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Chemistry

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Also known as: 141-94-6, Oraldene, Sterisil, Hexoral, Glypesin, Hextril
Molecular Formula
C21H45N3
Molecular Weight
339.6  g/mol
InChI Key
DTOUUUZOYKYHEP-UHFFFAOYSA-N
FDA UNII
852A84Y8LS

Hexetidine
A bactericidal and fungicidal antiseptic. It is used as a 0.1% mouthwash for local infections and oral hygiene. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797)
1 2D Structure

Hexetidine

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1,3-bis(2-ethylhexyl)-5-methyl-1,3-diazinan-5-amine
2.1.2 InChI
InChI=1S/C21H45N3/c1-6-10-12-19(8-3)14-23-16-21(5,22)17-24(18-23)15-20(9-4)13-11-7-2/h19-20H,6-18,22H2,1-5H3
2.1.3 InChI Key
DTOUUUZOYKYHEP-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CCCCC(CC)CN1CC(CN(C1)CC(CC)CCCC)(C)N
2.2 Other Identifiers
2.2.1 UNII
852A84Y8LS
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Bactidol

2. Doreperol

3. Duranil

4. Elsix

5. Hexigel

6. Hexoral

7. Hextril

8. Oraldene

9. Oraldine

10. Steri-sol

2.3.2 Depositor-Supplied Synonyms

1. 141-94-6

2. Oraldene

3. Sterisil

4. Hexoral

5. Glypesin

6. Hextril

7. Elsix

8. Sterilate

9. Triocil

10. Triscol

11. Collu Hextril

12. Duranil Aerosol

13. Hexetidinum

14. Steri/sol

15. Nsc-17764

16. 1,3-bis(2-ethylhexyl)-5-methyl-1,3-diazinan-5-amine

17. 5-amino-1,3-bis(2-ethylhexyl)hexahydro-5-methylpyrimidine

18. Nsc 17764

19. 5-pyrimidinamine, 1,3-bis(2-ethylhexyl)hexahydro-5-methyl-

20. Hexetidine, Mixture Of Stereoisomers

21. Mls002207232

22. 1,3-bis(2-ethylhexyl)-5-methylhexahydropyrimidin-5-amine

23. 5-amino-1,3-bis(2-ethylhexyl)-5-methylhexahydropyrimidine

24. 852a84y8ls

25. Hexetidine (inn)

26. Drossadin

27. Hexetidina

28. Oraseptic

29. Paradenyl

30. Hexetidine 100 Microg/ml In Acetonitrile

31. Pyrimidine, 5-amino-1,3-bis(2-ethylhexyl)hexahydro-5-methyl-

32. Hexetidine [inn]

33. Collu-hextril

34. Dsstox_cid_25297

35. Dsstox_rid_80788

36. Dsstox_gsid_45297

37. Steri/sol (van)

38. Hexigel

39. Caswell No. 033bb

40. Hexetidinum [inn-latin]

41. Hexetidina [inn-spanish]

42. 5-amino-1,3-bis(2-ethylhexyl)hexahydro-5-methylpyrimidine, Mix Of Diastereomers

