Novel Topical Cytokinin Improves Coarse Wrinkles and Skin Roughness Without Skin Irritation

July 2018 | Volume 17 | Issue 7 | Original Article | 772 | Copyright © 2018

Raymond L. Garcia MD,a Jerry L. McCullough PhD,b Barry Reece MS MBA,c Frank J. Massino BS LESd

aPrivate Practice, Irving, TX bDepartment of Dermatology, University of California, Irvine, CA cRCTS Labs, Irving, TX dPyratine LLC, Morro Bay, CA

Abstract

Objective: To evaluate the efficacy and tolerance of topical 4HBAP (para-topolin [6-(4-hydroxybenzylamino) purine], a new aromatic cytokinin, in subjects with mild to moderate facial photodamage. Methods: In this single-center, 12-week study subjects (n=39) applied topical 0.10% 4HBAP (the test article) and sunblock (SPF30) twice daily, in the early morning and in the evening. The efficacy and safety of the treatment were evaluated at study entry (baseline) and at 2, 4, 8 and 12 weeks. Results were evaluated by investigators and subjects using high resolution photography and objectively by transepidermal water loss (skin barrier function), and a Novameter® (skin moisture content). Results: Topical 4HBAP significantly improved the appearance of coarse wrinkles after 4, 8, and 12 weeks of continued use without irritating the skin or eliciting erythema. Topical 4HBAP also improved the appearance of fine wrinkles, hyperpigmentation, and skin roughness while significantly reducing facial erythema and the overall severity of acne lesions. The investigators global assessment, the overall severity of skin aging and skin color, showed significant improvement at weeks 8 and 12. Subject-assessed improvements were also highly favorable. In the 25 subjects that had acne at baseline, the number of non-inflammatory lesions and the total number of acne lesions decreased significantly at weeks 8 and 12. Topical 4HBAP significantly increased skin hydration at weeks 2, 8, and 12. Conclusion: Topical 4HBAP (0.10%) significantly improves the appearance of fine lines and coarse wrinkles, reduces skin roughness, hyperpigmentation, facial erythema, and non-inflammatory acne lesions, and improves skin hydration without any observed side effects. J Drugs Dermatol. 2018;17(7):772-779.

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INTRODUCTION

Cytokinins are plant growth factors that regulate cell growth and differentiation in plants.1 Kinetin (N6-furfuryladenine) is a cytokinin growth factor that has been shown to (1) delay age-related changes in morphological and biochemical characteristics of human skin fibroblasts2 and keratinocytes,3 (2) inhibit oxidative and glycoxidative damage to proteins in vitro,4 (3) protect DNA against oxidative damage,5 and (4) scavenge free radicals.6 The ability of cytokinins to maintain normal cell function in aging cells is the basis for their use in preserving the vitality of aging skin.An initial study7 of 32 patients with mild to moderately photodamaged facial skin showed that a 0.1% kinetin lotion and sunscreen applied twice daily for 24 weeks resulted in significant improvements in tactile skin roughness, mottled hyperpigmentation, and fine wrinkles at both 12 and 24 weeks. Tactile skin roughness improved first (24% by week 4), followed by mottled hyperpigmentation (25% by week 12), and fine wrinkles (13% by week 24) without causing skin irritation often found with other anti-aging medications. Treatments also produced an improvement in skin barrier function as shown by a 24% decrease in transepidermal water loss (TEWL).In 2006 Katz and Bruck,8 in a study of 18 similar patients treated twice daily on the face and neck with 0.1% kinetin cream combined with sunscreen, reported improvement in skin appearance without the cutaneous adverse effects encountered with other antiaging medications such as retinoids. Other plant cytokinins have been studied for their potentially beneficial effects.Related compounds have also been studied. One clinical study showed that zeatin (6-[4-hydroxy-3-methyl-but-2-enylamino] adenine) and PRK-124 (N-furfuryl-9-(2-tetrahydropyranyl) adenine (FPA), for example, have growth modulatory, anti-oxidative, and anti-senescent effects on human skin cells. Recent clinical studies show that treatment with topical zeatin (0.025%, 0.10%) for 12 weeks improved the appearance of photodamaged facial skin by decreasing fine wrinkles, roughness, and mottled hyperpigmentation.9A similar study has been conducted with topical FPA (0.1%), a new and advanced cytokinin structurally similar to kinetin. With the addition of a pyranyl group in the 9th position, FPA has enhanced biological activity, hence has been labeled a “super kinetin.” Multiple clinical trials at two medical centers showed

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