Olaflur

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Olaflur
Olaflur2.png
Clinical data
Other names{3-[Octadecyl(2-hydroxyethyl)aminio]propyl}bis(2-hydroxyethyl)amine dihydrofluoride
AHFS/Drugs.com International Drug Names
Pregnancy
category
  • No adequate studies
Routes of
administration
Topical (toothpaste, mouthwash, gel)
ATC code
Legal status
Legal status
Identifiers
  • N,N,N'-tris(2-hydroxyethyl)-N'-octadecylpropane-1,3-diamine dihydrofluoride
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.027.174 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H60F2N2O3
Molar mass 498.785 g·mol−1
3D model (JSmol)
  • F.F.OCCN(CCCN(CCCCCCCCCCCCCCCCCC)CCO)CCO
  • InChI=1S/C27H58N2O3.2FH/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-19-28(22-25-30)20-18-21-29(23-26-31)24-27-32;;/h30-32H,2-27H2,1H3;2*1H X mark.svgN
  • Key:ZVVSSOQAYNYNPP-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Olaflur (INN, or amine fluoride 297) is a fluoride-containing substance that is an ingredient of toothpastes and solutions for the prevention of dental caries. [1] It has been in use since 1966. Especially in combination with dectaflur, it is also used in the form of gels for the treatment of early stages of caries, sensitive teeth, and by dentists for the refluoridation of damaged tooth enamel. [2]

Contents

Overdosage

Overdosage leads to irritation of the oral mucosa. In especially sensitive persons, even standard doses of olaflur can cause irritation. [2] Like other fluoride salts, olaflur is toxic when given in high doses over an extended period of time. Especially in children, before the development of the permanent teeth, overdosage can lead to dental fluorosis, a discolouring and weakening of the enamel. [3] In acute cases of overdosage, for example when an olaflur containing preparation is swallowed, calcium in any oral form serves as an antidote. Often milk is used because it is usually at hand. [2]

Interactions

Because calcium fluoride is practically insoluble in water, calcium-containing drugs and food inhibit the action of olaflur. [2]

Chemistry and mechanism of action

Olaflur is a salt consisting of an alkyl ammonium cation and fluoride as the counterion. With a long lipophilic hydrocarbon chain, the cation has surfactant properties. It forms a film layer on the surface of teeth, which facilitates incorporation of fluoride into the enamel. The top layers of the enamel's primary mineral, hydroxylapatite, are converted into the more robust fluorapatite. The fluoridation reaches only a depth of a few nanometres, which has raised doubts whether the mechanism really relies on the formation of fluorapatite. [4]

Synthesis

The synthesis of olaflur starts from cattle's tallow. [5] The contained fatty acids, mainly stearic acid (C17H35COOH), are obtained by hydrolysis, and then converted to the corresponding amides, which in turn are reduced catalytically to the primary amines (largely octadecylamine). Addition of acrylonitrile, followed by another reduction, yields N-alkyl-1,3-propanediamines. The two nitrogen atoms react with ethylene oxide to form tertiary amines. Finally, hydrofluoric acid is added to give the end product. Because olaflur is produced from a mixture of fatty acids, some molecules have side chains that are longer or shorter than 18 carbon atoms. Other byproducts of the reaction include hydroxyethyl ethers resulting from addition of ethylene oxide to the free hydroxyl groups. The presence of these side products is clinically irrelevant. [5]

Olaflur synthesis.svg

See also

Related Research Articles

<span class="mw-page-title-main">Toothpaste</span> Substance to clean and maintain teeth

Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, assists in suppressing halitosis, and delivers active ingredients to help prevent tooth decay and gum disease (gingivitis). Owing to differences in composition and fluoride content, not all toothpastes are equally effective in maintaining oral health. The decline of tooth decay during the 20th century has been attributed to the introduction and regular use of fluoride-containing toothpastes worldwide. Large amounts of swallowed toothpaste can be toxic. Common colors for toothpaste include white and blue.

Fluoride is an inorganic, monatomic anion of fluorine, with the chemical formula F
, whose salts are typically white or colorless. Fluoride salts typically have distinctive bitter tastes, and are odorless. Its salts and minerals are important chemical reagents and industrial chemicals, mainly used in the production of hydrogen fluoride for fluorocarbons. Fluoride is classified as a weak base since it only partially associates in solution, but concentrated fluoride is corrosive and can attack the skin.

<span class="mw-page-title-main">Tooth enamel</span> Major tissue that makes up part of the tooth in humans and many other animals

Tooth enamel is one of the four major tissues that make up the tooth in humans and many other animals, including some species of fish. It makes up the normally visible part of the tooth, covering the crown. The other major tissues are dentin, cementum, and dental pulp. It is a very hard, white to off-white, highly mineralised substance that acts as a barrier to protect the tooth but can become susceptible to degradation, especially by acids from food and drink. Calcium hardens the tooth enamel. In rare circumstances enamel fails to form, leaving the underlying dentin exposed on the surface.

