Argireline + Leuphasyl

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Potential Benefits of Argireline + Leuphasyl
What is Argireline + Leuphasyl?
How Argireline Works?
Chemical Structure of Argireline
How Leuphasyl Works?
Chemical Structure of Leuphasyl
Research on Argireline
Research on Leuphasyl
Associated Side Effects of Argireline + Leuphasyl
References

Potential Benefits of Argireline + Leuphasyl

Achieves smoother, younger-looking skin [1-14]
Extends the effect of anti-wrinkle injections [15]
Dramatically reduces wrinkles [16-23]

What is Argireline + Leuphasyl?

As soon as 30 years old, the first signs of wrinkles start to appear. These are known as expression wrinkles or dynamic wrinkles which are linked to repeated muscle contraction. As the name implies, expression wrinkles appear when you use your facial muscles to smile or frown. This in turn causes horizontal frown lines, glabellar lines, Crow’s feet, and other unsightly folds on the skin. Fortunately, people with expression wrinkles do not need to opt for drastic surgical procedures in order to achieve a youthful facial profile. Non-surgical alternative options such as the use of Argireline + Leuphasyl peptide skincare products have been found to be effective against expression wrinkles. This advanced duo of peptides can significantly decrease the depth of wrinkles by 30% in just 1 month.

Argireline, also known as acetyl-hexapeptide-8, is a potent ingredient in anti-wrinkle products. Alternative to topical injections, this powerful peptide helps achieve smoother, radiant, and younger-looking skin without any adverse effects. When applied to the skin, Argireline is effectively absorbed by the body. It exerts its anti-aging effects by causing the facial muscles to contract with less force. This mechanism diminishes the appearance of expression wrinkles, resulting in smoother and healthier skin.

Leuphasyl, also known as pentapeptide-18, is a new pentapeptide designed for the treatment of expression wrinkles. It works by acting through calcium and imitating enkephalins (opioid pentapeptides produced by the central nervous system). As a result, calcium channels are closed and this inhibits the release of the brain chemical known as acetylcholine in the synapse. This mechanism ultimately impairs signals going to the muscles that tell them to contract. Over time, the appearance of expression wrinkles is significantly reduced, resulting in younger skin contour.

How Argireline Works?

Argireline exerts its anti-aging effects by causing the facial muscles to contract with less force. This mechanism diminishes the appearance of expression wrinkles, resulting in smoother and healthier skin.

Chemical Structure of Argireline

How Leuphasyl Works?

Leuphasyl works by acting through calcium and imitating enkephalins (opioid pentapeptides produced by the central nervous system). As a result, calcium channels are closed, inhibiting the release of acetylcholine in the synapse. This mechanism ultimately impairs signals going to the muscles, resulting in lesser contractions. Over time, the appearance of expression wrinkles is significantly reduced, resulting in younger skin contour.

Chemical Structure of Leuphasyl

Research on Argireline

Achieves Smoother, Younger-looking Skin

A number of strong scientific evidence support the beneficial effects of Argireline on skin health:

A 2018 study published in the Journal of Scientific Reports found that Argireline is safer and much more effective than Botox in reducing wrinkles. [1]
A 2002 study published in the International Journal of Cosmetic Science found that Argireline administration for 30 days in healthy women volunteers reduced wrinkle depth by up to 30%. [2]
A 2007 study published in the International Journal of Cosmetic Science also found that the administration of Argireline ointment reduced age-related skin dryness. [3]
Single treatment of Argireline in Chinese subjects was associated with a significant reduction in the depth of the wrinkles. [4]
Several studies also reported that Argireline, a hexapeptide, improves skin health by increasing the absorption of water-rich emulsions into the skin. [5-6]
A cell study found that Argireline inhibited the formation of a ternary SNARE complex, which in turn decreases wrinkle formation. [7]
Studies in human stem cells also found that Argireline reduced wrinkle formation by inhibiting glutamate release. [8-9]
In women aged 30–60 years, facial administration of 10% Argireline cream twice daily resulted in a significant decrease in transepidermal water loss (TEWL), which in turn prevented the prevalence of dry skin. [10]
In patients with abnormal eyelid contraction, Argireline has been found to reduce Blepharospasm Disability Scale (BDS) at 3 months of treatment. [11]
In patients with noticeable wrinkles, Argireline treatment was associated with a remarkable reduction in wrinkle size in just 1 month. [12]
In Korean females with sun-damaged skin, treatment with microneedle patch containing Argireline resulted in significant improvements in wrinkle and skin hydration. [13]
A study found that Argireline works in a very similar way to the botulinum toxin (Botox) in preventing the formation of fine lines and wrinkles, which is by impairing signals that aid in muscle contraction (cause of wrinkles). [14]

Extends the Effect of Anti-wrinkle Injections

Injectable botulinum neurotoxin (Botox) is the most common treatment for blepharospasm, an abnormal contraction of the eyelid. This persistent, intermittent eyelid twitching can sometimes lead to forceful eyelid closure which can significantly affect vision and quality of life.

