Hair growth restoration

Specific tetrapeptides in the dermal papillary fibroblast secretome compositions address the limitations of existing hair loss treatments by promoting hair growth with broad tolerance and efficacy across different skin types and ages, enhancing ECM proteins and maintaining hair growth signals.

WO2025215349A1PCT designated stage Publication Date: 2025-10-16THE BOOTS CO PLC
View PDF 5 Cites 0 Cited by

Patent Information

Application Number
PCT/GB2025/050737
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-04-08
Filing Date
2025-04-07
Publication Date
2025-10-16

AI Technical Summary

Technical Problem

Existing hair loss treatments, such as minoxidil and finasteride, have side effects and are not effective for all individuals, while hair transplantation is risky and expensive, highlighting a need for well-tolerated and effective hair growth treatments.

Method used

Compositions comprising specific tetrapeptides that stimulate hair growth by increasing and maintaining signature genes like FGF7 and β-catenin in the dermal papillary fibroblast secretome, derived from naturally occurring dermal extracellular matrix proteins, which are well-tolerated across various skin types and ages.

Benefits of technology

The compositions effectively stimulate hair growth with minimal side effects, offering a broad range of tolerance and efficacy for diverse subjects, including those with conditions like alopecia, by enhancing ECM proteins and maintaining hair growth signals.

✦ Generated by Eureka AI based on patent content.
Patent Text Reader

Abstract

A therapeutic method of stimulating hair growth comprising the application of a composition comprising peptides, compositions for use in said method, non-therapeutic uses of compositions comprising peptides to stimulate hair growth and non-therapeutic methods using compositions comprising peptides.
Need to check novelty before this filing date? Find Prior Art

