of the active agent, the hair can be rinsed and washed immediately thereafter (eg, within 1015 seconds after application). Preferably, the hair is rinsed and/or washed about 10 minutes or more after the final application of the active agent, for example about 15 to about 30 minutes, optionally about 20 minutes after the active agent is reapplied to the hair.

In general, the active agents are washed from the hair of the individual on the day they are applied. Conversely, traditional permanent treatments using only hydrogen peroxide (and no active agent) generally do not rinse off for at least 48 hours after application (washing hair earlier than 48 hours after traditional permanent treatments can result in significantly reduce the number of curls on the hair and / or cause damage to the hair).

The composition described herein improves the quality of the hair, such as appearance (eg, shine) and feel, and reduces hair breakage during processing, such as coloring or permanent waving.

In some embodiments, hair breakage is reduced by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% or more after treatment with the active agent compared to untreated hair from the same individual. Hair breakage is a significant problem encountered during dyeing and other treatments.

B. Chemical treatment of hair with a restorer.

In one embodiment of the invention, prior to treatment with the active agent, the hair is treated with a conditioner used for curling (also referred to herein as perm or perm) and/or coiling the hair.

a) Applying a reducing agent to the hair.

The first step in curling or coiling hair is to break the disulfide bonds formed by cysteine in order to generate free thiol moieties. The process of destruction of disulfide bonds formed by cysteine is carried out by applying a reducing agent. The restorer application process includes the following conventional perm or hair straightening procedures as are known to those skilled in the art. For example, when perming hair, the hair is first washed and wound into permanent curlers of various sizes. Next, a repair agent, such as a thioglycolate repair solution or lotion, is applied to the hair. The hair is allowed to take shape for a specified period of time, and then the thioglycolate solution is washed from the hair.

The application of hydrogen peroxide is optional in this method. In some methods, for example, when treating previously chemically treated hair, hydrogen peroxide is generally not used. In other methods, such as perming intact hair, peroxide may be added.

- 13 040937 hydrogen.

In such embodiments, hydrogen peroxide is typically added after the reductant has been washed off. The hydrogen peroxide is then rinsed from the hair before the active agent is added.

b) Application of the active agent.

After treatment with a reducing agent, one or more active agents or formulations thereof are applied to the hair. Although the agent is usually applied on the day of treatment with the reducing agent, it can be applied later, for example within 1-2 weeks after treatment with the reducing agent.

Generally, a sufficient amount of the active agent formulation is applied to saturate the hair. In general, the agent is rinsed from the hair and shampooed after the desired level of hair curl or curl has been achieved. In some embodiments of the invention, the active agent is washed from the hair immediately (eg, within 10, 15, 25, 30, 45, or 60 seconds after application) after the final application of the active agent. Alternatively, the hair may be rinsed and washed within about 30 minutes after application, preferably from about 5 to about 20 minutes, more preferably about 10 minutes after the final application of the active agent to the hair, depending on the type of hair. The active agent can be washed out of the hair within 10, 15, 25, 30, 45, 60 seconds after application to the hair and still achieve the desired level of hair curl or curl.

The active agent may be applied to the hair once, or the application of the agent may be repeated one or more times. Generally, enough of the active agent formulation is applied each time to saturate the hair. In some embodiments, the volume of the active agent formulation for each application to the hair may be from about 1 to about 10 ml per unit of perm curler. In some embodiments, application of the active agent may be repeated immediately (eg, within 10-15 seconds) or approximately 1, 5, 7.5, 10, 12.5, 15, 17.5, or 20 minutes after the first application. In some embodiments of the invention, the second application is carried out with an interval of from about 7 to about 10 minutes after the first application.

The active agent is washed off from the hair after it has been applied. The hair can be rinsed and washed immediately (eg, within 10-15 seconds after application) at the final application of the active agent. Alternatively, the hair may be rinsed and washed about 10 minutes or more after the final application of the active agent, eg, about 15 to about 30 minutes, preferably about 20 minutes, after the active agent has been reapplied to the hair.