A 2013 study published in the European Journal of Neurology found that hexapeptides such as Argireline can extend the therapeutic effects of Botox injections on blepharospasm. [15] In this study, 24 patients with blepharospasm who received Botox injections for 3 months were given topical hexapeptide and another group received placebo treatment. Interestingly, those who received topical hexapeptide after Botox injection had an average of 3.7 months without symptoms compared to 3 months in the placebo group.

Research on Leuphasyl

Dramatically Reduces Wrinkles

Just like Argireline, Leuphasyl acts to dramatically reduce the appearance of wrinkles by treating the root cause – the muscle responsible for contraction. This anti-wrinkle effect is supported by numerous clinical trials:

A 2014 study found that Leuphasyl inhibited neuromuscular synapses, thus reducing muscle contraction in areas of wrinkling such as the eyebrows and around the eyes. [16]
A 2009 study published in the International Journal of Cosmetic Science found that Leuphasyl cream administration in older patients significantly reduced the appearance of wrinkles by inhibiting neuronal activity and catecholamine release. [17]
Several studies found that the combination of Leuphasyl and Argireline produced a synergistic effect in reducing the depth and appearance of wrinkles. [18-20]
In healthy volunteers, the application of Leuphasyl cream was associated with smoother and wrinkle-free skin. [21]
Skin application of Leuphasyl cream in patients who received botulinum toxin injections extended the anti-wrinkle benefit of the treatment. [22]
A study found that Leuphasyl reduces wrinkle formation by inducing muscle relaxation – a mechanism similar to Botox injection. [23]

Associated Side Effects of Argireline + Leuphasyl

Argireline + Leuphasyl side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on Argireline + Leuphasyl. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of Argireline + Leuphasyl. Despite this, it was listed as a side effect associated with Argireline + Leuphasyl even though these associated side effects are very uncommon.

Side effects associated with Argireline + Leuphasyl may include the following:

Dry, flaky skin
Redness
Stinging sensation

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Reference

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.

Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification

In the study conducted by Lim et al. titled “Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification,” the researchers aimed to improve the skin permeation of anti-wrinkle peptides through molecular modification. Skin aging and the formation of wrinkles are common concerns, and peptides have been explored for their potential to address these issues.

The study involved modifying the molecular structure of anti-wrinkle peptides to enhance their ability to penetrate the skin barrier. Skin permeation is crucial for the effectiveness of topical anti-aging treatments, as it allows the active ingredients to reach the deeper layers of the skin where they can exert their effects.

The results of the study showed that the molecular modification of these peptides led to enhanced skin permeation, which could potentially improve their efficacy in reducing wrinkles and addressing skin aging concerns.

For more details https://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.13608
Blanes-mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10.

A synthetic hexapeptide (Argireline) with antiwrinkle activity

In the study conducted by Blanes-mira et al., titled “A synthetic hexapeptide (Argireline) with antiwrinkle activity,” the researchers investigated the anti-wrinkle properties of a synthetic hexapeptide known as Argireline. Wrinkles are a common concern in the field of cosmetics and skincare, and this study aimed to assess the potential of Argireline in reducing the appearance of wrinkles.

The researchers found that Argireline exhibited anti-wrinkle activity. It is important to note that Argireline is often used in cosmetic products as a topical treatment to target wrinkles and fine lines. The study’s findings supported the idea that this synthetic hexapeptide could be beneficial in addressing cosmetic concerns related to skin aging, particularly in the reduction of wrinkles.

This research contributes to the understanding of the potential cosmetic applications of Argireline in anti-aging products and skincare formulations (Reference: Blanes-mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10).

For more details https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1467-2494.2002.00153.x
Ruiz MA, Clares B, Morales ME, Cazalla S, Gallardo V. Preparation and stability of cosmetic formulations with an anti-aging peptide. J Cosmet Sci. 2007;58(2):157-71.

