(C) Peter Meiers - http://www.fluoride-history.de
Early dental fluoride preparations
see also: Eearly European Fluoride Research and The History of Monofluorophosphate
In his often-cited book on the history of dentistry, Walter Hoffmann-Axthelm claims that the first mention of the use of fluoride for "caries prevention" (if inserted into a tooth) was in a book by the French dentist Antoine Malagou Désirabode. However, the original text by Désirabode clearly describes the use of fluoride (then still called "fluate", as in "fluate de chaux" for calcium fluoride (fluorspar)) for the preparation of a dental filling material (page 409, Chapter "De l´obliteration ou plombage des dents", in his book "Nouveaux éléments complets de la science et de l´art du dentiste", Paris 1845), a technical use that was later filed in so many patents, without any reference to a "preventive" effect:
According to A. Rohrer, the first fluoride-containing oral care products (toothpaste, tooth powder, and mouth wash) were marketed since 1895. Inspired by the work of Albert Deninger, the Karl Friedrich Toellner Chemical Company of Bremen, Germany, sold these products under the brand name "Tanagra" (Alfred Rohrer: "Zahnpulver und Mundwässer", Verlag von Georg Siemens, Berlin 1910, p. 104).
Alvaro Francisco Carlos REYNOSO, of Paris, France: "Improvement in medical compounds", US Patent 146,781; filed Jan. 16, 1874, patented Jan. 27, 1874; ("Elixir" and "Sirup" containing fluorides of either potassium, sodium or ammonium; "elixir" is "invigorating, nutritious, and complemental to food", "fluorated sirup" is "...for infants at the period when the bones and teeth are in process of formation"; also contains "sugar in sufficient quantity"). Reynoso was a Cuban scientist who lived for many years in France.
Johann A. WÜLFING Company, of Berlin, Germany: "Verfahren zur Herstellung leicht resorbierbarer Fluorpräparate", German Patent (DE) 222,716; filed June 29, 1909, patented June 2, 1910; (Patent is based upon early European work, especially experiments carried out by the chemist Deninger (1896). It is claimed that there's generally not enough fluoride in a normal diet. To produce an easily absorbable fluoride preparation the company precipitates calcium fluoride (using sodium fluoride plus a calcium salt) together with a protein like egg-white, albumin, casein, to which it becomes adsorbed on co-precipitation.)
Emil LANGER, of Wien, Austria: "Verfahren zur Herstellung leicht löslicher, haltbarer Desinfektionsmittel zur Bereitung von Mund- und Spülwasser unter Verwendung von Natriumfluorid und Natriumsiliciumfluorid", German Patent (DE) 281,148; filed Nov. 28, 1911, patented Dec. 14, 1914; (a mouthwash and disinfectant made of sodium fluoride or sodium fluosilicate; tablets of 0.6 g each, containing 30 parts soda, 15 parts sodium fluoride or sodium fluosilicate, 15 parts tartaric acid, and essential oils to give them some taste: "... simply let the tablets slowly dissolve in the mouth as sodium fluoride and sodium fluosilicate are not toxic to humans ...", the patent says.)
Cecil Rudolph LIDGEY, East Twickenham, County of Middlesex: "Improvements in or relating to dentifrices", British Patent GB 3,034; filed Feb. 5, 1914; patented Febr. 5, 1915
("According to this invention a dentifrice comprises one or more fluorides amongst its constituents. ... Further a dentifrice according to this invention may comprise as a constituent the mineral fluor- apatite in a pulverized form, this mineral consisting of a mixture of triphosphate of calcium and calcium fluoride." Other fluorides to be used either alone or mixed are sodium fluoride and ammonium fluoride.)
Viggo Valdemar Julius ANDRESEN, of Kopenhagen, Denmark: "Verfahren zur Herstellung eines Härte- und Reinigungsmittels für Zähne", German Patent DE 386,339; filed April 18, 1919; pat. Dec. 8, 1923
Viggo Valdemar Julius ANDRESEN, of Kopenhagen, Denmark: "Improvements in or relating to dentifrices", British Patent GB 136,442; filed Apr. 18, 1919; pat. Dec. 18, 1919
Viggo Andresen patented several recipes on remineralizing (and bubbling) dentifrices, one of which contains calcium fluoride (1 part per 5 parts) along with calcium carbonate and sodium carbonate, and which may be mixed with any of the other compositions given (containing tartaric acid which -when mixed with the carbonate part- leads to the generation of carbon dixoide). In one of his publications he says that his powder mixture might either be brought on a toothbrush for cleaning the teeth, or spread on a moisturized tampon which then is held onto the surface of a tooth to be remineralized (Andresen V.: "Über Mineralisation und Remineralisation des Zahnschmelzes", Dtsch. Mschr. Zahnheilk. 39 (1921) 97).
