Azelaic acid

Last updated
Azelaic acid
Azelaic acid.png
Azelaic acid 3D ball.png
Names
Preferred IUPAC name
Nonanedioic acid
Identifiers
3D model (JSmol)
1101094
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.004.246 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-669-1
261342
KEGG
PubChem CID
UNII
  • InChI=1S/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13) Yes check.svgY
    Key: BDJRBEYXGGNYIS-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)
    Key: BDJRBEYXGGNYIS-UHFFFAOYAK
  • O=C(O)CCCCCCCC(=O)O
Properties
C9H16O4
Molar mass 188.22 g/mol
Appearancewhite solid
Density 1.443 g/mL
Melting point 109 to 111 °C (228 to 232 °F; 382 to 384 K) [1]
Boiling point 286 °C (547 °F; 559 K) at 100 mmHg [1]
2.14 g/L [2]
Acidity (pKa)4.550, 5.498 [2]
Pharmacology
D10AX03 ( WHO )
Topical
Pharmacokinetics:
Very low
12 h
Legal status
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319
P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Azelaic acid (AzA) is an organic compound with the formula HOOC(CH2)7 COOH. [3] This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of a number of hair and skin conditioners. [4] AzA inhibits tyrosinase. [5]

Contents

Production

Azelaic acid is industrially produced by the ozonolysis of oleic acid. The side product is nonanoic acid. It is produced naturally by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin. The bacterial degradation of nonanoic acid gives azelaic acid. [6]

Biological function

Plants biology

In plants, azelaic acid serves as a "distress flare" involved in defense responses after infection. [7] It serves as a signal that induces the accumulation of salicylic acid, an important component of a plant's defensive response. [8]

Human biology

The mechanism of action in humans is thought to be through the inhibition of hyperactive protease activity that converts cathelicidin into the antimicrobial skin peptide LL-37. [9]

Applications

Azelaic acid cream labeled in Russian 30g azelaic acid cream tube.png
Azelaic acid cream labeled in Russian

Esters of this dicarboxylic acid find applications in lubrication and plasticizers. In lubricant industries it is used as a thickening agent in lithium complex grease. With hexamethylenediamine, azelaic acid forms Nylon-6,9, which finds specialized uses as a plastic. [4]

Medical

Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne. [10] [11] It belongs to a class of medication called dicarboxylic acids. It works by killing acne bacteria that infect skin pores. It also decreases the production of keratin, which is a natural substance that promotes the growth[ clarification needed ] of acne bacteria. [12] Azelaic acid is also used as a topical gel treatment for rosacea, due to its ability to reduce inflammation. [11] It clears the bumps and swelling caused by rosacea.

In topical pharmaceutical preparations and scientific research AzA is typically used in concentrations between 15% and 20% but some research demonstrates that in certain vehicle formulations the pharmaceutical effects of 10% Azelaic acid has the potential to be fully comparable to that of some 20% creams. [13]

Acne treatment

Azelaic acid is effective for mild to moderate acne when applied topically at a 15%-20% concentration. [14] [15] [16] [17] In patients with moderate acne, twice daily application over 3 months of 20% AzA significantly reduced the number of comedones, papules, and pustules [18] ; [19] at this strength, it’s considered to be as effective as benzoyl peroxide 5%, tretinoin 0.05%, erythromycin 2%, and oral tetracycline at 500mg-1000mg. [20] [21] In a comparative review of effects of topical AzA, Salicylic acid, Nicotinamide, Sulfur, Zinc, and alpha-hydroxy acid, AzA had more high-quality evidence of effectiveness than the rest. [22] Results can be expected after 4 weeks of twice-daily treatment. The effectiveness of long term use is unclear, but it’s been recommended that AzA be used for at least 6 months continuously for maintenance. [20]

Whitening agent

Azelaic acid is used for treatment of skin pigmentation, including melasma and postinflammatory hyperpigmentation, particularly in those with darker skin types. It has been recommended as an alternative to hydroquinone. [23] As a tyrosinase inhibitor, [5] azelaic acid reduces synthesis of melanin. [24] According to one report in 1988, azelaic acid in combination with zinc sulfate in vitro was found to be a potent (90% inhibition) 5α-reductase inhibitor, similar to the hair loss drugs finasteride and dutasteride. [25] In vitro research during mid-1980s evaluating azelaic acid's depigmenting (whitening) capability concluded it is effective (cytotoxic to melanocytes) at only high concentrations. [26]

A 1996 review claimed 20% AzA is as potent as 4% hydroquinone after a period of application of three months without the latter's adverse effects and even more effective if applied along with tretinoin for the same period of time. [27] [19]

Brand names

Brand names for azelaic acid include Dermaz 99, [28] Crema Pella Perfetta (micronized azelaic acid, kojic dipalmitate, and liquorice extract), Azepur99, Azetec99, Azaclear (azelaic acid and niacinamide), AzClear Action, Azelex, White Action cream, Finacea, Finevin, Melazepam, Skinoren, Ezanic, Azelac, Azaderm, (Acnegen, Eziderm, Acnicam, Azelexin in Pakistan) [29]

Related Research Articles

<span class="mw-page-title-main">Acne</span> Skin condition characterized by pimples

Acne, also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back. The resulting appearance can lead to lack of confidence, anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.

