Use of cysteine precursor compound
The carboxymethyl cysteine compound in hair care compositions addresses age-related hair quality issues by enhancing melanin production and cellular metabolic activity, effectively reducing grey hair and improving hair thickness and elasticity.
Patent Information
- Application Number
- PCT/EP2024/088281
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-22
- Filing Date
- 2024-12-21
- Publication Date
- 2025-06-26
AI Technical Summary
As people age, hair undergoes undesirable changes such as greying, loss of elasticity, thinning, and fragility, with chemical hair dyes exacerbating these issues while failing to effectively address age-related hair quality changes.
The use of a carboxymethyl cysteine compound in hair care compositions to increase melanin production in melanocytes, reduce grey or white hair occurrence, and improve hair characteristics by enhancing cellular metabolic activity and melanin production beyond natural levels.
The carboxymethyl cysteine compound effectively reduces age-related hair pigmentation changes and improves hair quality by increasing melanin production, cellular metabolic activity, and reducing oxidative stress, thereby addressing the challenges of greying and hair thinning.
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Abstract
Description
[0001] USE OF CYSTEINE PRECURSOR COMPOUND
[0002] Field of the Invention
[0003] The present invention relates to a new use of a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound.
[0004] Background of the Invention
[0005] As a person ages, the appearance of hair can become less desirable. Hair greying and canities is a common sign of aging. Hair also loses its elasticity, becomes thinner and more fragile. Further, hair follicle diameter and hair number can also decrease giving a sparse appearance to the scalp.
[0006] To many consumers, maintaining colouring of hair and good thickness, volume and hair count is a way to alleviate the signs of aging. Many people choose to colour their hair to disguise age-related greying or whitening of the hair. However, colouring of hair does not help disguise other age-related changes in hair quality. Instead, conversely, chemical hair dyes are known to lead to increased damage of the hair over time.
[0007] There is still a long felt need to provide consumers with compositions that provide an effective reduction in age-related functional changes in hair pigmentation. It is also required to provide a composition which is also able to reduce or prevent other detrimental changes in hair associated with aging.
[0008] Surprisingly, it has been found that a cysteine precursor compound, a carboxymethyl cysteine compound is effective at reducing age-related functional changes in hair pigmentation, while also providing a beneficial improvement in further hair characteristics associated with aging. For example, carboxymethyl cysteine compounds have been surprisingly shown to increase the cellular metabolic activity and melanin production of melanocytes. Beneficially, the carboxymethyl cysteine compounds can increase the melanin production of melanocytes above natural pigmentation levels.
[0009] Summary of the Invention
[0010] In a first aspect, the present invention is directed to use of a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in hair e.g. grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, for increasing cellular metabolic activity. Preferably, the invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0011] In a second aspect, the present invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for use in the treatment for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity. Preferably, the present invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for use in a treatment for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the present invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for use in the treatment for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the present invention is directed to a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for use in the treatment for increasing the cellular metabolic activity of cells in a hair follicle, preferably for increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0012] In a third aspect, the present invention is directed to use of a hair care composition for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle and / or for increasing cellular metabolic activity. Preferably, the present invention is directed to use of a hair care composition for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the present invention is directed to a hair care composition for use in the treatment for increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0013] In a fourth aspect, the present invention is directed to a method for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age- related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, comprising application of a haircare composition comprising a cysteine precursor compound to the hair or scalp. Preferably, the method is for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the method is for increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes. The method comprising application to the hair or scalp of a cosmetic composition comprising a carboxymethyl cysteine compound.
[0014] In a fifth aspect, the present invention is directed to use of a carboxymethyl cysteine compound in a method for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle on the scalp, the method comprising application to the hair or scalp of a cosmetic composition comprising the carboxymethyl cysteine compound. Preferably, the present invention is directed to use of carboxymethyl cysteine compound in a method for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the method is for increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0015] In a sixth aspect, the present invention is directed to use of a carboxymethyl cysteine compound in the manufacture of medicants for increasing melanin production, reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle and / or for increasing cellular metabolic activity. Preferably, the present invention is directed to use of a carboxymethyl cysteine compound in the manufacture of medicants for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the present invention is directed to use of a carboxymethyl cysteine compound in the manufacture of medicants increasing cellular metabolic activity of melanocytes, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes. All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow.