<span class="mw-page-title-main">Tooth decay</span> Deformation of teeth due to acids produced by bacteria

Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complications may include inflammation of the tissue around the tooth, tooth loss and infection or abscess formation.

<span class="mw-page-title-main">Water fluoridation</span> Addition of fluoride to a water supply to reduce tooth decay

Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride. Fluoridated water operates on tooth surfaces: in the mouth, it creates low levels of fluoride in saliva, which reduces the rate at which tooth enamel demineralizes and increases the rate at which it remineralizes in the early stages of cavities. Typically a fluoridated compound is added to drinking water, a process that in the U.S. costs an average of about $1.17 per person-year. Defluoridation is needed when the naturally occurring fluoride level exceeds recommended limits. In 2011, the World Health Organization suggested a level of fluoride from 0.5 to 1.5 mg/L, depending on climate, local environment, and other sources of fluoride. Bottled water typically has unknown fluoride levels.

<span class="mw-page-title-main">Sodium fluoride</span> Ionic compound (NaF)

Sodium fluoride (NaF) is an inorganic compound with the formula NaF. It is a colorless or white solid that is readily soluble in water. It is used in trace amounts in the fluoridation of drinking water to prevent tooth decay, and in toothpastes and topical pharmaceuticals for the same purpose. In 2020, it was the 265th most commonly prescribed medication in the United States, with more than 1 million prescriptions. It is also used in metallurgy and in medical imaging.

<span class="mw-page-title-main">Fluorine deficiency</span> Medical condition

Fluoride or fluorine deficiency is a disorder which may cause increased dental caries and possibly osteoporosis, due to a lack of fluoride in diet. Common dietary sources of fluoride include tea, grape juice, wine, raisins, some seafood, coffee, and tap water that has been fluoridated. The extent to which the condition truly exists, and its relationship to fluoride poisoning has given rise to some controversy. Fluorine is not considered to be an essential nutrient, but the importance of fluorides for preventing tooth decay is well-recognized, despite the effect is predominantly topical. Prior to 1981, the effect of fluorides was thought to be largely systemic and preeruptive, requiring ingestion. Fluoride is considered essential in the development and maintenance of teeth by the American Dental Hygienists' Association. Fluoride incorporates into the teeth to form and harden teeth enamels. This makes the teeth more acid resistant, as well as more resistant to cavity forming bacteria. Caries-inhibiting effects of fluoride were first noticed 1902, when fluoride in high concentrations was found to stain teeth and prevent tooth decay.

<span class="mw-page-title-main">Hydroxyapatite</span> Naturally occurring mineral form of calcium apatite

Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. Hydroxyapatite is the hydroxyl endmember of the complex apatite group. The OH ion can be replaced by fluoride, chloride or carbonate, producing fluorapatite or chlorapatite. It crystallizes in the hexagonal crystal system. Pure hydroxyapatite powder is white. Naturally occurring apatites can, however, also have brown, yellow, or green colorations, comparable to the discolorations of dental fluorosis.

<span class="mw-page-title-main">Fluoride therapy</span> Medical use of fluoride

Fluoride therapy is the use of fluoride for medical purposes. Fluoride supplements are recommended to prevent tooth decay in children older than six months in areas where the drinking water is low in fluoride. It is typically used as a liquid, pill, or paste by mouth. Where public water supplies are fluoridated further fluoride by mouth is typically not needed. Fluoride has also been used to treat a number of bone diseases.

<span class="mw-page-title-main">Dental fluorosis</span> Medical condition

Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.

<span class="mw-page-title-main">Early childhood caries</span> Dental disease of young children

Early childhood caries (ECC), formerly known as nursing bottle caries, baby bottle tooth decay, night bottle mouth and night bottle caries, is a disease that affects teeth in children aged between birth and 71 months. ECC is characterized by the presence of 1 or more decayed, missing, or filled tooth surfaces in any primary tooth. ECC has been shown to be a very common, transmissible bacterial infection, usually passed from the primary caregiver to the child. The main bacteria responsible for dental caries are Streptococcus mutans and Lactobacillus. There is also evidence that supports that those who are in lower socioeconomic populations are at greater risk of developing ECC.

<span class="mw-page-title-main">H. Trendley Dean</span> American dentist (1893–1962)

Henry Trendley Dean was the first director of the United States National Institute of Dental Research and a pioneer investigator of water fluoridation in the prevention of tooth decay.