<span class="mw-page-title-main">Tinea versicolor</span> Skin disease

Tinea versicolor is a condition characterized by a skin eruption on the trunk and proximal extremities. The majority of tinea versicolor is caused by the fungus Malassezia globosa, although Malassezia furfur is responsible for a small number of cases. These yeasts are normally found on the human skin and become troublesome only under certain circumstances, such as a warm and humid environment, although the exact conditions that cause initiation of the disease process are poorly understood.

<span class="mw-page-title-main">Rosacea</span> Skin condition resulting in redness, pimples and swelling, usually on the face

Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarged nose may occur in severe disease, a condition known as rhinophyma.

<span class="mw-page-title-main">Benzoyl peroxide</span> Chemical compound with uses in industry and acne treatment

Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula (C6H5−C(=O)O−)2, often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (C6H5−C(=O)−, Bz) groups connected by a peroxide (−O−O−). It is a white granular solid with a faint odour of benzaldehyde, poorly soluble in water but soluble in acetone, ethanol, and many other organic solvents. Benzoyl peroxide is an oxidizer, which is principally used as in the production of polymers.

<span class="mw-page-title-main">Adapalene</span> Third-generation topical retinoid

Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions. Studies have found adapalene is as effective as other retinoids, while causing less irritation. It also has several advantages over other retinoids. The adapalene molecule is more stable compared to tretinoin and tazarotene, which leads to less concern for photodegradation. It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with benzoyl peroxide. Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. The Swiss company Galderma sells adapalene under the brand-name product Differin.

<span class="mw-page-title-main">Hyperpigmentation</span> Darkening of an area of skin or nails caused by increased melanin

Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.

<span class="mw-page-title-main">Melasma</span> Medical condition

Melasma is a tan or dark skin discoloration. Melasma is thought to be caused by sun exposure, genetic predisposition, hormone changes, and skin irritation. Although it can affect anyone, it is particularly common in women, especially pregnant women and those who are taking oral or patch contraceptives or hormone replacement therapy medications.

<span class="mw-page-title-main">Hydroquinone</span> Chemical compound

Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a para position. It is a white granular solid. Substituted derivatives of this parent compound are also referred to as hydroquinones. The name "hydroquinone" was coined by Friedrich Wöhler in 1843.

<span class="mw-page-title-main">Ammonium bituminosulfonate</span> Chemical compound

Ichthammol or ammonium bituminosulfonate is a medication derived from sulfur-rich oil shale. It is used as a treatment for different skin diseases, including eczema and psoriasis. It is applied on the skin as an ointments, most commonly containing 10% or 20% ichthammol.

<span class="mw-page-title-main">Comedo</span> Medical condition

A comedo is a clogged hair follicle (pore) in the skin. Keratin combines with oil to block the follicle. A comedo can be open (blackhead) or closed by skin (whitehead) and occur with or without acne. The word "comedo" comes from the Latin comedere, meaning "to eat up", and was historically used to describe parasitic worms; in modern medical terminology, it is used to suggest the worm-like appearance of the expressed material.

<span class="mw-page-title-main">Lentigo</span> Medical condition

A lentigo is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasia of melanocytes is restricted to the cell layer directly above the basement membrane of the epidermis where melanocytes normally reside. This is in contrast to the "nests" of multi-layer melanocytes found in moles. Because of this characteristic feature, the adjective "lentiginous" is used to describe other skin lesions that similarly proliferate linearly within the basal cell layer.

<span class="mw-page-title-main">Clindamycin/benzoyl peroxide</span> Type of medication

Clindamycin/benzoyl peroxide is a topical gel used for the treatment of acne. It is a fixed-dose combination of clindamycin, as the phosphate, an antibiotic, and benzoyl peroxide, an antiseptic.

<span class="mw-page-title-main">Liver spot</span> Age-related skin blemish

Liver spots are blemishes on the skin associated with aging and exposure to ultraviolet radiation from the sun. They range in color from light brown to red or black and are located in areas most often exposed to the sun, particularly the hands, face, shoulders, arms and forehead, and the scalp if bald.