[0016] Detailed Description of the Invention
[0017] A “cysteine precursor compound” can be understood according to the invention to be a compound which increases in vivo cysteine concentrations. For example, a cysteine precursor may be a compound that increases the availability of cysteine to cells, such a compound that provides delivery of cysteine to cells to increase the intracellular production of glutathione.
[0018] Surprisingly, it has been found that by including materials in a hair care composition that can be converted into cysteine in vivo, detrimental changes in hair associated with aging can be reduced or prevented as discussed above.
[0019] Without wishing to be bound by theory, it is thought that including materials in a hair care composition that can be converted into cysteine in vivo may increase the intracellular production of glutathione.
[0020] Glutathione (GSH) is a tripeptide that consists of glutamate, cysteine, and glycine. It is present in all mammalian tissues. It is the main antioxidant in the living body: it protects cells from oxidation by quenching reactive oxygen species. GSH and cysteine are also associated with melanogenesis pathways involved in formation of pigmented hair, particularly blonde and / or red hair. Biosynthesis of GSH occurs in the cell in a tightly regulated manner. The quantity of glutathione in cells depends to a large degree on the availability of cysteine in the cells. Therefore, it is thought that agents the provide delivery of cysteine materials to cells can increase the intracellular production of glutathione.
[0021] Cysteine, a composite amino acid of GSH, may increase cellular levels of GSH, but exposed sulfhydryl group of cysteine renders it unstable and reactive and also causes strong unpleasant odor. Therefore, it is preferable to administer a carboxymethyl cysteine compound which can be administered safely and converted to cysteine within the cell, the cysteine then being available for intracellular GSH production.
[0022] In some embodiments, the carboxymethyl cysteine compound is present in amount of 0.0001% to 5% of the total weight of the composition, more preferably at least 0.001 %, even more preferably at least 0.01 %, still even more preferably at least 0.1 %, and most preferably at least 0.4% by weight of the composition. Preferably, the carboxymethyl cysteine compound is present in amount of no greaterthan 3%, even more preferably no greater than 2%, still even more preferably no greater than 1.5%, and most preferably no greater than 1 % by weight of the composition.
[0023] The carboxymethyl cysteine compound refers to compounds selected from carboxymethyl cysteine, salt of carboxymethyl cysteine, ester of carboxymethyl cysteine, amide of carboxymethyl cysteine or a mixture thereof. Preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, ester of carboxymethyl cysteine, and / or salt of carboxymethyl cysteine. More preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, and / or salt of carboxymethyl cysteine. Even more preferably, carboxymethyl cysteine compound comprises salt of carboxymethyl cysteine. Still even more preferably the carboxymethyl cysteine compound comprises lysine carboxymethyl cysteinate and most preferably, the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate.
[0024] Preferably, the carboxymethyl cysteine compound is present in amount of from 0.0001 % to 5% of the total weight of the composition, more preferably at least 0.001 %, even more preferably at least 0.01%, still even more preferably at least 0.1%, and most preferably at least 0.4% by weight of the composition. Preferably, the carboxymethyl cysteine compound is present in amount of no greater than 3%, even more preferably no greater than 2%, still even more preferably no greater than 1.5%, and most preferably no greater than 1 % by weight of the composition.
[0025] Preferably, the lysine carboxymethyl cysteinate is present in amount of from 0.0001% to 5% of the total weight of the composition, more preferably at least 0.001%, even more preferably at least 0.01%, still even more preferably at least 0.1%, and most preferably at least 0.4% by weight of the composition. Preferably, the lysine carboxymethyl cysteinate is present in amount of no greater than 3%, even more preferably no greater than 2%, still even more preferably no greater than 1.5%, and most preferably no greater than 1% by weight of the composition.
[0026] Preferably the use is non-therapeutic. Preferably the method is non-therapeutic. The term non- therapeutic typically means for cosmetic purposes and not curative or therapeutic purposes.
[0027] The hair care composition of the present invention typically provides a greater benefit for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle. Preferably the benefit is selected from increasing melanin production and increasing cellular metabolic activity in melanocytes.
[0028] Preferably, the benefit is for increasing melanin production in melanocytes in a hair follicle. Preferably, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes. Preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the benefit is increasing metabolic activity in melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0029] Preferably, the carboxymethyl cysteine compound is used as an agent for increasing melanin production in melanocytes such as increasing melanin production and / or increasing cellular metabolic activity in melanocytes.
