CHLORHEXIDINE

CAS No.: 55-56-1
EC No.: 200-238-7

Synonyms:
CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; 1,1’-hexamethylenebis(5-(p-chlorophenyl)-biguanid; 1,6-bis(5-(p-chlorophenyl)biguandino)hexane; 1,6-bis(p-chlorophenyldiguanido)hexane; 1,6-di(4’-chlorophenyldiguanido)hexane; 2,4,11,13-tetraazatetradecanediimidamide,n,n’’-bis(4-chlorophenyl)-3,12-diim; chlorhexidin; fimeil; hexadol; 1,1'-HEXAMETHYLENEBIS[5-(4-CHLOROPHENYL)BIGUANIDE]; 1,6-DI(N-P-CHLOROPHENYL-DIGUANIDO) HEXANE; bis(5-(p-chlorophenyl)biguanidinio)hexane; CHLORHEXIDINE; CHLORHEXIDINE BASE; hexamethylenebis(5-(4-chlorophenyl)biguanide); LABOTEST-BB LT00440966; n,n'-bis(4-chlorophenyl)-3,12-diimino-tetraazatetradecanediimidamide; 1,1’-hexamethylenebis(5-(p-chlorophenyl)-biguanid; 1,6-bis(5-(p-chlorophenyl)biguandino)hexane; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; 1,6-bis(p-chlorophenyldiguanido)hexane; 1,6-di(4’-chlorophenyldiguanido)hexane; 2,4,11,13-tetraazatetradecanediimidamide,n,n’’-bis(4-chlorophenyl)-3,12-diim; chlorhexidin; fimeil; hexadol; nolvasan; rotersept; soretol; sterilon; bioscrub; chlorhexidine, free base; 1,6-bis[N'-(p-chlorophenyl)-N5-biguanido]hexane; {[(4-chlorophenyl)amino]iminomethyl}{[(6-{[({[(4-chlorophenyl)amino]iminomethy l}amino)iminomethyl]amino}hexyl)amino]iminomethyl}amine; {[(4-chlorophenyl)amino]iminomethyl}{[(6-{[({[(4-chlorophenyl)amino]iminomethyl}amino)iminomethyl]amino}hexyl)amino]iminomethyl}amine; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; 1,6-bis(5-(p-chlorophenyl)biguandino)hexane; 1,6-bis(5-(p-chlorophenyl)biguanidino)hexane; 1,6-bis(p-chlorophenyldiguanido)hexane; 1,6-di(4'-chlorophenyldiguanido)hexane; 1,6-di(N-p-chlorophenyldiguanido)hexane; exidine; 1,1'-hexamethylene bis(5-(p-chlorophenyl)biguanide); 1,1'-hexamethylenebis(5-(p-chlorophenyl)biguanide; 1,1'-hexamethylenebis(5-(p-chlorophenyl)biguanide); 1,1'-hexamethylenebis[5-(4-chlorophenyl)biguanide]; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; 1,1'-hexamethylenebis[5-(p-chlorophenyl)biguanide]; N,N''''-hexane-1,6-diylbis[N'-(4-chlorophenyl)(imidodicarbonimidic diamide)]; N,N''''-1,6-hexanediylbis[N'-(4-chlorophenyl)(imidodicarbonimidic diamide)]; hibispray; imidodicarbonimidic diamide, N,N''''-1,6-hexanediylbis[N'-(4-chlorophenyl)-; microderm; oro-clense; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; periochip; periogard; pharmaseal scrub care; prevacare R; savloclens; steri-stat; 2,4,11,13-tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; chlorhexidine; 55-56-1; Rotersept; Tubulicid; Fimeil; Hexadol; Soretol; Chlorhexidin; Chlorhexidinum; Chlorohexidine; Sterilon; Nolvasan; Cloresidina [DCIT]; Chlorhexidin [Czech]; Chlorhexidinum [INN-Latin]; Clorhexidina [INN-Spanish]; Hibistat; 1,6-Bis(p-chlorophenyldiguanido)hexane; 1,6-Di(4'-chlorophenyldiguanido)hexane; UNII-R4KO0DY52L; 1,6-Bis(5-(p-chlorophenyl)biguandino)hexane; 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide); 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide); 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; CHEMBL790; R4KO0DY52L; MLS001332388; CHEBI:3614; Cloresidina; Clorhexidina; Exidine; Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-; Chlorhexidine, 98%; 56-95-1; CAS-55-56-1; NCGC00016246-03; SMR000857146; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; Sterido; Savlon babycare; N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; DSSTox_CID_13314; DSSTox_RID_79062; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; DSSTox_GSID_33314; Chlorhexidine [INN:BAN]; Chlorhexidine dihydrochloride; MLS001304094; 1-(4-chlorophenyl)-3-[N-[6-[[N-[N-(4-chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]guanidine; N-(4-chlorophenyl)-1-3-(6-{N-[3-(4-chlorophenyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimidamidomethanimidamide; CCRIS 9230; Chlorhexidine (INN); C22H30Cl2N10; HSDB 7196; Merfen-incolore (TN); SR-01000799135; Nolvasan (*Diacetate*); 1,1'-Hexamethylenebis(5-[p-chlorophenyl]biguanide); SMR000718621; EINECS 200-238-7; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; Lisium (*Dihydrochloride*); BRN 2826432; 