Description

[0001]Hair Growth Restoration Technical Field The present invention relates to methods for stimulating hair growth and compositions for use in said methods. Background to the invention Hair, such as scalp hair, has a specific growth pattern consisting of three distinct phases — anagen, catagen, and telogen. These phases are tightly regulated and referred to as the hair cycle. Exposure of hair to internal and external factors including hormones, psychological stress, and the environment (e.g. pollution) can result in changes in the hair-growth cycle leading to hair loss. This cycle is regulated mainly by hair follicles located at the root of the hair within the skin and a specialised population of mesenchymal cells known as the dermal papilla (DP). The dermal papilla provides important regulatory signals to the hair follicle and so plays a pivotal role in hair induction, growth, and cycling. At the molecular level, the DP expresses a cocktail of regulatory molecules called the secretome afterexpression of signature g^^^^ ^^^^^^^^^ ^^^^^ ^^^^^ ^^^^^ ^^^^^-catenin signalling that stimulateinitiation of the anagen phase in the hair follicles leading to new hair induction and hair growth. Common treatments for hair loss include the conventional chemical approaches often involving the drugs minoxidil and finasteride, which have side effects ranging from scalp irritation to acne, and milder but less effective cosmetic ingredients such as herbal extracts. An alternative approach is hair transplantation, which is an option for those experiencing a high degree of hair loss. There are several drawbacks associated with hair transplantation, such as surgical risks, scarring, and significant expense. Existing hair loss treatments are not effective for all those in need. Where existing hair loss treatments do have some effect results are generally unsatisfactory, accompanied by adverse side effects, or both. There therefore remains a need for therapeutic and non-therapeutic treatments for hair loss that are effective for and well tolerated by a wide range of subjects. WO2022106054A1 discloses a peptide combination for use in cosmetic beauty applications, and compositions comprising said peptide combinations. This document teaches the benefits of the peptide combinations in relation to enhancing production of dermal extracellular matrix (ECM) proteins (such as fibrillin, fibronectin, decorin and collagen) in aging skin. Summary of the invention The present inventors have identified that the specific peptides previously applied as cosmetic skin treatments are effective in stimulating hair growth. It has been experimentally demonstrated that the compositions of the present invention increase and / or maintain signature genes such as FGF7, BMP2,^^^^^ ^^^^^-catenin, within the secretome released by dermal papillary fibroblasts.Without wishing to be bound by theory, to induce hair growth, or hair retention the composition of the secretome released by dermal papillary fibroblasts is essential. A secretome consists of all the different molecules which may include growth factors and cytokines that are released by cells into the extracellular environment. A secretome beneficial for hair growth induction and hair retention is composed of specific signature molecules which themselves are induced by specific genes. The compositions in the present invention, through extracellular matrix regulation, support the induction or retention of the hair growth sectretome, thus facilitating hair growth. The compositions described herein comprise peptides that occur naturally within mammalian skin from the remodelling of dermal extracellular matrix proteins (especially collagens and elastic fibre proteins). These naturally occurring peptides or “matrikines” stimulate skin cells to produce new protein and improve the quality of the extracellular matrix which in turn may have beneficial effects on hair growth. Given that the peptides are naturally derived from matrix proteins well conserved across all skin types, ages, genders and ethnicities and that the cell mediated response to these peptides appears similar in different skin, the peptides confer the additional advantage of being well tolerated by all skin, which is not the case for many existing treatments. Additionally, the requirement of conventional hair growth compositions such as minoxidil and finasteride and their associated side effects may be avoided. Therefore, there is provided in a first aspect of the present invention a composition for use in a therapeutic method of stimulating hair growth in a subject comprising the application of said composition to the skin of a subject, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. According to a second aspect of the present invention there is provided a non-therapeutic use of a composition for stimulating hair growth, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. According to a third aspect of the present invention there is provided a non-therapeutic method of stimulating hair growth in a mammalian species comprising applying a composition to one or more regions of the skin of a subject where hair growth is to be stimulated, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. According to a fourth aspect of the present invention there is provided a method of stimulating hair growth in a mammalian species comprising applying a composition to one or more regions of the skin of a subject where hair growth is to be stimulated, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, O R1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. It has been experimentally demonstrated that the compositions present in the present invention increaseand / or maintain signature genes, ^^^^^^^^^ ^^^^^ ^^^^^ ^^^^^ ^^^^^-catenin, within the secretomereleased by dermal papillary fibroblasts. Detailed description of the invention The present invention is directed toward a therapeutic method of stimulating hair growth and compositions for use therein, and non-therapeutic uses and methods of stimulating hair growth. The composition and methods enable the production of extracellular matric (ECM) proteins from the dermal papillary fibroblasts, including at least fibrillin, fibronectin, decorin and collagen, which enable regulation of the hair cycle through retention of the hair growth secretome, maintaining signals for hair growth. The subject may be a mammal, such as a human, primate, dog, cat, cattle, pig, horse or sheep. In preferred embodiments, the subject is a human. In some embodiments, the composition is applied directly to the area of skin where hair growth is to be stimulated. Hair loss in a subject may be due to a hair loss condition such as from alopecia areata, androgenetic alopecia, gynecologic alopecia, postpartum alopecia, seborrheic alopecia, non-rigid alopecia, senile alopecia, chemotherapy-induced alopecia, radiation-induced alopecia, male-pattern baldness, female-pattern baldness, cicatricial alopecia, alopecia areata telogen effluvium, traction alopecia, and anagen effluvium. Tetrapeptides The present invention is directed toward composition for use in therapeutic methods of stimulating hair growth, uses of compositions in stimulating hair growth, and methods of stimulating hair growth. The composition may comprise a tetrapeptide. The composition may comprise a second peptide. The composition may comprise a combination of two tetrapeptides. The composition may comprise a tetrapeptide in combination with a pentapeptide. The first tetrapeptide (a) has generic formulation U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. The tetrapeptide is preferably selected from the group consisting of SEQ ID No: 1, SEQ ID No: 2, SEQ ID No: 3, SEQ ID No: 4, SEQ ID No: 5, SEQ ID No: 6, SEQ ID No: 7, SEQ ID No: 8, SEQ ID No: 9, SEQ ID No: 10, SEQ ID No: 11 and SEQ ID No: 12. In another embodiment the tetrapeptide is preferably selected from the group consisting of SEQ ID No: 1, SEQ ID No: 9 and SEQ ID No: 8. In another embodiment the tetrapeptide is preferably selected from the group consisting of SEQ ID No: 1. In another embodiment the tetrapeptide is preferably selected from the group consisting of SEQ ID No: 9. In another embodiment the tetrapeptide is preferably selected from the group consisting of SEQ ID No: 8. In a preferred embodiment tetrapeptide a) is selected from the group consisting of U-LSVD-Z, U-LSVP-Z, U-LSVG-Z, U-LSDV-Z, U-LSDP-Z, U-LSDG-Z, U-LSPV-Z, U-LSPD-Z, U-LSPG-Z, U-LSGV-Z, U- LSGD-Z and U-LSGP-Z. In another embodiment, the tetrapeptides is selected from the group consisting of U-LSVD-Z, U-LSPG-Z and U-LSPD-Z. In another embodiment the tetrapeptide a) is Pal-LSVD-OH. In another embodiment the tetrapeptide a) is Pal-LSPG-OH. In another embodiment the tetrapeptide a) is Pal- LSPD-OH. The second peptide (b) has generic amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid selected from the group consisting of Lysine (K), Glutamic acid (E) and Serine (S) and mixtures thereof, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. In a preferred embodiment, peptide b) is selected from the group consisting of SEQ ID No: 13, SEQ ID No: 14, SEQ ID No: 15, SEQ ID No: 16 and SEQ ID No: 17. In a further preferred embodiment peptide b) is U-GPKG-Z. In a further preferred embodiment peptide b) is U-GPEG-Z. In a further preferred embodiment peptide b) is U-GPSG-Z. The third tetrapeptide (c) has the generic formulation U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids. X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof. At the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. The third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 25, SEQ ID No: 26, SEQ ID No: 27, SEQ ID No: 28, SEQ ID No: 29, SEQ ID No: 30, SEQ ID No: 31, SEQ ID No: 32, SEQ ID No: 33, SEQ ID No: 34, SEQ ID No: 35, SEQ ID No: 36, SEQ ID No: 37, SEQ ID No: 38, SEQ ID No: 39, SEQ ID No: 40, SEQ ID No: 41, SEQ ID No: 42, SEQ ID No: 43, SEQ ID No: 44, SEQ ID No: 45, SEQ ID No: 46, SEQ ID No: 47, SEQ ID No: 48, SEQ ID No: 49, SEQ ID No: 50, SEQ ID No: 51, SEQ ID No: 52, SEQ ID No: 53 and SEQ ID No: 54. In another embodiment the third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 25, SEQ ID No: 36, SEQ ID No: 44 and SEQ ID No: 51. In another embodiment the third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 25. In another embodiment the third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 36. In another embodiment the third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 44. In another embodiment the third tetrapeptide is preferably selected from the group consisting of SEQ ID No: 51. In a preferred embodiment the third tetrapeptide is selected from the group consisting of U-EKGD-Z, U- ELGD-Z, U-EAGD-Z, U-EIGD-Z, U-ERGD-Z, U-KEGD-Z, U-KLGD-Z, U-KAGD-Z, U-KIGD-Z, U- KRGD-Z, U-LEGD-Z, U-LKGD-Z, U-LAGD-Z, U-LIGD-Z, U-LRGD-Z, U-IEGD-Z, U-IKGD-Z, U- ILGD-Z, U-IAGD-Z, U-IRGD-Z, U-REGD-Z, U-RKGD-Z, U-RLGD-Z, U-RAGD-Z, U-RIGD-Z, U- AEGD-Z, U-AKGD-Z, U-ALGD-Z, U-AIGD-Z and U-ARGD-Z. In another embodiment, the third tetrapeptides is selected from the group consisting of U-EKGD-Z, U-LKGD-Z, U-IRGD-Z and U-AKGD- Z. In another embodiment the third tetrapeptide is U-EKGD-Z. In another embodiment the third tetrapeptide is U-LKGD-Z. In another embodiment the third tetrapeptide is U-IRGD-Z. In another embodiment the third tetrapeptide is U-AKGD-Z. The fourth tetrapeptide (d) has the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine. At the N-terminal end, U is selected from the group consisting of H, - CO-R1, -SO2 -R1or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N. Where, at the N-terminal, U is H then the amino acid is not modified. When, at the C-terminal, Z is OH then the amino acid is not modified. The tetrapeptide is thus not in derivatised form. When other than U is H and Z is OH, then the tetrapeptide is derivatised. Derivation of the tetrapeptide