[0030] Preferably, the present invention provides use of a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age- related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity .
[0031] Preferably the invention provides use of a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound. Preferably, the present invention provides use of a carboxymethyl cysteine compound or a haircare composition comprising carboxymethyl cysteine compound for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. Preferably, the present invention provides use of a carboxymethyl cysteine compound or a haircare composition comprising carboxymethyl cysteine compound for increasing cellular metabolic activity in melanocytes, preferably for increasing cellular metabolic activity in melanocytes in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes. Most preferably, the carboxymethyl cysteine compound is lysine caboxymethyl cysteinate.
[0032] More preferably, the present invention provides use of lysine caboxymethyl cysteinate or a hair care composition comprising for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle. More preferably, the present invention provides use of lysine caboxymethyl cysteinate ora haircare composition for increasing melanin production in melaoncytes, preferably for increasing melanin production in a hair follicle, for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, for increasing melanin production of melanocytes beyond natural pigmentation levels for increasing cellular metabolic activity of cells in a hair follicle, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle.
[0033] Preferably, the present invention is directed to use of a hair care composition for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity. Preferably, the present invention provides use of a hair care composition for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle, preferably for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, preferably for increasing melanin production of melanocytes beyond natural pigmentation levels, preferably for increasing cellular metabolic activity of cells in a hair follicle, preferably for increasing the cellular metabolic activity of melanocytes in a hair follicle, preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes, wherein the haircare composition comprises a carboxymethyl cysteine compound as an agent for increasing melanin production in melanocytes and / or for increasing cellular metabolic activity of melanocytes.
[0034] Preferably, the present invention provides use of a hair care composition for increasing melanin production in melanocytes, preferably for increasing melanin production in a hair follicle, wherein the hair care composition comprises a carboxymethyl cysteine compound as an agent for increasing melanin production. Most preferably, the carboxymethyl cysteine compound is lysine caboxymethyl cysteinate. Preferably, the present invention provides use of a haircare composition for increasing cellular metabolic activity of melanocytes, preferably for increasing cellular metabolic activity of melanocytes in a hair follicle, wherein the hair care composition comprises a carboxymethyl cysteine compound as an agent for increasing cellular metabolic activity of melanocytes. Most preferably, the carboxymethyl cysteine compound is lysine caboxymethyl cysteinate.
[0035] Preferably, the present invention is directed to a method for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age- related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity comprising application of a hair care composition comprising a carboxymethyl cysteine compound to the hair or scalp. Most preferably the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate. Preferably, the invention is direct to a method for increasing melanin production in melanocytes, preferably for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, preferably for increasing melanin production of melanocytes beyond natural pigmentation levels, preferably for increasing cellular metabolic activity in cells or combinations thereof, preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes. Preferably, the invention is directed to a method of increasing melanin production in melanocytes comprising application of a hair care composition comprising a carboxymethyl cysteine compound.
[0036] Preferably, the present invention is directed to use of a carboxymethyl cysteine compound in a method for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity, the method comprising application to the hair or scalp of a cosmetic composition comprising the carboxymethyl cysteine compound. Preferably, the invention is directed to use of a carboxymethyl cysteine compound in a method for increasing melanin production in melanocytes or increasing cellular metabolic activity in melanocytes or combinations thereof. Preferably, the invention is directed to use of a carboxymethyl cysteine compound for increasing melanin production in melanocytes. Preferably for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, preferably for increasing melanin production of melanocytes beyond natural pigmentation levels, Preferably, the invention is directed to use of a carboxymethyl cysteine compound for increasing cellular metabolic activity in melanocytes. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes Most preferably the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate. Preferably, the present invention provides use of a carboxymethyl cysteine compound in the manufacture of medicants for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity. Preferably, the invention is directed to use of a carboxymethyl cysteine compound in a method for increasing melanin production in melanocytes or increasing cellular metabolic activity in melanocytes or combinations thereof. Preferably, the invention provides use of a carboxymethyl cysteine compound in the manufacture of medicants for increasing melanin production in a hair follicle. Preferably for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, the invention provides use of a carboxymethyl cysteine compound in the manufacture of medicants for increasing cellular metabolic activity in a hair follicle. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes. Most preferably the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate.
