Introduction of Arbutin

1. Overview

Arbutin is commercially used as a skin-whitening agent in cosmetic industry. It works by competitive inhibition of the enzyme, , a key enzyme in the synthesis of . Depending on the spatial structure of the glycosidic linkage between glucose and , arbutin forms two epimers: α-arbutin and β-arbutin.

Product name CAS Number Molecular formula Molecular structure

Beta-Arbutin 497-76-7 C12H16O7

Alpha-Arbutin 84380-01-8 C12H16O7

2. Natural source and Industrial Process Method

Beta-Arbutin

Beta-Arbutin is often referred to as just Arbutin. It is can be naturally extracted from plants such as bearberry and synthesized by chemical method. Synthesized Beta-Arbutin is currently one of the most widely used hypopigmenting agents in cosmetics, while plant-derived drugs containing Beta-Arbutin were initially used for the treatment of urinary tract infections, cystitis, kidney stones, and as diuretics in the medical field.

Beta-Arbutin Flow chart

Alpha-Arbutin

Alpha-Arbutin is enzymatically synthesized from hydroquinone and saccharides through transglycosylation reaction. Various carbohydrate-active enzymes such as α-amylase, α-glucosidase, transglucosidase, sucrose phosphorylase, and dextransucrase have been employed to synthesize Alpha- Arbutin. It is one of the most advanced skin lightening ingredients on the market.

Alpha-Arbutin Flow chart

3. Specification

Product name Specification Beta-Arbutin 99.5% HPLC Alpha-Arbutin 99.5% HPLC

Beta-Arbutin Specification

ANALYSIS SPECIFICATION Assay ≥99% Appearance White crystalline powder Melting Point 199~201±0.5℃ PH(1%water solution) 5.0-7.0 Specific Optical Rotation -66±2° Loss on drying ≤0.5% Residue on ignition ≤0.5% Hydrochinone ≤10ppm Heavy metals ≤20ppm Arsenic ≤2ppm Total Plate Count ≤300cfu/g Total Yeast Count ≤100cfu/g

Alpha-Arbutin Specification

ANALYSIS SPECIFICATION Assay ≥99.5% HPLC Appearance White crystalline powder Hydroquinone ≤10ppm

Melting Point 203-206（±1）℃ Specific Optical Rotation [a]20D= + 174.0°- +186.0° Infrared peak value 1514cm-1; 1229 cm-1; 1215 cm-1; 1059 cm-1; 1034 cm-1 Soluble in water, slightly soluble in Clarity Solution should be clarify, none suspended matters PH（1% water solution） 5.0-7.0 Loss on drying ≤0.5% Residue on Ignition ≤0.5% Heavy metals ≤10ppm Lead ≤2ppm Arsenic ≤2ppm Mercury ≤1ppm Total Plate Count ≤100cfu/g Total Yeast & Mold ≤50cfu/g E.Coli Negative Salmonella Negative Staphylococcus Negative

4. Arbutin Working Mechanism

Skin whitening

Arbutin exhibits potent melanin-inhibiting properties and confers whitening effects on the skin. Sun damage and injury or inflammation to the skin from acne, eczema or psoriasis are the two main factors that cause melanin production on the skin. Arbutin can reduce the accumulation of pigment by inhibiting the production of melanin, which accumulates on the skin when tyrosine is oxidized. An enzyme called tyrosinase is the catalytic for this reaction. Scientists found arbutin has shown inhibitory actions against tyrosinase. When topically apply skincare products containing Arbutin, the inhabitation of tyrosinase results in the decrease of melanin, thus, a whiter complexion.

Hyperpigmentation in the epidermis is caused by excessive melanin synthesis due to UV irradiation, wound or stress. Tyrosinase is one of the key enzymes involved in melanin synthesis. The enzyme catalyses the first two steps in melanin synthesis: the hydroxylation of tyrosine to DOPA and the oxidation of DOPA to dopaquinone. Arbutin has an direct inhibitory function against tyrosinase, which leads to the prevention of melanin formation and a whitening effect on the skin.

5. Alpha-Arbutin V.S. Beta-Arbutin

Recent research showed that Alpha-Arbutin has a 10-fold stronger inhibitory effect on the activity of tyrosinase from human malignant melanoma cells than that of Beta-Arbutin. The α-glucosidic bond found in Alpha-Arbutin offers higher stability than the β form found in the related Beta-Arbutin. Moreover, Alpha-Arbutin hardly inhibited cell growth at 1 mmol/L, while Beta-Arbutin inhibits it significantly at the same concentration. It is, therefore, considered that Alpha-Arbutin is an effective and safe ingredient for cosmetics. Alpha arbutin is very expensive. That is the one downside.

Differences between Alpha-Arbutin V.S. Beta-Arbutin

Tyrosinase Production Stability Safety Price inhibitory efficacy

Alpha- enzymatically More 10 times stronger higher safer Arbutin synthesized expensive

Extracted; or inhibit cell Beta-Arbutin chemically weaker lower cheaper growth synthesized

Alpha-Arbutin Water Solubility

6. Feature of PLAMED Arbutin

1. Beta-Arbutin is produced by environment friendly new tech, annual productivity 100mts, table supply. 2. Loss on drying strictly controlled, less than 0.5% 3. Hydroquinone residue less than 10ppm, Hydroquinone is poisonous and is forbidden in cosmetics. The residue control is very important.