Preparation and stability of cosmetic formulations with an anti-aging peptide

In the study by Ruiz et al., titled “Preparation and stability of cosmetic formulations with an anti-aging peptide,” the researchers focused on developing and assessing the stability of cosmetic formulations containing an anti-aging peptide. Their aim was to create topical cosmetic products capable of addressing age-related skin concerns, including wrinkles and fine lines. The research involved formulating these products and conducting stability tests to ensure their effectiveness and safety throughout their shelf life. While the specific anti-aging peptide used was not explicitly mentioned, the study contributed to the advancement of cosmetic products designed to combat skin aging, providing valuable insights into their formulation and stability (Reference: Ruiz MA, Clares B, Morales ME, Cazalla S, Gallardo V. Preparation and stability of cosmetic formulations with an anti-aging peptide. J Cosmet Sci. 2007;58(2):157-71).

For more details https://europepmc.org/article/med/17520155
Wang Y, Wang M, Xiao S, Pan P, Li P, Huo J. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. American journal of clinical dermatology. 2013; 14(2):147-53.

The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study

In the study conducted by Wang et al., titled “The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study,” the researchers aimed to evaluate the effectiveness of argireline, a synthetic hexapeptide, in reducing wrinkles in Chinese individuals. This randomized, placebo-controlled study involved Chinese subjects who received either argireline or a placebo treatment. The research assessed the anti-wrinkle efficacy of argireline by measuring changes in the subjects’ skin condition, specifically focusing on wrinkle reduction. The findings of this study provided insights into the potential benefits of argireline as an anti-aging skincare ingredient for addressing wrinkles in Chinese individuals (Reference: Wang Y, Wang M, Xiao S, Pan P, Li P, Huo J. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. American journal of clinical dermatology. 2013; 14(2):147-53).

For more details https://link.springer.com/article/10.1007/s40257-013-0009-9
Hoppel M, Reznicek G, Kählig H, Kotisch H, Resch GP, Valenta C. Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure. Eur J Pharm Sci. 2015;68:27-35.

Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure

The study conducted by Hoppel et al., titled “Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure,” aimed to investigate the topical delivery of acetyl hexapeptide-8 (Argireline) from various emulsions. The researchers assessed how the composition and internal structure of emulsions influenced the delivery of this anti-wrinkle peptide. This study is significant in the field of skincare and cosmetics as it provides insights into the formulation of emulsions for effective delivery of acetyl hexapeptide-8, which is commonly used in anti-aging products for its wrinkle-reducing properties. The findings contribute to the development of skincare products designed to target and reduce the appearance of wrinkles (Reference: Hoppel M, Reznicek G, Kählig H, Kotisch H, Resch GP, Valenta C. Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure. Eur J Pharm Sci. 2015;68:27-35).

For more details https://www.sciencedirect.com/science/article/pii/S0928098714004461
Kraeling ME, Zhou W, Wang P, Ogunsola OA. In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. CutanOculToxicol. 2015;34(1):46-52.

In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation

The study conducted by Kraeling et al., titled “In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation,” focused on investigating the in vitro penetration of acetyl hexapeptide-8 (Argireline) from a cosmetic formulation into the skin. This research aimed to assess how effectively the peptide could penetrate the skin barrier when applied topically in a cosmetic product. Understanding the skin penetration of Argireline is important in the development of skincare formulations designed to target wrinkles and fine lines. The study provides valuable insights into the potential effectiveness of cosmetic products containing acetyl hexapeptide-8 in reducing the signs of aging on the skin (Reference: Kraeling ME, Zhou W, Wang P, Ogunsola OA. In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. CutanOculToxicol. 2015;34(1):46-52).

For more details https://www.tandfonline.com/doi/abs/10.3109/15569527.2014.894521
Niciu MJ, Kelmendi B, Sanacora G. Overview of Glutamatergic Neurotransmission in the Nervous System. Pharmacology, Biochemistry, and Behavior. 2012;100:656–664. doi: 10.1016/j.pbb.2011.08.008.

Overview of Glutamatergic Neurotransmission in the Nervous System

The article titled “Overview of Glutamatergic Neurotransmission in the Nervous System” by Niciu et al. provides a comprehensive overview of glutamatergic neurotransmission, a crucial signaling system in the nervous system. Glutamate is the primary excitatory neurotransmitter in the brain, and this review delves into its role in synaptic transmission, neuronal plasticity, and various neurological and psychiatric disorders. The authors discuss the complex mechanisms involved in glutamate release, receptor activation, and reuptake, highlighting the importance of maintaining a delicate balance for proper brain function. The article also explores the potential therapeutic implications of modulating glutamatergic neurotransmission in the treatment of neuropsychiatric conditions (Reference: Niciu MJ, Kelmendi B, Sanacora G. Overview of Glutamatergic Neurotransmission in the Nervous System. Pharmacology, Biochemistry, and Behavior. 2012;100:656–664. doi: 10.1016/j.pbb.2011.08.008).

