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Skincare information file Azeco Cosmeceuticals

Azco99

High purity cosmetic grade of 100% biobased azelaic acid (obtained from high refined Sunflower oil of European origin), COSMOS approved.

Product Information Azelaic acid is a naturally occurring straight-chained saturated dicarboxylic acid naturally present in rye, wheat, and barley. A sin- gle mechanism of action has not been identified to explain the several beneficial effects of azelaic acid on the skin. In fact, it is well known in the art, from the results of several accurate experimental scientific works, topical azelaic acid has anti-inflammatory and an- tibacterial properties, in addition to comedolytic action. It also competitively inhibits tyrosinase, an enzyme involved in the conversion of tyrosine to melanin, and may reduce epidermal hyperkeratinization. So AZCO99 is an antibacterial and anti-proliferative agent that can be used to treat skin by reducing the growth of bacteria in the follicle, rebalancing keratinization It has applications in anti-aging formulation, hair growth stimulation, hyper-pigmentation reduction products.

AZCO99 cosmetic-grade based products are the industry standard for cosmetic product quality and assurance of global supply.It is COSMOS approved.

General information

INCI NAME and Chemical Identification

AZELAIC ACID NONANEDIOIC ACID, CAS: 123-99-9

APPEARANCE

White to off-white micronised powder

ORIGIN

100% biobased product obtained from Sunflower Oil

AZCO99 is obtained by oxidative cleavage of the double bond of oleic chain of the triglyceride of the Sunflower oil, according to the following reaction:

MANUFACTURING PROCESS

R = H, alkyl group

PURITY

99% minimum

Soluble in glycols, glycerin and alcohols, easily dispersible in polar esters thanks to its unic particle size distributi- on.

SOLUBILITY

AZCO99 normalises the microflora on the skin. AZCO99 has anticomedonal effect by decreasing the amount of hyperkeratinization of the skin. AZCO99 decreases tyrosinase activity and melanin synthesis to reduce overall skin pigmentation. AZCO99 induces skin lightening effect. AZCO99 reduces the appearance of pigmented spots. AZCO99 is self-preserving AZCO99 has an excellent safety profile

COSMETIC PROPERTIES

APPLICATIONS

AZCO99 can be used in gel-emulsions and both low and high viscosity w/o and o/w emulsions and microemulsi- ons

RECOMMENDED DOSAGE

5 – 15 % by weight

Phone : +31 475 20 60 70 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

AZECO COSMECEUTICALS — your preferred partner for the formulation of azelaic acid based skin care products AZECO Cosmeceuticals is the world’s leading supplier of cosmetic-grade azelaic acid. We earned this distinction by providing excep- tional purity levels (unic product in the world market having this feature), consistently reliable supply, and outstanding technical and regulatory support. Our high purity azelaic acid is manufactured and handled according to the ISO 9001:2015 certification. It is obtained by using a continuous process 24 hours a day, seven days a week. This not only ensures ready availability, it also eliminates the batch-to-batch inconsistencies often found in azelaic acid from other suppliers. Azelaic acid from AZECO COSMECEUTICALS has European, 100% biobased and palm free origin and it is REACH (Registration Evaluation and Authorization of CHemicals) compliant. How AZCO99 works on skin When used in cosmetic formulations, azelaic acid penetrates the skin effectively and stimulates cellular activity. Azelaic acid is able to assist in normalisation of the microflora on the skin. Organisms that have become opportunistic are normalised to their normal level, including P.acnes, and it thus assists in many cases in clearing and preventing acne. The mode of action has not been fully elucidated, but in numerous preclinical and clinical studies it has been demonstrated that azelaic acid displays three main beneficiall properties on impure skin: 1. It normalizes the disturbed follicular keratinization that leads to the formation of comedones.. The reduction in the count of comedones has subsequently been demonstrated in various clinical studies. 2. Azelaic acid has a significant antibacterial effect on the follicular Propionibacterium acnes and Staphylococcus epidermidis (in vitro). This effect is primarily bactericidal but may in vivo be modified to a bacteriostatic one. 3. In addition azelaic acid also reveals direct anti-inflammatory activities by reducing the production and release of reactive oxygen species. Azelaic acid is also an effective inhibitor of tyrosinase, the enzyme involved in the conversion of tyrosine to melanin. So AZCO99, according to its high purity characteristic and natural origin, can be safely used in whitening/lightening cosmetic products both for Asian and Caucasian skin. The competitive inhibition of tyrosinase by AZCO99 (see the scheme below) results in a decreased produc- tion of melanin.

