Ammonium bituminosulfonate

{{Infobox drug

| drug_name = Ichthammol

| INN =

| type =

| image = File:Ichthyol-Salbe.jpg

| alt =

| caption = A tube of medicinal ammonium bituminosulfonate (ichthyol)

| pronounce =

| tradename = Ichthyol

| Drugs.com =

| MedlinePlus =

| pregnancy_AU =

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration =

| ATCvet =

| ATC_prefix =

| ATC_suffix =

| legal_AU =

| legal_AU_comment =

| legal_BR =

| legal_BR_comment =

| legal_CA =

| legal_CA_comment =

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK =

| legal_UK_comment =

| legal_US =

| legal_US_comment =

| legal_EU =

| legal_EU_comment =

| legal_UN =

| legal_UN_comment =

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action=

| excretion =

| CAS_number = 8029-68-3

| PubChem =

| DrugBank = DB11341

| UNII = NQ14646378

| synonyms = ammonium bituminosulfonate; ammonium bituminosulphonate; bituminosulfonates

| IUPAC_name =

| chemical_formula =

| molecular_weight =

}}

Ichthammol or ammonium bituminosulfonate (brand name Ichthyol), also known as black ointment, is a medication derived from sulfur-rich oil shale (bituminous schists). It is used (sometimes in combination with zinc oxide) as a treatment for different skin diseases, including eczema and psoriasis (see below). It is applied on the skin as an ointments, most commonly containing 10% or 20% ichthammol.

Bituminosulfonates are considered topical therapeutic agents with very good tolerability.{{cite book | vauthors = Schmid-Wendtner MH, Korting HC, Sterry W | chapter = Bituminosulfonate. | title = Therapeutische Verfahren in der Dermatologie–Dermatika und Kosmetika | location = Berlin, Wien| publisher = Blackwell Wissenschafts-Verlag | date = 2001 | pages = 165–171 }}

The use of ichthammol in dermatology was promoted by German physician Paul Gerson Unna.Paul Gerson Unna: About Ichthyol. In: Monatshefte für praktische Dermatologie, Band XXV, 1897 (in German).{{Cite web | work = Deutsche Biographie|title=Unna, Paul Gerson - Deutsche Biographie|url=https://www.deutsche-biographie.de/sfz107295.html|access-date=2021-07-19 |language=de}}{{Cite web| work = Deutsches Ärzteblatt | publisher = Deutscher Ärzteverlag GmbH, Redaktion Deutsches|date=1995-03-10|title=110 Jahre Ichthyol-Schieferöl: Klassiker mit breitem Spektrum an Indikationen|url=https://www.aerzteblatt.de/archiv/82498/110-Jahre-Ichthyol-Schieferoel-Klassiker-mit-breitem-Spektrum-an-Indikationen|access-date=2021-07-19 |language=de}}

Ichthammol ointments, commonly known as black ointment or drawing salve, should not be confused with black salve, an escharotic (corrosive) paste intended to destroy skin tissue.{{cite journal | vauthors = Laskey D, Tran M | title = Facial eschar following a single application of black salve | journal = Clinical Toxicology | volume = 55 | issue = 7 | pages = 676–677 | date = August 2017 | pmid = 28426257 | doi = 10.1080/15563650.2017.1312428 | s2cid = 29076775 }} In contrast, ichthammol does not have any corrosive properties on the skin.

Production

Ichthammol is obtained through three steps from bituminous schists: dry distillation, sulfonation of the resulting oil (or purified fractions thereof), and finally neutralization with ammonia.

Properties

Ichthammol is a viscous, water-soluble substance with a characteristic bitumen-like odor. It is incompatible with acids, alkali carbonates or hydrates and alkaloidal salts. It is a thick reddish brown liquid, possessing a bituminous odor and taste. It is soluble in water and miscible with glycerin, but is nearly insoluble in strong alcohol or concentrated ether. It contains a large percentage of organically combined sulfur.