43. Hexetidine [inn:ban]

44. Sr-01000872662

45. Einecs 205-513-5

46. Hexopyrimidine

47. Esetidina

48. Hexetidin

49. Hexocil

50. Unii-852a84y8ls

51. Ai3-15546

52. P 252

53. Hsdb 7828

54. Ncgc00016404-01

55. Cas-141-94-6

56. Prestwick_800

57. Spectrum_000236

58. 1,3-bis(2-ethylhexyl)-5-amino-hexahydro-5-methylpyrimidin

59. Hexetidine [mi]

60. Prestwick0_000551

61. Prestwick1_000551

62. Prestwick2_000551

63. Prestwick3_000551

64. Spectrum2_000953

65. Spectrum3_000271

66. Spectrum4_000395

67. Spectrum5_001435

68. Hexetidine [hsdb]

69. Hexetidine [inci]

70. Hexetidine [mart.]

71. Hexetidine [who-dd]

72. Schembl56672

73. Bspbio_000621

74. Bspbio_001742

75. Kbiogr_000949

76. Kbioss_000716

77. Divk1c_000280

78. Spectrum1500633

79. Spbio_000946

80. Spbio_002542

81. Bpbio1_000685

82. Chembl144673

83. Dtxsid1045297

84. Chebi:94339

85. Hms500n22

86. Kbio1_000280

87. Kbio2_000716

88. Kbio2_003284

89. Kbio2_005852

90. Kbio3_001242

91. 1,3-bis(2-ethylhexyl)hexahydro-5-methyl-5-pyrimidiamine

92. 5-amino-1,3-bis(2-ethylhexyl)-5-methyl-hexhydropyrimidine

93. Hexetidine [ep Monograph]

94. Ninds_000280

95. Hms1569p03

96. Hms1921m09

97. Hms2096p03

98. Hms3713p03

99. Pharmakon1600-01500633

100. Hy-b0996

101. Nsc17764

102. Tox21_110424

103. Ccg-39752

104. Mfcd00010428

105. Nsc757394

106. S6408

107. Akos000277944

108. Akos024348907

109. Tox21_110424_1

110. Cs-4490

111. Db08958

112. Nsc-757394

113. Idi1_000280

114. Ncgc00094819-01

115. Ncgc00094819-02

116. Ncgc00094819-03

117. Ncgc00094819-04

118. Ncgc00094819-07

119. As-56257

120. Smr000059080

121. Hexetidine, Mixture Of Stereoisomers, 97%

122. Sbi-0051566.p002

123. Db-042594

124. Ab00052133

125. Ft-0627047

126. D07068

127. D94751

128. Ab00052133_06

129. 141h946

130. Pyrimidine,3-bis(2-ethylhexyl)hexahydro-5-methyl-

131. Q419749

132. Sr-01000872662-1

133. Sr-01000872662-2

134. 5-pyrimidinamine,3-bis(2-ethylhexyl)hexahydro-5-methyl-

135. 5-pyrimidinamine,1,3-bis(2-ethylhexyl)hexahydro-5-methyl-

136. Hexetidine, European Pharmacopoeia (ep) Reference Standard

137. 1,3-bis(2-ethylhexyl)-5-methylhexahydro-5-pyrimidinamine #

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 339.6 g/mol
Molecular Formula C21H45N3
XLogP35.7
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count3
Rotatable Bond Count12
Exact Mass339.361348448 g/mol
Monoisotopic Mass339.361348448 g/mol
Topological Polar Surface Area32.5 Ų
Heavy Atom Count24
Formal Charge0
Complexity292
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count2
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

A bactericidal and fungicidal antiseptic. It is used as a 0.1% mouthwash for local infections and oral hygiene.

Natiional Library of Medicine; MeSH Heading for hexetidine. Available from, as of August 6, 2010: https://www.nlm.nih.gov/cgi/mesh/2010/MB_cgi?term=Hexetidine


MEDICATION (VET): Hexetidine is a cationic antiseptic with a wide spectrum of actions against Gram-positive and Gram-negative bacteria, as well as some fungi and parasites. In veterinary medicine, it is indicated for use in horses as a shampoo, at low concentrations, for topical application to the skin. The use of hexetidine as teat disinfectant, both as teat dip and teat spray, is also known.

European Medicines Agency (EMA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Hexetidine, Summary Report (April 1998). Available from, as of July 14, 2010: https://www.ema.europa.eu/pdfs/vet/mrls/038298en.pdf


Hexetidine is a nonantibiotic antimicrobial agent that possesses broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi such as Candida albicans. Several studies have identified the antiplaque activity of hexetidine. Hexetidine has been shown to be effective against isolates of Staphylococcus aureus and Pseudomonas aeruginosa in planktonic form and against biofilms of the same microorganisms on PVC. Hexetidine has also been reported to reduce the adherence of Candida albicans to human buccal epithelial cells in vitro. Hexetidine has been shown to be a promising candidate antimalarial agent with IC50 values being comparable with those of quinine chlorohydrate and chloroquine sulfate.

Table: Minimum Inhibitory Concentrations (MICs) for Hexetidine [Table#7543]

Rowe, R.C., Sheskey, P.J., Quinn, M.E.; (Eds.), Handbook of Pharmaceutical Excipients 6th edition Pharmaceutical Press, London, England 2009, p. 304-5



This examiner-blind, parallel group, controlled clinical study examined the effectiveness of a hexetidine (0.1%) mouthwash both in inhibiting the development of supragingival plaque and in reducing gingivitis. One hundred and thirty-four adult subjects completed the 2-week experimental gingivitis model study. Following baseline examinations, which included plaque index, modified gingival index and gingival bleeding index, subjects received a full dental prophylaxis. Subjects were randomly assigned to one of three mouthwashes (hexetidine 0.1%, chlorhexidine 0.12% (positive control) or a 5% hydroalcohol negative control) and commenced three times daily supervised rinsing as their sole method of oral hygiene. All indices were rescored after 2 weeks. Compared to the negative control group, the hexetidine group demonstrated a statistically significant inhibition and reduction of supragingival plaque and gingival inflammation with reductions of 6.3%, 33.5% and 56% for gingivitis, plaque and gingival bleeding, respectively. The results of the chlorhexidine group were used to validate the study. The study confirms the efficacy of a hexetidine rinse in reducing supragingival plaque and gingival inflammation.

PMID:12834495 Sharma NC et al; J Clin Periodontol 30 (7): 590-4 (2003)


For more Therapeutic Uses (Complete) data for Hexetidine (8 total), please visit the HSDB record page.