is intended to increase the bioavailability of the peptide by improving the ability of the tetrapeptide to pass through the skin. An increase in bioavailability can also be achieved through vectoring, for example by encapsulation of the peptide. In a preferred embodiment the tetrapeptide of the composition is modified at the N-terminal and / or the C- terminal end. In a preferred embodiment, R1and / or R2is an alkyl chain of from 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms. In a further preferred embodiment U is an acyl group -CO-R1and Z is selected from the group consisting of OH, methoxy, ethoxy and NH2, preferably OH. In a further embodiment, U is preferably independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle and lipoyle. In a preferred embodiment of the present U is independently selected from lauroyl (C12), myristoyl (C14) and palmitoyl (C16). In a further preferred embodiment Z is OH and U is independently selected from the group consisting of palmitoyl (C16), myristoyl (C14) and lauroyl (C12). Most preferably U is palmitoyl (C16) and Z is OH. The tetrapeptides may comprise amino acids in the D- or L- configuration. The tetrapeptides may comprise an acid C-terminus such as -CO2 H. The amino acids making up the tetrapeptides according to the invention may be optically pure, be made up of L or D isomers or a mixture thereof. L isomers are those present in the natural state and may be preferred. Further derivatives of the tetrapeptide are envisioned and included, including for example modification and / or addition of a chemically functional group to one or more of the amino acids but without a change in the carbon skeletal. Further analogues of the tetrapeptide are also envisioned and included, including modification and / or addition of a chemically functional group to one or more of the amino acids with a change in the carbon skeletal and complexes of the tetrapeptide with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and others). Tetrapeptides are also envisaged in the form of salts, including hydrochloric salt, or acetate. The combination of tetrapeptides show synergistic benefit in that they offer markedly improved levels of hair growth stimulation in comparison the peptides singularly. The Composition The present invention is directed toward composition for use in therapeutic methods of stimulating hair growth, uses of compositions in stimulating hair growth, and methods of stimulating hair growth. In some embodiments, the uses or methods are non-therapeutic uses or methods, such as cosmetic uses or methods. In some embodiments, the use may be a non-therapeutic use, such as a cosmetic use. In some embodiments the method may be a non-therapeutic method, such as a cosmetic method. In these embodiments the composition may be a cosmetic composition. A cosmetic composition is a product designed for use by a consumer and is preferably a skincare cosmetic composition for application to the scalp or any other region where stimulation of hair follicle production is desired. The tetrapeptides are preferably incorporated into the cosmetic composition in amounts of from 0.10ppm to 10,000ppm, preferably from 0.50ppm to 5,000ppm, more preferably from 1ppm to 1000ppm, and most preferably from 1ppm to 500ppm. These are again based on a % w / w basis. Thus 100,000ppm is 10% by weight of the composition. In some embodiments, the use and methods of the present invention may be therapeutic uses and methods. For therapeutic uses and methods, the composition may be a pharmaceutical composition. A pharmaceutical composition is a product designed for use by a subject and is preferably a pharmaceutical composition for application to the scalp or any other region where stimulation of hair follicle production is desired. The present invention also encompasses pharmaceutical compositions comprising the tetrapeptide combination. The tetrapeptides are preferably incorporated into the pharmaceutical composition in amount of from 0.10ppm to 10,000ppm, preferably from 0.50ppm to 5,000ppm, more preferably from 1ppm to 1000ppm, and most preferably from 1ppm to 500ppm. These are again based on a % w / w basis. Thus 100,000ppm is 10% by weight of the composition. Where the composition comprises a combination of a first tetrapeptide and a second peptide, the first tetrapeptide and second peptide may be present in the composition in a weight ratio of from 20:80 to 80:20, such as 30:70 to 80:20, 40:60 to 80:20, 50:50 to 80:20, 60:40 to 80:20, or 70:30 to 80:20, based on the total weight of the first tetrapeptide and a second peptide. The first tetrapeptide and second peptide may be present in the composition in a weight ratio of from 20:80 to 80:20, such as 20:80 to 70:30, 20:80 to 60:40, 20:80 to 50:50, 20:80 to 40:60, or 20:80 to 30:70, based on the total weight of the first tetrapeptide and a second peptide. The first tetrapeptide and second peptide may be present in the composition in a weight ratio of from 20:80 to 80:20, such as 30:70 to 70:30, or 40:60 to 60:40, based on the total weight of the first tetrapeptide and a second peptide. The composition may be aqueous or non-aqueous and comprise of a single-phase system or multiple phase system. The composition may include but is not limited to liquids, gels, balms, oils or solids. For example, the composition may be an emulsion, cream, gel, serum, spray, or oil. In some embodiments, the composition may be incorporated into a shampoo or soap for hair care. Single or multiple phase compositions are envisaged. Multiple phase systems include but are not limited to microemulsions, emulsions, and products with discrete separate phases. Emulsions include water-in-oil, oil-in-water emulsions and multiple emulsions (water in oil in water or oil in water in oil for example). Products with discrete separate phases include bi or triphasic systems where the individual water or oil phases can be visibly seen. Where the composition is aqueous, it preferably comprises from 10% to 99.9% by weight water. In a preferred embodiment, aqueous compositions comprise from 20% to 80 % by weight water. In a preferred embodiment, aqueous compositions comprise from 40% to 70% by weight water. Where the composition is non-aqueous it preferably comprises 0% to up to 10% water, more particularly from 0.1 to 8%, most preferably from 0.5 to 5% water. Where the composition is an emulsion it comprises an oil and a water phase. The oil phase of an emulsion can be provided by any suitable oily component. Suitable oils for the oil phase may comprise for example: a) hydrocarbon oils, such as paraffin or mineral oils; b) waxes, such as beeswax or paraffin wax; c) natural oils, such as sunflower oil, apricot kernel oil, shea butter or jojoba oil; d) silicone oils, such as dimethicone, silicone elastomer, cyclomethicone or cetylidimethicone; e) fatty acid esters and ethers, such as isopropyl palmitate or isopropyl myristate and polypropylene glycol-15 stearyl ether; f) fatty alcohols, such as cetyl alcohol or stearyl alcohol; or g) mixtures thereof, for example, the blend of waxes available commercially under the trade name Cutina (BASF). The emulsion may comprise 0.1% to 55% by weight of the emulsion of oil phase. In one embodiment, the emulsion may comprise 3% to 25% by weight of the emulsion of oil phase, more preferably from 5% to 20% by weight of the emulsion of oil phase. In an alternative embodiment, the emulsion may comprise 10% to 50% by weight of the emulsion of oil phase, more preferably from 25-50% by weight of the emulsion of oil phase. Preferably the oil phase of the emulsion comprises oil at a level between 50% and 100% by weight of the oil phase. More preferably the oil phase comprises oil at a level of from 60% to 100%, more preferably from 70% to 100%, and even more preferably from 80% to 100% by weight of the oil phase. Alternatively, the oil phase of the emulsion may comprise a combination of oil, wax or butter. Waxes and butters are hydrocarbons that consist of long aliphatic alkyl chains and may include aromatic groups. They are generally lipophilic and typically solid or malleable at room temperature. Melting points vary depending on the alkyl chain, chain length and associations. Silicone waxes are preferred type of suitable wax based on alkylmethylsiloxane. Oils are typically lipophilic and liquid at room temperature with lower molecular weights than waxes. Where present wax or butter may be present at up to 40% of the oil phase of the emulsion. More preferably the oil phase may contain wax or butter at levels of up to 20% of the oil phase of the emulsion. In an alternative embodiment the oil phase may contain wax or butter at levels of up to 10% of the oil phase of the emulsion. Preferably the oil phase of the water-in-oil emulsion comprises a silicone oil. Where present, the silicone- containing oil phase preferably comprises an organopolysiloxane oil. The organopolysiloxane oil for use in the composition may be volatile, non-volatile, or a mixture of volatile and non-volatile silicones. The term "non-volatile" as used in this context refers to those silicones that are liquid or gel under ambientconditions and have a flash point (under one atmosphere ^^ ^^^^^^^^^ ^^ ^^^^^^^ ^^^^ ^^^^^^ ^^^ ^^^^"volatile" as used in this context refers to all other silicone oils. Suitable organopolysiloxanes can be selected from a wide variety of silicones spanning a broad range of volatilities and viscosities. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes. Preferred for use herein are organopolysiloxanes selected from the group consisting of polyalkylsiloxanes which include low, medium and high molecular weight dimethicone and dimethiconols alkyl substituted dimethicones such as cetyl dimethicone and caprylyl methicone , cyclic organopolysiloxanes having from 3 to 6 silicon atoms are included, for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane etc, these are termed cyclomethicones. Also included are silicone resins of the type MQ and T-Propyl also known as trimethylsiloxysilicates and polypropylsilsesquioxane, polyalkylaryl siloxanes, and mixtures thereof. More preferred for use herein are polyalkylsiloxanes and cyclomethicones. Preferred among the polyalkylsiloxanes are dimethicones. Alternatively, the silicone oil may be a silicone elastomer. Suitable for use herein are silicone elastomers which can be emulsifying or non-emulsifying crosslinked siloxane elastomers or mixtures thereof. No specific restriction exists as to the type of curable organopolysiloxane composition that can serve as starting material for the crosslinked organopolysiloxane elastomer. Examples in this respect are addition reaction- curing organopolysiloxane compositions which cure under platinum metal catalysis by the addition reaction between SiH-containing diorganopolysiloxane and organopolysiloxane having silicon- bonded vinyl groups; condensation-curing organopolysiloxane compositions which cure in the presence of an organotin compound by a dehydrogenation reaction between hydroxyl-terminated diorganopolysiloxane and SiH- containing diorganopolysiloxane and condensation-curing organopolysiloxane compositions which cure in the presence of an organotin compound or a titanate ester. Preferred silicone elastomers include dimethicone crosspolymer and Polysilicone-11. Preferably the oil phase comprises silicone, and most preferably, a silicone elastomer. Preferably, the emulsion composition includes from 20% to 35%, by weight of the emulsion composition, of the silicone elastomer raw material. When the composition is a water-in-oil emulsion it preferably comprises an emulsifier. In a preferred embodiment, the composition comprises from 0.1% to 10% emulsifier, more preferably from 0.25% to 7.5%, still more preferably from 0.5% to 5%, emulsifier by weight of the composition. The emulsifier helps disperse and suspend the aqueous water phase within the oil phase. Emulsifiers The composition may comprise an emulsifier. Suitable emulsifiers include all those suitable for the purpose and known by those skilled in the art for use in skin care products. Preferably these emulsifiers have an HLB value of or less than 14, more preferably from 2 to 14, and still more preferably from 4 to 14. Silicone emulsifiers are preferred. A wide variety of silicone emulsifiers are useful herein. These silicone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled in the art as silicone surfactants. Useful silicone emulsifiers include dimethicone copolyols. These materials are polydimethyl siloxanes which have been modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and chains comprising moieties derived from both ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, i.e., compounds which comprise C2-C30 pendant side chains. Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric and zwitterionic pendant moieties. Nonlimiting examples of dimethicone copolyols and other silicone surfactants useful as emulsifiers herein include polydimethylsiloxane polyether copolymers with pendant polyethylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant mixed polyethylene oxide and polypropylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant mixed poly (ethylene) (propylene) oxide side chains, polydimethylsiloxane polyether copolymers with pendant organobetaine side chains, polydimethylsiloxane polyether copolymers with pendant carboxylate side chains, polydimethylsiloxane polyether copolymers with pendant quaternary ammonium side chains; and also further modifications of the preceding copolymers comprising pendant C2-C30 straight, branched, or cyclic alkyl moieties. A particularly preferred emulsifier is PEG / PPG-18 / 18 dimethicone. Suitable, cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate or as a mixture with hexyl laurate and polyglyceryl-3 oleate. Other nonlimiting examples of dimethicone copolyols also include lauryl dimethicone copolyol, dimethicone copolyol acetate, diemethicone copolyol adipate, dimethicone copolyolamine, dimethicone copolyol behenate, dimethicone copolyol butyl ether, dimethicone copolyol hydroxy stearate, dimethicone copolyol isostearate, dimethicone copolyol laurate, dimethicone copolyol methyl ether, dimethicone copolyol phosphate, and dimethicone copolyol stearate. Among the non-silicone-comprising emulsifiers useful herein are various non-ionic and anionic emulsifying agents such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, Cl-C30 fatty acid esters of Cl-C30 fatty alcohols, alkoxylated derivatives of Cl-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of Cl-C30 fatty acids, C1- C30 esters of polyols, Cl-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, and mixtures thereof. Nonlimiting preferred examples of these non-silicon-comprising emulsifiers include: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth- 10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG-100 stearate, and mixtures thereof. Further peptides The compositions may comprise further peptides. Preferably said additional peptides are selected from the group consisting of dipeptides, tripeptides, additional tetrapeptides, pentapeptides and mixtures thereof. By tripeptides, it is meant compound comprising an uninterrupted sequence of three amino acids. By tetrapeptides, it is meant a compound comprising an uninterrupted sequence of four amino acids and when using further tetrapeptides, the tetrapeptides are referred to as ‘additional tetrapeptides’. By pentapeptide it is meant a compound comprising an uninterrupted sequence of five amino acids. Dipeptides: The compositions may comprise a dipeptide selected from the group consisting of acetyl dipeptide 1 cetyl ester, acetyl dipeptide 3 aminohexanoate, azelaoyl bisdipeptide 10, coumaroyl dipeptide 3, dicetyl dipeptide 9, dipeptide diamino butyroyl benzylamide diacetate, dipeptide 1, dipeptide 10, dipeptide 11, dipeptide 12, dipeptide 15, dipeptide 16, dipeptide 17, dipeptide 18, dipeptide 19, dipeptide 2, dipeptide 20, dipeptide 3, dipeptide 4, dipeptide 5, dipeptide 6, dipeptide 7, dipeptide 8, dipeptide 8 HCL, dipeptide 9, hexanoyl dipeptide 3 norleucine acetate, methyl undecylenoyl dipeptide 16, nicotinoyl dipeptide 22, nicotinoyl dipeptide 23, nicotinoyl dipeptide 24, nicotinoyl dipeptide 26, oleoyl dipeptide 15, palmitoyl dipeptide 10, palmitoyl dipeptide 13, palmitoyl dipeptide17, palmitoyl dipeptide 5 diaminobutyroyl hydroxythreonine, palmitoyl dipeptide 5 diaminohydroxybutyrate, palmitoyl dipeptide 7 and mixtures thereof. Dipeptides are preferably incorporated into the composition at a level of from 0.1 to 50000ppm, more preferably from 1 to 5000 ppm, most preferably from 10 to 500ppm. Tripeptides: The compsotions preferably comprise a tripeptide. Said tripeptide may be naturally occurring or of synthetic origin. Suitable tripeptides include tripeptide 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, derivatives thereof and mixtures thereof. Particularly preferred tripeptides comprise one or more His-based tripeptides. However, another suitable tripeptide may be Arg-Lys-Arg. Particularly preferred tripeptides are based on the structure GlU-His-Lys and its analogs and derivatives thereof. These are collectively known herein as GHK-tripeptides. Indeed, the preferred tripeptide in accordance with this aspect of the invention has this exact sequence of amino acids. Analogs of the preferred tripeptide useful herein include those in which one or more of the three amino acids are reorganized or rearranged within the sequence (e.g., GlU-Lys-His) and / or where no more than two amino acids are substituted (e.g., His-Ala-Orn). However, most preferably, amino acids substituted for Gly include an aliphatic side chain such as, without limitation, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) and Ile. Most preferred are Ala, Leu and Ile. The most preferable amino acid substituted for Lys or His include those having a side chain that includes, predominantly, a charged nitrogen at a pH of 6, such as, without limitation, Pro, Lys, Arg, His, Desmosine and Isodesmosine. Most preferably, Lys is replaced with Orn, Arg, or Citrulline. Derivatives are also considered to be encompassed by the term GHK-tripeptides in accordance with the present invention, (and therefore also the more generic term tripeptides). Derivatives of GHK-tripeptides in accordance with the present invention include derivatives of the substituted and rearranged tripeptides described herein. These derivatives include, inter alia, acyl-derivatives, which are tripeptides substituted with one or more straight-chain or branched-chain, long or short chain, saturated or unsaturated, substituted with a hydroxy, amino, acyl amino, sulfate or sulfide group, or unsubstituted, which can be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel oil fatty acid, lanolin fatty acid and the like. Preferable examples of the acyl group include an acetyl group, a palmitoyl group, an elaidoyl group, a myristyl group, a biotinyl group and an octanoyl group. These may be substituted or unsubstituted. When substituted, they are preferably substituted with hydroxyl or sulphur comprising groups such as, without limitation SO3 H, SH or S-S. His-based tripeptides include at least one histidine amino acid. The other two amino acids in the sequence may be the same or different. Thus, contemplated are, without limitation, His-Xaa-Xaa, His-Xaa-Xbb, His- Xbb-Xaa, Xbb-His-Xbb, Xbb-His-Xaa, Xaa-His-Xbb, Xaa-Xaa-His, Xaa-Xbb-His, Xbb-Xaa-His and Xbb- Xbb-His, where Xaa and Xbb are two different amino acids, although either can be His. Preferably, at least one of the other amino acids is Gly, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) or Ile. Preferably, at least one of the other amino acids is Pro, Lys, Arg, His, Desmosine and Isodesmosine. Most preferably, Lys is replaced with Orn, Arg, or Citrulline. Derivatives are also considered to be encompassed by the term His-based tripeptides in accordance with the present invention, (and therefore also the more generic term tripeptides). These derivatives include, inter alia, acyl-derivatives, which are tripeptides substituted with one or more straight-chain or branched- chain, long or short chain, saturated or unsaturated substituted or unsubstituted acyl group(s) having from 1 to 29 carbon atoms. The acyl groups which can be used are the same as those described for the GHK- tripeptides. Particularly preferred embodiments of tripeptides in accordance with the present invention include N-Acyl- GlU-His-Lys and most preferably, N-Palmitoyl-GlU-His-Lys. Preferred commercially available tripeptide and tripeptide derivative comprising compositions include Biopeptide-CL from SEDERMA, Maxilip(R) from SEDERMA, Biobustyl(R) from SEDERMA. The tripeptides where included are preferably incorporated into the composition in amounts of from 0.10ppm to 10,000ppm, preferably from 0.50ppm to 5,000ppm, more preferably from 1ppm to 1000ppm, and most preferably from 1ppm to 500ppm. These are again based on a % w / w basis. Thus 100,000ppm is 10% by weight of the emulsion. Additional tetrapeptides: The composition may comprise an additional tetrapeptide. These may be one or more rigin-based tetrapeptides, one or more ALAMCAT-tetrapeptides or mixtures thereof. These tetrapeptides may be naturally occurring or of synthetic origin. Suitable tetrapeptides for use in the present composition include those selected from the group consisting of well-known tetrapeptide 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 ,20, 21, 22, 23, 24, 25,26 , 27, 28, 29, 30, 34, 35, derivatives thereof and mixtures thereof. Rigin-based tetrapeptides in accordance with the present invention are based on the structure Gly-Gln-Pro- Arg (Rigin) and include its analogs and derivatives thereof. Rigin is an additional tetrapeptide. Analogs of the tetrapeptide rigin useful in accordance with the present invention include those in which one or more of the four amino acids are reorganized or rearranged within the sequence and / or where no more than two of the amino acids are substituted (e.g., Ala-Gln-Thr-Arg. More preferably, at least one of the amino acids within the sequence is Pro or Arg and most preferably the tetrapeptide includes both Pro and Arg although their order and position may vary. The amino acid substitutions can be from amongst any amino acid as defined herein. Particularly preferred rigin-based tetrapeptides include Xaa-Xbb-Arg-Xcc, Xaa-Xbb-Xcc- Pro, Xaa-Xbb-Pro-Arg, wherein Xaa-Xbb-Pro-Xcc, Xaa-Xbb-Xcc-Arg, Xaa, Xbb and Xcc may be the same or different and selected from the following Xaa is Gly or the amino acids that may be substituted therefore, Xbb is Gln or the amino acids that may be substituted therefore and Xcc may be Pro or Arg or the amino acids substituted therefore. The most preferable amino acids substituted for Gly include an aliphatic side chain such as, without limitation, beta-Ala, Ala, Val, Leu, Pro, Sarcosine (Sar) and Ile. The most preferable amino acids substituted for Gln include a side chain that includes an amine group that is predominantly uncharged at neutral pH (pH 6-7) such as, without limitation, Asn, Lys, Orn, 5- hydroxyproline, Citrulline and Canavanine. When Arg is substituted, it is preferably replaced with an amino acid having a side chain that includes, predominantly, a charged nitrogen at a pH of 6, such as, without limitation, Pro, Lys, His, Desmosine and Isodesmosine. Derivatives are also considered to be encompassed by the term rigin-base tetrapeptides, (and therefore also the more generic term tetrapeptides). Derivatives include derivatives of the substituted and rearranged rigin- based tetrapeptides described herein. These derivatives include, inter alia, acyl-derivatives, which are tetrapeptides substituted with one or more straight-chain or branched-chain, long or short chain, saturated or unsaturated, substituted with a hydroxy, amino, amino acyl, sulfate or sulfide group or unsubstituted having from 1 to 29 carbon atoms. N-acyl-derivatives include those acyl groups which can be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidoic acid, 2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel oil fatty acid, lanolin fatty acid and the like. Preferable examples of the acyl group include an acetyl group, a palmitoyl group, an elaidoyl group, a myristyl group, a biotinyl group and an octanoyl group. These may be substituted or unsubstituted. When substituted, they are preferably substituted with hydroxyl or sulphur comprising groups such as, without limitation SO3 H, SH or S-S.Derivatives are also considered to include peptide-divalent ion complexes. Cu2+-peptide derivatives are preferred as this may provide increased biological effect compared to the peptide alone. ALAMCAT tetrapeptides are tetrapeptides which include at least one amino acid including an aliphatic group comprising side chain. These amino acids include, without limitation, Gly, beta-Ala, Ala, Val, Leu, Sarcosine (Sar) and Ile. These tetrapeptides also include at least one amino acid including at least one NH2 comprising side chain. These amino acids include a side chain that has an amine group that is predominantly uncharged at neutral pH (pH 6-7) such as, without limitation, Gln, Asn, Lys, Orn, 5-hydroxyproline, Citrulline and Canavanine. The ALAMCAT-tetrapeptides also include at least one amino acid having at least one side chain including at least one cationic amine (predominant species is charged such as NH3+ , NH2+ , etc.