In general, the active agents are washed from the hair of the individual on the day they are applied. Conversely, traditional permanent treatments using only hydrogen peroxide (and no active agent) generally do not rinse off for at least 48 hours after application (washing hair earlier than 48 hours after traditional permanent treatments can result in significantly reduce the number of curls on the hair and / or cause damage to the hair).

The compositions described herein can be applied to the hair to improve the quality of the hair, such as appearance (eg, shine) and feel, as well as to reduce hair breakage in a subsequent hair treatment, such as coloring.

In some embodiments, hair breakage is reduced by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% or more after application of the active agent compared to untreated hair of the same individual. Hair breakage is a significant problem encountered during dyeing and other treatments.

C. Treatment of the skin or nails with the active agent.

In one embodiment of the invention, a composition containing one or more active agents is applied to the skin or nails. Application of the active agent formulation to the skin or nails can help repair disulfide bonds damaged by normal wear and tear or natural aging.

In some embodiments, the active agent formulation is in the form of a cream or lotion suitable for application to the skin or nails. In other embodiments, the active agent formulation is in the form of a gel or polish suitable for application to nails. Typically, a sufficient amount of the active agent formulation is applied to treat damaged keratin in the skin or nails. The active agent formulation may be applied to the skin or nails once, or the application of the formulation may be repeated one or more times, as needed, to achieve the desired effect of repairing keratin damage and/or strengthening the skin or nails.

IV. Kit.

Hair treatment kits available. In one embodiment, the kit typically contains a first hair color composition. Hair coloring compositions typically contain a reducing agent capable of reducing disulfide bonds in the hair in order to generate free thiol groups. In addition, the kit contains a second composition containing an effective amount of the active agent.

The kit may additionally contain a bottle of developer, gloves, shampoo, conditioner and/or deodorant. In addition, instructions for use are usually provided.

- 14 040937 set.

Typically, the kit contains more than one container (or more than one compartment in the supplied container) to ensure that the clarifying agent (eg, peroxide) or coloring agent is stored separately from the active agent.

a) The first composition.

The first composition in the kit may be a coloring agent. The first formulation may be formulated as two or more components which may be mixed prior to application to the hair. For example, the first composition may be in the form of two components such as a dye precursor and an oxidizing agent. Typically, the hair coloring composition contains a reducing agent capable of reducing disulfide bonds in the hair to generate reduced free thiol groups. Suitable reducing agents include, but are not limited to, thioglycolic acid, thiolactic acid, dihydrolipoate, thioglycerol, mercaptopropionic acid, sodium bisulfite, ammonium bisulfide, zinc formaldehyde sulfoxylate, sodium formaldehyde sulfoxylate, sodium metabisulfite, potassium borohydride, pegylated thiols, and hydroquinone. The first formulation contains sufficient reducing agent to break sufficient disulfide bonds to efficiently diffuse the coloring ingredients into the hair, as will be appreciated by one of skill in the art.

The ingredients of the first composition may differ depending on the type of hair coloring procedure desired (eg, semi-permanent, semi-permanent or permanent hair coloring), hair texture, client skin sensitivity, and the like. Hair coloring formulations for various hair coloring procedures, hair textures and hair sensitivities are known to those skilled in the art.

b) The composition of the active agent.

The second composition contains one or more active agents in an effective amount. Suitable formulations containing active agents have been discussed above. The second composition may take any suitable form. Suitable forms include, but are not limited to, low to moderate viscosity liquids, lotions, milks, mousses, sprays, gels, creams, shampoos, conditioners, and the like. The second composition will be supplied in a suitable container, which depends on the form of the composition.

In one embodiment, the active agent formulation is provided as two or more separate ingredients. For example, the active agent may be supplied in the form of a dry powder in a sealed package, and the excipient may be supplied in a vial or other container. A suitable container may be provided for mixing the active agent and excipient.