[0037] Preferably, the lysine carboxymethyl cysteinate is used as an agent for increasing melanin production in melanocytes, for reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity in the hair care composition. Preferably for increasing the melanin production level of melanocytes above the level in unstressed melanocytes, preferably for increasing melanin production of melanocytes beyond natural pigmentation levels. Preferably, for increasing the cellular metabolic activity level of melanocytes above the level in unstressed melanocytes.
[0038] The haircare composition comprising lysine carboxymethyl cysteinate typically provides a greater benefit compound for increasing melanin production in melanocytes, reducing the occurrence of grey or white hairs of an individual, for reducing age-related functional changes in hair pigmentation, for increasing melanin production in grey hair, for increasing cell proliferation, for increasing melanocyte proliferation, for increasing melanosome transfer, for increasing the level and / or activity of tyrosinase, for increasing gene and / or protein expression in pigmentation pathways associated with hair, for reducing oxidative stress of the scalp and / or a hair follicle, and / or for increasing cellular metabolic activity in comparison to a hair care composition that does not contain lysine carboxymethyl cysteinate.
[0039] Preferably, carboxymethyl cysteine compounds and compositions of the invention increase melanin production in melanocytes in the skin and / or hair. Preferably, the cysteine precursor compounds and compositions of the invention increase melanin production in a hair follicle.
[0040] Preferably, a hair care composition according to the invention further comprises a glutamate source selected from the group consisting of glutamine, glutamine ester, glutamic acid, pyroglutamic acid, salts, and mixtures thereof. More preferably, the composition comprises pyroglutamic acid and / or salt of pyroglutamic acid. Even more preferably, the composition comprises sodium salt of pyroglutamic acid. Preferably, the glutamate source is present in amount of 0.0001 to 10% by weight of the composition, more preferably 0.001 to 6%, even more preferably 0.01 to 3% by weight of the composition.
[0041] Preferably, the composition comprises polyhydric alcohol. Polyhydric alcohols may be selected from group of glycerin, propylyene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1 ,3-butylene glycol, isoprene glycol, ethoxylated glycerol, propoxylated glycerol, pentylene glycol or a mixture thereof. Most preferred polyhydric alcohol is glycerol known also as glycerin or pentylene glycol. The amount of polyhydric alcohol may range anywhere from 0.1 to 20%, preferably 0.5 to 15% and more preferably 2 and 10% by weight of the composition.
[0042] Compositions for use in the invention (as described above) may include additional actives for improving the physical and / or aesthetic characteristics of the scalp and / or the hair. Examples include amino acids, vitamins, minerals and / or antioxidants, emollients, humectants, sunscreens, anti-irritants, exfoliating agents, botanical extracts (such as pomegranate, white birch, green tea, chamomile and licorice extracts) and mixtures thereof, preservatives (such as sodium benzoate, potassium sorbate, phenoxyethanol, pentylene glycol and sodium metabisulfite), pH adjusters and fragrances (such as essential oils, flower oils, natural extracts from resins, gums, balsams, beans, mosses and other plants, as well as synthetic aromatic materials).
[0043] In some embodiments, preferably the composition of the invention further comprises a thickening agent. Suitable thickening agents are selected from polyacrylic acids, cross-linked polymers of acrylic acid, copolymers of acrylic acid with a hydrophobic monomer, copolymers of carboxylic acidcontaining monomers and acrylic esters, cross-linked copolymers of acrylic acid and acrylate esters, heteropolysaccharide gums and crystalline long chain acyl derivatives. The long chain acyl derivative is desirably selected from ethylene glycol stearate, alkanolamides of fatty acids having from 16 to 22 carbon atoms and mixtures thereof. Ethylene glycol distearate and polyethylene glycol 3 distearate are preferred long chain acyl derivatives, since these impart pearlescence to the composition. Polyacrylic acid is available commercially as Carbopol 420, Carbopol 488 or Carbopol 493. Polymers of acrylic acid cross-linked with a polyfunctional agent may also be used; they are available commercially as Carbopol 910, Carbopol 934, Carbopol 941 and Carbopol 980. An example of a suitable copolymer of a carboxylic acid containing monomer and acrylic acid esters is Carbopol 1342. All Carbopol (trademark) materials are available from Goodrich. Suitable crosslinked polymers of acrylic acid and acrylate esters are Pemulen TR1 or Pemulen TR2. A suitable heteropolysaccharide gum is xanthan gum, for example that available as Kelzan mu.