7. Arbutin Application and Reference amount

Arbutin is used as a skin whitening agent, a sunscreen agent and an antioxidant in cosmetic formulations. Arbutin soap, cream, serum and lotion are among the major lightening products you will found in the market.

Product name Reference amount Beta-Arbutin 1-3% Alpha-Arbutin 0.2-2%

Arbutin’s advantage over traditional skin-whitening products:

Arbutin can inhibit melanogenesis without causing melanocyte toxicity, unlike traditional depigmenting agents such as hydroquinone, corticosteroids, and kojic acid.

8. Note 1. Arbutin breaks down easily in acidic conditions, so the pH value of cosmetics containing Arbutin should be greater than 6.0. 2. Please dissolve arbutin in 50℃ hot water before adding it to skin whitening products. (Arbutin is soluble in hot water, methanol or alcohol. Arbutin is partially soluble in cold water. Arbutin is insoluble in aether, or .) 3. Antioxidants should be added to cosmetics containing Arbutin. 9. Arbutin Reference Formula

Whitening cream：

Ingredient Content(%) Ingredient Content(%)

Vaseline 39 Arbutin 1 Stearyl alcohol 15 Vitamin E 1

Beeswax 15 Fragrance 0.5 Glycerin monostearate 0.5 Distilled water 27 Polyethylene glycol monooleate 1 Anti-freckle whitening essence:

Ingredient Content(%) Ingredient Content(%) Vitamin C 2-4 Arbutin 4-6

Glycerin 4-6 Antioxidant 0.09-0.2 Ethanol 43-45 Angelica sinensis 9-11 Caisson 0.09-0.2 Ligusticum wallichii 7-9 Vitamin E 4-6 Scutellaria baicalensis 9-11 Liquorice 9-11 Preparation method:

Heat water phase(Vitamin C, Glycerin, Ethanol, Caisson) and oil phase(Vitamin E, Antioxidant) to

50-60℃ respectively, slowly pour water phase into oil phase, then add Angelica sinensis, Ligusticum wallichii, Scutellaria baicalensis, Liquorice and Arbuti, stir well, then obtain the essence.

Whitening toner:

Ingredient Content(%) Ingredient Content(%)

Arbutin 0.1-3 Guava leaves extracts 1-5 Group Deionized water 63-89.8 Guava fruit extract 3-5 A Hydrolyzed pearl Hyaluronic acid 5-10 1-5 solution Group Propylene glycol 0.1-1 Glycerin 5-10 B Preparation method:

Weigh above ingredients of Group A and put them to the water phase bottle; under the condition of stirring rate of 10r/min, heat to 75℃, hold for 10min, then get the water phase. Put the Group B ingredients into oil phase bottle, under the condition of stirring rate of 20r/min, heat to 80℃, hold for 15min, then get the oil phase. Mix the two phases for 500s, cool to 30℃, then get the toner.

Others：

Arbutin compounding with vitamin C derivatives can make skin more moisturizing and transparent.

With hyaluronic acid can relieve dry skin;

With glycyrrhizic acid can repair sunburn.

Application cases of Arbutin in cosmetics brand around the world:

Country Brand Product Main ingredient

Eyes Gel Strip Arbutin , olive leaf extract, mulberry extract, Japan DHC Masks peony extract

Arbutin white Arbutin, Portulaca Oleracea Extract, Aloe Winona moisturizing face extract, Camellia Sinensis extract、horse

mask chestnut extract Alpha Arbutin Taiwan Don Du Alpha Arbutin , Tranexamic acid, Hyaluronic Whitening Aqua Ciel Acid Gel Taiwan Annie's Brightening Jelly Arbutin, Hyaluronic Acid way Mask Beauty Facial Arbutin, Licorice root extract, witch hazel The Elixir Mask extract, hyaluronic acid Korea Arbutin, Water, rice bran extract, Glycerin, KFB Arbutin Mask sheet copolymer, sodium hyaluronate, tocophetrl BARONESS acetate, carbomer, hydrolyzed collagen Water, propylene glycol, glyceryl stearate, Cape fear Super alpha arbutin stearic acid, dimethicone, steareth-2, steareth-20, naturals cream alpha arbutin, retinyl palmitate (retinol-a), USA vitamin e acetate, methyl and propyl parabens. Alpha Arbutin 2% The Ordinary Alpha Arbutin + HA Qrxlabs Skin Lightening Kojic Acid, Alpha Arbutin, Organic Licorice

Serum extract, Lemon Balm extract Sweetsation Kojic Acid, Alpha Arbutin, Niacinamide, Lumiessence Therapy Papaya and Pineapple extract Vitamin C, Hyaluronic Acid, Alpha Arbutin, Del organics All-In-One Serum Niacinamide, Wakame Bioferment, Astaxanthin, Peptide Kojic Acid, Alpha Arbutin, Glycolic acid, Skin Whitening DNA CODE Salicylic, Lactic Acid, Papaya, Pineapple, Peel Pads Argireline, DMAE

10. Safety The Catalog Of the International Cosmetics Raw Material Standard English Name issued by CTFA and CAFFCI in 2010 and On the Announcement of Name List of Cosmetics Raw Material published by China Food and Drug Administration (FDA) in 2014 both have specified Alpha Arbutin and Beta Arbutin as cosmetic ingredient. 11. Storage

Please tightly seal Arbutin in containers. Store it in a cool dry place and away from sunlight and oxidizing agents.

Packed in 25kg paper drum, 1kg aluminum foil package inside.