Chemically speaking ichthammol is a sulfonated shale oil. From elemental analysis, the composition of ichthammol was calculated to be C₂₈H₃₆S₅O₆(NH₄)₂.{{cite journal | vauthors = Baumann E, Schotten C | title = Über das "Ichthyol". | journal = Monatshefte für praktische Dermatologie. | date = 1883 | volume = 2 | page = 257 }} However, as a product of natural origin, it is a mixture of many different compounds.{{cite journal| vauthors = Scheibler H |title=Über die chemischen Bestandteile der schwefelreichen, bituminösen Teeröle (Ichthyolöle) |journal=Berichte der Deutschen Chemischen Gesellschaft |volume=48 |issue=2 |pages=1815–26 |date=1915 |doi=10.1002/cber.19150480276 |url=https://zenodo.org/record/1426593 }}

Similar materials

Similar substances can be made by altering the starting material. An "ammonium sufobitol" (Tumenol-Ammonium), made from light shale oil of the Messel pit, was sold until 2000 in Germany.{{cite web | url = https://www.pharmazeutische-zeitung.de/pharm1-09-2000/ | title = Ammoniumbituminosulfonat statt Ammoniumsulfobitol | work = Pharmazeutische Zeitung | date = 28 February 2000 }} The Chinese material labelled as "ichthammol" are actually an ersatz product made from vegetable oil.

= Ichtasol =

{{Infobox drug

| drug_name = Ichtasol

| pronounce =

| tradename = Ichthyol-Pale

| Drugs.com =

| MedlinePlus =

| pregnancy_AU =

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration =

| ATCvet =

| ATC_prefix = D10

| ATC_suffix = BX01

| CAS_number = 12542-33-5

| CAS_supplemental = {{CAS|1340-06-3}} (cosmetic-grade)

| PubChem =

| DrugBank = DB11341

| UNII = NQ14646378

| KEGG = D04495

| synonyms = sodium shale oil sulfonate (former INCI); Ichthyolic Acid, Sodium Salt; sodium salt of light bitumenosulfonate

|DTXSID=none

| IUPAC_name =

| chemical_formula =

| molecular_weight =

}}

Ichtasol (USAN: Ictasol) is produced from the light (as opposed to heavy) fraction of distilled shale oil. It has a pale appearance.{{cite web |title=Ichthyol® Pale - Ichthyol| work = Ichthyol-Gesellschaft |url=https://www.ichthyol.de/en/raw-materials-for-corporate-customers/ichthyol-pale/ |date=1 April 2022}} There appears to be an oral preparation made from this mixture.

= Chinese vegetable oil product =

"Ichthammol" ({{lang|zh|鱼石脂}} Yushizhi) made in China does not meet standards for ichthammol as specified in United States Pharmacopoeia (USP), European Pharmacopoeia (Ph.Eur), or for the CAS number. Instead of requiring bituminous schists like these definitions, the Chinese Pharmacopoeia definition for "ichthammol" uses ordinary vegetable oil:

Ichthammol is a mixture obtained by sulfurization of vegetable oils (soybean oil, tung oil, corn oil, etc.), sulfonation, and neutralization with ammonia. Organic sulfur content ≥ 5.5%, ammonium content ≥ 2.5%. — Chinese definition according to ChP 10People's Republic of China Pharmacopoeia, 2010 edition. ([https://db.ouryao.com/yd2020/view.php?id=f14d752022 Chinese text for 2020 edition])

As a result, Chinese "ichthammol" is very different from standard ichthammol. The characteristic bitumen-like odor (originating from the bituminous source material) is missing with Chinese material.{{cite journal | veditors = Bracher F, Heisig P, Langguth P, Mutschler E, Rücker G, Scriba G, Stahl-Biskup E, Troschütz R | title = Ammoniumbituminosulfonat | journal = Kommentar zum Europäischen Arzneibuch, Wissenschaftliche Erläuterungen zum Arzneibuch | language = de | trans-journal = Commentary to the Pharmacopoeia Europaea, Scientific explanations of the Pharmacopoeia | volume = 4 | publisher = Wissenschaftliche Verlagsgesellschaft | location = Stuttgart | date = 2014 }}