-basic amino acids which are positively charged at pH 6.0). These amino acids include, without limitation, Pro, Arg, Lys, His, Desmosine and Isodesmosine. The remaining amino acid can be any amino acid, but is preferably one comprising an aliphatic group, pendant amino group or pendant cationic group. Derivatives are also considered to be encompassed by the term ALAMCAT-tetrapeptides in accordance with the present invention, (and therefore also the more generic term tetrapeptides). These derivatives include, inter alia, acyl-derivatives, which are tetrapeptides substituted with one or more straight-chain or branched-chain, substituted or unsubstituted long or short chain, saturated or unsaturated acyl group(s) having from 1 to 29 carbon atoms. The acyl groups which can be used are the same as those described for the rigin-based tetrapeptides. Preferred embodiments include Peptide E, arg-ser-arg-lys, N-acyl-Gly-Gln-Pro-Arg peptides, most preferably N-palmitoyl-Gly-Gln-Pro-Arg. Preferred commercially available sources of tetrapeptides include RIGIN, EYELISS, Haloxyl, and MATRIXYL 3000, which comprise between 50 to 500 ppm of palmitoyl-Gly-Gln-Pro-Arg, and other ingredients, such as peptides, chalcones and an excipient, commercially available from SEDERMA, France. Tego Pep 417 available from Evonik. These may be used to produce compositions of the present invention by adding thereto at least one tripeptide as described herein. The additional tetrapeptides when used are preferably incorporated into the composition in amounts from 0.1 ppm (0.00001% w / w also referred to herein as "weight percent", "weight %" or simply by weight) to 10,000 ppm (1.0% w / w), preferably from 0.5 ppm to 1000 ppm (0.1% w / w), and most preferably from 1 ppm to 500ppm (0.05% w / w) by weight of the composition. The combination of tripeptides and additional tetrapeptides, can be particularly preferred. When present, the preferred ratio of additional tetrapeptide to tripeptide, or indeed the ratio of molecules having four amino acids to those having three amino acids can range from 100:1 to 1:100; more preferably from 50:1 to 1:50, even more preferably from 30:1 to 1:30 and even more preferably between 10:1 to 1:10. Most preferably, the ratio of additional tetrapeptide to tripeptide ranges from between 3:1 to 1:3. These ratios are on a weight basis (% w / w-e.g. mg of pure peptide per Kilogram in the final formulation). In a particularly preferred embodiment, the amount of tripeptide used is greater than the amount of additional tetrapeptide used when considered in terms of their amounts in parts per million, again based on overall weight of the composition. In a particularly preferred embodiment, the composition comprises an additional tetrapeptide of the sequence Gly-Gln-Pro-Arg, its analogs and derivatives in combination with one or more tripeptide of the sequences Gly-His-Lys, its analogs and derivatives. Pentapeptides: The compositions may optionally comprise a pentapeptide, derivatives of pentapeptides, and mixtures thereof. As used herein, "pentapeptides" refers to both the naturally occurring pentapeptides and synthesized pentapeptides. Also, useful herein are naturally occurring and commercially available compositions that comprise pentapeptides. Suitable pentapeptides are those selected from the group consisting of pentapeptide1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 33, 34, 35, 36, 38, 39, derivatives thereof and mixtures thereof. Suitable pentapeptides for use herein are the pentapeptide, lys-thr-thr-lys-ser, Arg-asp-lys-tyr-val (pentapeptide -1) and derivatives thereof. A preferred commercially available pentapeptide derivative- comprising composition is Matrixyl which comprises 100 ppm of palmitoyl-lys-thr-thr-lys-ser and is commercially available from Sederma, France. The pentapeptides when used are preferably incorporated into the composition in amounts from 0.1 ppm (0.00001% w / w also referred to herein as "weight percent", "weight %" or simply by weight) to 10,000 ppm (1.0% w / w), preferably from 0.5 ppm to 1000 ppm (0.1% w / w), and most preferably from 1 ppm to 500ppm (0.05% w / w) by weight of the composition. Hexapeptides: The compositions may optionally comprise a hexapeptide, derivatives of hexapeptides, and mixtures thereof. As used herein, "hexapeptides" refers to both the naturally occurring hexapeptides and synthesized hexapeptides. Also, useful herein are naturally occurring and commercially available compositions that comprise hexapeptides. The hexapeptides when used are preferably incorporated into the pharmaceutical composition in amounts from 0.1 ppm (0.00001% w / w also referred to herein as "weight percent", "weight %" or simply by weight) to 10,000 ppm (1.0% w / w), preferably from 0.5 ppm to 1000 ppm (0.1% w / w), and most preferably from 1 ppm to 500ppm (0.05% w / w) by weight of the composition. Matrix metalloproteinase inhibitors (MMPi) The term "matrix metalloproteinase inhibitor" relates to all molecule and / or plant or bacterial extracts having an inhibitory activity on at least one of the matrix metalloproteinases expressed or synthetized by or in the skin. The family of the matrix metalloproteinases is formed of several well-defined groups on the basis of their resemblance regarding structure and substrate specificity (Woessner J. F.1991, Faseb Journal, vol.5, , 2145). Among these groups, there are collagenases able to degrade fibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase, MMP- 13 or collagenase 3, MMP-18 or collagenase 4), gelatinases degrading type IV collagen or other denatured collagen form (MMP-2 or A gelatinase (72 kDa), MMP-9 or B gelatinase (92 kDa)), stromelysins (MMP-3 or stromelysin 1, MMP- 10 or stromelysin 2, MMP-11 or stromelysin 3) whose broad spectrum of activity targets proteins of the dermal extracellular matrix such as glycoproteins (fibronectin, laminin), proteoglycanes etc., matrilysin (MMP-7), metalloelastase (MMP- 12) or metalloproteinases (MMP- 14, MMP- 15, MMP- 16 and MMP- 17). Metalloproteinases (MMPs) are proteases that use a metal, (mostly zinc) coordinated to 3 cysteine residues and to a methionine in their active site, that degrade macromolecular components of the dermal extracellular matrix and of basal layers at neutral pH (collagen, elastin, etc ...). This group of enzymes is inactivated by metal chelators. The principal activity regulators of MMPs are the tissue inhibitors of metalloproteinases or TIMPs such TIMP-I, TIMP-2, TIMP-3 and TIMP-4 (Woessner J. F., Faseb Journal, 1991). Furthermore, MMP expression is also regulated by growth factors, cytokines, oncogene products (ras, jun), or also matrix constituents. The term "matrix metalloproteinase inhibitors " according to the present invention means all molecules able to reduce the MMP’s activity regarding the gene expression (transcription and translation) or regarding the activation of the zymogen form of the MMP, or else regarding the local control of active forms. Furthermore, the metalloproteinase inhibitors according to the present invention can also be MMP-1 inhibitors of natural or synthetic origin. The terms "natural origin" or "synthetic origin" mean both a metalloproteinase inhibitor at a pure state or in solution at different concentrations, but natural origin termed inhibitors are obtained by different extraction methods from a natural element (for example lycopene from a tomato) whereas the inhibitors of synthetic origin are all obtained via chemical synthesis. Preferred MMPi are selected from the group consisting of retinoid, N-acetyl cysteine, glutathione, 2- furildioxime, vitamin C, flavones, isoflavones, hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, dihydroxy methyl chromone, kudzu extract, vitis vinifera extract, Oenothera biennis extract Anogeissus leiocarpus extract and mixtures thereof. Where present, MMPi are present at a level of from 0.01% to 10%, more preferably 0.1% to 5% and most preferably from 0.5% to 2.5% by weight of the composition. Skin Conditioning Agent The compositions may optionally comprise a skin conditioning agent. Said skin conditioning agents may preferably be selected from the group consisting of humectants, emollients, moisturisers, or mixtures thereof. Where present, they are preferably present at a level of from 0.01% to 20%, more preferably from 0.1% to 10%, most preferably from 0.5% to 7% by weight of the composition. Preferred skin conditioning agents are selected from the group consisting of guanidine, urea, glycolic acid and glycolate salts, salicylic acid, lactic acid and lactate salts, aloe vera, shea butter, polyhydroxy alcohols, such as sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanitriol, (di) propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, sugars (e.g. fructose, glucose, xylose, honey, mannose, xylose), gluconodeltalactone, and starches and their derivatives, pyrrolidone, carboxylic acid, hyaluronic acid and salts thereof, lactamide monoethanolamine, acetamide monoethanolamine, panthenol, allantoin and mixtures thereof. More preferably said skin conditioning agent is selected from the group consisting of glycerine, arabinogalactan, butylene glycol, hyaluronic acid, shea butter, propylene glycol, ethylhexyl glycerine, hyaluronate and mixtures thereof. Penetration Enhancers The compositions may further comprise a solvent that acts as a penetration enhancer. The solvent referred to herein increases the solubility of the peptide in the composition, and thus improves the penetration of the composition, particularly the active agent, into the epidermis. This improvement in the transfer of the biologically active agent into the epidermis provides improved efficiency in the delivery of the active agent to the epidermis, particularly, the stratum corneum (SC) of the epidermis.The solvent may be a dimethyl silane. The solvent may be a monosaccharide ether. The dimethyl silane referred to herein is a water-soluble silicone. It is also clear in water (i.e., without the appearance of oil droplets or a hazy appearance). The dimethyl silane may be or comprise a silicone wax or a silicone oil. A silicone wax refers to a silicone wax with a melting point above 39°C. A