MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Leuphasyl Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Leuphasyl (Pentapeptide-18, CAS 64963-01-5) is a synthetic cosmetic anti-wrinkle peptide developed by Lipotec/Lubrizol. Its sequence, Tyr-D-Ala-Gly-Phe-Leu, mimics the opioid leucine-enkephalin, with a D-alanine swap at position 2 that resists enzymatic breakdown. Like enkephalins, it binds neuronal opioid (enkephalin) receptors on motor-nerve terminals supplying facial mimetic muscles; the resulting G-protein modulation closes calcium channels and opens potassium channels, reducing acetylcholine release and softening dynamic expression lines without paralysis. It is a topical cosmeceutical used at 2-10% twice daily, frequently paired with Argireline (the Argirelox blend) for synergy. Manufacturer studies report roughly 11-12% wrinkle reduction for Leuphasyl alone and about 25% (up to ~47%) for the combination after 28 days. Leuphasyl is regulated as a cosmetic ingredient, not an approved drug, and is never administered by injection clinically.
Reconstitute: Add 2 mL bacteriostatic water → 5 mg/mL concentration.
Easy measuring: At 5 mg/mL, 1 unit = 0.01 mL = 0.0500 mg (50 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen; reconstituted refrigerated (2-8 C); avoid repeated freeze-thaw.
Half-life: No formal human plasma half-life is published; Leuphasyl acts locally in skin and is not meaningfully absorbed systemically. The D-Ala-2 substitution greatly extends its enzymatic stability versus native enkephalin (half-life of minutes).
Route: Topical only in real-world use: 2-10% in serums and creams applied twice daily to forehead, glabella, and crow's-feet. The subcutaneous reconstitution figures on this page are an educational conversion, not an injection protocol.
Status: Not FDA- or EMA-approved as a drug. Regulated globally as a cosmetic ingredient (INCI: Pentapeptide-18); raw peptide is sold for research use only.
About Leuphasyl
Leuphasyl (Pentapeptide-18) is a synthetic enkephalin-mimicking pentapeptide developed as a cosmeceutical anti-wrinkle ingredient[1]. Clinically it is a topical product: it is applied to the skin as a 2-10% serum or cream twice daily, not injected, and it carries no approved systemic or subcutaneous indication[2]. The subcutaneous reconstitution figures below are an educational reference that mirrors how this site standardizes every protocol; they are not a clinical injection regimen and should not be used to inject the peptide.
Educational guide for reconstitution and daily dosing
Frequency: Inject once daily subcutaneously (educational model only). A 10 mg vial reconstituted with 2.0 mL of bacteriostatic water yields 5 mg/mL, so each 50 mcg of peptide equals 1 unit on a U-100 syringe and the per-injection doses below land on clean, readable marks. To follow the real-world Leuphasyl dosage instead, use the topical twice-daily schedule described in the FAQ and How It Works sections, where it is also commonly layered with Argireline[1][2].
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 2.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake).
Let the solution sit until completely clear, then refrigerate at 2-8 C.
For the educational subcutaneous model, draw the prescribed units slowly and steadily; do not aspirate.
Interactive Leuphasyl Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 2mL water yields 5.00 mg/mL. To evaluate a 250mcg dose, pull to 5.0 units (5 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Weeks 1-4 (introduction) | 250 mcg | 5 units (0.05 mL) |
| Weeks 5-8 (build-up) | 500 mcg | 10 units (0.10 mL) |
| Weeks 9-12 (maintenance) | 750 mcg | 15 units (0.15 mL) |
| Weeks 13-16 (optional extension) | 1000 mcg (1 mg) | 20 units (0.20 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Leuphasyl, 10 mg each):
- check8 weeks ~ 3 vials
- check12 weeks ~ 5 vials
- check16 weeks ~ 7 vials
Insulin Syringes (U-100):
- checkPer week: 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- check16 weeks: 112 syringes
Bacteriostatic Water (10 mL bottles): Use 2.0 mL per vial for reconstitution.