For more details https://www.sciencedirect.com/science/article/pii/S0091305711002747
Lipotec ARGIRELINE® peptide – Argireline Technical Report, https://www.lipotec.com/en/products/argireline-reg-peptide/ (2017).

Enhanced skin permeation of anti-wrinkle peptides via molecular modification

The technical report on Lipotec’s ARGIRELINE® peptide, titled “Argireline Technical Report,” provides valuable information about this synthetic hexapeptide and its cosmetic applications. ARGIRELINE® is known for its anti-wrinkle properties and is commonly used in skincare products. This report offers details about the peptide’s mechanism of action, its benefits in reducing the appearance of wrinkles, and its compatibility with various formulations. It also includes information on recommended usage levels and regulatory considerations. The report is a valuable resource for cosmetic formulators and professionals in the skincare industry (Reference: Lipotec ARGIRELINE® peptide – Argireline Technical Report, [URL](https://www.lipotec.com/en/products/argireline-reg-peptide/) (2017)).

For more details https://www.nature.com/articles/s41598-017-18454-z
Victor AK, Reiter LT. Dental pulp stem cells for the study of neurogenetic disorders. Human molecular genetics. 2017;26:R166–r171. doi: 10.1093/hmg/ddx208.

Dental Pulp Stem Cells for the Study of Neurogenetic Disorders

The study by Victor and Reiter titled “Dental Pulp Stem Cells for the Study of Neurogenetic Disorders” provides insights into the use of dental pulp stem cells as a valuable resource for researching neurogenetic disorders. Dental pulp stem cells (DPSCs) have gained attention due to their potential to differentiate into neural cell types, making them a promising tool for studying the underlying mechanisms of various neurogenetic disorders. This review discusses the characteristics of DPSCs, their potential for modeling neurogenetic disorders, and their applications in disease modeling and drug screening. The article highlights the significance of DPSCs in advancing our understanding of neurogenetic disorders and the development of potential therapeutic strategies (Reference: Victor AK, Reiter LT. Dental pulp stem cells for the study of neurogenetic disorders. Human molecular genetics. 2017;26:R166–r171. doi: 10.1093/hmg/ddx208).

For more details https://academic.oup.com/hmg/article-abstract/26/R2/R166/3861328
Raikou V, Varvaresou A, Panderi I, Papageorgiou E. The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study. J ClinDermatol. 2017;15:271–278.

The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3

The study conducted by Raikou et al., titled “The Efficacy Study of the Combination of Tripeptide-10-Citrulline and Acetyl Hexapeptide-3,” is a prospective, randomized controlled study that aimed to evaluate the effectiveness of a combination of two peptides: tripeptide-10-citrulline and acetyl hexapeptide-3. These peptides are commonly used in skincare products for their potential anti-aging properties. The study assessed their efficacy in improving various skin parameters related to aging, such as wrinkles, firmness, and elasticity. The findings of this research contribute to our understanding of the potential benefits of peptide-based skincare formulations in addressing age-related skin concerns (Reference: Raikou V, Varvaresou A, Panderi I, Papageorgiou E. The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study. J Clin Dermatol. 2017;15:271–278).

For more details https://onlinelibrary.wiley.com/doi/abs/10.1111/jocd.12314
Available from https://clinicaltrials.gov/ct2/show/results/NCT00942851?view=results.
Available from https://www.researchgate.net/publication/288201888_Evaluation_of_the_anti-wrinkle_efficacy_of_cosmetic_formulations_with_an_anti-aging_peptide_ArgirelineR.
Available from https://anndermatol.org/DOIx.php?id=10.5021/ad.2019.31.3.263.
Grosicki M, Latacz G, Szopa A, Cukier A, Kieć-Kononowicz K. The study of cellular cytotoxicity of argireline – an anti-aging peptide. Acta Biochim Pol. 2014;61(1):29-32.

The study of cellular cytotoxicity of argireline – an anti-aging peptide.

The study titled “The study of cellular cytotoxicity of argireline – an anti-aging peptide” conducted research on the cytotoxicity of Argireline, an anti-aging peptide. The study aimed to investigate whether Argireline has any cytotoxic effects on cells.

They assessed cellular cytotoxicity using various cell lines and concentrations of Argireline. The results of the study provided insights into the safety profile of Argireline, suggesting that it does not exhibit significant cytotoxicity under the tested conditions. This information is important for evaluating the potential use of Argireline in cosmetic and skincare products.