silicone oil refers to a siloxane polymer that is a liquid at 25°C and at atmospheric pressure (760 mmHg). The dimethyl silane may be or comprise an ether of dimethyl silane (ether dimethyl silane). Preferably the ether of the dimethyl silane is or comprises a PEG methyl ether dimethyl silane, such as a bis-PEG methyl ether dimethyl silane. Most preferably the dimethyl silane is or comprises bis-PEG- 18 methyl ether dimethyl silane. The monosaccharide ether referred to herein may be used as a humectant. The monosaccharide ether may be or comprise a triose ether, a pentose ether, a hexose ether or a heptose ether. Preferably the monosaccharide ether is or comprises a hexose ether, such as a glucose ether. The monosaccharide ether may be or comprise an alkoxylated alkyl monosaccharide ether. The alkoxylate may be Cl to C5. The alkyl may be Cl to C5. Preferably, the alkoxylate is C2 and the alkyl is Cl . Preferably, therefore, the alkoxylated alkyl monosaccharide ether is an ethoxylated methyl monosaccharide ether. The alkoxylated monosaccharide ether (e.g., an ethoxylated methyl monosaccharide ether) may be or comprise an alkoxylated alkyl triose ether, an alkoxylated alkyl pentose ether, an alkoxylated alkyl hexose ether or an alkoxylated alkyl heptose ether. Preferably the alkoxylated alkyl monosaccharide ether is or comprises an alkoxylated alkyl hexose ether. More preferably the alkoxylated hexose ether is or comprises an alkoxylated alkyl glucose ether, such as an ethoxylated methyl glucose ether. Preferably, the ethoxylated methyl glucose ether is or comprises methyl- gluceth-20. Methyl-gluceth 20 is an extremely effective humectant. Thus the solvent of the composition may be one or more solvents selected from the group consisting of: an ether of dimethyl silane; a monosaccharide ether; and mixtures thereof. The composition according to the invention may further comprise one or more members selected from the group consisting of: solvents (such as glycerides, sorbitan esters, polyglycerin esters, non- silicone fatty compounds, and esters), water- soluble solvents, surfactants (such as sorbitan esters and polyglycerin esters) and mixtures thereof. The composition may further comprise one or more solvents selected from the group consisting of: glycerides, sorbitan esters, polyglycerin esters, non-silicone fatty compounds, esters, and mixtures thereof. The term “water-soluble solvent” is interchangeable with the term “water-miscible solvent” and means a compound that is liquid at 25°C and at atmospheric pressure (760 mmHg), and it has a solubility of at least 50% in water under these conditions. In some cases, the water-soluble solvent has a solubility of at least 60%, 70%, 80%, or 90% in water. The solvents can be volatile or non-volatile compounds. Non- limiting examples of water-soluble solvents may be one or more members selected from the group consisting of glycerin, alcohols (for example, C1-30, C1-15, C1-10, or C1-4 alcohols), organic solvents, polyols (polyhydric alcohols), glycols (e.g., butylene glycol, caprylyl glycol, etc.), and mixtures thereof. Also suitable are one or more glycols and polyols selected from the group consisting of monomethyl, monoethyl and monobutyl ethers of ethylene glycol, propylene glycol, hexylene gycol or ethers thereof such as, for example, monomethyl ether of propylene glycol, butylene glycol, hexylene glycol, dipropylene glycol as well as alkyl ethers of diethylene glycol, , 1,2,6-hexanetriol, trimethylolpropane, diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, 2-butene-l,4-diol, 2- ethyl-l,3-hexanediol, 2-methyl-2,4-pentanediol, (caprylyl glycol), 1,2- hexanediol, 1,2-pentanediol, and 4- methyl-l,2-pentanediol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether acetate, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-propyl ether, ethylene glycol mono- iso- propyl ether, diethylene glycol mono-iso-propyl ether, ethylene glycol mono-n-butyl ether, ethylene glycol mono-t-butyl ether, diethylene glycol mono-t-butyl ether, 1 -methyl- 1-methoxybutanol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono-t-butyl ether, propylene glycol mono-n-propyl ether, propylene glycol mono-iso-propyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol mono-n-propyl ether, and dipropylene glycol mono-iso-propyl ether; 2-pyrrolidone, N-methyl-2-pyrrolidone, l,3-dimethyl-2- imidazolidinone, formamide, acetamide, dimethyl sulfoxide, sorbit, sorbitan, acetine, diacetine, triacetine, sulfolane, and mixtures thereof Also suitable are one or more polyhydric alcohols selected from the group consisting of tripropylene glycol, 1,3-butanediol, 2,3-butanediol, 1,4-butanediol, 3-methyl-l,3-butanediol, 1,5- pentanediol, tetraethylene glycol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, polyethylene glycol, 1,2,4-butanetriol, 1,2,6-hexanetriol, and mixtures thereof. Polyol compounds may also be used e.g., ethoxylation of polyols producing methyl gluceth-20. Ethoxylated water dispersible waxes may be used e.g., Bis PEG- 18 methyl ether dimethyl silane. Antioxidant Agent The compositions may optionally comprise an antioxidant agent. Suitable antioxidant agents may include: a) ascorbic acid its salts, esters, glucosides and glucosamines, particularly sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl palmitate and ethyl ascorbic acid b) vitamin E (tocopherol) and its esters, particularly tocopheryl acetate, as well as Dimethyl methoxy chromanol which is a synthetic analogue of gamma tocopherol, available from Lipotec S.A. polygon Industrial Camri Ral, under the tradename Lipochroman-6 c) herbal extracts, particularly gingko biloba, such as that available under the trade name "Gingko Biloba Leaf Powder" from Univar PLC, morus alba, such as that available under the trade name "Mulberry Concentrate" from Solabia, origanum vulgare, such as that available under the trade name "Pronalen Origanum HSC" from S Black Ltd, panax ginseng, such as that available under the trade name "Panax ginseng 1.1 extract 4294"from S Black Ltd or "Phytexcell Panax ginseng" available from Croda Chemicals Ltd, birch extract such as those available from Cosmetochem (U. K.) Ltd under the trade names "Super Herbasol Extract Birch" and "HP Herbasol Betula" and those available from Blagden Chemicals under the tradenames "Phytelene of Birch" and "Aqueous Spray Dried Birch", camellia sinensis, such as that available under the trade name "Herbal Extract Green Tea 75% Solids" from Nichimen Europe, rosmarinus officinalis, such as that available under the trade name "Pronalen Rosemary" from S. Black, Acerola cherry powder, such as that available as Acerola PE from Gee Lawson, Emblica extract sold under the tradename EmblicaTMby Merck Speciality chemicals, and Grape Seed oil, such as that available from Chesham Chemicals Limited. The amounts of antioxidant agents used in the cosmetic composition are expressed as dry weights, as understood by a man skilled in the art. The total amount of antioxidant agents optionally present in the composition may range from 0.005% to 10% by weight, preferably 0.5% to 5%, most preferably 0.2% to 1.5% by weight of the composition. Particularly preferred synergistic combinations of antioxidant agents suitable for inclusion in the composition are selected from the group consisting of : i) panax ginseng, morus alba and magnesium ascorbyl phosphate; ii) panax ginseng, morus alba and sodium ascorbyl phosphate; iii) panax ginseng, morus alba and rosmarinus officinalis; iv) ginkgo biloba, phyllanthus emblica and Dimethylmethoxy chromanol; v) morus alba, camellia sinensis and dimethylmethoxy chromanol; vi) morus alba, camellia sinensis and tocopheryl acetate; vii) panax ginseng, morus alba and origanum vulgare, viii) camellia sinensis, tocopheryl acetate and dimethylmethoxychromanol, viv) morus alba, tocopheryl acatete and dimethylmethoxychromanol. In these preferred combinations (a) the panax ginseng is preferably present in an amount of 0.005% to 0.1%, more preferably 0.01% to 0.05% by weight of the composition; (b) the morus alba is preferably present in an amount of 0.0005% to 0.01%, more preferably 0.001% to 0.005% by weight of the composition; (c) the sodium, magnesium ascorbyl phosphate or ethyl ascorbic acid is preferably present in an amount of 0.05% to 2.5%, preferably 0.1% to 2%, most preferably 0.15% to 1.5% by weight of the composition;(d) the rosmarinus officinalis or origanum vulgare or phyllanthus emblica is preferably present in an amount of 0.01% to 0.5%, more preferably 0.05% to 0.2% by weight of the composition e) the dimethylmethoxy chromanol is preferably present in an amount of 0.0005% to 0.1%, more preferably from 0.005% to 0.05% by weight of the composition ; f) the camellia sinensis is preferably present in an amount of 0.005% to 0.2%, more preferably from 0.01% to 0.1% and the g) Tocopherol acetate is preferably present in an amount of 0.01 to 0.5%, more preferably from 0.05% to 0.25% Vitamins The compositions may comprise one or more vitamins. The compositions may comprise ascorbates, for example vitamin C, vitamin C derivatives, ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate and ethyl ascorbic acid. The composition may comprise vitamin B, vitamin B derivatives, vitamin B1 to vitamin B12 and their derivatives. In a further embodiment the composition comprising the Vitamin B3 derivative niacinamide. In an alternative embodiment the composition comprises vitamin K, vitamin K derivatives, vitamin H, vitamin D, vitamin D derivatives and mixtures thereof. In an alternative embodiment of the composition comprises vitamin E, vitamin E derivatives such as tocopherol and tocopheryl acetate, and provitamins thereof, such as panthenol and mixtures thereof. In a further embodiment the composition comprises retinoid compounds, including retinoic acid, retinaldehyde, retinol and derivatives thereof. In one embodiment the composition comprises retinyl palmitate, retinyl acetate, retinyl retinoate, retinyl proprionate, retinyl ascorbate, retinyl linoleate, retinyl retinoate, retinyl sunflowerseedate and mixtures thereof. The vitamin compounds may be included as the substantially pure material, or as an extract obtained by suitable physical and / or chemical isolation from natural (e. g. plant) sources. In one embodiment, when vitamin compounds are present in the compositions of the instant invention, the emulsion compositions comprise from about 0.0001% to 50%, more preferably from 0.001% to 10%, still more preferably from 0.01% to 8%, and still more preferably from 0.1% to 5%, by weight of the composition, of the vitamin compound. Salicylic Acid Compound The compositions may comprise a salicylic acid compound, its esters, its salts, or combinations thereof. In one embodiment of the compositions of the present invention, the salicylic acid compound preferably comprises from 0.0001% to 25%, more preferably from 0.001% to 15%, even more preferably from 0.01% to 10%, still more preferably from 0.1% to 5%, and even more preferably from 0.01% to 2%, more preferably 0.1% to 2% by weight of the composition, of salicylic acid. Other Optional Ingredients The composition may comprise a thickener. The thickener may be present in an amount of from 0.5 to 10% by weight of the composition. Non-limiting examples of various types of thickeners include: a. Carboxylic Acid Polymers These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and esters of these acrylic acids and the substituted acrylic acids, wherein the crosslinking agent contains two or more carbon-carbon double bonds and is derived from a polyhydric alcohol. Examples of commercially available carboxylic acid polymers useful herein include the carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerythritol. The carbomers are available as the CARBOPOL 900 series from Lubrizol (e.g., Carbopol® 980). In addition, other suitable carboxylic acid polymeric