In some embodiments, the active agent formulation (or second formulation) is mixed with the first formulation (or hair colorant) and the mixture is applied to the hair.

c) Other materials in the kit.

The kit optionally contains shampoos and conditioners. Suitable shampoos and conditioners include, but are not limited to, LiQWd® Hydrating Shampoo and LiQWd® Hydrating Conditioner.

In addition, the kit may contain an odor remover. The odor remover may be incorporated into the first or second formulation, or a mixture thereof. Alternatively, the deodorant is supplied in a suitable container for use before or after rinsing the second composition from the hair. Some suitable odor removers are known to those of ordinary skill in the art.

It is to be understood that the disclosed method and formulations are not limited to the methodology, protocols, and reagents specifically described as they may vary. Furthermore, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention and is not intended to limit the scope of the present invention, which will be limited only by the appended claims.

Examples

Example 1 Color retention and texture of dyed hair treated with an active agent formulation.

General description.

Three hair samples were obtained from a human subject and cut into strands 1/2 inch wide.

Composition for coloring. The permanent hair color formulation was sourced from L'Oreal® Permanent Hair Color Service (L'Oreal® Majirel #10 Permanent Color with 20% Peroxide).

The composition of the active agent. Used maleic acid with a concentration of 200 mg in 10 g of the total solution (water).

Ways.

The hair samples were washed with clarifying shampoo and dried with a towel. The samples were then dyed with L'Oreal® Permanent Hair Color Service, which was left on the hair samples for approximately 35-40 minutes.

The first treated sample (control) of the hair treated with the coloring procedure was subsequently rinsed and washed five times with Liqwd® Hydrating Shampoo and Conditioner before photographing.

The composition of the active agent was applied to the second and third samples of the treated hair with a spray bottle and rubbed with the fingers. The active agent formulation was left on the second hair sample for about 1 minute and on the third sample for about 10 minutes. The hair samples were then rinsed and then washed five times with Liqwd® Hydrating Shampoo and Conditioner before photographing.

Results.

The hair samples treated with the active agent formulation showed better dye retention, more shine and less frizz than the controls. Hair samples treated with the active agent formulation were smoother to the touch, coupled with less frizz and added sheen, giving a healthier overall appearance than controls.

Example 2 Comparison of dye retention in conventionally permed hair and permed hair using active agent formulations.

Way.

A strand of a 1/2 inch wide hair sample from a human subject was washed with clarifying shampoo and towel dried. Ammonium thioglycolate or dithiothreitol was mechanically forced several times through the hair with a wide and thin fine-toothed comb, after which it was left on the hair for a period of 10 minutes to 1 hour. Then the hair was rinsed with water for 30 seconds to 1 minute, after which it was dried with a towel.

Next, the active agent formulation described in Example 1 (maleic acid in water) was applied with a needle-nose applicator, saturating the hair, and left for 7.5 minutes. This step was repeated with a total duration of 15 min. The hair was then rinsed for 1-2 minutes, shampooed, and further conditioned with various brands of salon shampoo and conditioner, including LiQWd® Hydrating Shampoo and Conditioner.

The second hair sample was straightened as described above, but hydrogen peroxide was used instead of the active agent formulation. The hair samples were repeatedly washed and conditioned.

Hair color comparison.

After hair samples were washed five times with both LiQWd® Hydrating Shampoo and LiQWd® Hydrating Conditioner, the samples were examined for color retention.

Results.

The hair sample treated with the active agent formulation showed a color closer in intensity to the hair sample before the first wash compared to the hair treated with hydrogen peroxide.

Example 3 Comparison of hair treated with a highlight formulation applied simultaneously with an active agent formulation with hair treated with the highlight formulation alone.

The composition of the active agent in example 1 contained maleic acid in concentrations of 2.0 g in 10 g of the total solution (water).

Two strands of human hair were tested. The sample was taken from one head, 1 inch wide, and divided in half. The color was a moderate brown and the sample had been pre-dyed with an unknown professional hair dye.

