The Clinical Evidence-Based Paradigm of Topical Anti-Aging Skincare Formulations Enriched with Bio-Active Peptide SA1-III (KP1) as Collagen Modulator: From Bench to Bedside

Figures & data

Figure 1 The pathogenesis of premature/extrinsic aging of the skin.² Reprinted from Kim M, Hyun Jeong, Park. Molecular mechanisms of skin aging and rejuvenation. In: Shiomi H, editor. Molecular Mechanisms of the Aging Process and Rejuvenation. London: IntechOpen; 2016:57–76. © 2016 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License.

Abbreviations: ROS, reactive oxygen species; AhR, arylhydrocarbon receptor; NF-kB, nuclear factor kappa‐B; IL, interleukin; TNF-α, tumor necrosis factor; CCN1, cysteine-rich protein 61; MAPK, mitogen‐activated protein kinase; AP‐1, activator protein 1; MMPs, matrix metalloproteinases; ROS, reactive oxygen species; UV, ultraviolet; VEGF, vascular endothelial growth factor.

Figure 2 Effect of SA1-III (20 mM) peptide and TGF-beta (10 ng/mL) on the secretion and activation of gelatinases MMP-9 (upper right panel) and MMP-2 (lower panel) in culture medium.¹¹ *P<0.05 statistically significant difference (Student’s t-test for paired data) from the corresponding control. Reproduced from Cipriani C, Pascarella S, Errante F, et al. Serpin A1 and the modulation of type I collagen turnover: effect of the C-terminal peptide 409–418 (SA1-III) in human dermal fibroblasts. Cell Biol Int. 2018;42(10):1340–1348. Copyright 2018, John Wiley and Sons.

Abbreviations: CTRL, control; MMP, matrix metalloprotease; TGF-B1, transforming growth factor beta-1.

Table 1 Ingredients of KP1 Serum, Face Cream and Eye Contour Cream

KP1 Serum	KP1 Cream		KP1 Eye Contour Cream
Common key ingredients
Acetyl SH-Decapeptide-4 SP amide trifluoroacetate (KP1): peptide inhibitor of collagen degradation Sodium hyaluronate: high-molecular-weight (1.800 kDa) for superficial hydration Hydrolyzed hyaluronic acid: low-molecular-weight (50 kDA) for deeper hydration and smoothened wrinkles Creatine: improves clinical signs of skin ageing by stimulating dermal collagen
Product-specific key ingredients
Niacinamide: reduction in fine lines and wrinkles, hyperpigmented spots, red blotchiness and skin sallowness (yellowing); improved elasticity			-
-	Tocopheryl Acetate: antioxidant; protects the skin from various deleterious effects of solar radiation (free-radical scavenger)
Active Tuber magnatum (white truffle) Extract: increases skin elasticity and hydration; reduces dark circles and wrinkles	Salicyloyl Phytosphingosine (SP): repair of photo-aged skin^Citation21		Crosslinked Sodium Hyaluronate: rapidly and deeply hydrates the skin; rapidly reduces wrinkles^Citation33 Acetyl Hexapeptide-8 (Argireline): neurotransmitter inhibitor peptide emulating the action of botulinum toxin; reduces expression lines in the short-term^Citation23 Acetyl Tetrapeptide-5 (Eyeseryl): inhibits angiotensin-converting enzyme; reduces eye edema and dark circles (draining and decongestant effects); increases hydration and elasticity in the periocular area^Citation24
Other ingredients
Aqua, Glycerin, Butylene glycol, Panthenol Sodium lactate, Sodium PCA, Sodium benzoate, Xanthan gum, Parfum, Potassium sorbate, Citric acid, EDTA, Fructose, Glycine, Urea, Inositol, Lactic acid, Hexyl cinnamal, Limonene, Linalool	Aqua, Caprylic/Capric Triglyceride, Isoamyl Cocoate, Ethylhexyl Stearate, Glycerin, Glyceryl Stearate, Stearyl Alcohol, Persea gratissima (Avocado) Oil, Propylene Glycol, Glyceryl Stearate Citrate, Stearic Acid, Panthenol, Phenoxyethanol, Bis-PEG / PPG-20/ 5 PEG/ PPG-20/ 5 Dimethicone, Methoxy PEG / PPG-25 / 4 Dimethicone, Dimethicone, Parfum, Sodium Lactate, Sodium PCA, Carbomer, Ethylhexylglycerin, Sodium Benzoate, Sodium Hydroxide, Disodium EDTA, BHT, Fructose, Glycine, Inositol, Lactic Acid, Urea, Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinnamate		Aqua, Caprylic/Capric Triglyceride, Isoamyl Cocoate, Propylene glycol, Glyceryl Stearate, Glyceryl Stearate Citrate, Stearyl alcohol, Butylene Glycol, Persea gratissima (Avocado) oil, Ethylhexyl Palmitate, Stearic acid, Phenoxyethanol, Ethylhexyl Stearate, Tocopheryl acetate, Panthenol, Dimethicone, Butyrospermum parkii (Shea) Butter, Carbomer, Parfum, Polyglyceryl-4 Diisostearate / Polyhydroxystearate/ Sebacate, Sodium Isostearate, Ethylhexylglycerin, Sodium Benzoate, Sodium Hydroxide, Disodium EDTA, BHT, Caprylyl Glycol