agents include Ultrez® 10 or Ultrez® 30 (Lubrizol) and copolymers of C10-30 alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., C1-4 alcohol) esters, wherein the crosslinking agent is an allyl ether of sucrose or pentaerythritol. These copolymers are known as acrylates / C10-C30 alkyl acrylate crosspolymers and are commercially available as Carbopol® 1382, Ultrez® 21, Pemulen TR-1, Pemulen TR-2 and Pemulen EZ-4U from Lubrizol. In other words, examples of carboxylic acid polymer thickeners useful herein are those selected from carbomers, acrylates / C10-C30 alkyl acrylate crosspolymers, and mixtures thereof. b. Crosslinked Polyacrylate Polymers The compositions of the present disclosure can optionally contain crosslinked polyacrylate polymers useful as thickeners or gelling agents including both cationic and nonionic polymers. Examples of crosslinked polyacrylate polymers include Polyacrylate crosspolymer-6. c. Polyacrylamide Polymers The compositions of the present disclosure can optionally contain polyacrylamide polymers, especially nonionic polyacrylamide polymers including substituted branched or unbranched polymers. Among these polyacrylamide polymers is the nonionic polymer given the CTFA designation polyacrylamide and isoparaflin and laureth-7, available under the Tradename Sepigel 305 from Seppic. Other polyacrylamide polymers useful herein include multi-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids. Commercially available examples of these multi-block copolymers include Hypan 5R150H, 55500V, SSSOOW, SSSA100H, from Lipo Chemicals, Inc. The compositions may also contain thickening and texturising gels of the type as exemplified by the product range 40 called Lubrajel® from United Guardian. These gels have moisturizing, viscosifying, stabilizing properties. d. Polysaccharides A wide variety of polysaccharides can be useful herein. "Polysaccharides" refer to gelling agents that contain a45 backbone of repeating sugar (i.e., carbohydrate) units. Nonlimiting examples of polysaccharide gelling agents include those selected from the group consisting of cellulose, carboxymethylhydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Also, useful herein are the alkyl-substituted celluloses. e. Gums Other thickening and gelling agents useful herein include materials which are primarily derived from natural sources. Nonlimiting examples of these gelling agent gums include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, scierotiurn gum, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, biosacharide gum, and mixtures thereof. Additional examples of water-soluble thickeners include water-soluble natural polymers, water-soluble synthetic polymers, clay minerals and silicic anhydride. Non-limiting examples of water- soluble natural polymers include gum arabic, tragacanth gum, karaya gum, guar gum, gellan gum, tara gum, locust bean gum, tamarind gum, sodium alginate, alginic acid propyleneglycol ester, carrageenan, farcelluran,agar, high-methoxy pectin, low-methoxy pectin, xanthine, chitosan, starch, fermentation polysaccharide (for example, xanthan gum, pullulan, carciran, dextran), acidic heteropolysaccharide derived from callus of plants belonging to Polyantes sp. (for example, tuberous polysaccharide), proteins (for example, sodium casein, gelatin, albumin), chondroitinsulfate, and hyaluronic acid. Non-limiting examples of water-soluble synthetic polymers include polyvinyl alcohol, sodium polyacrylate, sodium polymethacrylate, polyacrylic acid glycerin ester, carboxyvinyl polymer, polyacrylamide, polyvinyl pyrrolidone, polyvinyl methylether, polyvinyl sulfone, maleic acid copolymer, polyethylene oxide, polydiallyl amine, polyethylene imine, water soluble cellulose derivatives (for example, carboxymethyl cellulose, methyl cellulose, methylhydroxypropylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, cellulose sulfate sodium salt), Additionally, the one or more thickeners may include polymeric thickeners selected from the group consisting of ammonium polyacryloyldimethyl taurate, ammonium acryloyldimethyltaurate / VP copolymer, sodium polyacrylate, acrylates copolymers. Preferred thickeners are selected from the group consisting of xanthan gum, ammonium acryloyldimethyltaurate / vinyl pyrrolidone copolymer, dimethicone crosspolymer, carbomer, hydroxyethyl cellulose, polyacrylamide, polyacrylate crosspolymer-6, and mixtures thereof. The compositions of the present invention may also optionally comprise one or more of the following optional ingredients. Preservatives may be added to the emulsion such as 2-bromo2-nitropropane-1,3-diol (bronopol, which is available commercially under the trade name Myacide RTM), benzyl alcohol, diazolidinyl urea, imidazolidinyl urea, methyl paraben, phenoxy ethanol, ethyl paraben, propyl paraben, sodium methyl paraben, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolone and sodium propyl paraben, suitably in an amount of from 0.01% to 10% by weight of the emulsion. Sequestering agents may be added to the emulsion composition, such as ethylenediamine tetraacetic acid and salts thereof, suitably in an amount of from 0.005% to 0.5% by weight of the composition. The composition may also include waxes such as cocoa butter suitably in an amount of from 1% to 99% by weight of the composition. The composition may also comprise suitable, cosmetically acceptable diluents, carriers and / or propellants such as dimethyl ether. The composition may also include pearlising agents such as stearic monoethanolamide and / or mica, suitably in an amount of from 0.01% to 10% by weight of the composition. Perfumes may be added suitably in an amount of from 0.01% to 2% by weight of the composition, as may water soluble dyes such as tartrazine, suitably in an amount of from a trace amount (such as 1 x 10-5 %) to 0.1 % by weight of the composition. The composition may also include pH adjusting agents such as sodium hydroxide, aminomethyl propanol, triethanolamine, suitably in an amount of from 0.01 % to 10% by weight of the composition. The composition may be buffered by means well known in the art, for example by use of buffer systems comprising succinic acid, citric acid, lactic acid, and acceptable salts thereof, phosphoric acid, mono-or disodium phosphate and sodium carbonate. Suitably, the composition may have a pH between 3 and 10, preferably between 4 and 8. In some embodiments, the compositions for use in stimulating hair growth, uses of compositions for stimulating hair growth and methods for stimulating hair growth promote hair strength, hair restoration, hair thickening, or combinations thereof in said subject. In some embodiments, the method increases hair density or hair growth rate of said subject. It will be understood that improved hair strength, hair restoration, hair thickening, hair density, hair growth rate and combinations thereof are all functions of hair growth stimulation. In some embodiments, the hair is scalp hair, eyelash hair, eyebrow hair, or facial hair. The methods and uses comprise applying the composition defined herein to the skin of a subject where hair growth is to be stimulated. In some embodiments, this is the scalp region, eye brow region, face region, chest region or pubic region of the body. The methods and uses may therefore comprise applying the composition to these specific regions. Examples Tetrapeptide synthesis The tetrapeptides of the present disclosure with generic formulation pal-X1X2X3X4-OH are prepared by peptidic synthesis. In a first step the N-terminal of X4is coupled with a resin via the terminal acid functionality in the presence of a coupling agent. The N terminal amine is then reacted with the next amino acid in the sequence X3in the presence of a coupling agent. The same process is repeated until the required sequence is obtained and a suitable C terminal functionality added. Suitable coupling agents include DCC (dicyclohexylcarbodiimide) / NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazole-1-yl)-1,1,3,3- tetramethyluronium hexafluorophosphate) / HOBT (1-hydroxy-benzotriazole)). The resulting peptide is then cleaved from the resin in an acidic medium and after precipitation, washing and drying, the peptide is obtained in solid form. Example Formulations Example 1 – Shampoo Material % w / w Decyl glucoside 3 Sodium cocoamphoacetate 3 Cocamidopropyl betaine 7.5 PEG-18 Glyceryl Oleate / Cocoate 5 Butylene glycol 2 Citric acid 0.58 Tetrasodium EDTA 0.05 Phenoxyethanol 0.4 Caprylyl glycol & Ethylhexylglycerin 0.4 Fragrance 0.2 Peptide plus excipient composition 3.0 Aqua To 100% Method of manufacture 1. To water add and dissolve tetrasodium EDTA, butylene glycol and citric acid. 2. Stir together decyl glucoside, sodium cocoamphoacetate, cocamidopropyl betaine. 3. Add PEG-18 Glyceryl Oleate / Cocoate and stir until thickened. 4. Add Phenoxyethanol, Caprylyl glycol & Ethylhexylglycerin and fragrance and stir until uniform. 5. Stir in peptide and excipient composition 6. Make to weight with water and stir smooth. Example 2 – Conditioning Shampoo Material % w / w Sodium laureth sulphate 20 Cocamidopropyl betaine 8 Cocamide DEA 1.5 Sodium chloride 1.5 Sodium benzoate 0.3 Sodium methylparaben 0.2 Tetrasodium EDTA 0.05 Citric acid 0.05 Sodium hydroxide 0.05 Glycerin 2 Polyquaternium-10 0.2 Peptide plus excipient composition 3.0 Aqua To 100% Method of manufacture 1. To water add and dissolve citric acid, glycerin, sodium hydroxide, sodium chloride, sodium benzoate, sodium methylparaben and tetrasodium EDTA. 2. Stir in sodium laureth sulphate. 3. Stir in cocamide DEA. 4. Stir in cocamidopropyl betaine. 5. Stir in Polyquaternium-10 6. Stir in peptide and excipient blend 7. Make to weight with water and stir until uniform. Example 3 – Representative oil-in-water emulsion cosmetic composition for scalp Material % w / w Dimethicone 5.00 Glycerin 4.00 Dimethicone crosspolymer & Dimethicone 0.75 Phenoxyethanol & Methylparaben & Ethylparaben 0.75 Glyceryl stearate & PEG-100 stearate 2.00 Cetearyl alcohol 2.00 Sodium polyacrylate 0.50 Xanthan gum 0.10 Tetrasodium EDTA 0.05 Peptide excipient composition comprising propanediol 3.00 & Pentylene glycol & Decyl glucoside & Water excipient composition Aqua To 100% Method of manufacture 1. To water add glycerine and dissolve tetrasodium EDTA. 2. Using homogenisation sprinkle in xanthan gum and continue to homogenise for 5 minutes or until hydrated. 3. Heat water phase to 70-75ºC. 4. In a separate vessel weigh out oil phase and heat to 70-75ºC. (Dimethicone, cetearyl alcohol, glyceryl stearate & PEG-100 stearate) When at temperature stir in the sodium polyacrylate. 5. With both phases at 70-75ºC add the oil phase to the water phase and homogenise for 2 minutes. 6. Add dimethicone crosspolymer & dimethicone and homogenise for 2 minutes. 7. Cool to room temperature. 8. Stir in phenoxyethanol & methylparaben & ethylparaben and peptide & propanediol & pentylene glycol & decyl glucoside & water. 9. Stir in peptide and excipient composition 10. Make to weight with water and stir smooth. Example 4 – Representative Gel-based cosmetic composition for scalp Material % w / w Glycerin 6.00 Propanediol 1.50 Acrylates / C10-30 alkyl acrylate crosspolymer 0.75 Alcohol denat. 0.50 Phenoxyethanol & Methylparaben & Ethylparaben 0.50 Potassium hydroxide 0.27 Tetrasodium EDTA 0.05 Peptide / s and excipient composition 3.00 Water To 100% Method of manufacture 1. To water add glycerine and propanediol and dissolve tetrasodium EDTA. 2. Using homogenisation sprinkle in acrylates / C10-30 alkyl acrylate crosspolymer and continue to homogenise for 5 minutes or until hydrated. 3. Stir in potassium hydroxide to form gel. 4. Stir in alcohol denat., phenoxyethanol & methylparaben & ethylparaben and peptide & propanediol & pentylene glycol & decyl glucoside & water. 5. Stir in peptide and excipient composition 6. Make to weight with water and stir smooth.

