Docosanol: properties, uses, pros, cons, safety

Docosanol also known as Behenyl alcohol is a saturated long-chain aliphatic alcohol with 22 carbon atoms. In food use it has the ability to solidify and structure oil in fats.

The name describes the structure of the molecule:

• Behenyl comes from 'behenic acid', the name of the fatty acid from which behenyl alcohol is derived. The term 'behenic' is derived from 'Ben', a word of Persian origin referring to a type of tree (Moringa oleifera) whose seeds contain a high amount of behenic acid.
• Alcohol indicates the presence of a hydroxyl group (-OH) in the molecule, which is characteristic of all alcohols. In the case of behenyl alcohol, this -OH group is linked to a long carbon chain.

The synthesis process takes place in different steps:

• Preparation of behenic acid. Behenic acid, a fatty acid with 22 carbon chains, is often derived from natural sources such as rapeseed oil or canola oil.
• Reduction. The carboxylic acid group (-COOH) of behenic acid is reduced to an alcohol group (-OH) using a reducing agent. This can be done using hydrogen gas in the presence of a catalyst (a process known as hydrogenation), or using other chemical reducing agents.

Safety

From a safety point of view, studies published so far have not revealed any hazards (1).

What it is for and where

Cosmetics

It is used as a surfactant in cosmetic products (2) and acts as follows INCI:

Binder agent. Ingredient that is used in cosmetic, food and pharmaceutical products as an anti-caking agent with the function of making the product in which it is incorporated silky, compact and homogenous. The binder, either natural such as mucilage, gums and starches or chemical, may be in the form of a powder or liquid.

Skin conditioning agent - Emollient. Emollients have the characteristic of enhancing the skin barrier through a source of exogenous lipids that adhere to the skin, improving barrier properties by filling gaps in intercorneocyte clusters to improve hydration while protecting against inflammation. In practice, they have the ability to create a barrier that prevents transepidermal water loss.  Emollients are described as degreasing or refreshing additives that improve the lipid content of the upper layers of the skin by preventing degreasing and drying of the skin. The problem with emollients is that many have a strong lipophilic character and are identified as occlusive ingredients; they are oily and fatty materials that remain on the skin surface and reduce transepidermal water loss. In cosmetics, emollients and moisturisers are often considered synonymous with humectants and occlusives.

Emulsion stabiliser. Emulsions are thermodynamically unstable. Emulsion stabilisers improve the formation and stability of single and double emulsions. as well as their shelf-life. It should be noted that in the structure-function relationship, the molar mass of the ingredient used plays an important role.

Viscosity control agent. It controls and adapts, Increasing or decreasing, viscosity to the required level for optimal chemical and physical stability of the product and dosage in gels, suspensions, emulsions, solutions. 

Medical

Docosanol (chemically behenyl alcohol, typically in a 10% cream) has been evaluated in clinical studies as a topical treatment for recurrent cold sores and is generally well tolerated, with possible mild local effects (e.g., irritation). It is known for being the first topical antiviral approved for over-the-counter (OTC) use for recurrent cold sores (e.g., docosanol-based products such as Abreva). In practice, the aim is to shorten lesion and symptom duration if applied early (at the very first signs). 

Behenyl alcohol studies

• Molecular Formula: C₂₂H₄₆O
• Molecular Weight: 326.6 g/mol
• CAS: 661-19-8
• UNII  9G1OE216XY
• EC Number: 211-546-6
• DSSTox Substance ID: DTXSID4027286
• MDL number  MFCD00002939
• Beilstein/REAXYS Number: 1770470
• NSC  759235

Sinonimi: 

• Docosanol
• Behenic alcohol

• Lanette 22

• Lidavol

• Lidakol
• Stenol 1822
• Tadenan

References_________________________________________________________________

(1) Iglesias G, Hlywka JJ, Berg JE, Khalil MH, Pope LE, Tamarkin D. The toxicity of behenyl alcohol. II. Reproduction studies in rats and rabbits. Regul Toxicol Pharmacol. 2002 Aug;36(1):80-5. doi: 10.1006/rtph.2002.1566.

Abstract. Behenyl alcohol is a saturated 22-carbon, long-chain aliphatic alcohol, which has potential for use in foods as an oil-structuring and -solidifying agent in fats. Previously completed studies with behenyl alcohol indicated an absence of mutagenic or genotoxic potential. In addition, subchronic toxicity studies in rats and dogs reported no adverse effects following gross and histopathological examinations. Compound-related effects were limited to the observation of pale feces in dogs treated with high doses of behenyl alcohol, and were attributable to unabsorbed behenyl alcohol. The reproductive effects of behenyl alcohol were investigated in a fertility and reproduction study, and an embryonic development study in rats and rabbits, respectively. No evidence of maternal or fetal toxicity was observed in either study. Behenyl alcohol demonstrated no effects on the fertility or reproduction of rats dosed up to 1000 mg/kg body weight. Similarly, behenyl alcohol had no reproductive effects on rabbits treated with doses up to 2000 mg/kg body weight. The observation of pale feces was the only compound-related effect reported, limited to rabbits treated with 2000 mg behenyl alcohol/kg body weight. Based on these findings, there is no evidence to suggest that behenyl alcohol is teratogenic or embryotoxic.

(2) Arnarson T, Elworthy PH. Effects of structural variations of non-ionic surfactants on micellar properties and solubilization: surfactants based on erucyl and behenyl (C22) alcohols. J Pharm Pharmacol. 1980 Jun;32(6):381-5. doi: 10.1111/j.2042-7158.1980.tb12947.x.

(3) Leung DT, Sacks SL. Docosanol: a topical antiviral for herpes labialis. Expert Opin Pharmacother. 2004 Dec;5(12):2567-71. doi: 10.1517/14656566.5.12.2567.

Abstract. Recurrent herpes labialis is a painful and potentially disfiguring infection affecting an estimated 40 million people in the US alone. The majority of recurrences are caused by herpes simplex virus type 1. Various oral and topical formulations of nucleoside analogues have demonstrated efficacy for this indication. Over-the-counter treatments are palliative in nature and do not reduce time to healing. Docosanol is a compound with a unique mechanism of action involving viral fusion inhibition. In randomised, clinical trials, a 10% docosanol cream formulation, initiated within 12 h of symptoms onset, demonstrated efficacy in reduction of time-to-healing compared with a polyethylene glycol control. Despite its potential to be a mild irritant, this novel antiviral was well-tolerated in clinical trials. Docosanol is the first topical antiviral approved for over-the-counter use in recurrent herpes labialis.

Sadowski LA, Upadhyay R, Greeley ZW, Margulies BJ. Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2. Viruses. 2021 Jun 25;13(7):1228. doi: 10.3390/v13071228. 

Abstract. Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaherpesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that we provide interventions to keep them at bay, especially in immunocompromised patients. While numerous experimental vaccines are under consideration, current intervention consists solely of antiviral chemotherapeutic agents. This review explores all of the clinically approved drugs used to prevent the worst sequelae of recurrent outbreaks by these viruses.