Strand 1, 1/2 inch wide and 8 inches long, was lightened with conventional lightening ingredients mixed with an active agent formulation. 1 oz of Joico Verocolor Veroxide Volume 20 Developer was mixed with 1 oz of Joico Verolight Lightening Powder to form a highlight formulation. Next, 9 ml of the active agent formulation was added to the highlighting formulation to obtain a mixture.

The mixture was applied to hair strand 1 with a brush applicator while the hair lay on aluminum foil. Next, the foil was wrapped around the strand and the process was allowed to proceed for 35 minutes. The strand was rinsed and washed once with shampoo.

Strand 2, control, 1/2 inch wide and 8 inches long, was lightened with conventional lightening ingredients in the absence of an active agent formulation. 1 oz of Joico Verocolor Veroxide Volume 20 Developer was mixed with 1 oz of Joico Verolight Illuminator Powder to create a creamy Illuminator.

The brightening composition was applied to the hair strand 2 with a brush applicator as the hair lay on the aluminum foil. Next, the foil was wrapped around the strand and the process was allowed to proceed for 35 minutes. The strand was rinsed and washed once with shampoo.

Results.

There was an obvious difference in hair quality between strand 1 and strand 2. Hair strand 1

- 16 040937 was softer, less frizzy, hydrated, with more shine than control 2.

Both strands were washed and conditioned 5 more times, seeing the same clear benefits of strand 1 (treated with a mixture of brightening composition and composition of the active agent) compared to the control strand 2 (treated with only brightening composition).

Example 4 Comparison of hair treated with a lightening formulation applied simultaneously with an active agent formulation and hair treated with the lightening formulation alone.

General description.

Two hair samples were obtained from a human subject and cut into 1/2 inch wide strands.

Ways.

(1) 0.5 oz of bleach powder (Clairol Professional, basic white) and 0.5 oz of conditioning developer in cream form (Redken, frosty blonde) were combined to make a bleach blend. 3.5 g of 2-(methacryloyloxy)ethane-1-aminium (Z)-3-carboxylate (12 wt% in water) was added to the clarifying mixture and thoroughly mixed with a brush.

(2) The finished bleaching mixture was applied to the hair strands with a brush to completely cover the hair shafts. The hair covered with the mixture was wrapped in aluminum paper and left at room conditions for 2 hours.

(3) After a two-hour bleaching period, the hair strands were washed with shampoo, after which the hair was allowed to air dry.

Results.

There was an obvious difference in hair quality between strand 1 and strand 2. Hair strand 1 showed no visible breakage, was more pleasant to the touch and looked healthy, while the control (treated with bleach only) showed some breakage, was rough to the touch, shabby and looked unhealthy.

Example 5 Comparison of hair treated with a lightening formulation applied simultaneously with an active agent formulation and hair treated with the lightening formulation alone.

General description.

Two hair samples were obtained from a human subject and cut into 1/2 inch wide strands.

Ways.

(1) 0.5 oz of bleach powder (Clairol Professional, basic white) and 0.5 oz of conditioning developer in cream form (Redken, frosty blonde) were combined to make a bleach blend. 3.5 g of prop-2-en-1-aminium (Z)-3-carboxyacrylate (10 wt.% in water) was added to the clarifying mixture and thoroughly mixed with a brush.

(2) The finished bleaching mixture was applied to the hair strands with a brush to completely cover the hair shafts. The hair covered with the mixture was wrapped in aluminum paper and left at room conditions for 2 hours.

(3) After a two-hour bleaching period, the hair strands were washed with shampoo, after which the hair was allowed to air dry.

Results.

There was an obvious difference in hair quality between strand 1 and strand 2. Hair strand 1 showed no visible breakage, was more pleasant to the touch and looked healthy, while the control (treated with bleach only) showed some breakage, was rough to the touch, shabby and looked unhealthy.