1,6-Di(N-p-chlorophenyldiguanido)hexane; Hibisol; Dentisept [veterinary] (TN); 1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane; Prestwick_53; Chlorhexidine (1); Hibidil (Salt/Mix); Hibisol (Salt/Mix); Chlorhexidine diacetate salt hydrate; Hibitane (Salt/Mix); Hibiscrub (Salt/Mix); Hibispray (Salt/Mix); NSC526936; Spectrum_000237; Savloclens (Salt/Mix); 3697-42-5; Prestwick0_000143; Prestwick1_000143; Prestwick2_000143; Prestwick3_000143; Spectrum2_000135; Spectrum3_000339; Spectrum4_000277; Spectrum5_001322; chlorhexidine diacetate salt; EC 200-238-7; SCHEMBL3984; Chlorhexidine, >=99.5%; BSPBio_000246; BSPBio_001977; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; KBioGR_000774; KBioSS_000717; 4-12-00-01201 (Beilstein Handbook Reference); MLS001332387; MLS002154209; DivK1c_000761; SPBio_000210; SPBio_002185; BPBio1_000272; DTXSID2033314; BDBM51937; BDBM64773; cid_9552079; KBio1_000761; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; KBio2_000717; KBio2_003285; KBio2_005853; KBio3_001197; 2,4,11,13-Tetraazatetradecanediimidamide, N1,N14-bis(4-chlorophenyl)-3,12-diimino-; cid_12303047; NINDS_000761; REGID_for_CID_9552079; BDBM152706; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; HMS1568M08; HMS2095M08; HMS2233B16; HMS3712M08; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine; HY-B1248; Tox21_110325; Tox21_201404; Tox21_303445; BDBM50170723; s5397; SBB057564; STK089248; AKOS005394319; Tox21_110325_1; CCG-220143; CS-4958; DB00878; EBD2224760; MCULE-4644073142; 2,4,11,13-Tetraazatetradecanediimidamide, N,N'-bis(4-chlorophenyl)-3,12-diimino-; IDI1_000761; N,N''''-hexane-1,6-diylbis[N'-(4-chlorophenyl)(imidodicarbonimidic diamide)]; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradeca- nediimidamide; QTL1_000020; NCGC00016246-01; NCGC00016246-02; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; NCGC00016246-04; NCGC00016246-05; NCGC00016246-06; NCGC00016246-07; NCGC00016246-09; NCGC00016246-13; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; NCGC00091025-01; NCGC00091025-02; NCGC00091025-04; NCGC00247766-01; NCGC00257242-01; NCGC00258955-01; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylene]amino]methylene]amino]hexyl]-1-[amino-(4-chloroanilino)methylene]guanidine; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; AS-12648; SC-17656; Chlorhexidine, purum, >=99.0% (HPLC); SBI-0051301.P003; AB00053427; C06902; D07668; AB00053427-24; AB00053427-28; AB00053427_29; 009C673; Q-200828; SR-01000799135-5; 1,1''-Hexamethylene bis(5-(p-chlorophenyl)biguanide); BRD-K52256627-300-03-3; BRD-K52256627-300-05-8; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; SR-01000799135-10; SR-01000799135-11; Chlorhexidine, European Pharmacopoeia (EP) Reference Standard; 1,1'-(Hexane-1,6-diyl)bis[5-(4-chlorophenyl)biguanide] diacetate; Chlorhexidine, United States Pharmacopeia (USP) Reference Standard; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; Chlorhexidine, Pharmaceutical Secondary Standard; Certified Reference Material; N'',N''''''''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; N,N''-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylene]amino]methylene]amino]hexyl]-1-[amino-(4-chloroanilino)methylene]guanidine;hydrochloride; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine;hydrochloride; (1E)-2-[6-[[azanyl-[(E)-[azanyl-[(4-chlorophenyl)amino]methylidene]amino]methylidene]amino]hexyl]-1-[azanyl-[(4-chlorophenyl)amino]methylidene]guanidine; (1E)-2-[6-[[azanyl-[(E)-[azanyl-[(4-chlorophenyl)amino]methylidene]amino]methylidene]amino]hexyl]-1-[azanyl-[(4-chlorophenyl)amino]methylidene]guanidine;hydrochloride; {[(4-chlorophenyl)amino]iminomethyl}{[(6-{[({[(4-chlorophenyl)amino]iminomethy l}amino)iminomethyl]amino}hexyl)amino]iminomethyl}amine; 2-[amino-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexylimino]methyl]-1-(4-chlorophenyl)guanidine; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin; 2-[amino-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexylimino]methyl]-1-(4-chlorophenyl)guanidine;hydrochloride; CHLORHEXIDINE; Chlorhexidine; KLORHEKSİDİN; klorheksidin