Lecinwerk Dr. E. LAVES, Hannover, Germany: "Verfahren zur Herstellung kolloidallöslicher Fluorcalcium-Amylodrextrinpräparate", German Patent DE 325,561; filed March 12, 1919; patented Sept. 13, 1920 (calcium fluoride preparation made by precipitation from a mixture of sodium fluoride, calcium chloride and amylodextrin; for therapeutic and bakery technical use)
Philip Adolph KOBER, Evanston, Illinois, assignor to G. D. Searle & Company, of Chicago, Illinois, a corporation of Illinois: "Mineral Food Composition and Process of Making Same", US Patent (US) 1,813,936; filed May 19, 1927, patented July 14, 1931 (a calcium, magnesium and phosphate preparation as a food supplement, also containing 350 mg NaF per 1,624 g of the product).
Roy CROSS, Kansas City, Mo., assignor to Silica Products Company, Kansas City, Mo., a corporation of Delaware: "Dental preparation", U.S. Patent 1,943,856; filed July 10, 1929; pat. Jan. 16, 1934
"Hardening properties are given in part by the use of sodium fluoride. The combination of magnesium oxide and sodium fluoride is particularly valuable in my dental preparation. ... Sodium fluoride also prevents decay."
The American Dental Association, however, was not very happy about that invention. The ADA´s Council of Dental Therapeutics concluded in 1937: "1. The fact that a patented fluoride dentifrice was not demonstrably toxic when tested for typical fluoride toxicity in feeding experiments on rats does not mean that this dentifrice is not potentially toxic under all dental conditions. 2. Conditions of dental usage and pathologic states in the mouth might promote absorption of fluoride and toxicity. 3. The use of fluoride in dentifrices is unscientific and irrational, and therefore should not be permitted." (J. Am. Dent. Ass. 24 (1937) 307-309)
Jean RIPERT, Paris, France, assignor to Thibaud, Gibbs & Cie, Paris, France: "Dentifrice Product", U.S. Patent 2,059,396; filed July 12, 1934; pat. Nov. 3, 1936; as well as Swiss Patent CH 180,581: "Produit dentifrice", filed Dec. 19, 1934; pat. Oct. 31, 1935
Another interesting dentifrice patent, which includes "the double fluoride of potassium and magnesium". Interestingly, this dentifrice also contains asbestos (in one or more of different forms) as abrasive: muscovite, paragonite, lepidolite, zinnwaldite, biotite, phlogopite (all listed in the U.S. Patent Version); the Swiss Patent in addition mentions chrysotile, serpentine, crocidolite, amphibole, anthophyllite.
Reinhol GRUETER, Berlin-Charlottenburg, Germany: "Herstellung von Zubereitungen, die Calciumfluorid in leichter resorbierbarer Form enthalten", German Patent DE 695,874; filed October 22, 1935; patented August 8, 1940 (a preparation containing calcium fluoride made from sodium fluoride and a calcium phosphate)
Charles Somerville DILLON, of Old Chapel House, Gordon Square, Scotland: "Improved Tooth Powder or Preparation"; British Patent GB 572,352; Provisional Specification filed Feb. 26, 1944; Complete Specification left on Sept. 11, 1944; pat. Oct. 3, 1945
The provisional specification contained 1/20th part sodium fluoride (which was omitted in the complete specification) along with the calcium phosphate and calcium carbonate.
Lyon P. STREAN, Montreal, Quebec, Canada, assignor, by mesne assignments, to Ayerst, McKenna and Harrison Limited, New York, N.Y.: "Oral fluoride-vitamin preparation", US Patent 2,449,184; filed March 8, 1944; patented Sept. 14, 1948 (calcium fluoride - containing preparation for the formation of fluor-apatite in bones and teeth; author refers to Deaf Smith County where a low prevalence of caries has been reported, and claims "the same is generally true with regard to the prevalence of rickets.")