Then AZCO99 is a natural skin bleaching agent and an effective lightener for the skin. It has the advantage of giving a paler skin, naturally. Many accurate scientific publications are available in the art relatively to the mechanism of action of Azelaic acid on the skin. At the end of this document, in the paragraph dedicated to “References”, some of them are listed.

The standard for azelaic acid in pharma & cosmetics

Mussenberg 1 • 6049 GZ Roermond • The Netherlands

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The standard for azelaic acid in pharma & cosmetics

Mussenberg 1 • 6049 GZ Roermond • The Netherlands

Ideal for a variety of products AZCO99 is ideal for use in a variety of personal care products (also COSMOS / ECOCERT approved) for skin, providing important benefits that consumers desire. Here’s a brief overview:

Benefits/Claims

Applications

Moisturizing skin creams, serum and lotions, cleansers and toners. Men’s skin care products. Moisturizing skin creams, serum and lotions, cleansers and toners. Men’s skin care products. Creams, serums, lotions, cleansers, and toners designed to reduce the signs of aging. Skin peeling products. Men’s skin care products. Moisturizing skin creams, serum and lotions, Moisturizing skin creams, serum and lotions. Men’s skin care products. Acne treatment combinations, skin lightening combinations, sunscreen combinati- ons. Men’s skin care products.

Effective in the treatment of oily and impure skin. Provides a progressive brightening effect for a more uniform complexion Reduces skin pigmentation and color irregularities such as age spots , revealing smoother, brighter, more supple skin with fewer irregularities Whitening activity proven on Asian skin. Improving the appearance of sun damaged skin and fighting skin aging Enhancing performance of certain topical over-the-counter , drugs or quasi-drugs and prescription products

Examples of skin care formulations based on AZECO99 Anti-acne preparations, Asian and European formulas:

SC001 Anti- acne - Asian Formula. Triple action: anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name % by weight Function A Aqua Water 56.45 Solvent Betaine Betafin BP20 [1] 5.00 Emulsifier Glycerine Pricerine 9083 [2] 2.00 Humectant

Sodium Hydroxide, 18% Aqueous Solution

Aqua, Sodium Hydroxyde

1.50

Neutralizer

B Azelaic acid

AZCO99

Active ingredient

Cetearyl Isononanoate

Cetiol SN [4]

5.00

Emollient

Cetearyl Alcohol

Lanette O [4]

4.00

Body agent

PEG-20 Glyceryl Stearate

Cutina E24 [4]

4.00

Emulsifier

Tripelargonin

Matrìlox CP601M [5]

3.00

Emollient

Steareth-2

Brij 72 [2]

3.00

Emulsifier

Steareth-21

Brij 721 [2]

3.00

Emulsifier

Diethylhexyl Adipate [2]

Crodamol DOA

2.00

Emollient

C Phenoxyethanol Sorbitan Caprylate

Nipaguard SCP [3]

1.00

Preservative

D Parfum

0.15

Fragrance

Phone : +31 475 20 60 70 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Suppliers : [1] Dupont / Danisco Finnfeeds Oy [2] Croda Oleochemicals [3] Clariant / Nipa Preservatives [4] BASF / Cognis [5] Matrìca

Cream Specifications: Appearance

soft cream

Colour Odour

white

characteristic

4,9 – 5,6

Typical:

5,2

Brookfield Viscosity (S4, 20 rpm, 25°C)

3,500 – 4,400 cPs

Typical:

3,850 cPs

Manufacturing instructions: 1.

