Octenidine dihydrochloride

Octenidine dihydrochloride[1]
Names
IUPAC name
1,1′-(Decane-1,10-diyl)bis(N-octylpyridin-4(1H)-imine)—hydrogen chloride (1/2)
Other names
N,N′-(decane-1,10-diyldi-1(4H)-pyridyl-4-ylidene)bis(octylammonium) dichloride
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.068.035 Edit this at Wikidata
EC Number
  • 274-861-8
UNII
  • InChI=1S/C36H62N4.2ClH/c1-3-5-7-9-15-19-27-37-35-23-31-39(32-24-35)29-21-17-13-11-12-14-18-22-30-40-33-25-36(26-34-40)38-28-20-16-10-8-6-4-2;;/h23-26,31-34H,3-22,27-30H2,1-2H3;2*1H
    Key: SMGTYJPMKXNQFY-UHFFFAOYSA-N
  • InChI=1/C36H62N4.2ClH/c1-3-5-7-9-15-19-27-37-35-23-31-39(32-24-35)29-21-17-13-11-12-14-18-22-30-40-33-25-36(26-34-40)38-28-20-16-10-8-6-4-2;;/h23-26,31-34H,3-22,27-30H2,1-2H3;2*1H
  • CCCCCCCCN=C1C=CN(C=C1)CCCCCCCCCCN2C=CC(=NCCCCCCCC)C=C2.Cl.Cl
Properties
C36H64Cl2N4
Molar mass 623.84 g·mol−1
Pharmacology
R02AA21 (WHO) A01AB24 (WHO), QA01AB24 (WHO), combination codes: D08AJ57 (WHO), G01AX66 (WHO)
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Octenidine dihydrochloride is a cationic surfactant, with a gemini-surfactant structure, derived from 4-aminopyridine. It is active against Gram-positive and Gram-negative bacteria. Since 1987, it has been used primarily in Europe as an antiseptic prior to medical procedures, including on neonates.

Medical uses

Since 1987, octenidine has been used in Europe as an antiseptic, in concentrations of 0.1 to 2.0%.[citation needed] It is a substitute for chlorhexidine, with respect to its slow action and concerns about the carcinogenic impurity 4-chloroaniline.[citation needed] Octenidine preparations are less expensive than chlorhexidine and no resistance had been observed as of 2007.[3] They may contain the antiseptic phenoxyethanol.[4] It is not listed in the Annex V of authorized preservatives of the European Cosmetic Regulation 1223/2009.

Efficacy

Octenidine dihydrochloride is active against Gram-positive and Gram-negative bacteria.[5]

In vitro suspension tests with 5 minute exposure time have shown that octenidine requires lower effective concentrations than chlorhexidine to kill common bacteria like Staphylococcus aureus, Escherichia coli, Proteus mirabilis and the yeast Candida albicans.[6]

Comparison between octenidine and chlorhexidine determined by the suspension test after 5 minutes of exposure.
  Effective concentration, %
Octenidine dihydrochloride Chlorhexidine digluconate
Staphylococcus aureus 0.025 >0.2
Escherichia coli 0.025 0.1
Proteus mirabilis 0.025 >0.2
Candida albicans 0.01 0.025
Pseudomonas aeruginosa 0.025 >0.2

An observational study of using octenidine on the skin of patients in 17 intensive care units in Berlin in 2014 showed decreasing nosocomial infection rates.[7]

In a survey of German neonatal intensive-care units octenidine without phenoxyethanol and octenidine were the most common skin antiseptics used for intensive-care procedures. Skin complications included blistering, necrosis and scarring, which has not been previously reported in this population.[4]

In a 2016 study of pediatric cancer patients with long-term central venous access devices using octenidine/isopropanol for the disinfection of catheter hubs and 3-way stopcocks as part of a bundled intervention, the risk of bloodstream infections decreased.[8]

Safety

Octenidine is absorbed neither through the skin, nor through mucous membranes, nor via wounds and does not pass the placental barrier. However, cation-active compounds cause local irritation and are extremely poisonous when administered parenterally.[6]

In a 2016 in vitro study of mouth rinses on gingival fibroblasts and epithelial cells octenidine showed a less cytotoxic effect, especially on epithelial cells, compared to chlorhexidine after 15 min.[9] Wound irrigation with octenidine has caused severe complications in dogs,[10] aseptic necrosis and chronic inflammation in penetrating hand wounds in humans.[11][12]