Table 2 Results of Instrumental and Subjective Evaluations of SA1-III Face Cream and Face Serum

Product	Face Cream (ISPE, 2018)^Citation25	Face Serum (ISPE, 2022)^Citation26
Study characteristics	Included 20 female volunteers aged 40 to 70 years (average age of 60.0 years) All volunteers applied KP1 face cream twice daily for 4 weeks)	Included 20 female volunteers aged 40 to 70 years (average age of 60.0 years) All volunteers applied KP1 face cream twice daily for 4 weeks)
Results (baseline vs end of study)
Skin hydration (cu)	52.2 ± 5.3 vs 74.7 ± 8.2 (Δ22.5; 43.1%; p<0.0001)	52.5 ± 9.6 vs 69.3 ± 11.0 (Δ16.8; 32.0%; p<0.0001)
Skin deep hydration (%)	NR	49.9 ± 5.1 vs 53.2 ± 4.0 (3.3; p<0.01)
Skin extensibility (mm)	0.230 ± 0.056 vs 0.197 ± 0.058 (Δ−0.033; −14.3%; p<0.0001)	0.296 ± 0.084 vs 0.212 ± 0.084 (Δ−0.084; −28.4%; p<0.0001)
Gross elasticity	0.591 ± 0.066 vs 0.625 ± 0.063 (Δ0.034; 5.8%; p<0.0001)	0.668 ± 0.110 vs 0.726 ± 0.103 (Δ0.058; 8.7%; p<0.0001)
Skin echogenicity/density (%)	31.54 ± 6.04 vs 33.77 ± 5.22 (2.23; p<0.001)	30.15 ± 6.53 vs 32.82 ± 6.81 (Δ2.67; p<0.0001)
Average skin roughness (μm)	66.4 ± 4.4 vs 58.8 ±15.3 (Δ−8.6; −13.0%; p<0.01)	46.2 ± 12.2 vs 40.0 ± 8.8 (Δ−6.2; −13.4%; p<0.001)
Average maximum roughness (μm)	849 ± 145 vs 763 ± 193 (−86; −10.1%; p<0.001)	540.1 ± 123.2 vs 462.7 ± 114.4 (−77.4; −14.3%; p<0.001)

Figure 3 3D skin images obtained by Primos Pico Optical 3D Skin Measuring Device on a heathy volunteer before and after 4 months of treatment with KP1 serum. Courtesy of ISPE S.r.l.

Figure 4 Digital images of skin echogenicity/density obtained by Ultrasound Scanner Dermascan showing increased echogenic dermal fibers after 4 weeks of treatment. (A) Facial serum. (B) Face cream. Courtesy of ISPE S.r.l.

Figure 5 Photographs of selected participants before and after 4 weeks of treatment with a KP1 face serum. Courtesy of DERMING, S.r.l.

Figure 6 Photographs of selected participants before and after 4 weeks of treatment with a KP1 face cream. Courtesy of DERMING, S.r.l.

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