- check8 weeks (3 vials): 6 mL -> 1 x 10 mL bottle
- check12 weeks (5 vials): 10 mL -> 1 x 10 mL bottle
- check16 weeks (7 vials): 14 mL -> 2 x 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs -> 2 x 100-count boxes
- check12 weeks: 168 swabs -> 2 x 100-count boxes
- check16 weeks: 224 swabs -> 3 x 100-count boxes
Mechanism of Action (MOA)
Leuphasyl is the cosmetic trade name for Pentapeptide-18 (INCI: Pentapeptide-18; CAS 64963-01-5), a synthetic pentapeptide with the sequence H-Tyr-D-Ala-Gly-Phe-Leu-OH, molecular formula C29H39N5O7 and a molecular weight of approximately 569.6 Da. It is a deliberate analog of the endogenous opioid leucine-enkephalin (Tyr-Gly-Gly-Phe-Leu): substituting a D-alanine residue for glycine at position 2 sharply increases resistance to aminopeptidase cleavage, so the molecule survives in a cosmetic formulation far longer than native enkephalin, whose biological half-life is only minutes [1][2]. Mechanistically, Leuphasyl behaves as an enkephalin mimic at the neuromuscular junction of facial mimetic muscles. It binds neuronal enkephalin (delta/mu opioid) receptors on motor-nerve terminals; the activated G-protein subunits close voltage-gated calcium channels and open potassium channels, hyperpolarizing the terminal. Reduced calcium influx limits synaptic-vesicle fusion and therefore decreases acetylcholine release into the synaptic cleft. With less acetylcholine reaching the muscle, contraction of the underlying expression muscle is attenuated and dynamic wrinkles (glabellar frown lines, forehead furrows, crow's feet) soften [1][5]. This is a pre-synaptic, reversible modulation of neurotransmitter release, mechanistically distinct from botulinum toxin, which enzymatically cleaves SNAP-25 to produce months-long chemodenervation; Leuphasyl's effect is milder, fully reversible and preserves natural facial expressivity [1][6]. Pharmacokinetically, Leuphasyl is a topical agent, not a systemic drug. Applied in 2-10% serums or creams, its dermal penetration is limited by the stratum corneum, and commercial products often rely on penetration enhancers or liposomal carriers to deliver peptide to the cutaneous nerve endings supplying mimetic muscle [7]. A formal human plasma half-life has not been characterized because the molecule is designed to act locally and is not meaningfully absorbed into the circulation; the D-Ala-2 substitution governs its cutaneous stability rather than any systemic clearance value [2]. Onset is gradual and cumulative over weeks of twice-daily use, and the effect fades after discontinuation. Leuphasyl is frequently co-formulated with Argireline (Acetyl Hexapeptide-8), the SNARE-targeting hexapeptide, in the Argirelox blend, because the two peptides inhibit acetylcholine signaling at different points of the contraction cascade and act synergistically. Manufacturer in vivo studies report mean glabellar wrinkle reductions of roughly 11-12% for Leuphasyl alone versus about 25% (with maxima near 47%) for the 5% Leuphasyl plus 5% Argireline combination after 28 days [2][6]. Reported benefits are modest relative to injectable neurotoxin but come with an excellent topical safety profile [1][3].
Clinical Trial Efficacy Highlights
- starIn a controlled cosmetic evaluation, Dragomirescu and colleagues formulated Leuphasyl into 0.5%, 1% and 2% oil-in-water emulsions and measured glabellar (between-the-eyebrow) wrinkles by pro-derm Analyser imaging; the study reported measurable relaxation of the mimetic muscle and reduction of expression wrinkles with good tolerability, with the higher tested concentrations producing the clearest effect while remaining safe [1].
- starManufacturer-sponsored in vivo studies summarized in the cosmeceutical-peptide literature report mean wrinkle reductions of approximately 11.64% for 5% Leuphasyl applied alone, 16.26% for 5% Argireline alone, and 24.62% for the two combined, after 28 days of twice-daily application, supporting a synergistic rather than merely additive effect [2][6].
- starThe 5% Leuphasyl plus 5% Argireline blend (marketed as Argirelox) has been reported to achieve maximum individual wrinkle-depth reductions as high as roughly 46.53%, attributed to the two peptides interrupting acetylcholine signaling at different stages of the muscle-contraction cascade [2][6].
- starReviews of bioactive dermatologic oligopeptides classify Pentapeptide-18 among the neurotransmitter-inhibiting ('Botox-like') cosmetic peptides; they note that, like the parent enkephalin, it modulates presynaptic acetylcholine release, that efficacy is lower than botulinum toxin, and that it preserves facial expressivity with no reported adverse effects [1][5].
- starSkin-permeation research on anti-wrinkle peptides shows that small peptides such as the enkephalin- and SNARE-derived actives cross the intact stratum corneum poorly, so demonstrated efficacy depends heavily on formulation strategies (penetration enhancers, molecular modification, or liposomal delivery) to reach cutaneous nerve endings [7].
- starTopical anti-aging peptide reviews consistently rate Leuphasyl as well tolerated with negligible systemic exposure, classifying it as a cosmetic ingredient rather than a transdermal drug and noting the absence of large, independent, randomized comparative trials against injectable neuromodulators [3][4].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningUsed as intended (a topical cosmetic), Leuphasyl is generally very well tolerated; the most common reactions are mild, transient erythema, stinging, or a sensation of tightness at the application site, especially when layered with retinoids or exfoliating acids.