The water phase (Phase A) is prepared by combining the ingredients. The water phase shall be alkaline as to (partially) neu- tralise azelaic acid present in the oil phase. Ignoring to do so will inhibit emulsion formation. The water phase is heated to 70-75°C.

2. The oil phase (Phase B) is made by combining the ingredients and heating to 70-75°C. The oil phase shall be completely clear, and has a slight yellowish colour.

Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

The standard for azelaic acid in pharma & cosmetics

Phone : 0031475 782540 • info@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com Muss nberg 1 • 6049 GZ Roermond • The N therlands

SC002 Anti-acne European Formula Triple action: anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name % by weight Function A Aqua Water 45.45 Solvent Betaine Betafin BP20 [1] 5.00 Emulsifier Glycerine Pricerine 9083 [2] 5.00 Humectant

Sodium Hydroxide, 18% Aqueous Solution

Aqua, Sodium Hydroxyde

1.50

Neutralizer

B Azelaic acid

AZCO99

Active ingredient

Caprylic/Capric Triglyceride

Myritol 318 [4]

12.00

Emollient

Cetearyl Alcohol

Lanette O [4]

2.00

Body agent

PEG-20 Glyceryl Stearate

Cutina E24 [4]

3.00

Emulsifier

Tripelargonin

Matrìlox CP601M [5]

3.00

Emollient

Glyceryl Stearate, Ceteareth-12, Cetea- reth-20, Cetearyl Alcohol, Cetyl Palmitate Emulgade SE [2]

10.00

Emulsifier

Diethylhexyl Adipate [2]

Crodamol DOA

2.00

Emollient

C Phenoxyethanol Sorbitan Caprylate

Nipaguard SCP [3]

1.00

Preservative

D Parfum

0.15

Fragrance

Suppliers: [1] Dupont / Danisco Finnfeeds Oy [2] Croda Oleochemicals [3] Clariant / Nipa Preservatives [4] BASF / Cognis [5] Matrìca

Specifications: Appearance

soft cream

Colour Odour

white

characteristic

4,9 – 5,6

Typical:

5,2

Brookfield Viscosity (S4, 20 rpm, 25°C)

7,200 – 11,400

Typical:

8,450 cPs

Phone : +31 475 20 60 70 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Manufacturing instructions: 1.

2. The oil phase (Phase B) is made by combining the ingredients and heating to 70-75°C. The oil phase shall be completely clear, and has a slight yellowish colour.

3. The oil phase is added to the water phase at 70-75°C while stirring with a planetary mixer. The mixture, that is still unstable, is stirred during 5 minutes (on a laboratory scale). Subsequently the mixture is homogenised using a high velocity rotor-stator mixer at maximum capacity. The pre-emulsion is cooled to 40-45°C and re-homogenised adding the preservative (Phase C). The obtained emulsion is white and is still low viscous. Upon further cooling the viscosity will continue to increase. At 25°C the fragrance is added (Phase D); stirring is continued during 15 minutes. 4. The pH is adjusted to the specifications with an 18% aqueous sodium hydroxide solution. The lotion is kept in quarantine for 5 days and committed for microbiological analysis. After 5 days the analytical data of the lotion may be adjusted to the specifications, if required. After the quarantine period the lotion may be committed for confectioning or transferred to bulk storage, provided it satisfies the specifications. INCI list: Ingredients: Aqua, Caprylic/Capric Triglyceride, Azelaic Acid, Glyceryl Stearate, Betaine, Glycerin, Isopropyl Myristate, PEG-20 Glyce- ryl Stearate, Cetearyl Alcohol, Diethylhexyl Adipate, Ceteareth-20, Ceteareth-12, Cetyl Palmitate, Parfum, Phenoxyethanol, Sorbitan Caprylate. SC003 Oil-free serum for skin with disorders (skin prone to acne) - Triple action: anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name / Other name % by weight Function A Aqua Water 10.00 Solvent Propanediol Propylen Glycol 10.00 Humectant Heptyl glucoside Sepiclear G7 [1] 10.00 Emulsifier Azelaic acid AZCO99 10.00 Active Ingredient B Xylityl sesquicaprylate Hebeatol plus [2] 0.5 Antimicrobial and Moisturizing Agent Tocopheryl Acetate Vitamin E acetate 0.05 Antioxidant, Antiaging agent C Phenoxyethanol - 0.30 Preservative Sodium Polyacryloyldimethyl Taurate Aristoflex silk [3] 1.00 Rheology Modifier Aqua Water 57,9 Solvent Dimethyl Isosorbide (and) Hydroxypinacolone Retinoate Granactive Retinoid [4] 0.10 Antiaging agent D Parfum - 0.15 Fragrance Phenoxyethanol Sorbitan Caprylate Nipaguard SCP [3] 1.00 Preservative Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

