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Eyerix® FOR DARK UNDER EYE CIRCLES Dark under eyes are more common in darker skin tones (Fitzpatrick 3-5) Pharmaclinix.com Reasons? In a Review of 45 patients with Dark Under-eye circles, • 35% had Chronic Allergy or sinus disease. • 2% were Chronic eye rubbers • 54% had family history of dark eye circles • 82% had prominent Vascular component Ref:Textbook -Techniques of Cosmetic Eyelid Surgery,Joseph A Muriello Jr MD. Publishers-Lippincott,Williams&Wilkins. Pharmaclinix.com Exclude Anatomical causes: • Hollow eyes-Lack of fat around the eyeball so the eye is buried deep inside the orbit. • Arcus Marginalis deformity-This tissue holds the lower eyelid skin to the orbital bone. If too tight, it causes the skin of the lower lid above the Arcus to fall over & downwards creating a deep shadow under the lower eye-lid. Can present in childhood & is hereditary. This shadow follows the lower eye-lid. Pharmaclinix.com Exclude Anatomical causes: • Tear Trough deformity-Presents in the 40-50 year group. Occurs due to loss of Malar fat on the cheek bones & descent of Skin & fat pad .It is much lower than Arcus ring and tends to continue over the cheek bone. • Periorbital melanosis (pigmentary demarcation lines) ; presents as a sharp line between pigmented & light skin & continue over the cheeks. STUDY-In 1033 women in Saudi Arabia, 144(14%) had at least one facial (PDL) line with onset at age 16. REF-Indian Journal of Dermatology,Venereology&Leprosy.2010/Volume:76/Issue:4/Pages 378 Pharmaclinix.com Exclude other Medical conditions: • Nasal or Sinus congestion -Blocked nose, Nasal discharge, Mouth-breathing patients causes blockage of venous drainage of under-eye skin leading to congested veins which are visible through thin, translucent skin. • Iron deficiency &Hypothyroidism • Inflammation of skin-Contact eczema, Lupus or Lichen Planus, which can all cause itching & chronic rubbing. Pharmaclinix.com Eyerix is a complete complex with a high concentration of: •Depigmenters •Vascular restorers Which is formulated in a base that will penetrate the thin, sensitive layer of the skin, without irritation. Pharmaclinix.com HYPERPIGMENTATION • Arbutin & Harunoside 4% • Xanthumol 3% • Di-acetyl boldine 3% • Liqorice extract 2% • Sodium ascorbyl phosphate 2% Pharmaclinix.com ARBUTIN & HAROUNOSIDE (Arcto uva-urs+Mitra Scab extr) 4% IN-VITRO: 1% Etioline totally inhibits Tyrosinase synthesis. EX-VIVO: In the presence of 5% Etioline, Melanin production was totally absent from human skin biopsy in the presence of L-DOPA. Ref-ETIOLINE -SEDERMA,FRANCE. Pharmaclinix.com XANTHUMOL 3% (Humulus Lupulus ext) • Prevents Release of Cytokine (GM-CSF-Granulocyte macrophage colony stimulating factor) in response to UVA&UVB which activates Melanocytes. • Prevents release of MITF (Micro-opthalmia transcription factor) which controls Melanocytes. Pharmaclinix.com IN-VITRO: Inhibits Melanin synthesis by 84.6% at 0.5% while Kojic Acid 0.3%inhibits by only 66% EX-VIVO: Totally prevents Melanocyte activation after Irradiation. In 28 Melasma patient study applying 3% twice daily, 64% showed significant improvement after 4 weeks & 75% after 8 weeks. Ref:-Sederma,France Pharmaclinix.com DI-ACETYL BOLDINE 3% + MANGANESE COATED TITANIUM DIOXIDE (LUMISPHERE) Acts on skin by: •Inhibiting alpha-adrenergic receptors In skin to inhibit melanocyte stimulation. •Calcium flow regulation to stabilize Tyrosinase in its Inactive form. 27 Patient phototypes 3-4 skins using twice daily showed 78% significant benefit in 28 days and 96% in 56 days. Ref-Sederma,France Pharmaclinix.com LICORICE EXTRACT 2% (Glabridin & Liquertin) Glabridin has proven activity 15 times stronger than that of Kojic Acid. Chalcone type of Polyphenol called liquertin in licorice extract is 5.4 times more active than Kojic Acid 20 Patient split face study on Melasma patients in Egypt showed a 70% improvement while only 20% improvement on control side of face using Liquertin twice daily. Ref 1-American J Clinic Dermatol2011.April 1;12(2):87-99.PIH :Etiologic&therapeutic consideration. Ref 2-Inter J Dermat.2000 April;39(4):299-301.Topical Liquertin improves