Azelaic acid: Difference between revisions

{{short description|Organic chemical compound}}

{{Redirect-synonym|Finevin|a former settlement in [[Sutherland]], [[Scotland]]}}

| Watchedfields = changed

| verifiedrevid = 458792195

| ImageSize = 255px

| ImageAlt = Skeletal formula of azelaic acid

| ImageFile1 = Azelaic acid 3D ball.png

| ImageSize1 = 255px

| ImageAlt1 = Ball-and-stick model of the azelaic acid molecule

| PIN = Nonanedioic acid

| OtherNames =

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 7484

| EC_number = 204-669-1

| Beilstein = 1101094

| Gmelin = 261342

|Section2={{Chembox Properties

| C=9 | H=16 | O=4

| Appearance = white solid

| Density = 1.443 g/mL

| MeltingPtC = 109 to 111

| MeltingPt_ref = <ref name=aldrich>[http://www.sigmaaldrich.com/catalog/search/ProductDetail/aldrich/246379 Sigma-Aldrich catalog] {{webarchive |url=https://web.archive.org/web/20080409115856/http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/11470 |date=April 9, 2008 }}</ref>

| BoilingPtC = 286

| BoilingPt_notes = at 100 mmHg<ref name=aldrich/>

| Solubility = 2.14 g/L<ref name=pka>{{cite journal |title=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 |last1=Bretti|first1=C.|last2=Crea|first2=F.|last3=Foti|first3=C.|last4=Sammartano|first4=S. |journal=J. Chem. Eng. Data |year=2006 |volume=51 |issue=5 |pages=1660–1667 |doi=10.1021/je060132t}}</ref>

| pKa = 4.550, 5.498<ref name=pka/>

|Section6={{Chembox Pharmacology

| ATCCode_prefix = D10

| ATCCode_suffix = AX03

| HalfLife = 12 h

| Excretion =

| Legal_status =

| Legal_UK =

| Legal_AU = [[Standard for the Uniform Scheduling of Medicines and Poisons|S2]] (Pharmacy Only)

| Legal_CA =

| Pregnancy_category =

| Pregnancy_AU =

}}

|Section7={{Chembox Hazards

| GHSPictograms = {{GHS07}}

| GHSSignalWord = Warning

| HPhrases = {{H-phrases|315|319}}

| PPhrases = {{P-phrases|264|280|302+352|305+351+338|321|332+313|337+313|362}}

}}

'''Azelaic acid''' ('''AzA''') is an [[organic compound]] with the formula HOOC(CH₂)₇[[carboxylic acid|COOH]].<ref>{{Cite journal|last=Del Rosso|first=James Q.|date=2006-02-01|title=The use of topical azelaic acid for common skin disorders other than inflammatory rosacea|url=https://pubmed.ncbi.nlm.nih.gov/16566285/|journal=Cutis|volume=77|issue=2 Suppl|pages=22–24|issn=0011-4162|pmid=16566285}}</ref> 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.<ref name=Boy/> AzA inhibits [[tyrosinase]].<ref name="TyrosinaseInhibitor"/>

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 [[Pelargonic acid|nonanoic acid]] gives azelaic acid.<ref>{{Cite book|url=https://www.worldcat.org/oclc/982188831|title=Integrative medicine|date=2018|others=David Rakel|isbn=978-0-323-35868-2|edition=Fourth|location=Philadelphia, PA|chapter=|oclc=982188831}}</ref>

===Plants biology===

In plants, azelaic acid serves as a "distress flare" involved in defense responses after infection.<ref>{{cite journal | author = Sarah Everts | title = Vegetative Warfare | journal = [[Chemical & Engineering News]] | date=January 31, 2011 | volume = 89 | issue = 5 | pages = 53–55 | doi = 10.1021/cen-v089n005.p053 | url=http://cen.acs.org/articles/89/i5/Vegetative-Warfare.html |url-access=subscription }}</ref> It serves as a signal that induces the accumulation of [[salicylic acid]], an important component of a plant's defensive response.<ref>{{Cite journal | last1 = Jung | first1 = H. W. | last2 = Tschaplinski | first2 = T. J. | last3 = Wang | first3 = L. | last4 = Glazebrook | first4 = J. | last5 = Greenberg | first5 = J. T. | title = Priming in Systemic Plant Immunity | journal = Science | volume = 324 | issue = 5923 | pages = 89–91 | year = 2009 | pmid = 19342588 | doi = 10.1126/science.1170025| bibcode = 2009Sci...324...89W | s2cid = 206518245 }}</ref>

===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.<ref>{{cite journal | pmc=3346901| year=2012| last1=Reinholz| first1=M.| title=Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease| journal=Annals of Dermatology| volume=24| issue=2| pages=126–135| last2=Ruzicka| first2=T.| last3=Schauber| first3=J.| doi=10.5021/ad.2012.24.2.126| pmid=22577261}}</ref>