<span class="mw-page-title-main">Arbutin</span> Glycoside

Arbutin is a glycoside; a glycosylated hydroquinone extracted from the bearberry plant in the genus Arctostaphylos among many other medicinal plants, primarily in the family Ericaceae. Applied topically, it inhibits tyrosinase and thus prevents the formation of melanin. Arbutin is therefore used as a skin-lightening agent. Very tiny amounts of arbutin are found in wheat, pear skins, and some other foods. It is also found in Viburnum opulus and Bergenia crassifolia. Arbutin was also produced by an in vitro culture of Schisandra chinensis.

Hidradenitis is any disease in which the histologic abnormality is primarily an inflammatory infiltrate around the eccrine glands. This group includes neutrophilic eccrine hidradenitis and recurrent palmoplantar hidradenitis.

<span class="mw-page-title-main">Nadifloxacin</span> Chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

<span class="mw-page-title-main">Pimple</span> Type of comedo

A pimple or zit is a kind of comedo that results from excess sebum and dead skin cells getting trapped in the pores of the skin. In its aggravated state, it may evolve into a pustule or papule. Pimples can be treated by acne medications, antibiotics, and anti-inflammatories prescribed by a physician, or various over the counter remedies purchased at a pharmacy.

<span class="mw-page-title-main">Azerizin</span>

Azerizin is claimed to be a proprietary blend of the natural ingredients nicotinamide, azelaic acid, quercetin and curcumin that purportedly combine the anti-inflammatory and antimicrobial properties, along with inhibiting effects on sebum production.

<span class="mw-page-title-main">Medical uses of salicylic acid</span>

Salicylic acid is used as a medicine to help remove the outer layer of the skin. As such it is used to treat warts, skin tags, calluses, psoriasis, dandruff, acne, ringworm, and ichthyosis. For conditions other than warts, it is often used together with other medications. It is applied to the area affected.

<span class="mw-page-title-main">Glyceryl octyl ascorbic acid</span> Chemical compound

Glyceryl octyl ascorbic acid (GO-VC) is an amphipathic derivative of vitamin C consisting of two ether linkages: a 1-octyl at position 2 and a glycerin at position 3. The chemical name is 2-glyceryl-3-octyl ascorbic acid. The isomer in which these two groups are swapped is also known.