Phone : +31 475 20 60 70 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Suppliers: [1] Evonik [2] Croda [3] Clariant [4] Jan Dekker / IMCD

Specifications: Appearance

Soft cream

Colour Odour

White

Characteristic Not applicable

Typical:

Not applicable

Brookfield Viscosity (R4, 50 rpm, 25°C)

2150 ± 25 % mPas

Typical:

2150 mPas

Manufacturing instructions: 1. Mix all the ingredients of the phase A until homogeneous (indicative time 5 minutes), measure the pH of the obtained mix- ture (6.00-7.00). 2. Mix all the ingredients of the phase B until homogeneous (indicative time 5 minutes), heat at 60 ° C until a transparent and homogeneous melt is obtained. 3. Add AZCO99 and Tocopheryl Acetate to Phase B, keep the temperature on and let it mix until it forms a homogeneous creamy white / beige compound without dots (about 1 hour). 4. Add very slowly the Phase A to the mix of the Phase B+C, taking care to completely incorporate the phase each time. only halfway it is possible to increase the input speed. Mix only with moderate blades. disturb for 5 minutes only at the end of the entran- ce of Phase A. a fluid emulsion is obtained. Stop the turbine as soon as it thickens. 5. Add the fragrance INCI list: Ingredients: Aqua, Azelaic Acid, Octyldodecanol, Ethylhexyl Palmitate, Isopropyl Isostearate, Propanediol, C12-15 Alkyl Benzoate, PEG-30 Dipolyhydroxystearate, Tocopheryl Acetate, Butyrospermum Parkii Butter, Magnesium Sulfate, Caprylyl Glycol, Glyceryl Ca- prylate, Ethylhexylglycerin, Parfum

Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Suppliers : [1] Seppic [2] Chemyunion [3] Clariant [4] Grant

Specifications: Appearance

Fluid Gel

Colour Odour

From whitish to slightly yellowish

Characteristic

3.40-3.60

Typical:

3.50

Brookfield Viscosity (R6, 100 rpm, 25°C)

5000 ± 25% mPas

Typical:

5000 mPas

Manufacturing instructions: 1. In a melter, heat to 60 ° C and mix until homogeneous: a yellowish transparent fluid gel is obtained. Cool to T <30 ° C. 2. Once phase A has cooled, add and mix Hebeatol and Tocopheryl Acetate . Indicative time 10 min, until transparency. 3. In turbo-emulsifier, sprinkle the Aristoflex Silk while stirring. Continue until a homogeneous gel is formed 4. Flush, possibly only gentle mixing and possibly with a very low force turbine, to avoid incorporating air. A whitish-yellowish gel is obtained. INCI list: Ingredients: Aqua, Azelaic Acid, Propanediol, Heptyl Glucoside, Sodium Polyacryloyldimethyl Taurate, Xylityl Sesquicaprylate, Hy- droxypinacolone Retinoate, Tocopheryl Acetate, Dimethyl Isosorbide Phenoxyethanol, Parfum

Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

SC004 Whitening oil-free serum . Multiple action: whitening, anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name / Other name % by weight Function A Aqua Water 10.00 Solvent Propanediol Propylen Glycol 10.00 Humectant Heptyl glucoside Sepiclear G7 [1] 10.00 Emulsifier Azelaic acid AZCO99 10.00 Active Ingredient B Xylityl sesquicaprylate Hebeatol plus [2] 0.5

Antimicrobial and Moisturizing Agent

Tocopheryl Acetate

Vitamin E acetate

0.05

Antiaging agent

Phenoxyethanol

0.30

Preservative

Sodium Polyacryloyldimethyl Taurate

Aristoflex silk [3]

1.00

Rheology Modifier

Aqua

Water

57,9

Solvent

Water & Hydrolyzed Myrtus communis Leaf Extract Longevicell [4]

0.10

Antioxidant, Antiaging agent

Parfum

0.15

Fragrance

Phone : 0031475 782540 • info@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Suppliers: [1] Seppic [2] Chemyunion [3] Clariant [4] Silab

Specifications: Appearance

Fluid Gel

Colour Odour

From whitish to slightly yellowish

Characteristic

3.40-3.60

Typical:

3.50

Brookfield Viscosity (R6, 100 rpm, 25°C)

5000 ± 25% mPas

Typical:

5000 mPas

Manufacturing instructions: 5. In a melter, heat to 60 ° C and mix until homogeneous: a yellowish transparent fluid gel is obtained. Cool to T <30 ° C. 6. Once phase A has cooled, add and mix Hebeatol and Tocopheryl Acetate . Indicative time 10 min, until transparency. 7. In turboemulsifier, sprinkle the Aristoflex Silk while stirring. Continue until a homogeneous gel is formed 8. Flush, possibly only gentle mixing and possibly with a very low force turbine, to avoid incorporating air. A whitish-yellowish gel is obtained. INCI list: Ingredients: Aqua, Azelaic Acid, Propanediol, Heptyl Glucoside, Sodium Polyacryloyldimethyl Taurate, Xylityl Sesquicaprylate, Hydroly- zed Myrtus Communis Leaf Extract, Tocopheryl Acetate Phenoxyethanol, Parfum Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred packaging: tube, 30 ml. SC005 Whitening Cream (w/o). Multiple action: whitening, anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name / Other name % by weight Function A Aqua Water 66.35 Solvent Propanediol Propylen Glycol 3.00 Humectant Magnesium sulfate Magnesium sulfate heptahydrate 0.80 Viscosity controlling B Octyldodecanol - 5.00 Emollient, Masking Agent. Ethylhexyl palmitate Tegosoft OP [1] 5.00 Emollient Isopropyl isostearate Crodamol IPIS [2] 4.00 Emollient C12-15 Alkyl benzoate - 3.00 Emollient PEG-30 Dipolyhydroxystearate Cithrol DPHS [2] 1.50 Emulsifier Butyrospermum parkii butter - 0.20 Emollient Caprylyl glycol, Glyceryl caprylate, Ethylhexylglycerin Neofect 403 [3] 1.00 Antimicrobial agent C Tocopheryl Acetate Vitamin E acetate 0.05 Antiaging agent Azelaic Acid AZCO99 10.00 Whitening agent, active ingredient D Parfum - 0.10 Fragrance

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Suppliers: [1] Evonik [2] Croda [3] Jan Dekker / IMCD

Specifications: Appearance

Soft cream

Colour Odour

White

Characteristic Not applicable

Typical:

Not applicable

Brookfield Viscosity (R4, 50 rpm, 25°C)

2150 ± 25 % mPas

Typical:

2150 mPas

Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

SC006 Whitening / Brightening Organo-gel for Uneven Complexion Multiple action: whitening, anti-imperfections, anti-residual marks, anti-aging. INCI Name Trade name / Other name % by weight