[[File:30g azelaic acid cream tube.png|thumb|128px|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.<ref name=Boy>{{cite encyclopedia|first1=Boy |last1=Cornils |first2=Peter |last2=Lappe |title=Dicarboxylic Acids, Aliphatic |encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry |date=2006 |publisher=Wiley-VCH |location=[[Weinheim]] |doi=10.1002/14356007.a08_523|isbn=3527306730 }}</ref>

===Medical===

Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne.<ref>{{cite web|url=http://www.webmd.com/skin-problems-and-treatments/acne/azelaic-acid-for-acne-vulgaris |title=Azelaic Acid for Acne|website=[[WebMD]]}}</ref><ref name="drugs.com">{{cite web|url=https://www.drugs.com/mtm/azelaic-acid-topical.html |title=Azelaic acid topical|website=Drugs.com}}</ref> It belongs to a class of medication called [[dicarboxylic acid]]s. 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{{clarify|reason=Not wrong, but feels very off describing the main component of skin like this…|date=December 2021}} of acne bacteria.<ref>{{cite journal | title = Azelaic acid in the treatment of papulopustular rosacea – A systematic review of randomized controlled trials | last1 = Liu | first1 = R. H. | last2 = Smith | first2 = M. K. | last3 = Basta | first3 = S. A. | last4 = Farmer | first4 = E. R. | journal = Archives of Dermatology | volume = 142 | issue = 8 | pages = 1047–1052 | year = 2006 | doi =10.1001/archderm.142.8.1047 | pmid = 16924055 }}</ref> Azelaic acid is also used as a [[Topical gels|topical gel]] treatment for [[rosacea]], due to its ability to reduce inflammation.<ref name="drugs.com"/> 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.<ref>{{Cite journal|date=2016-10-01|title=New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability|url=https://www.sciencedirect.com/science/article/abs/pii/S0753332216306278|journal=Biomedicine & Pharmacotherapy|language=en|volume=83|pages=771–775|doi=10.1016/j.biopha.2016.07.014|issn=0753-3322|last1=Burchacka|first1=E.|last2=Potaczek|first2=P.|last3=Paduszyński|first3=P.|last4=Karłowicz-Bodalska|first4=K.|last5=Han|first5=T.|last6=Han|first6=S.|pmid=27484346}}</ref>

====Acne treatment====

Azelaic acid is effective for mild to moderate acne when applied topically at a 15%-20% concentration.<ref name="Sieber2014">{{cite journal|vauthors=Sieber MA, Hegel JK|date=November 2013|title=Azelaic acid: Properties and mode of action|journal=Skin Pharmacology and Physiology|type=Review|volume=27 Suppl 1|issue=Supplement 1|pages=9–17|doi=10.1159/000354888|pmid=24280644|s2cid=8848543}}</ref><ref name="Pugashetti2013">{{cite journal|vauthors=Pugashetti R, Shinkai K|date=July 2013|title=Treatment of acne vulgaris in pregnant patients|journal=Dermatologic Therapy|type=Review|volume=26|issue=4|pages=302–11|doi=10.1111/dth.12077|pmid=23914887|s2cid=5750718|doi-access=free}}</ref><ref>{{Cite journal|last1=Gollnick|first1=H. P.|last2=Graupe|first2=K.|last3=Zaumseil|first3=R. P.|year=2004|title=15% Azelainsauregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien|trans-title=Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies|url=http://europepmc.org/article/med/16281587|journal=Journal der Deutschen Dermatologischen Gesellschaft|volume=2|issue=10|pages=841–847|doi=10.1046/j.1439-0353.2004.04731.x|pmid=16281587|s2cid=58809558 |access-date=2021-05-14}}</ref><ref>{{Cite journal|last=Thiboutot|first=Diane|date=January 2008|title=Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris|url=https://pubmed.ncbi.nlm.nih.gov/18246693/|journal=Journal of Drugs in Dermatology|volume=7|issue=1|pages=13–16|issn=1545-9616|pmid=18246693}}</ref> In patients with moderate [[acne]], twice daily application over 3 months of 20% AzA significantly reduced the number of comedones, papules, and pustules;<ref>{{Cite web |title=Azelaic Acid And Its Benefits |url=https://chemistatplay.com/blogs/news/azelaic-acid-and-its-benefits |access-date=2022-03-10 |website=Chemist at Play |language=en}}</ref><ref name=":0">{{Cite journal|last1=Fitton|first1=A.|last2=Goa|first2=K. L.|date=May 1991|title=Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders|url=https://pubmed.ncbi.nlm.nih.gov/1712709/|journal=Drugs|volume=41|issue=5|pages=780–798|doi=10.2165/00003495-199141050-00007|issn=0012-6667|pmid=1712709|s2cid=46960738}}</ref> at this strength, it’s considered to be as effective as benzoyl peroxide 5%, tretinoin 0.05%, erythromycin 2%, and oral tetracycline at 500&nbsp;mg-1000&nbsp;mg.<ref name="Herb2010">{{cite journal|vauthors=Morelli V, Calmet E, Jhingade V|date=June 2010|title=Alternative therapies for common dermatologic disorders, part 2|journal=Primary Care|type=Review|volume=37|issue=2|pages=285–96|doi=10.1016/j.pop.2010.02.005|pmid=20493337}}</ref><ref name=":1">{{Cite journal|last1=Woolery-Lloyd|first1=Heather C.|last2=Keri|first2=Jonette|last3=Doig|first3=Stefan|date=2013-04-01|title=Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color|url=https://pubmed.ncbi.nlm.nih.gov/23652891/|journal=Journal of Drugs in Dermatology|volume=12|issue=4|pages=434–437|issn=1545-9616|pmid=23652891}}</ref> In a comparative review of effects of topical AzA, [[Salicylic acid]], [[Nicotinamide]], Sulfur, Zinc, and [[Alpha hydroxy acid|alpha-hydroxy acid]], AzA had more high-quality evidence of effectiveness than the rest.<ref>{{Cite journal|last1=Liu|first1=Haibo|last2=Yu|first2=Haiyan|last3=Xia|first3=Jun|last4=Liu|first4=Ling|last5=Liu|first5=Guanjian|last6=Sang|first6=Hong|last7=Peinemann|first7=Frank|date=2020-11-01|title=Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review|url=https://pubmed.ncbi.nlm.nih.gov/33034949/|journal=Journal of Evidence-Based Medicine|volume=13|issue=4|pages=275–283|doi=10.1111/jebm.12411|issn=1756-5391|pmid=33034949|s2cid=222236883}}</ref> 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.<ref name="Herb2010" />

