Hexapeptide-9 vs Pentapeptide-18
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Collaxyl, Collaxyl IS
Hexapeptide-9 is a collagen-inspired signaling peptide sold as Collaxyl (originally from Vincience, now Ashland) for anti-wrinkle and firming skincare. The idea is that a small repeat of a collagen sequence nudges skin cells to rebuild the junction between the outer and inner skin. It is a cosmetic ingredient, and the evidence for the original peptide is mostly old, small and company-run, although a 2025 trial on a modified cyclic version is more interesting.
Also: Leuphasyl, Tyr-Ala-Gly-Phe-Leu
Pentapeptide-18 is Lipotec's Leuphasyl, a 'Botox-like' cosmetic peptide modeled on enkephalins, the body's own calming neuropeptides. It is mostly sold alongside Argireline, with the claim that the two relax expression lines better together. It is a cosmetic ingredient, and the evidence is small and mostly manufacturer-run.
Key Comparison Insights
- Both peptides belong to the Skin & Hair category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Hexapeptide-9 | Pentapeptide-18 |
|---|---|---|
| Category | Skin & Hair | Skin & Hair |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | Hexapeptide-9 is Gly-Pro-Gln-Gly-Pro-Gln, a repeat taken from collagen sequences. Ashland says the sequence is found in collagen IV and XVII and works as a matrikine, a matrix fragment that signals cells to make more matrix proteins. The claimed targets are the dermal-epidermal junction (collagen IV, laminin-5, integrins) and collagen production. The original patent describes it as designed to improve cell adhesion and possibly support matrix production. One weakness is stability: the linear peptide is easily broken down by collagen-digesting enzymes, which is why a Chinese group built a ring-shaped (cyclized) version to make it last longer in skin. | Pentapeptide-18 is Tyr-Ala-Gly-Phe-Leu, a close copy of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) with one amino acid swapped. The theory is that it binds enkephalin receptors on nerve endings, which dampens nerve activity and lowers acetylcholine release at the junction with facial muscles. Argireline works at a different step (the SNARE complex inside the nerve ending), which is why the two get marketed as a combo. The same big caveat as Argireline applies: it is sold on a nerve-to-muscle mechanism, but nobody has shown in living skin that a topical cream delivers enough peptide to the muscle to do this. |
| Common Dosing | Low single-digit percent of the ingredient in a finished product Once or twice daily | About 2-5% of the commercial solution in a finished product Once or twice daily |
| Administration | Topical (serums, creams) | Topical (serums, creams) |
| Typical Duration | 4-8 weeks in studies; ongoing use to maintain any effect | 28 days to 2 months in studies; ongoing use to maintain any effect |
| Best Time to Take | Morning and/or evening, on clean skin | Morning and/or evening, on clean skin |
Possible Side Effects May vary by individual |
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| Research Summary | The oldest human data is a 2004 study from Vincience, the lab behind Collaxyl: a double-blind, placebo-controlled test of a gel containing 3% of a 'collagen-like hexapeptide' plus a 1% booster ingredient, applied around the eyes of 20 women for four weeks. It reported fewer and shallower wrinkles on skin replicas, but the booster and the small size mean it cannot prove the peptide alone did the work. Supplier material cites other 28-day studies in about 20 volunteers that we could not trace to journals. The newest and best-designed study is a 2025 randomized, double-blind trial in the Journal of Cosmetic Dermatology (96 adults aged 30-55 in China) comparing a cyclized hexapeptide-9 serum at 0.002% with 0.002% retinol and a vehicle for 56 days. The cyclized peptide beat both on wrinkle, elasticity and hydration measures, with no treatment-related side effects. Two caveats: it tested a modified molecule, not the Collaxyl peptide in most products, and several authors are affiliated with cosmetic companies. Bottom line: the concept has some support, the cyclic version looks promising, but regular hexapeptide-9 in a store-bought cream rests on thin evidence. | The most quoted numbers come from a Lipotec study: about 11% wrinkle reduction with 5% Leuphasyl alone over 28 days in a small panel, and about 25% with 5% Leuphasyl plus 5% Argireline. The company calls that synergy, but on its own figures the combination roughly equals the two effects added together, so 'synergistic' is a stretch. The one journal paper we found is Dragomirescu and colleagues (2014, Cosmetics, MDPI), which tested 0.5%, 1% and 2% emulsions around the eyebrows and eyes for efficacy and safety. Trade summaries say only the 2% cream gave a significant improvement after two months in about 20 volunteers; we could not read the full paper to confirm the numbers. A 2020 review of cosmetic peptides lists it among the neurotransmitter-inhibitor peptides and notes that much of the support comes from the manufacturer. Bottom line: safe enough as a skincare ingredient and plausible on paper, but expect subtle softening at most, not anything close to an injection. |
Frequently Asked Questions: Hexapeptide-9 vs Pentapeptide-18
What is the difference between Hexapeptide-9 and Pentapeptide-18?
Hexapeptide-9 is a skin & hair peptide that hexapeptide-9 is a collagen-inspired signaling peptide sold as collaxyl (originally from vincience, now ashland) for anti-wrinkle and firming skincare. the idea is that a small repeat of a collagen sequence nudges skin cells to rebuild the junction between the outer and inner skin. it is a cosmetic ingredient, and the evidence for the original peptide is mostly old, small and company-run, although a 2025 trial on a modified cyclic version is more interesting. Pentapeptide-18 is a skin & hair peptide that pentapeptide-18 is lipotec's leuphasyl, a 'botox-like' cosmetic peptide modeled on enkephalins, the body's own calming neuropeptides. it is mostly sold alongside argireline, with the claim that the two relax expression lines better together. it is a cosmetic ingredient, and the evidence is small and mostly manufacturer-run. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Hexapeptide-9 or Pentapeptide-18?
Neither is universally "better" - the choice depends on your specific goals. Hexapeptide-9 is typically used for skin & hair purposes, while Pentapeptide-18 is used for skin & hair. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Hexapeptide-9 and Pentapeptide-18 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Hexapeptide-9 and Pentapeptide-18 together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.