Richard S. Manly is a former student of Harold C. Hodge, University of Rochester
Richard S. MANLY, assignor to the Procter & Gamble Company: "Improvements in and relating to preparations for use in contact with the teeth"; British Patent GB 644,339; application made in U.S.A. March 12, 1947; filed March 11, 1948; pat. Oct. 11, 1950
"Examples of fluoride complexes coming within the scope of the invention are: potassium fluotitanate, ammonium fluozirconate, potassium fluohafniate, sodium fluostannate, lithium fluozirconate, and potassium fluogermanate."
Philip ZUTAVERN & Kurt KRAFT, both of Heidelberg, Germany, assignors to Knoll A. G., Ludwigshafen: "Verfahren zur Herstellung von organischen Salzen der Fluorwasserstoffsäure", German Patent DE 855,118; filed Dec. 5, 1950; pat. Nov. 10, 1952
Specifies the preparation of mono-, di-, and tri-ethanolamine hydrofluoride, the first amine fluorides to be used for toothpaste
Otto MÜLLER, Company of Berlin-Charlottenburg: "Verfahren zur Herstellung von Keime und Mikroorganismen abtötenden Mitteln", German Patent DE 831,000; filed August 17, 1950; pat. Jan. 10, 1952
This patent describes the preparation of oxychinoline derivatives containing fluoride claimed to be brought into an organic bond by addition of hydrogen peroxide to an alcaline solution of the oxychinoline and fluoride components. This is the patent on which the mouthwash "One Drop Only" ("Ondroly", "Nur ein Tropfen") is based. The inventor refused to be named, but Heinrich Wegmann, in his thesis, refers to it as an American - German cooperation product (Wegmann H.: "Die Wirkung des amerikanisch-deutschen Fluor-Präparates "Nur ein Tropfen" bzw. "Ondroly" auf entzündliche Veränderungen der Mundschleimhaut unter Berücksichtigung der besonderen Verhältnisse in Heil- und Pflegeanstalten, hier Kaufbeuren/Allgäu", Dissertation, University of Munich, 1952).
Oskar EICHLER & Kurt KRAFT, both of Heidelberg, Germany; assignors to Knoll A. G., Ludwigshafen: "Verfahren zur Herstellung einer alkalischen, seifenfreien, reagibles Fluor neben Calciumcarbonat enthaltenden Zahnpasta", German Patent DE 971,375; filed August 26, 1951, pat. March 5, 1953 / Jan. 15, 1959; also patented in Austria (# 187,629), France (# 1,066,270), and Belgium (# 513,724)
This is the first patented fluoride toothpaste containing an amine fluoride (Ethanolamine-HF) as the active fluoride ingredient. This toothpaste was marketed by the KNOLL A. G. under the brand name "Biox Fluor" (Dtsch. Zahnärztl. Z. 7 (1952) pp. 702 & 708), examined and endorsed by Oskar Eichler and Ilse Appelt of the University of Heidelberg.
William F. BRUCE, assignor to Wyeth Incorporated, Philadelphia, Pa.: "Potassium stannous fluoride", US Patent 2,606,812; filed Aug. 31, 1951; pat. Aug. 12, 1952
William H. NEBERGALL, assignor to Indiana University Foundation, Bloomington, Indiana: "Dentifrice preparations", US Patent 2,876,166; filed July 8, 1953; pat. Mar. 3, 1959
the (?) CREST patent (-> see also the Nebergall patents filed in 1955) ?
