By using this site you agree to the use of cookies to propose services and offers tailored to your centres of interest.

For more information and cookie configuration
My account  |   Newsletter Subscription  |   Contact us  |  
established expression wrinkles supporting dermo-aesthetic care
Bibliographical summary
  • INCI name : Caprooyl tetrapeptide-3
  • Pure molecule obtained by Biosynthesis


Peptide-4 Pro-collagen is a complex containing an active sequence of three amino acids: glycin (G), histidin (H) and lysin (K). This sequence, also called tripeptide GHK, was discovered in 1973 by Loren Pickart. It is a biomimetic peptide, naturally present in humans, and skin in particular. This peptide has several biological activities including the activation of tissue repair, stimulation of collagen biosynthesis, attraction of immunity cells, anti-inflammatory and anti-oxidizing effects and angiogenesis stimulation.

Given its major role in skin biology, tripeptide GHK preparations have been used in several applications such as healing skin wounds, post-laser treatment or simply when the skin is altered

The chosen form corresponds to a tetrapeptide (sequence of 4 amino acids) revolving around the stabilised G-H-K sequence and grafted onto a fatty acid allowing it to be more bioavailable in skin.



In molecular terms, tripeptide GHK helps rebuild new skin by stimulating angiogenesis, producing components of the extracellular matrix and renewing secretion of TGF-β 1 by fibroblasts. GHK also has anti-inflammatory and chemiotactical properties.

Tripeptide GHK acts on the biosynthesis of new skin tissues

Tripeptide GHK stimulates angiogenesis by inducing an increase in the expression of the basic fibroblast growth factor (β-FGF) and of the vascular endothelial growth factor (VEGF) [1]. It also stimulates the proliferation of fibroblasts [1].

GHK tripeptide redensifies the skin by stimulating biosynthesis of components in the extracellular matrix

GHK stimulates synthesis of collagen, proteoglycans and glycosaminoglycans (dermatan sulphate and heparan sulphate) [2, 3, 4]. These molecules are key components in the extracellular matrix and are intimately linked to the firmness and density of skin.
GHK activates part of MMP-2 metalloproteinase production and their TIMP-1 and 2 inhibitors in order to remove damaged protein from the extracellular matrix and activate the synthesis of new proteins to rebuild this extracellular matrix [5]. Furthermore, GHK reduces the secretion of TGF-β 1 (factor inducing scar formation) by fibroblasts [6].

In vivo, Peptide-4 Pro-collagen significantly reduces the depth of fine lines and wrinkles

In vivo (clinical test), Peptide-4 Pro-collagen has been tested on volunteers in a 2.5% formulation. Applied twice a day on healthy skin for 56 days, it reduces fine lines and wrinkles by an average 27%. Treatment with this peptide reveals a significant increase in dermal intensity for 78% of volunteers as well as increased homogeneity of the dermis for 70% of volunteers [7].

Regaining younger skin biologically requires two interdependent processes: the elimination of damaged proteins and atypical skin lesions and their replacement by healthy tissue [8]. This process is similar to the scar remodelling phase whereby scar tissue is removed by restoring skin to its initial state. In young children, this process is very rapid and damaged skin is rapidly eliminated. In adults this process is much slower and scars can remain for several years

Peptide-4 Pro-collagen acts like an inducer of the second phase of healing: when the remodelling process repairs tissues and rebuilds healthy skin. Likewise, when applied on mature skin, Peptide-4 helps regain biologically younger skin and reduce existing fine lines and wrinkles.



In this synthetic tetrapeptide, the active part is the tripeptide GHK (combination of 3 amino acids: glycin, histidin, lysin). It is scientifically proved that this tripeptide helps skin reconstruction by stimulating the production of constituents in the extracellular matrix.

The GHK tripeptide redensifies skin by stimulating biosynthesis of collagen, proteoglycans and glycoaminoglycans naturally contained in the dermis. It is good quality dermis that gives skin its firmness and density.

In a clinical study, it was shown that tripeptide GHK significantly reduced the depth of wrinkles and fine lines. It is therefore an interesting anti-ageing molecule that should be used over a long period of time (several months) as the expected dermal redensifying effect is obviously not instant.



All publications and scientific studies, the uses of this active and the opinion of our expert combine to recommend the use of this active at a dose of 2.5%, i.e. 7 µg of peptide-4 per 15 ml bottle.



[1] Effects of Copper Tripeptide on the Growth and Expression of Growth Factors by Normal and Irradiated Fibroblasts. Pollard JD et al. Arch. Facial Plast Surg, 7: 25-31. 2005.

[2] Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Maquart FX et al., FEBS Letter, 238(2): 343-346. 1988.

[3] Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Wegrowski Y et al., Life Sciences. 51(13): 1049-1056. 1992.

[4] The human tri-peptide GHK and tissue remodeling. Pickart L. J Biomater Sci. 19(8) : 969-988. 2008.

[5] The tripeptide-copper complex glycyl-L-histidyl-Llysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Siméon A et al., Life Sciences. 67 : 2257-2265. 2000.

[6] The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model. McCormack MC et al., Arch Facial Plast Surg. 3(1): 28-32. 2001.

[7] Clinical trial. Study manager: Loing E. Unipex, 2009. (Supplier document)


Activity Method and length
Tested product and dose

Wrinkle smoothing

Study on 2 female volunteers aged between 40 and 65 with healthy skin. The volunteers applied a placebo cream on the temple randomly with the cream containing Peptide-4 pro-collagen on the other side of the face. Applications were repeated twice a day for 56 days.

Measurement of wrinkle depth of crow's feet by taking an imprint and profilometric analysis.

A sound scan survey was conducted to analyse dermal structures on the crow's feet at D0 and after 168 days of application.

Cream containing 5 ppm of Peptide-4 Pro-collagen

Placebo cream

Wrinkle smoothing effect: After 28 days of application, a significant reduction in fine lines and wrinkles (16% on average) was observed, with a maximum reduction of 29% against the placebo. For women aged between 50 and 65, there was an average reduction of -14% at D28 and -27% at D56

Dermal structures : treatment with the peptide revealed a significant increase in entropy for 78% of volunteers and a significant increase in homogeneity of the dermis for 70% of volunteers. The peptide can therefore restore collagenic structures of the dermis and reverse signs of ageing.

[8] 8. Copperceuticals and the Skin. Pickart L. Cosmetics & Toiletries, pages 24-28. Juillet 2003.