Synthesis

The secondary amine (3) is formed by reaction of octan-1-amine (1) and 4-bromopyridine (2). Treatment of this with 1,10-dichlorodecane (4) yields octenidine as its dihydrochloride salt.[13][14][15]

References

  1. ^ EC no. 274-861-8, ECHA
  2. ^ "List of nationally authorised medicinal products - Active substance: octenidine" (PDF). www.ema.europa.eu.
  3. ^ Al-Doori, Z.; Goroncy-Bermes, P.; Gemmell, C. G.; Morrison, D. (June 2007). "Low-level exposure of MRSA to octenidine dihydrochloride does not select for resistance". The Journal of Antimicrobial Chemotherapy. 59 (6): 1280–1281. doi:10.1093/jac/dkm092. ISSN 0305-7453. PMID 17439976.
  4. ^ a b C.D. Biermann; A. Kribs; B. Roth; I. Tantcheva-Poor (2016). "Use and Cutaneous Side Effects of Skin Antiseptics in Extremely Low Birth Weight Infants - A Retrospective Survey of the German NICUs". Klinische Pädiatrie. 228 (4): 208–12. doi:10.1055/s-0042-104122. PMID 27362412. S2CID 5099338.
  5. ^ Sedlock, D M; Bailey, D M (December 1985). "Microbicidal activity of octenidine hydrochloride, a new alkanediylbis[pyridine] germicidal agent". Antimicrobial Agents and Chemotherapy. 28 (6): 786–790. doi:10.1128/AAC.28.6.786. ISSN 0066-4804. PMC 180329. PMID 3909955.
  6. ^ a b Hans-P. Harke (2007), "Disinfectants", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, pp. 1–17, doi:10.1002/14356007.a08_551, ISBN 978-3-527-30673-2
  7. ^ Gastmeier P, Kämpf K, Behnke M, Geffers C, Schwab F (2016). "An observational study of the universal use of octenidine to decrease nosocomial bloodstream infections and MDR organisms". Journal of Antimicrobial Chemotherapy. 71 (9): 2569–76. doi:10.1093/jac/dkw170. PMID 27234462.
  8. ^ Furtwängler, Rhoikos; Laux, Carolin; Graf, Norbert; Simon, Arne (2015). "Impact of a modified Broviac maintenance care bundle on bloodstream infections in paediatric cancer patients". GMS Hygiene and Infection Control. 10: Doc15. doi:10.3205/dgkh000258. PMC 4657435. PMID 26605135.
  9. ^ Schmidt, J.; Zyba, V.; Jung, K.; Rinke, S.; Haak, R.; Mausberg, R. F.; Ziebolz, D. (2016). "Cytotoxic effects of octenidine mouth rinse on human fibroblasts and epithelial cells – an in vitro study". Drug and Chemical Toxicology. 39 (3): 322–330. doi:10.3109/01480545.2015.1121274. PMID 26654138. S2CID 19546288.
  10. ^ Kaiser, S.; Kramer, M.; Thiel, C. (2015). "Severe complications after non-intended usage of octenidine dihydrochloride. A case series with four dogs". Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere. 43 (5): 291–298. doi:10.15654/TPK-150029. PMID 26353826. S2CID 80926611.
  11. ^ Lachapelle, JM. (2014). "A comparison of the irritant and allergenic properties of antiseptics". European Journal of Dermatology. 24 (1): 3–9. doi:10.1684/ejd.2013.2198. PMID 24492204.
  12. ^ Franz, T.; Vögelin, E. (2012). "Aseptic tissue necrosis and chronic inflammation after irrigation of penetrating hand wounds using Octenisept®". The Journal of Hand Surgery, European Volume. 37 (1): 61–64. doi:10.1177/1753193411414353. PMID 21816890. S2CID 29175202.
  13. ^ US patent 4206215, Denis M. Bailey, "Antimicrobial bis-[4-(substituted-amino)-1-pyridinium]alkanes", issued 1980-06-03, assigned to Sterling Drug Inc 
  14. ^ Bailey, Denis M.; DeGrazia, C. George; Hoff, Stephanie J.; Schulenberg, Patsy L.; O'Connor, John R.; Paris, Donald A.; Slee, Andrew McKenzie (1984). "Bispyridinamines: a new class of topical antimicrobial agents as inhibitors of dental plaque". Journal of Medicinal Chemistry. 27 (11): 1457–1464. doi:10.1021/jm00377a014. ISSN 0022-2623. PMID 6492075.
  15. ^ "Octenidine". Pharmaceutical Substances. Thieme. Retrieved 2024-07-21.