- warningAllergic contact dermatitis to Pentapeptide-18 itself is uncommon, but reactions to other components of the finished formulation (preservatives, fragrance, penetration enhancers) can produce eczematous patches and warrant dermatologic evaluation if persistent.
- warningBecause the peptide is used near the eyes and forehead, accidental ocular contact may cause transient conjunctival irritation, watering, or burning; keep the product off the eye margin and rinse promptly with water if it migrates onto the ocular surface.
- warningNo systemic neuromuscular adverse events (dysphagia, ptosis, generalized weakness) have been reported, because the peptide is not meaningfully absorbed into the circulation through intact skin and does not produce the chemodenervation associated with botulinum toxin.
- warningSafety data in pregnancy, lactation, and pediatric use are absent; on a precautionary basis, cosmetic peptide products are generally avoided during pregnancy and breastfeeding despite the very low theoretical risk of systemic exposure.
- warningThe subcutaneous reconstitution figures on this page are an educational conversion only. Leuphasyl is not validated, sterile-tested, or approved for injection; injecting research-grade cosmetic peptide carries risks of infection, local reactions, contaminant exposure, and unknown systemic effects and should not be done.
- warningRegulatory status is cosmetic, not pharmaceutical: Leuphasyl is sold for topical cosmetic formulation and, in raw form, for research use only. It has not undergone drug-style efficacy or toxicology review by the FDA or EMA.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Leuphasyl dosage?expand_more
In real-world cosmetic use, Leuphasyl (Pentapeptide-18) is a topical peptide, not an injectable. Finished serums and creams typically contain 2-10% Leuphasyl, applied as a thin layer to the forehead, glabella, and crow's-feet twice daily, often alongside Argireline. There is no established systemic or subcutaneous Leuphasyl dosage; the 250-1000 mcg per-injection figures shown on this page are an educational reconstitution reference, not a clinical regimen.
Is Leuphasyl FDA approved?expand_more
No. Leuphasyl is not an FDA- or EMA-approved drug. It is regulated as a cosmetic ingredient under the INCI name Pentapeptide-18 and marketed for topical formulation by Lipotec/Lubrizol. As a cosmetic active it must meet cosmetic safety requirements but does not undergo drug-style efficacy approval. Raw Leuphasyl powder is sold for research use only.
How do you reconstitute Leuphasyl?expand_more
For the educational subcutaneous model on this page, draw 2.0 mL of bacteriostatic water and inject it slowly down the wall of a 10 mg vial, then swirl gently (do not shake) until the solution is clear. This yields 5 mg/mL, so 50 mcg equals 1 unit on a U-100 syringe. Note this is a conversion reference only; in practice Leuphasyl is used as a pre-formulated topical product, not reconstituted for injection.
What is the half-life of Leuphasyl?expand_more
A formal human plasma half-life for Leuphasyl has not been published, because it is designed to act locally in the skin and is not meaningfully absorbed into the bloodstream. The key stability feature is the D-alanine substitution at position 2, which makes it far more resistant to aminopeptidase breakdown than native leucine-enkephalin (whose biological half-life is only minutes), extending its useful lifetime within a topical formulation.
Can Leuphasyl be stacked with other peptides like Argireline?expand_more
Yes. Leuphasyl is most commonly combined with Argireline (Acetyl Hexapeptide-8) in the Argirelox blend, where the two inhibit acetylcholine signaling at different points of the muscle-contraction cascade for a synergistic, greater-than-additive wrinkle-smoothing effect. It is also formulated with Matrixyl, GHK-Cu, hyaluronic acid, and antioxidants. Stacking multiple potent actives can increase the chance of irritation.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Leuphasyl, plus the universal dosing calculator.
Academic References & Study Citations
Dragomirescu AO, Andoni M, Ionescu D, Andrei F. The Efficiency and Safety of Leuphasyl-A Botox-Like Peptide. Cosmetics. 2014;1(2):75-81. View Scientific Paper →
Errante F, Ledwon P, Latajka R, Rovero P, Papini AM. Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Front Chem. 2020;8:572923. View Scientific Paper →
Schagen SK. Topical Peptide Treatments with Effective Anti-Aging Results. Cosmetics. 2017;4(2):16. View Scientific Paper →
Gorouhi F, Maibach HI. Role of topical peptides in preventing or treating aged skin. Int J Cosmet Sci. 2009;31(5):327-345. View Scientific Paper →
Reddy BY, Jow T, Hantash BM. Bioactive oligopeptides in dermatology: Part II. Exp Dermatol. 2012;21(8):569-575. View Scientific Paper →
Blanes-Mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-310. View Scientific Paper →
Lim SH, Sun Y, Thiruvallur Madanagopal T, Rosa V, Kang L. Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification. Sci Rep. 2018;8(1):1596. View Scientific Paper →