Melasma.Amer M,Metevalli M. Pharmaclinix.com SODIUM ASCORBYL PHOPHATE 2% (STAY C-50) Stay C Promotes the synthesis of collagen 1 & 3 by 57.5% Ref: Asia-Pacific Skin Testing center ,Facial cream 12 week usage study. Japanese Ministry of Health has approved STAY-C 50 as a quasi-drug for skin whitening products In-vivo study on 39 female Asian volunteers, showed 25% lightening effect over 12 weeks. Pharmaclinix.com VASCULAR STRENGTH RESTORERS: • • • • Albizia julibrissin extract 2% (PRODIZIA) Palmitoyl tripeptide 38 (Matrixyl Synth6-S)2% Green tea extract 1% Caffeine 1% Pharmaclinix.com ADVANCED GLYCATION END PRODUCTS (AGEs) & RECEPTOR (RAGES) Other than oxidation creating ROS(Reactive oxygen species ie oxygen atom with a missing electron) & Matrix Mettaloproteinases (MMPs) there is a very important mechanism causing Ageing. AGEs are produced when sugar non-enzymically binds to proteins & lipids eg collagen and elastin in skin. They activate the Receptor for AGEs called RAGES. Pharmaclinix.com ADVANCED GLYCATION END PRODUCTS (AGEs) & RECEPTOR (RAGES) AGE bound RAGEs stimulate Nuclear factor –kB & blocks NO (Nitric oxide) activity leading to increased permeability to macro-molecules of blood vessels. This results in up-regulation of Inflammation & tissue destructive mechanisms in Euglycaemic patients in Ageing. . Pharmaclinix.com Ref 1) Circulation:2006;114:597-605,AMERICAN HEART ASSOCIATION.Joshua A Beckman MD et al Ref 2) Advanced Glycation Endproducts(AGEs)&RAGE.A common thread in Ageing,Diabetes,Neurodegeneration&Inflammation.Ramasamy et al.GlycoBiology.2005Jul:15(7):16R-28R. Ref 3) Receptor for Advanced Glycation Endproducts (RAGE):Yau SF,D Agati et al:Dept of Surgery,Columbia University Med Centre,New York NY10032 USA.Current Mol Med 2007Dec;7(8):699-710. Pharmaclinix.com Albizia julibrissin extract 2% (PRODIZIA) • Increases Glyoxalase (detoxyfying enzyme)+41% • Increases Proteosome Activity (detoxify AGEs) • Decreases Carboxymethyllysine (an AGE) production(-45%) & Fluorescent AGEs(-23%) • Decrease Glycation induced Vascular Damage. Clinical Studies show a decrease Inhibition & Deglycation of AGEs in vivo & restructuring of disorganized skin fibres. (INHIBITION AND DECREASE) Ref-Glycation & Glycotoxins in Skin.Inhibition & Reversal Karl Lintner PhD,Philippe Mondon.SEDERMA. Pharmaclinix.com MATRIXYL SYNTH 6 (SEDERMA) 2% Palmitoyl-Lysyl-Dioxymethionil-Lysine IN VITRO Increases all six components of skin matrix • Collagen 1(+37%) • Collagen 3(+104%) • Fibronectin (+104%) • Hyaluronic Acid (+174%) • Collagen4 (+42%) • Laminins (+75%) Pharmaclinix.com IN VITRO 25 Women using Matrixyl synth 6 2% for 2 months Revealed: Anti-wrinkle effect on Forehead wrinkle: •Reduction of main wrinkle (-31%) •Reduction of skin roughness(-28%) Ant-wrinkle effect on crows feet: •Decrease in surface area of deep wrinkles (-28.5%) •Decrease in volume of main wrinkles (-21%) REF-SEDERMA.FRANCE Pharmaclinix.com GREEN TEA EXTRACT 1% •Anti-oxidant •Anti-inflammatory •Photoprotective Ref: Curr Drug Target Immune Endocr Metab Disorders.2003 Sep;3(3):234-42.Skin Photoprotection by green tea.Anti-oxidant& Immunomodulatory effects. Ref: Treatment of green tea polyphenols in hydrophilic cream prevents UVB induced oxidation of lipids & proteins ,depletion of anti-oxidant enzymes &phosphorylation of MAPK proteins in SKH -hairless mouse skin.Carcinogenesis.2003 May;24(5):927-36.Vayalil PK et al.Det of Dermatol,University of Alabama at Birmingham,1670 University Blvd,Volker Hall 557,35294 USA. Pharmaclinix.com CAFFEINE 1% • Competes with Adenosine for Adrenergic receptors on the skin under the eyes to cause vasoconstriction. This constriction reduces the leakage of skin capillaries in the skin under the eyes-reducing puffiness. • Photo protection agent • Easily absorbed into skin REF-Photodermatol Photoimmunol Photomed.2007 Apr-Jun;23(2-3):86-94. Ref: Research & Development Division, Kose Co. Ltd., Tokyo, Japan. [email protected] Topical application of plant extracts containing xanthine derivatives can prevent UV-induced wrinkle formation in hairless mice. Mitani H, Ryu A, Suzuki T, Yamashita M, Arakane K, Koide C. 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