Example 6 Comparison of traditional perm versus perm using maleic acid.

General description.

Hair samples were obtained from a human subject and cut into strands 1/2 inch wide.

Restorers. Ammonium thioglycolate (ATG) was obtained from a permanent waving kit manufactured by Zotos. In addition, 300 mg of dithiothreitol in 10 g of solution was used as a reducing agent.

The composition of the active agent. Used maleic acid at a concentration of 200 mg in 10 g of the total solution (water).

Ways.

A method for perming hair using an active agent.

The hair was washed with a clarifying shampoo, dried with a towel, and then wound on curlers for permanent waving. Then, ammonium thioglycolate or dithiothreitol was applied to the hair and left on the hair for a period of 10 minutes to 1 hour. After that, the hair was rinsed for 30 seconds to 1 minute, and then dried to dryness with a towel.

The active agent formulation was applied to the hair with a needle-nose applicator, impregnating the hair. The active agent formulation was left on the hair for approximately 7.5 minutes. The hair was then sprayed a second time with the active agent formulation and left for another 7.5 minutes, for a total of 15 minutes. After that, the hair was rinsed with water for about 1-2 minutes and removed from the curlers for permanent fixation.

Claims (25)

vines. After the hair was removed from the perm curlers, the hair was washed with shampoo and conditioned with various brands of salon shampoo and conditioner, including LiQWd® Hydrating Shampoo and Conditioner. The washing and drying steps were repeated 40 times. The second part of the hair was permed as described above, except that hydrogen peroxide was used in place of the active agent formulation. Results. Both perms (active agent formulation or hydrogen peroxide) showed only a slight reduction in total curls after 40 washes and dries with the same shampoo and conditioner. However, the appearance and texture of the curls obtained with the active agent formulation showed more luster and less frizz compared to the hydrogen peroxide perm. Example 7 Comparison of hair breakage resulting from repeated application of a traditional perm and active agent formulation. Ways. Two hair samples were obtained. Both samples were treated with dithiothreitol or ammonium thioglycolate as described in Example 4. One of the hair samples was further treated with the active agent formulation (maleic acid in water) while the other was neutralized with hydrogen peroxide. The process was completed on the same day for the hair treated with the active agent formulation. The process was completed in three days in the case of hydrogen peroxide (traditional perm). The procedure was repeated three times for each hair sample over a period of 48 hours. Results. On visual inspection, the second hair sample treated with the active agent formulation showed little or no signs of breakage. However, the first hair sample treated with hydrogen peroxide showed significant brittleness. Example 8 Comparison of the degree of damage to hair pre-straightened with a Japanese straightener. Ways. Two hair samples were obtained, the first of which was previously straightened with a Japanese straightener (Yuko) and the second was previously straightened with a non-alkaline straightener (African Pride Miracle Deep Conditioning). The samples were processed as described in examples 4 and 5 using the formulation of the active agent (maleic acid in water). Another hair sample was obtained, which was previously straightened with a non-alkaline straightener (African Pride Miracle Deep Conditioning). The sample was treated with a traditional chemical hair straightener (Zotos). Results. Hair samples treated with the active agent formulation showed no visible damage. However, the conventionally treated sample showed significant brittleness, even during application. CLAIM 1. A method for reducing or preventing hair damage during a lightening process, comprising: (a) mixing the clarifying agent powder and the developer to form a first composition; (b) mixing a second formulation containing an active agent with a first formulation to form a mixture, wherein the active agent is maleic acid; and (c) applying the mixture to the hair; moreover, the active agent is in the mixture at a concentration in the range from 0.1 to 5 wt.%; and wherein the active agent reduces or prevents hair damage caused by the hair lightening treatment. 