CHLORHEXIDINE

Chlorhexidine (commonly known by the salt forms chlorhexidine gluconate (CHG) or chlorhexidine acetate), is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments. It may be used both to disinfect the skin of the patient and the hands of the healthcare providers. It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking.
It is used as a liquid or powder.Side effects may include skin irritation, teeth discoloration, and allergic reactions.
It may cause eye problems if direct contact occurs. Use in pregnancy appears to be safe. Chlorhexidine may come mixed in alcohol, water, or surfactant solution. It is effective against a range of microorganisms, but does not inactivate spores.
 
Chlorhexidine came into medical use in the 1950s. Chlorhexidine is available over the counter (OTC) in the United States. It is on the World Health Organization's List of Essential Medicines. In 2017, it was the 286th most commonly prescribed medication in the United States, with more than one million prescriptions.

Uses
Chlorhexidine is used in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eye drops, active substance in wound dressings and antiseptic mouthwashes). A 2019 Cochrane review concluded that based on very low certainty evidence in those who are critical ill "it is not clear whether bathing with chlorhexidine reduces hospital‐acquired infections, mortality, or length of stay in the ICU, or whether the use of chlorhexidine results in more skin reactions."
 
In endodontics, chlorhexidine is used for root canal irrigation and as an intracanal dressing, but has been replaced by the use of sodium hypochlorite bleach in much of the developed world.
Antiseptic
There is tentative evidence that it is more effective than povidone-iodine.
 
CHG is active against Gram-positive and Gram-negative organisms, facultative anaerobes, aerobes, and yeasts. It is particularly effective against Gram-positive bacteria (in concentrations ≥ 1 μg/l). Significantly higher concentrations (10 to more than 73 μg/ml) are required for Gram-negative bacteria and fungi. Chlorhexidine is ineffective against polioviruses and adenoviruses. The effectiveness against herpes viruses has not yet been established unequivocally.
Chlorhexidine, like other cation-active compounds, remains on the skin. It is frequently combined with alcohols (ethanol and isopropyl alcohol).
 
Dental use
Perichlor brand 0.12% chlorhexidine gluconate solution
Use of a CHG-based mouthwash in combination with normal tooth care can help reduce the build-up of plaque and improve mild gingivitis. There is not enough evidence to determine the effect in moderate to severe gingivitis. About 20 mL twice a day of concentrations of 0.1% to 0.2% is recommended for mouth-rinse solutions with a duration of at least 30 seconds.
Such mouthwash also has a number of adverse effects including damage to the mouth lining, tooth discoloration, tartar build-up, and impaired taste. Extrinsic tooth staining occurs when chlorhexidine rinse has been used for 4 weeks or longer.
 
Chlorhexidine is a cation which interacts with anionic components of toothpaste, such as sodium lauryl sulfate and sodium monofluorophosphate, and forms salts of low solubility and antibacterial activity. Hence, to enhance the antiplaque effect of chlorhexidine, "it seems best that the interval between toothbrushing and rinsing with CHX [chlorhexidine] be more than 30 minutes, cautiously close to 2 hours after brushing.".

Topical
Nepal was the first country in the world to use chlorhexidine to treat the umbilical cord of newborn babies, and received a USAID Pioneers Prize for reducing the neonatal death rate. Chlorhexidine is very effective for poor countries like Nepal and its use is growing in the world for treating the umbilical cord. A 2015 Cochrane review has yielded high-quality evidence that within the community setting, chlorhexidine skin or cord care can reduce the incidence of omphalitis (inflammation of the umbilical cord) by 50% and also neonatal mortality by 12%.
Chlorhexidine gluconate is used as a skin cleanser for surgical scrubs, a cleanser for skin wounds, for preoperative skin preparation and germicidal hand rinses. 
Chlorhexidine eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis.
 