Function

A Phosphatidylcholine, Tocopherol, Ascorbyl palmitate Phospholipon 90G

8.000

Liposome former, skin conditioning and moisturizing

Isopropyl myristate

Isopropyl Myristate [1]

11.500

Emollient

20.000

Humectant

Propanediol

Propylen Glycol

AZCO99

Whitening agent, active ingredient

Azelaic Acid

5.000

Aqua

Water

54.400

Solvent

Imidazolydinil Urea

Sepicide CI [2]

0.300

Preservative

Phenoxyethanol

0.800

Preservative

Suppliers : [1] Phospholipid GmbH [2] BASF [3] Seppic

Specifications: Appearance

Soft cream

Colour Odour

White

Characteristic Not applicable

Typical:

Not applicable

Brookfield Viscosity (R5, 30 rpm, 25°C)

7770 ± 25% mPas

Typical:

7770 mPas

Manufacturing instructions: 1. Mix slowly all the ingredients of the Phase A until completely dissolved. Can be heated to max 50 ° C to speed up the achie- vement of homogeneity. 2. Mix all the ingredients of the phase B until homogeneous 3. Add the Phase B to the Phase A flushing very slowly and waiting for the final phase to be homogeneous. 4. Mix all the ingredients of the phase C until homogeneous. Add the obtained Phase to the A+B, mixing until homogeneous. INCI list: Ingredients: Aqua, Propanediol, Isopropyl Myristate, Phosphatidylcholine, Azelaic Acid, Phenoxyethanol, Imidazolidinyl Urea, Tocop- herol, Ascorbyl Palmitate

Shelf life: 3 years after production, 12 months after opening. Store at ambient temperature, out of direct sun light. Preferred pack- aging: tube, 30 ml.

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

Efficacy testing on skin with some disorders The Anti-Acne European composition (SC002) was tested in 8 patients suffering from infected closed comedones. The composition was applied on the affected two times per day for 30 days. The following visual scale was used:

Visual observation rating:

0-1 No improvement 2-3 Clearly noticeable improvement 4-6 Good improvement 7-9 Excellent improvement 10 Complete recovery

Volunteer

Gender

Age

Day

Day #0 Day #5 Day #10 Day #15 Day #20 Day #25 Result #30

Female

Positive

Female

Positive

Female

Negative

Female

Positive

Male

Negative

Male

Positive

Male

Positive

Male

Positive

The results are at least promising. In conclusion, AZCO99 can be regarded as a functional cosmetic ingredient which can successfully be used in formulations for the management of skin disorders.

Phone : +31 475 20 60 70 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

References

Available scientific evidences for the application of Azelaic acid in the therapy of skin disorders and in skin whitening/brightening formulations.