For more details http://ojs.ptbioch.edu.pl/index.php/abp/article/view/1919
Lungu C, Considine E, Zahir S, Ponsati B, Arrastia S, Hallett M. Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. Eur J Neurol. 2013;20(3):515-8.

Pilot study of topical acetyl hexapeptide‐8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy

In the pilot study titled “Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy,” the researchers conducted a study to investigate the potential therapeutic effects of topical acetyl hexapeptide-8 in patients with blepharospasm who were already receiving botulinum toxin therapy.

Blepharospasm is a neurological disorder characterized by involuntary contractions of the muscles around the eyes. Botulinum toxin injections are a common treatment for this condition. The researchers aimed to determine whether the addition of topical acetyl hexapeptide-8 could further improve the symptoms of blepharospasm in these patients.

For more details https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.12009
Available from https://www.researchgate.net/publication/307822529_The_Efficiency_and_Safety_of_Leuphasyl-A_Botox-Like_Peptide.
Available from https://onlinelibrary.wiley.com/doi/full/10.1111/j.1468-2494.2009.00490.x
Available from https://www.academia.edu/32981416/Role_of_topical_peptides_in_preventing_or_treating_aged_skin
Gorouhi, F.; Maibach, H. Role of topical peptides in preventing or treating aged skin. Int. J. Cosmet. Sci. 2009,31, 327–345.

Role of topical peptides in preventing or treating aged skin

In the study titled “Role of topical peptides in preventing or treating aged skin,” conducted by Gorouhi and Maibach in 2009, the authors explored the use of topical peptides for preventing or treating skin aging. The research examined various peptides and their potential benefits in improving the appearance and health of aging skin. The study discussed the mechanisms by which these peptides may work, such as stimulating collagen production, reducing wrinkles, and enhancing skin hydration. It also reviewed the safety and efficacy of different peptide formulations in skincare products. This comprehensive review provides valuable insights into the potential role of topical peptides in addressing the challenges of aged skin.

For more details https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1468-2494.2009.00490.x
Leuphasyl a New Pentapeptide for Expression Wrinkles. Available online: http://docplayer.net/15401907-Leuphasyl-a-new-pentapeptide-for-expression-wrinkles-code-pd080-date-june-2005-revision-1-a-gmppeptide-for-cosmetic-applications.html.

Leuphasyl: A New Pentapeptide for Expression Wrinkles

The document titled “Leuphasyl: A New Pentapeptide for Expression Wrinkles” provides information about Leuphasyl, a pentapeptide designed for cosmetic applications to target expression wrinkles. This peptide is intended to address wrinkles and fine lines caused by facial expressions. The document discusses its potential benefits and cosmetic applications. Please note that the provided link appears to be a direct reference to the document, which may contain details about the peptide’s properties and potential uses in cosmetics.

For more details https://www.mdpi.com/2079-9284/1/2/75
Rull, M.; Davi, C.; Cañadas, E.; Almiñana, N.; Delgado, R. Peptide Approach to Enhance Anti-wrinkle Efficacy Between Injections. Available online: http://www.cosmeticsandtoiletries.com/formulating/category/antiaging/PeptideApproach to-Enhance-Anti-wrinkle-Efficacy-Between-Injections-premium273052431.html.

Peptide Approach to Enhance Anti-wrinkle Efficacy Between Injections

The article titled “Peptide Approach to Enhance Anti-wrinkle Efficacy Between Injections” discusses a peptide-based approach to improving the effectiveness of anti-wrinkle treatments between cosmetic injections. It explores the use of peptides in skincare formulations to target wrinkles and enhance their appearance. The article likely provides insights into how peptides can be used to complement cosmetic procedures for wrinkle reduction. You can access the full article online using the provided link for more detailed information.

For more details http://www.cosmeticsandtoiletries.com/formulating/category/antiaging/PeptideApproach to-Enhance-Anti-wrinkle-Efficacy-Between-Injections-premium273052431.html.
Availabel from https://www.mdpi.com/2079-9284/1/2/75/htm.

Cosmetic Potential of Peptides Derived from Human Insulin-Like Growth Factor 1

The provided link leads to an article titled “Cosmetic Potential of Peptides Derived from Human Insulin-Like Growth Factor 1” published in the journal Cosmetics. This article explores the cosmetic potential of peptides derived from human insulin-like growth factor 1 (IGF-1) in skin care formulations. It discusses how these peptides may have applications in promoting skin health and aesthetics.

For more details https://www.mdpi.com/2079-9284/1/2/75/htm

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