Side effects
Chlorhexidine is ototoxic; if put into an ear canal which has a ruptured eardrum, it can lead to deafness.
 
Chlorhexidine does not meet current European specifications for a hand disinfectant. Under the test conditions of the European Standard EN 1499, no significant difference in the efficacy was found between a 4% solution of chlorhexidine digluconate and soap.In the U.S., between 2007 and 2009, Hunter Holmes McGuire Veterans Administration Medical Center conducted a cluster-randomized trial and concluded that daily bathing of patients in intensive care units with washcloths saturated with chlorhexidine gluconate reduced the risk of hospital-acquired infections.

Whether prolonged exposure over many years may have carcinogenic potential is still not clear. The Food and Drug Administration (FDA) in the USA recommendation is to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months.
Once digested chlorhexidine is poorly absorbed into gastrointestinal tract. If aspirated into the lungs at high enough concentration, as reported in one case, it can be fatal due to the high risk of acute respiratory distress syndrome.
 
Mechanism of action
At physiologic pH, chlorhexidine salts dissociate and release the positively charged chlorhexidine cation. The bactericidal effect is a result of the binding of this cationic molecule to negatively charged bacterial cell walls. At low concentrations of chlorhexidine, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death.
 
Chemistry
It is a cationic polybiguanide (bisbiguanide).It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).
 
Deactivation
Chlorhexidine is deactivated by forming insoluble salts with anionic compounds, including the anionic surfactants commonly used as detergents in toothpastes and mouthwashes, anionic thickeners such as carbomer, and anionic emulsifiers such as acrylates/C10-30 alkyl acrylate crosspolymer, among many others. For this reason, chlorhexidine mouth rinses should be used at least 30 minutes after other dental products. For best effectiveness, food, drink, smoking, and mouth rinses should be avoided for at least one hour after use. Many topical skin products, cleansers, and hand sanitizers should also be avoided to prevent deactivation when chlorhexidine (as a topical by itself or as a residue from a cleanser) is meant to remain on the skin.
Synthesis

Terminology
The name "Chlorhexidine" breaks down as chlor(o) + hex(ane) + id(e) + (am)ine), is a cationic polybiguanide. It is used primarily as its gluconate salt.
 
ABSTRACT
Chlorhexidine which is a cationic bisbiguanide biosit, is effective against wide spectrum of microorganisms, has lower toxicity and wide spectrum of antibacterial effect. This antiseptic agent, first described in 1954. since that day chlorhexidine is using in clinics safely. Lots of clinical study has been doing about the success of using chlorhexidine postsurgically and using as antiplaque agent and treatment in gingivitis and periodontitis. Chlorhexidine salts are incompatible with soaps and other anionic materials because of cationic nature. Effectiveness of chlorhexidine reduces if used after cleaning of teeth with toothpaste. Gastrointestinal absorbtion of chlorhexidine is very low or none therefore toxicity is low. Chlorhexidine and salts are using in parentheral and non-parentheral medication all over the world with licenses. Using of chlorhexidine causes staining of teeth and tongue. Special feature of chlorhexidine is retention in oral tissue and releasing in a period. Because of this specialty chlorhexidine has long lasting effect according to other antiseptic agents. Example researches about the effectiveness of chlorhexidine and alternative usage apart from surgical area are presented. Chlorhexidine, which is using in practice for long time confidently, is presented with mechanism of action, usage spectrum and effectiveness. Chlorhexidine's ability in reducing of the microbiological population and the most effective antiplaque agent is approved. Using chlorhexidine before and after oral surgery will cause better healing condition and less complication rate.
As a cationic bis-biguanide biocide, chlorhexidine has a strong antibacterial effect and is effective against many microorganisms. Today generally used safely as an antiseptic, chlorhexidine is effective against gram positive and gram negative bacteria; and has a wide range of antibacterial activity. Chlorhexidine is an effective oral antimicrobial agent used in the prevention of the formation of dental plaque in the oral cavity, treatment of gingivitis and periodontitis, prevention of caries in periodontal therapy, prevention of infection that may develop after surgery and in general oral infections. The concentrations of chlorhexidine used in dentistry are usually between 2% and 0.12%; and its 2% concentration is used as an endodontic irrigation and intra-canal medication agent. Its cytotoxic effects are both locally and systemically at low levels. Discolouration of teeth and tongue in the oral cavity can be observed after the use of chlorhexidine. The use of chlorhexidine as an irrigation solution in endodontics is recommended due to its properties such as low toxicity, broad spectrum, strong antibacterial activity and increased lasting activity.