4.2 Drug Warning

Oral disinfectants containing chlorhexidine or hexetidine are able to produce disturbances of taste, as demonstrated by Krarup's electrogustometric method and the gustometric method of Harris and Kalmus. Hypo- and dysgeusia are characterized by dissociated disturbances, the most prominent of which concerns the sweet perception. The bitter taste is least affected, whereas the effects on salty and acidic tastes range between that for sweet and bitter. Taste disturbances which include ageusia for 48 hr were observed when the tongue was touched with a 20% solution of chlorhexidine. Not only the disinfectants themselves provoked dysgeusia but also other "taste improving" agents (particularly, the volatile /oils/). In addition to dysgeusia, the authors found disturbances of the mucous membrane sensitivity caused by the test substances.

PMID:711516 Schaupp H, Wohnaut H; HNO 26 (10): 335-41 (1978)


The study in situ measured enamel erosion by acidified sodium chlorite, essential oil and hexetidine mouthrinses over 15-day study periods. The study was a 5 treatment, single blind cross over design involving 15 healthy subjects using orange juice, as a drink, and water, as a rinse, as positive and negative controls respectively. 2 enamel specimens from unerupted human third molar teeth were placed in the palatal area of upper removable acrylic appliances which were worn from 9 a.m. to 5 p.m., Monday to Friday for 3 weeks. Rinses were used 2x daily and 250 ml volumes of orange juice were imbibed 4x daily. Enamel loss was determined by profilometry on days 5, 10 and 15. The study in vitro involved immersing specimens in the 4 test solutions together with a reduced acid acidified sodium chlorite formulation for a period of 4 hr under constant stirring; Enamel loss was measured by profilometry every hour. Enamel loss was in situ progressive over time with the 3 rinses and orange juice but negligible with water. Acidified sodium chlorite produced similar erosion to orange juice and significantly more than the two proprietary rinses and water. The essential oil and hexetidine rinses produced similar erosion and significantly more than water. Enamel loss in vitro was progressive over time, and the order from low to high erosion was reduced acid acidified sodium chlorite, acidified sodium chlorite, Essential oil, and hexetidine mouthrinses and orange juice. Based on the study in situ, it is recommended that low pH mouthrinses should not be considered for long term or continuous use and never as pre-brushing rinses. In view of the plaque inhibitory efficacy of acidified sodium chlorite, short- to medium-term applications similar to those of chlorhexidine would be envisaged.

PMID:11314887 Pontefract H et al; J Clin Periodontol 28 (4): 319-24 (2001)


Hexetidine has been used in human medicine as an antiseptic agent for over 40 years. Although, mild buccal irritation has been reported on rare occasions, there is no evidence of any significant toxic effect from hexetidine in man (eg, if swallowed when being used as a mouthwash).

European Medicines Agency (EMA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Hexetidine, Summary Report (April 1998). Available from, as of July 14, 2010: https://www.ema.europa.eu/pdfs/vet/mrls/038298en.pdf


In a few individuals mild irritation (described as sore mouth, burning or itching) of the tongue and/or buccal tissues has been reported. Other side effects which are reported very rarely include transient anesthesia and taste impairment.

Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Oraldene (contains 0.1% w/v hexetidine), (Last updated December 2009). Available from, as of July 14, 2010: https://www.medicines.org.uk/EMC/medicine/7181/SPC/Oraldene/


It is not known whether hexetidine is excreted in human breast milk, however, in view of the negligible amount of hexetidine which could be predicted to be systemically absorbed, it is unlikely that concentrations of hexetidine in the milk will present any risk to the neonate/infant.

Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Oraldene (contains 0.1% w/v hexetidine), (Last updated December 2009). Available from, as of July 14, 2010: https://www.medicines.org.uk/EMC/medicine/7181/SPC/Oraldene/


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Anti-Infective Agents, Local

Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects. (See all compounds classified as Anti-Infective Agents, Local.)


Antifungal Agents

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)


5.2 ATC Code

A01AB12

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


A - Alimentary tract and metabolism

A01 - Stomatological preparations

A01A - Stomatological preparations

A01AB - Antiinfectives and antiseptics for local oral treatment

A01AB12 - Hexetidine


G - Genito urinary system and sex hormones

G01 - Gynecological antiinfectives and antiseptics

G01A - Antiinfectives and antiseptics, excl. combinations with corticosteroids

G01AX - Other antiinfectives and antiseptics

G01AX16 - Hexetidine


5.3 Absorption, Distribution and Excretion

Because of its cationic nature, hexetidine is absorbed to the mucous membranes and dental plaque after oral administration and is not easily removed. Studies in human beings with radiolabeled hexetidine have shown that it is retained on buccal tissues for 8 to 10 hours after a single oral rinse and it has been possible to detect the continued presence of it on the oral tissues for as long as 65 hours after application.

European Medicines Agency (EMA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Hexetidine, Summary Report (April 1998). Available from, as of July 14, 2010: https://www.ema.europa.eu/pdfs/vet/mrls/038298en.pdf


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