===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]].<ref>{{cite journal | last= Draelos |first=Z. | title = Skin lightening preparations and the hydroquinone controversy. | journal = Dermatologic Therapy | volume = 20 | issue = 5 | pages = 308–313 | date = Sep–Oct 2007 | pmid = 18045355 | doi=10.1111/j.1529-8019.2007.00144.x|s2cid=24913995 | doi-access = free }}</ref> As a [[tyrosinase]] inhibitor,<ref name="TyrosinaseInhibitor">{{Cite journal|last1=Pillaiyar|first1=Thanigaimalai|last2=Manickam|first2=Manoj|last3=Namasivayam|first3=Vigneshwaran|date=2017-01-18|title=Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors|journal=Journal of Enzyme Inhibition and Medicinal Chemistry|volume=32|issue=1|pages=403–425|doi=10.1080/14756366.2016.1256882|issn=1475-6366|pmc=6010116|pmid=28097901}}</ref> azelaic acid reduces synthesis of [[melanin]].<ref name="Grimes2007">{{cite book|last=Grimes|first=Pearl E.|title=Aesthetics and Cosmetic Surgery for Darker Skin Types|url=https://books.google.com/books?id=ALt93yGZccQC&pg=PA74|access-date=9 August 2011|date=2007-07-01|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8403-0|pages=74 ff}}</ref> 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]].<ref name=pmid3207614>{{cite journal |doi=10.1111/j.1365-2133.1988.tb03474.x |pmid=3207614 |title=Inhibition of 5α-reductase activity in human skin by zinc and azelaic acid |journal=British Journal of Dermatology |volume=119 |issue=5 |pages=627–32 |year=1988 |last1=Stamatiadis |first1=D |last2=Bulteau-Portois |first2=Marie-Claire |last3=Mowszowicz |first3=Irene |s2cid=28506969 }}</ref> In vitro research during mid-1980s evaluating azelaic acid's depigmenting (whitening) capability concluded it is effective (cytotoxic to [[melanocyte]]s) at only high concentrations.<ref>{{Cite journal|last1=Pathak|first1=M. A.|last2=Ciganek|first2=E. R.|last3=Wick|first3=M.|last4=Sober|first4=A. J.|last5=Farinelli|first5=W. A.|last6=Fitzpatrick|first6=T. B.|date=September 1985|title=An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent|journal=The Journal of Investigative Dermatology|volume=85|issue=3|pages=222–228|doi=10.1111/1523-1747.ep12276684|issn=0022-202X|pmid=4031538|doi-access=free}}</ref>

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.<ref>{{Cite journal|last=Breathnach|first=A. S.|date=1996-01-01|title=Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies|url=https://pubmed.ncbi.nlm.nih.gov/8654129/|journal=Cutis|volume=57|issue=1 Suppl|pages=36–45|issn=0011-4162|pmid=8654129}}</ref><ref name=":0" />

==Brand names==

Brand names for azelaic acid include Dermaz 99,<ref>https://pharmaceutical.basf.com/en/APIs-Raw-Materials/Dermaz.html{{full citation needed|date=September 2018}}{{Dead link|date=June 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> 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)<ref>{{Cite web|title=Azelaic Acid brands in Pakistan|url=http://www.druginfosys.com/availablebrands.aspx?query=20%2520%25w/w&form=Cream&drugCode=807&drugName=Azelaic%2520Acid&type=1&Ing==1|access-date=2021-04-17|website=www.druginfosys.com}}</ref>

==References==

{{reflist|30em}}

* {{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a603020.html |title=Azelaic Acid Topical |website=[[MedlinePlus]]}}

{{Androgenics}}

{{Navbox linear saturated dicarboxylic acids}}

[[Category:5α-Reductase inhibitors]]

[[Category:Skin whitening]]