Medical use

= Skin disorders =

It is used to treat a variety of skin disorders as e.g. eczema, psoriasis, Acne rosacea and acne.{{cite journal | vauthors = Boyd AS | title = Ichthammol revisited | journal = International Journal of Dermatology | volume = 49 | issue = 7 | pages = 757–760 | date = July 2010 | pmid = 20618493 | doi = 10.1111/j.1365-4632.2010.04551.x | s2cid = 7367995 }}{{cite journal | vauthors = Warnecke J, Wendt A | title = Anti-inflammatory action of pale sulfonated shale oil (ICHTHYOL pale) in UVB erythema test | journal = Inflammation Research | volume = 47 | issue = 2 | pages = 75–78 | date = February 1998 | pmid = 9535545 | doi = 10.1007/s000110050282 | s2cid = 9014012 }}{{cite journal | vauthors = Fisher S, Ziv M | title = Efficacy of topical ichthammol 10% for hidradenitis suppurativa: Case series and systematic review of its use in dermatology | journal = Dermatologic Therapy | volume = 33 | issue = 6 | pages = e13868 | date = November 2020 | pmid = 32558051 | doi = 10.1111/dth.13868 | s2cid = 219907385 | doi-access = free }}

According to the "list of preferred Specials" by the British Association of Dermatologists (BAD) ichthammol can be used in dermatology prescribing to treat acutely inflamed atopic eczema, among others.Buckley DA, Root T and Bath S, Specials Recommended by the British Association of Dermatologists for Skin Disease, Clinical Standards Unit of the British Association of Dermatologists, London, UK, 2014, p. 9 (www.bad.org.uk/specials accessed October 2nd, 2015) A corresponding recommendation exists for bituminosulfonates in Germany. According to “guideline atopic eczema” bituminosulfonates can be considered for treatment of atopic eczema based on general clinic experience.{{cite journal | vauthors = Werfel T, Aberer W, Ahrens F, Augustin M, Biedermann T, Diepgen T, Fölster-Holst R, Gieler U, Heratizadeh A, Kahle J, Kapp A, Nast A, Nemat K, Ott H, Przybilla B, Roecken M, Schlaeger M, Schmid-Grendelmeier P, Schmitt J, Schwennesen T, Staab D, Worm M | display-authors = 6 | title = [Not Available] | journal = Journal der Deutschen Dermatologischen Gesellschaft | volume = 14 | issue = 1 | pages = e1-75 | date = January 2016 | pmid = 26713660 | doi = 10.1111/ddg.12884 | s2cid = 203739944 }} In the European Dermatology Forum (EDF) guidelines for treatment of atopic eczema ichthammol is recommended as a useful addition to the basic treatment regimen, especially in mild disease or if TCS treatment is not possible from a patient’s perspective, e.g. corticophobia (steroid phobia).{{cite journal | vauthors = Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, Gieler U, Girolomoni G, Lau S, Muraro A, Czarnecka-Operacz M, Schäfer T, Schmid-Grendelmeier P, Simon D, Szalai Z, Szepietowski JC, Taïeb A, Torrelo A, Werfel T, Ring J | display-authors = 6 | title = Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I | journal = Journal of the European Academy of Dermatology and Venereology | volume = 32 | issue = 5 | pages = 657–682 | date = May 2018 | pmid = 29676534 | doi = 10.1111/jdv.14891 | doi-access = free }}