[0044] “Penetration enhancers” can be understood according to the invention as compounds which can penetrate the hair follicle and / or scalp to reversible decrease barrier resistance and increase the bioavailability of actives to the site of action in the hair follicle and / or scalp e.g. to increase the bioavailability of actives to the hair bulb.
[0045] In some embodiments, the penetration enhancer is selected from glycols such as polyethylene glycol; phospholipids for example in the form of one or more liposomes, non-ionic emulsifiers such as polysorbate, laurocapram, isohexadecane, dodecane, DMSO, ethanol, decanol, dimethyl isosorbide and / or combinations thereof.
[0046] In some embodiments, the penetration enhancer is present in amount of from 0.01 % to 20% of the total weight of the composition, more preferably at least 0.1%, even more preferably at least 1%, still even more preferably at least 2%, and most preferably at least 6% by weight of the composition. Preferably, the penetration enhancer is present in amount of no greater than 15%, even more preferably no greater than 10%, still even more preferably no greater than 8%, and most preferably no greater than 3% by weight of the composition.
[0047] In some embodiments the penetration enhancer is selected from ethanol, dimethyl isosorbide or combinations thereof. Preferably, the penetration enhancer is a combination of dimethyl isosorbide and ethanol.
[0048] In some preferred embodiments the penetration enhancer is dimethyl isosorbide. In one embodiment, dimethyl isosorbide is included in an amount of from 0.01 to 10% of the total weight of the composition, or in the alternative of from to 0.1 to 5% of the total weight of the composition, or from 1 to 3% of the total weight of the composition such as 2.5% of the total weight of the composition.
[0049] In some embodiments the penetration enhancer is ethanol.
[0050] Preferably, the ethanol is present in amount of from 0.01 % to 20% of the total weight of the composition, more preferably at least 0.1%, even more preferably at least 1%, still even more preferably at least 2%, and most preferably at least 3% by weight of the composition. Preferably, the ethanol is present in amount of no greater than 15%, even more preferably no greater than 10%, still even more preferably no greater than 8%, and most preferably no greater than 7% by weight of the composition.
[0051] The hair care compositions of the invention are primarily intended for application to the hair and / or scalp of a human subject in order to improve hair properties.
[0052] Preferably, the hair care composition is selected from a rinse-off hair composition, a hair mask, a leave-on hair care composition, and a pre-treatment hair care composition, and most preferably selected from a rinse-off hair composition, a hair mask and a leave-on composition. The treatment composition is preferably a leave-on haircare composition. The hair care compositions of the invention may also be a "rinse-off " compositions to be applied to the hair and then, in part, rinsed away.
[0053] Rinse off composition for use in the invention are typically left on wet hair for 1 to 2 minutes before being rinsed off. Typically, from about 1g to about 50g of the composition is applied to the hair or scalp.
[0054] Hair masks for use in the present invention are treatments that are typically left on the hair for 3 to 10 minutes, preferably from 3 to 5 minutes, more preferably 4 to 5 minutes, before being rinsed off.
[0055] Leave-on compositions for use in the invention are typically applied to the hair and left on the hair for more than 10 minutes, and preferably are applied to the hair after washing and not rinsed out until the next wash. The haircare compositions of the invention will generally comprise from about 20% to about 95% of water, preferably at least 30%, more preferably at least 40%, still more preferably at least 50%, even more preferably at least 60% or even at least 70%, but typically not more than 94%, preferably not more than 93%, more preferably not more than 92%, still more preferably not more than 91%, even more preferably not more than 90% or even not more than 80% by weight based on total weight. Other organic solvents may also be present, such as lower alkyl alcohols and polyhydric alcohols. Examples of lower alkyl alcohols include C1 to C6 monohydric alcohols such as ethanol and isopropanol. Examples of polyhydric alcohols include propylene glycol, hexylene glycol, glycerin, and propanediol. Mixtures of any of the above-described organic solvents may also be used.
[0056] The features disclosed in the foregoing description, or in the following claims, as appropriate, may separately, or in any combination of such features, be utilised for realising the invention.
[0057] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.
[0058] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations. Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.