<span class="mw-page-title-main">Tin(II) fluoride</span> Chemical compound

Tin(II) fluoride, commonly referred to commercially as stannous fluoride (from Latin stannum, 'tin'), is a chemical compound with the formula SnF2. It is a colourless solid used as an ingredient in toothpastes.

<span class="mw-page-title-main">Fluorapatite</span> Phosphate mineral

Fluorapatite, often with the alternate spelling of fluoroapatite, is a phosphate mineral with the formula Ca5(PO4)3F (calcium fluorophosphate). Fluorapatite is a hard crystalline solid. Although samples can have various color (green, brown, blue, yellow, violet, or colorless), the pure mineral is colorless, as expected for a material lacking transition metals. Along with hydroxylapatite, it can be a component of tooth enamel, but for industrial use both minerals are mined in the form of phosphate rock, whose usual mineral composition is primarily fluorapatite but often with significant amounts of the other.

<span class="mw-page-title-main">Fluoride varnish</span> Highly concentrated form of fluoride

Fluoride varnish is a highly concentrated form of fluoride which is applied to the tooth's surface, by a dentist, dental hygienist or other health care professional, as a type of topical fluoride therapy. It is not a permanent varnish but due to its adherent nature it is able to stay in contact with the tooth surface for several hours. It may be applied to the enamel, dentine or cementum of the tooth and can be used to help prevent decay, remineralise the tooth surface and to treat dentine hypersensitivity. There are more than 30 fluoride-containing varnish products on the market today, and they have varying compositions and delivery systems. These compositional differences lead to widely variable pharmacokinetics, the effects of which remain largely untested clinically.

<span class="mw-page-title-main">Remineralisation of teeth</span>

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Dectaflur (INN) is a fluoride-containing substance used for the prevention and treatment of dental caries, sensitive teeth, and the refluoridation of damaged tooth enamel, typically in combination with olaflur.

<span class="mw-page-title-main">Amine fluoride</span>

Amine fluorides are dental drugs.

<span class="mw-page-title-main">Tooth pathology</span> Medical condition

Tooth pathology is any condition of the teeth that can be congenital or acquired. Sometimes a congenital tooth diseases are called tooth abnormalities. These are among the most common diseases in humans The prevention, diagnosis, treatment and rehabilitation of these diseases are the base to the dentistry profession, in which are dentists and dental hygienists, and its sub-specialties, such as oral medicine, oral and maxillofacial surgery, and endodontics. Tooth pathology is usually separated from other types of dental issues, including enamel hypoplasia and tooth wear.

Topical fluorides are fluoride-containing drugs indicated in prevention and treatment of dental caries, particularly in children's primary dentitions. The dental-protecting property of topical fluoride can be attributed to multiple mechanisms of action, including the promotion of remineralization of decalcified enamel, the inhibition of the cariogenic microbial metabolism in dental plaque and the increase of tooth resistance to acid dissolution. Topical fluoride is available in a variety of dose forms, for example, toothpaste, mouth rinses, varnish and silver diamine solution. These dosage forms possess different absorption mechanisms and consist of different active ingredients. Common active ingredients include sodium fluoride, stannous fluoride, silver diamine fluoride. These ingredients account for different pharmacokinetic profiles, thereby having varied dosing regimes and therapeutic effects. A minority of individuals may experience certain adverse effects, including dermatological irritation, hypersensitivity reactions, neurotoxicity and dental fluorosis. In severe cases, fluoride overdose may lead to acute toxicity. While topical fluoride is effective in preventing dental caries, it should be used with caution in specific situations to avoid undesired side effects.

References

  1. Ganss C, Klimek J, Brune V, Schürmann A (2004). "Effects of two fluoridation measures on erosion progression in human enamel and dentine in situ". Caries Research. 38 (6): 561–6. doi:10.1159/000080587. PMID   15528912. S2CID   12683542.
  2. 1 2 3 4 Haberfeld H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN   978-3-85200-196-8.
  3. Abanto Alvarez J, Rezende KM, Marocho SM, Alves FB, Celiberti P, Ciamponi AL (February 2009). "Dental fluorosis: exposure, prevention and management". Medicina Oral, Patologia Oral y Cirugia Bucal. 14 (2): E103-7. PMID   19179949.
  4. Müller F, Zeitz C, Mantz H, Ehses KH, Soldera F, Schmauch J, et al. (December 2010). "Elemental depth profiling of fluoridated hydroxyapatite: saving your dentition by the skin of your teeth?". Langmuir. 26 (24): 18750–9. doi:10.1021/la102325e. PMID   21090577.
  5. 1 2 USpatent 6464962,Heckendorn R, Gosteli J,"N-Alkyldiethanolamine hydrofluorides and oral hygiene compositions containing them",published 2001-07-05, assigned to GABA International AG