= Ear infections =

In otology, a mixture of glycerol and ichthammol (G & I) is used for the topical treatment of ear infections.{{cite journal | vauthors = Masood A, Moumoulidis I, Ray S, Chawla O, Panesar J | title = A randomised controlled trial comparing Triadcortyl with 10% glycerine-ichthammol in the initial treatment of severe acute otitis externa | journal = European Archives of Oto-Rhino-Laryngology | volume = 265 | issue = 8 | pages = 881–885 | date = August 2008 | pmid = 17922130 | doi = 10.1007/s00405-007-0463-1 | s2cid = 26976193 }} It is effective against Gram-positive bacteria. The anti-inflammatory action is explained by its influence on the formation, secretion, and effect of inflammation mediators.{{cite journal | vauthors = Czarnetzki BM | title = Inhibitory effects of shale oils (Ichthyols) on the secretion of chemotactic leukotrienes from human leukocytes and on leukocyte migration | journal = The Journal of Investigative Dermatology | volume = 87 | issue = 6 | pages = 694–697 | date = December 1986 | pmid = 2878051 | doi = 10.1111/1523-1747.ep12456630 | doi-access = free }}{{cite journal | vauthors = Schewe C, Schewe T, Rohde E, Diezel W, Czarnetzki BM | title = Inhibitory effects of sulfonated shale oils (ammonium bituminosulphonates, Ichthyols) on enzymes of polyenoic fatty acid metabolism | journal = Archives of Dermatological Research | volume = 286 | issue = 3–4 | pages = 137–141 | date = 1994 | pmid = 7911653 | doi = 10.1007/bf00374208 | s2cid = 12647893 }}

Availability

Ichthammol is available in pharmacies for compounding medications. Different sources of information exist for exemplary formulations (creams, shake lotions, suppositories, etc.).{{cite book | vauthors = Altmeyer P | title = Therapielexikon Dermatologie und Allerlogie | publisher = Springer | location = Berlin | edition = 2nd | date = 2005 | pages = 1024, 1040, 1051 }}{{cite book | vauthors = Langley CA, Belcher D | chapter = Suppositories and pessaries | title = Pharmaceutical Compounding and Dispensing | publisher = Pharmaceutical Press | location = London, UK | edition = 2nd | date = 2012 | page = 143 | isbn = 978-0-85711-055-8 }}{{cite journal | vauthors = Staubach P, Metz M | title = Magistral formulations and pruritus therapy - What is established, what is confirmed, what is new? | journal = Journal der Deutschen Dermatologischen Gesellschaft | volume = 11 | issue = 11 | pages = 1049–1055 | date = November 2013 | pmid = 24119119 | doi = 10.1111/ddg.12230 | doi-access = free }}

Pharmacology

Ichthammol has anti-inflammatory, bactericidal, and fungicidal properties.{{cite journal | vauthors = Gayko G, Cholcha W, Kietzmann M | title = [Anti-inflammatory, antibacterial and antimycotic effects of dark sulfonated shale oil (ichthammol)] | journal = Berliner und Munchener Tierarztliche Wochenschrift | volume = 113 | issue = 10 | pages = 368–373 | date = October 2000 | pmid = 11084753 }}

Veterinary use

The European Medicines Agency published a summary report on ichthyol-substances (synonym: bituminosulfonates) during the course of the European Maximum Residue Limits (MRL) procedure{{cite web

|title=Veterinary MRL: Report on ICHTHYOL-substances |url=http://www.emea.europa.eu/pdfs/vet/mrls/091004en.pdf

|publisher=European Medicines Agency

|date=September 2004

|url-status=dead

|archive-url=https://web.archive.org/web/20060718184519/http://www.emea.europa.eu/pdfs/vet/mrls/091004en.pdf

|archive-date=2006-07-18

}} in veterinary medicine. The Committee for Medicinal Products for Veterinary Use (CVMP) decided that due to good tolerance and safety, there is no need to establish an MRL for ichthyol-substances. As a result, ichthyol-substances can be applied topically in all mammalian food-producing species without restriction.