[0059] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
[0060] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about’ one particular value, and / or to “about’ another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about’ in relation to a numerical value is optional and means for example + / - 10%.
[0061] The invention will now be further described by reference to the following Examples. All percentages are by weight based on total weight, unless otherwise specified.
[0062] Examples
[0063] Example 1 : Hair Care Lotion
[0064] A vessel was filled with deionized water. Separately, carbomer and Lysine Carboxymethyl Cysteinate powder was dispersed and then added to the vessel ensuring proper hydration is achieved. The vessel was heated to 60°C then preservatives including pentylene glycol was added until solubilized. The vessel was cooled to room temperature. Once at 35°C or below the remaining ingredients where added and mixed. The pH of the solution was then adjusted to 4.5-5.0 using sodium hydroxide and / or citric acid solution as needed.
[0065] Table 1
[0066] Example 2: Melanin Content Assay
[0067] Adult primary human epidermal melanocytes were cultured in melanocyte culture medium supplemented with melanocyte growth supplements and maintained at 37°C in a humified chamber with 5% CO2 atmosphere. Cells were sub-cultured in microtiter plates at a density of 35,000 cells / well. Upon reaching 70% confluence (TO), cells were treated with various concentrations of lysine carboxymethyl cysteinate for 48 hours (T48). Untreated and 1 pM menadione only treated cells were also cultured in parallel under the same conditions. Melanin content was assayed atT48 in cell supernatants.
[0068] AtT48, cell supernatant was harvested and assayed for melanin content. Melanin was assessed using a fluorescence-based melanin assay. A Fluorometric Melanin Assay Kit was used. The kit uses a substate that generates a fluorescent product upon reaction with melanin. Its fluorescence intensity is proportional to the amount of melanin in a sample.
[0069] Table 2
[0070] Example 3: Cellular Metabolic Activity Study
[0071] Adult primary human epidermal melanocytes were cultured in melanocyte culture medium supplemented with melanocyte growth supplements and maintained at 37°C in a humified chamber with 5% CO2 atmosphere. Cells were sub-cultured in microtiter plates at a density of 35,000 cellsA / vell . Upon reaching 70% confluence (TO), cells were treated with with various concentrations of lysine carboxymethyl cysteinate for 48 hours (T48). Untreated and 1 pM menadione only treated cells were also cultured in parallel under the same conditions. Metabolic activity was assayed at TO and T48.
[0072] The alamarBlue™ Cell Viability Reagent was used to quantify cell viability including cell cytotoxicity and cell proliferation. The alamarBlue™ dye is a redox indicator that yields a colorimetric change and fluorescent signal in response to metabolic activity where damaged and / or non-viable cells have a lower innate metabolic activity and generate a proportionally lower signal. To quantify metabolic activity, 700pl media+10% alamarBlue reagent was added directly to cells in each well and incubated at 37°C in a humidified chamber with 5% CO2 atmosphere for 1 hour, protected from light. Detection of alamarBlue™ signal was detected by excitation at 544nm and emission at 590nm using the Tecan Spark® plate reader.
[0073] Table 3
[0074] An increase in fluorescence indicates an increase in metabolic activity of the cells.
[0075] The data presented shows that the cysteine precursors according to the invention increase the melanin production of cells and improve cells cellular metabolic activity. The results indicate that compositions of the invention comprising cysteine precursors can increase the melanin production in hairs, reducing age-related functional changes in hair pigmentation.
[0076] Example 4 - Dichlorofluorescein Diacetate (DCFDA) Assay
[0077] Adult primary human epidermal melanocytes were cultured in melanocyte medium supplemented with melanocyte growth factor mix and antibiotic mix in T75 flasks maintained at 37°C in a humidified chamber with 5% CO2. Cells were further sub-cultured in microtiter plates at a density of ~5x104cells / well and incubated at 37°C in a humidified chamber with 5% CO2 as above for 24 hours. After 24hours, cells were treated with test materials or combinations of test materials at desired concentrations along with 5pM menadione and further incubated as above for 6hrs. Post incubation, cells were assessed for ROS levels by incubating the cells for 45 mins in DCFDA dye. The cells were then washed, and the fluorescence was measured at Excitation: 485nm and emission 535nm. The experiment was run in duplicate (n=2) on 3 different donor cells (n=3). The data was represented as % ROS levels compared to menadione. Test Material Concentrations in Cell medium:
[0078] Lysine Carboxymethyl Cysteinate (LCC) - 0.16%
[0079] Statistical analysis
[0080] For every test, data was shown as a percent difference from a menadione treated control using an average of two replicates across three distinct experiments. T-test statistical significance was performed for comparisons against menadione control vs respective treatment.