1. Aodan C. Breathnach, et Alters, Azelaic Acid Therapy in Disorders of skin Pigmentation, Clinics in Dermatology, Volume 7, Issue 2, April–June 1989, Pages 106-119; 2. Aprian,E.F. et Alters, Formulation, characterization and in vitro testing of Azelaic acid ethosome-based cream against Propi- onibacterium acnes for the treatment of acne, J.Adv. Pharm. Technol. Res. (2019), 10, 75-80; 3. Nazzaro-Porro M, Passi S, Picardo M, Breathnach A, Clayton R, Zina G. Beneficial effect of 15% azelaic acid cream on acne vulgaris. Br J DermatolJul;109(1):45-8 (1983); 4. Jaideep Bajaj and Dinesh Sharma, Formulation and evaluation of topical azelaic acid gel, Journal of Chemical and Pharma- ceutical Research, 2015, 7(10):616-620; 5. M.A. Sieber and J.K.E. Hegel, Azelaic Acid: Properties and Mode of Action, Skin Pharmacol Physiol 2014;27(suppl 1):9–17, DOI: 10.1159/000354888; 6. M. C. Young, P.M. Zito, Azelaic Acid in Acne Vulgaris, Journal of the Dermatology Nurses’ Association, 10 – 3, 2018; 7. A. K. Mohiuddin, Skin Lightening & Management of Hyperpigmentation, Review Article, Pharmaceutical Sciences & Analyti- cal Research Journal, Volume 2; Issue 2, June 18, 2019; 8. Nazzaro-Porro, M., et alters (1979a) Identification of tyrosinase inhibitors in cultures ai Pityrosporum and their melanocyto- toxic effect. In: Pigment cell 4: Biologic basis of pigmemation (Ed. By S.N.Klaus), p. 234. S. Karger, Basel; 9. C. Couteau and L. Coiffard, Overview of Skin Whitening Agents: Drugs and Cosmetic Products, Cosmetics 2016, 3, 27; 10. E. Burchacka et Alters, New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability, Biomedicine & Pharmacotherapy 83 (2016) 771–775; 11. M.D. Detmar et Alters, Effects of azelaic Acid on proliferation and ultrastructure of mouse keratinocytes in vitro, The J. of Invest. Dermatology, Vol. 93, N°1, July 1989; 12. J.P. Ebanks et Alters, Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration, Int. J. Mol. Sci. 2009, 10, 4066-4087; doi:10.3390/ijms10094066; 13. A. Mastrofrancesco et alters, Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation, Exp Dermatol. 2010 Sep;19(9):813-20. 14. Shin, J.W.; Park, K.C. Current clinical use of depigmenting agents. Dermatol Sin. 2014, 32, 205–210. 15. Nazzaro-Porro M, Passi S (1978) Identification of tyrosinase inhibitors in cultures of Pityrosporum. J Invest Dermatol 71:205– 208. 16. Lowe, N.J.; Rizk, D.; Grimes, P.; Billips, M.; Pincus, S. Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darker-skinned patients. Clin. Ther. 1998, 20, 945–959; 17. Webster, G. Combination azelaic acid therapy for acne vulgaris. J. Am. Acad. Dermatol. 2000, 43, S47–S50; 18. Draelos, Z. Multiple mechanisms of action of azelaic acid: New findings. J. Am. Acad. Dermatol. 2009, 60, AB86; 19. Rossi A.B., Nocera T., Lapalud P., Study sponsored by Pierre Fabre Dermo-Cosmétique, Poster presented at AAD Meeting –Washington DC., March 4-8, 2016; 20. J. Zeichner, New Insights Into Azelaic Acid, Practical Dermatology, March 2013; 21. Quan H, Nguyen, M.D., And Tran P. Bui, B.S., Azelaic Acid: Pharmacokinetic And Pharmacodynamic Properties And Its The- rapeutic Role In Hyperpigmentary Disorders And Acne, Internationa! journ.Ti of Dermatology, Vol, ,M, No, 2, bebruary 1995; 22. P. Lanzafame, Bactericidal activity of some acids towards microorganisms involved in etiopathogenesis of acne, Trends in Medicine, October 2011 Volume 11 Number 4;

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

For more information, visit https://azeco-cosmeceuticals.com/ or call +31 475 20 60 70

The information set forth herein is furnished free of charge and based on technical data that AZECO COSMECEUTICALS BV believes to be reliable. It is intended for use by persons having technical skill, at their own risk. Because conditions of use are outside our con- trol, AZECO COSMECEUTICALS makes no warranties, expressed or implied, and assumes no liability in connection with any use of this information. Nothing herein is to be taken as a license to operate under, or a recommendation to infringe any patents or patent applications.

Phone : 0031475 782540 • service@azeco-cosmeceuticals.com • www.azeco-cosmeceuticals.com

For technical and / or sales service contact

Azeco Cosmeceuticals BV | The Netherlands Ms. Annet Verhaegen service@azeco-cosmeceuticals.com

www.azeco-cosmeceuticals.com

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