Claims

Claims 1. A composition for use in a therapeutic method of stimulating hair growth in a subject comprising the application of said composition to skin of a subject, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids; X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof; at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched,cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine; at the N-terminal end, U is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle, lipoyle; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N.

2. A non-therapeutic use of a composition for stimulating hair growth, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group,which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids; X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof; at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine; at the N-terminal end, U is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle, lipoyle; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N.

3. A non-therapeutic method of stimulating hair growth in a mammalian species comprising applying a composition to one or more regions of the skin of a subject where hair growth is to be stimulated, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2areindependently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids; X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof; at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2-R1or a biotinyl group; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine; at the N-terminal end, U is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle, lipoyle; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, saidgroups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N.

4. A method of stimulating hair growth in a mammalian species comprising applying a composition to one or more regions of the skin of a subject where hair growth is to be stimulated, the composition comprising a first tetrapeptide, a second peptide, a third tetrapeptide, a fourth tetrapeptide or a combination of the first tetrapeptide and the second peptide, wherein: a) the first tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z wherein L is used to denote amino acid Leucine and S is used to denote Serine, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), at the N- terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C- terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; b) the second peptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-GPXG-Z wherein G is used to denote amino acid glycine and P denotes the amino acid proline, as per the internationally recognised single letter code for amino acids, X denotes an amino acid independently selected from the group consisting of Lysine (K), Glutamic acid (E), Proline (P) and Serine (S) and mixtures thereof, or a pentapeptide having the amino acid sequence according to SEQ ID No:17, at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group, at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2. R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; c) the third tetrapeptide is selected from the group consisting of tetrapeptides having the amino acid sequence U-XXGD-Z wherein G is used to denote amino acid Glycine and D is used to denote amino acid Aspartic acid, as per the internationally recognised single letter code for amino acids; X denotes an amino acid selected from the group consisting of Glutamic acid (E), Lysine (K), Leucine (L), Alanine (A), Isoleucine (I), Arginine (R) and mixtures thereof; at the N-terminal end, U is selected from the group consisting of H, -CO-R1, -SO2 -R1or a biotinyl group; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consistingof alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N; and d) the fourth tetrapeptide is a tetrapeptide having the amino acid sequence U-QTAV-Z wherein Q is used to denote amino acid Glutamine, T is used to denote amino acid Threonine, A is used to denote amino acid Alanine and V is used to denote amino acid Valine; at the N-terminal end, U is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle, lipoyle; at the C-terminal end, Z is selected from the group consisting of OH, OR1, NHR1or NR1R2; R1and R2are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and / or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms O, S and / or N.

5. The composition for use of claim 1, the non-therapeutic use of claim 2, the non-therapeutic method of claim 3, or the method of claim 4, wherein the composition is applied to the scalp.

6. The composition for use, non-therapeutic use, or the method of any preceding claim wherein the tetrapeptide a) is selected from the group consisting of SEQ ID No: 1, SEQ ID No: 2, SEQ ID No: 3, SEQ ID No: 4, SEQ ID No: 5, SEQ ID No: 6, SEQ ID No: 7, SEQ ID No: 8, SEQ ID No: 9, SEQ ID No: 10, SEQ ID No: 11 and SEQ ID No: 12, preferably SEQ ID No: 1, SEQ ID No: 9 and SEQ ID No:

8.

7. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein tetrapeptide a) is U-LSVD-Z, U-LSPG-Z or U-LSPD-Z.

8. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein the peptide b) is selected from the group consisting of SEQ ID No: 13, SEQ ID No: 14, SEQ ID No: 15, SEQ ID No: 16 and SEQ ID No:

17.

9. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein peptide b) is U-GPKG-Z, U-GPEG-Z, or U-GPSG-Z.

10. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein U of the tetrapeptide is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle and lipoyle.

11. The composition for use, non-therapeutic use, or the method of any preceding claim wherein the third tetrapeptide is selected from the group consisting of SEQ ID No: 25, SEQ ID No: 26, SEQ ID No: 27, SEQ ID No: 28, SEQ ID No: 29, SEQ ID No: 30, SEQ ID No: 31, SEQ ID No: 32, SEQ ID No: 33, SEQ ID No: 34, SEQ ID No: 35, SEQ ID No: 36, SEQ ID No: 37, SEQ ID No: 38, SEQ ID No: 39, SEQ ID No: 40, SEQ ID No: 41, SEQ ID No: 42, SEQ ID No: 43, SEQ ID No: 44, SEQ ID No: 45, SEQ ID No: 46, SEQ ID No: 47, SEQ ID No: 48, SEQ ID No: 49, SEQ ID No: 50, SEQ ID No: 51, SEQ ID No: 52, SEQ ID No: 53 and SEQ ID No: 54, preferably from the list consisting of SEQ ID No: 25, SEQ ID No: 36, SEQ ID No: 44 and SEQ ID No:

51.

12. The composition for use, non-therapeutic use, or the method of any preceding claim wherein the third tetrapeptide (c) is selected from the group consisting of Pal-AKGD-OH, Pal-EKGD-OH, Pal-LKGD-OH, Pal-IRGD-OH.

13. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein U of the tetrapeptide is independently selected from the group consisting of lauroyl (C12), myristoyl (C14) and palmitoyl (C16).

14. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein tetrapeptide a) and / or peptide b), or tetrapeptide c), or tetrapeptide d) are individually present at from 0.1ppm to 10,000ppm by weight of the composition.

15. The composition for use, non-therapeutic use, non-therapeutic method or the method of any preceding claim wherein the composition further comprises additional further peptides selected from the group consisting of dipeptides, tripeptides, additional tetrapeptides, pentapeptides, hexapeptides and mixtures thereof.

Citation Information

Patent Citations

  • Composition, containing RGD motif-containing peptide or fragment thereof, for treating burns and glaucoma, alleviating skin wrinkles, and promoting hair growth

    CN107206047A

  • Pentapeptide derivatives for promoting hair growth

    US20130209551A1

  • Use of a peptide as a therapeutic agent

    WO2009033681A2

  • Tetrapeptide and compositions comprising tetrapeptides

    WO2022106054A1

  • Cosmetic compositions

    WO2023025416A1