[0081] Table 4
[0082] Menadione induces oxidative stress in melanocytes by generating reactive oxygen species (ROS). The antioxidant effect of the test materials on melanocyte cells stressed with menadione was assessed by comparing the level of ROS of treated and untreated stressed cells. LCC was able to reduce the level of ROS compared to the level of ROS in menadione stressed cells. This indicates that the inclusion of LCC in a formulation improves the antioxidant activity of the melanocytes.
[0083] Example 5 - Catalase Activity Assay
[0084] Adult primary human epidermal melanocytes were cultured in melanocyte medium supplemented with melanocyte growth factor mix and antibiotic mix in T75 flasks maintained at 37°C in a humidified chamber with 5% CO2. Cells were further sub-cultured in microtiter plates at a density of -5x104 cellsA / vell and incubated at 37°C in a humidified chamber with 5% CCLas above for 24 hours. After 24 hours, cells were then treated with test materials or combinations of test materials at desired concentrations along with 5pM menadione and further incubated as above for 6hrs. Post incubation cells were assessed for catalase activity using the Catalase Colorimetric Activity Kit. The experiment was run in duplicate (n=2) on 3 different donor cells (n=3). The data was represented as % Catalase activity compared to menadione. Test Material Concentrations in Cell medium:
[0085] Lysine Carboxymethyl Cysteinate (LCC) - 0.16% Statistical analysis
[0086] For every test, data was shown as a percent difference from a menadione treated control using an average of two replicates across three distinct experiments. T-test statistical significance was performed for comparisons against a menadione control vs respective treatment. Table 5
[0087] Menadione induces oxidative stress in melanocytes by generating reactive oxygen species (ROS). The antioxidant effect of the test materials on melanocyte cells stressed with menadione was assessed by comparing the catalase activity of treated and untreated stressed cells. An enhancement in catalase activity indicates an increased ability for cells to reduce oxidative stress.
[0088] The catalase activity of cells treated with LCC showed a statistically significant increase in catalase activity compared to untreated stressed cells.
Claims
Claims1 . Use of a carboxymethyl cysteine compound or a hair care composition comprising a carboxymethyl cysteine compound for increasing melanin production in melanocytes and / or for increasing cellular metabolic activity in melanocytes.
2. The use according to claim 1 wherein the use is for increasing melanin production.
3. The use according to claim 1 wherein the use is for increasing cellular metabolic activity.
4. The use according to any of the preceding claims wherein the carboxymethyl cysteine compound is selected from carboxymethyl cysteine, salt of carboxymethyl cysteine, ester of carboxymethyl cysteine, amide of carboxymethyl cysteine or a mixture thereof, preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, ester of carboxymethyl cysteine, and / or salt of carboxymethyl cysteine, more preferably, the carboxymethyl cysteine compound comprises carboxymethyl cysteine, and / or salt of carboxymethyl cysteine, even more preferably, carboxymethyl cysteine compound comprises salt of carboxymethyl cysteine, even more preferably the carboxymethyl cysteine compound comprises lysine carboxymethyl cysteinate and most preferably, the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate.
5. The use according to any of the preceding claims wherein the carboxymethyl cysteine compound is lysine carboxymethyl cysteinate.
6. The use according to any of the preceding claims wherein the carboxymethyl cysteine compound is present in an amount of 0.0001 % to 5% of the total weight of the composition, more preferably at least 0.001 %, even more preferably at least 0.01 %, still even more preferably at least 0.1 %, and most preferably at least 0.2% by weight of the composition, preferably, the carboxymethyl cysteine compound is present in amount of no greater than 3%, even more preferably no greater than 2%, still even more preferably no greater than 1.4%, and most preferably no greater than 1 % by weight of the composition.
7. The use according to any one of the preceding claims is non-therapeutic.
8. A method for increasing melanin production in melanocytes, for increasing cellular metabolic activity in melanocytes comprising application to the hair or scalp of a hair care composition comprising a carboxymethyl cysteine compound.
9. The method according to claim 8 is non-therapeutic.
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