2. The method of claim 1 wherein the second formulation further comprises one or more cosmetically acceptable excipients selected from the group consisting of water, surfactants, vitamins, natural extracts, preservatives, chelating agents, antioxidants, proteins, amino acids, moisturizers agents, fragrances, emollients, penetrants, thickeners, viscosity modifiers, hair fixers, film formers, emulsifiers, opacifiers, propellants, liquid bases, carriers, salts, pH adjusting agents, neutralizing agents, buffers, hair conditioning agents, antistatic agents, anti-frizz agents, anti-dandruff agents, and combinations thereof. 3. The method according to any one of claims 1, 2, in which the active agent is present in the second composition in an amount varying from 1 to 25 wt.%. 4. The method according to any one of claims 1, 2, in which the active agent is present in the second composition in an amount varying from 1 to 15 wt.%. - 18 040937 5. The method according to any one of claims 1, 2, in which the active agent is present in the second composition in an amount varying from 1 to 3 wt.%. 6. The method according to any one of claims 1, 2, in which the active agent is present in the second composition in an amount varying from 1 to 10 wt.%. 7. The method according to any one of claims 1, 2, in which the active agent is present in the second composition in an amount varying from 0.5 to 3 wt.%. 8. The method according to any one of claims 1 to 7, wherein the active agent is present in an amount ranging from 0.1 to 3% by weight of the mixture. 9. The method according to any one of claims 1 to 8, wherein the second composition is in the form of a liquid, gel, cream or lotion. 10. The method according to any one of claims 1 to 9, wherein step (c) is repeated one or more times. 11. The method according to any one of claims 1-10, further comprising: (d) rinsing and shampooing the hair, step (d) being performed after steps (a), (b) and (c). 12. The method according to any one of claims 1 to 11, wherein the first composition and the second composition are mixed to form a mixture during use, prior to application. 13. The method according to any one of paragraphs. 1-12, in which the second composition has a pH of 3-8. 14. The use of a maleic acid active agent to reduce or prevent damage to the hair during the lightening process, wherein the active agent is applied simultaneously with the lightening composition formed by mixing the powder of the lightening agent and the developer, and the active agent reduces or prevents damage to the hair caused by the lightening treatment hair, and the active agent is present in an amount ranging from 0.1 to 5 wt.% from the mass of the mixture of the clarifying composition with the active agent. 15. Use according to claim 14, wherein the hair is human hair. 16. Use according to any one of claims 14 or 15, wherein the active agent is present in an active agent formulation that is mixed with the lightening composition prior to application to the hair. 17. Application according to any one of paragraphs. 14-16, in which the active agent is present in an amount ranging from 0.1 to 3 wt.% from the mass of the mixture of the clarifying composition with the active agent. 18. Use according to claim 16, wherein the active agent is present in an active agent formulation, wherein the active agent formulation further comprises one or more cosmetically acceptable excipients selected from the group consisting of water, surfactants, vitamins, natural extracts, preservatives, chelating agents, antioxidants, proteins, amino acids, wetting agents, fragrances, emollients, penetrants, thickeners, viscosity modifiers, hair fixers, film formers, emulsifiers, opacifiers, propellants, liquid bases, carriers, salts, pH adjusting agents , neutralizing agents, buffers, hair conditioning agents, antistatic agents, anti-frizz agents, anti-dandruff agents, and combinations thereof. 19. Use according to claim 16, wherein the active agent is present in an amount ranging from 1 to 25% by weight of the active agent formulation. 20. Use according to claim 16, wherein the active agent is present in an amount ranging from 1 to 15% by weight of the active agent formulation. 21. Use according to claim 16, wherein the active agent is present in an amount ranging from 1 to 10% by weight of the active agent formulation. 22. The use according to claim 16, wherein the active agent is present in an amount ranging from 1 to 3% by weight based on the weight of the active agent formulation. 23. Use according to claim 16 wherein the active agent formulation is in the form of a liquid, gel, cream or lotion. 24. Use according to any one of claims 16 or 18-23, wherein the active agent formulation has a pH of 3-8. 25. Use according to any one of claims 16-24, wherein the composition of the active agent is an aqueous composition. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2