References

  1. 1 2 Sigma-Aldrich catalog Archived April 9, 2008, at the Wayback Machine
  2. 1 2 Bretti, C.; Crea, F.; Foti, C.; Sammartano, S. (2006). "Solubility and Activity Coefficients of Acidic and Basic Nonelectrolytes in Aqueous Salt Solutions. 2. Solubility and Activity Coefficients of Suberic, Azelaic, and Sebacic Acids in NaCl(aq), (CH3)4NCl(aq), and (C2H5)4NI(aq) at Different Ionic Strengths and at t = 25 °C". J. Chem. Eng. Data. 51 (5): 1660–1667. doi:10.1021/je060132t.
  3. Del Rosso, James Q. (2006-02-01). "The use of topical azelaic acid for common skin disorders other than inflammatory rosacea". Cutis. 77 (2 Suppl): 22–24. ISSN   0011-4162. PMID   16566285.
  4. 1 2 Cornils, Boy; Lappe, Peter (2006). "Dicarboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a08_523. ISBN   3527306730.
  5. 1 2 Pillaiyar, Thanigaimalai; Manickam, Manoj; Namasivayam, Vigneshwaran (2017-01-18). "Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors". Journal of Enzyme Inhibition and Medicinal Chemistry. 32 (1): 403–425. doi:10.1080/14756366.2016.1256882. ISSN   1475-6366. PMC   6010116 . PMID   28097901.
  6. Integrative medicine. David Rakel (Fourth ed.). Philadelphia, PA. 2018. ISBN   978-0-323-35868-2. OCLC   982188831.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  7. Sarah Everts (January 31, 2011). "Vegetative Warfare" . Chemical & Engineering News . 89 (5): 53–55. doi:10.1021/cen-v089n005.p053.
  8. Jung, H. W.; Tschaplinski, T. J.; Wang, L.; Glazebrook, J.; Greenberg, J. T. (2009). "Priming in Systemic Plant Immunity". Science. 324 (5923): 89–91. Bibcode:2009Sci...324...89W. doi:10.1126/science.1170025. PMID   19342588. S2CID   206518245.
  9. Reinholz, M.; Ruzicka, T.; Schauber, J. (2012). "Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease". Annals of Dermatology. 24 (2): 126–135. doi:10.5021/ad.2012.24.2.126. PMC   3346901 . PMID   22577261.
  10. "Azelaic Acid for Acne". WebMD .
  11. 1 2 "Azelaic acid topical". Drugs.com.
  12. Liu, R. H.; Smith, M. K.; Basta, S. A.; Farmer, E. R. (2006). "Azelaic acid in the treatment of papulopustular rosacea – A systematic review of randomized controlled trials". Archives of Dermatology. 142 (8): 1047–1052. doi:10.1001/archderm.142.8.1047. PMID   16924055.
  13. Burchacka, E.; Potaczek, P.; Paduszyński, P.; Karłowicz-Bodalska, K.; Han, T.; Han, S. (2016-10-01). "New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability". Biomedicine & Pharmacotherapy. 83: 771–775. doi:10.1016/j.biopha.2016.07.014. ISSN   0753-3322. PMID   27484346.
  14. Sieber MA, Hegel JK (November 2013). "Azelaic acid: Properties and mode of action". Skin Pharmacology and Physiology (Review). 27 Suppl 1 (Supplement 1): 9–17. doi:10.1159/000354888. PMID   24280644. S2CID   8848543.
  15. Pugashetti R, Shinkai K (July 2013). "Treatment of acne vulgaris in pregnant patients". Dermatologic Therapy (Review). 26 (4): 302–11. doi: 10.1111/dth.12077 . PMID   23914887. S2CID   5750718.
  16. Gollnick, H. P.; Graupe, K.; Zaumseil, R. P. (2004). "15% Azelainsauregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien" [Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies]. Journal der Deutschen Dermatologischen Gesellschaft. 2 (10): 841–847. doi:10.1046/j.1439-0353.2004.04731.x. PMID   16281587. S2CID   58809558 . Retrieved 2021-05-14.
  17. Thiboutot, Diane (January 2008). "Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris". Journal of Drugs in Dermatology. 7 (1): 13–16. ISSN   1545-9616. PMID   18246693.
  18. "Azelaic Acid And Its Benefits". Chemist at Play. Retrieved 2022-03-10.
  19. 1 2 Fitton, A.; Goa, K. L. (May 1991). "Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders". Drugs. 41 (5): 780–798. doi:10.2165/00003495-199141050-00007. ISSN   0012-6667. PMID   1712709. S2CID   46960738.
  20. 1 2 Morelli V, Calmet E, Jhingade V (June 2010). "Alternative therapies for common dermatologic disorders, part 2". Primary Care (Review). 37 (2): 285–96. doi:10.1016/j.pop.2010.02.005. PMID   20493337.
  21. Woolery-Lloyd, Heather C.; Keri, Jonette; Doig, Stefan (2013-04-01). "Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color". Journal of Drugs in Dermatology. 12 (4): 434–437. ISSN   1545-9616. PMID   23652891.
  22. Liu, Haibo; Yu, Haiyan; Xia, Jun; Liu, Ling; Liu, Guanjian; Sang, Hong; Peinemann, Frank (2020-11-01). "Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review". Journal of Evidence-Based Medicine. 13 (4): 275–283. doi:10.1111/jebm.12411. ISSN   1756-5391. PMID   33034949. S2CID   222236883.
  23. Draelos, Z. (Sep–Oct 2007). "Skin lightening preparations and the hydroquinone controversy". Dermatologic Therapy. 20 (5): 308–313. doi: 10.1111/j.1529-8019.2007.00144.x . PMID   18045355. S2CID   24913995.
  24. Grimes, Pearl E. (2007-07-01). Aesthetics and Cosmetic Surgery for Darker Skin Types. Lippincott Williams & Wilkins. pp. 74 ff. ISBN   978-0-7817-8403-0 . Retrieved 9 August 2011.
  25. Stamatiadis, D; Bulteau-Portois, Marie-Claire; Mowszowicz, Irene (1988). "Inhibition of 5α-reductase activity in human skin by zinc and azelaic acid". British Journal of Dermatology. 119 (5): 627–32. doi:10.1111/j.1365-2133.1988.tb03474.x. PMID   3207614. S2CID   28506969.
  26. Pathak, M. A.; Ciganek, E. R.; Wick, M.; Sober, A. J.; Farinelli, W. A.; Fitzpatrick, T. B. (September 1985). "An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent". The Journal of Investigative Dermatology. 85 (3): 222–228. doi: 10.1111/1523-1747.ep12276684 . ISSN   0022-202X. PMID   4031538.
  27. Breathnach, A. S. (1996-01-01). "Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies". Cutis. 57 (1 Suppl): 36–45. ISSN   0011-4162. PMID   8654129.
  28. https://pharmaceutical.basf.com/en/APIs-Raw-Materials/Dermaz.html%5B%5D%5B%5D
  29. "Azelaic Acid brands in Pakistan". www.druginfosys.com. Retrieved 2021-04-17.