Charles H. ELBREDER and Edward J. ROSS, St. Louis, Mo., assignors to Charles J. Nemanick, St. Louis, Mo., "Therapeutic Composition", US Patent 2,967,131; filed Feb. 8, 1954, patented Jan. 3, 1961 (water-treating fluoride tablets)
William H. NEBERGALL, assignor to Indiana University Foundation, Bloomington, Ind.: "Stannous chlorofluoride, method of preparing same, and dentifrice compositions therewith", US Patent 2,836,544; filed Feb. 7, 1955; pat. May 27, 1958
Richard E. HAGER, Carroll R. REISS, assignors to Procter & Gamble Company, Cincinnati, Ohio: "Dentifrice containing a stannous compound and a carboxylated alkyl cellulose ether", US Patent 2,839,448; filed Feb. 9, 1955; pat. June 17, 1958
Stannous fluoride as the fluoride ingredient
William H. NEBERGALL, assignor to Indiana University Foundation, Bloomington, Ind.: "Distannousmonochlorotrifluoride and dentifrice compositions therewith", US Patent 2,882,204; filed May 31, 1955; pat. Apr. 14, 1959
Joe E. GILLILAND, Raymond RAY, and Wayne E. WHITE, assignors to Ozark-Mahoning Company, Tulsa, Oklahoma: "Method of production of stannous fluoride", US Patent 2,924,508; filed Sept. 20, 1956; pat. Feb. 9, 1960
commercially available substantially chemically pure tin powder is reacted with anhydrous or substantially anhydrous hydrogen fluoride
Joe E. GILLILAND, Raymond RAY, and Wayne E. WHITE, assignors to Ozark-Mahoning Company, Tulsa, Oklahoma: "Method of production of stannous fluoride", US Patent 2,955,914; filed Aug. 26, 1957; pat. Oct. 11, 1960
hydrofluoric acid added to a mass of pure metallic tin to prepare stannous fluoride
Joe E. GILLILAND, Raymond RAY, and Wayne E. WHITE, assignors to Ozark-Mahoning Company, Tulsa, Oklahoma: "Hydrogen fluoride detinning process and production of stannous fluoride", US Patent 3,097,063; filed Feb. 8, 1960; pat. July 9, 1963
"... the basic raw material for the can manufacturing industry is sheet steel of usually 0.01 inch thickness with a coating of pure tin averaging less than 1 percent of the weight of the steel. This tin makes the scrap unsuitable for return to steel furnaces as well as providing a material of importance as a source of tin metal. ... Therefore, an object of the invention is to provide an extremely rapid process of removing the coating from plated metals which are themselves unreactive toward hydrogen fluoride [while the tin is dissolved as stannous fluoride] ... Stannous fluoride is presently of great commercial interest as an additive for dentifrices to supply fluorine values to human teeth for the purpose of reducing the incidence of dental caries."
William E. COOLEY, Robert J. GRABENSTETTER, and Robert W. BROGE, assignors to the Procter & Gamble Company, Cincinnati,Ohio: "Abrasive for dentifrice composition", US Patent 3,151,027; filed June 7, 1961; pat. Sept. 29, 1964
"... object of this invention is to provide a preferred dentifrice in which a substantial amount of stannous and fluoride ions do not react with the cleaning agent and thus remain available for treatment of the tooth surfaces on use."
Riyad R. IRANI, assignor to Monsanto Company: "Fluoridation", US Patent 3,279,992; filed May 18, 1962; pat. Oct. 18, 1966 (fluoridated table salt)
Joseph C. MUHLER, assignor to Indiana University Foundation: "Oral compositions for caries prophylaxis containing stannous fluorozirconate", US Patent 3,266,996; filed June 27, 1963; pat. Aug. 16, 1966
Wayne E. WHITE, Albert W. JACHE, assignors to Ozark-Mahoning Company, Tulsa, Oklahoma: "Stannous Hexafluorozirconate", US Patent 3,337,295; filed Feb. 8, 1965; pat. Aug. 22, 1967
preparation for use in caries prevention
Gert-Ulfert HEESE, of München, Gerhard Ferdinand SCHNEIDER, of Haar, Fritz STANISLAUS, of München, Dietrich HENSCHLER, of Würzburg, Germany: "Orale Arzneimittel für die Kariesprophylaxe", German Patent DE 3,127,984, filed July 15, 1981, patented Febr. 3, 1982
Gunnar ABERG, Thomas Patrick JERUSSI, John R. McCULLOUGH, assignors to Sepracor Inc., Marlborough, Mass.: "NSAID / Fluoride periodontal compositions and methods", US Patent 5,807,541; filed Apr. 22, 1996; pat. Sept. 15, 1998 ("It is also known that under certain circumstances sodium fluoride and fluoroaluminates can activate G proteins and thereby induce prostaglandin production in endothelial cells and leukotriene production in platelets, granulocytes and monocytes. The metabolites of arachidonic acid have been implicated as important biochemical mediators of tissue destruction in various inflammatory diseases. ... We have found that fluoride, in the concentration range in which it is emplyed for the prevention of dental caries, stimulates the production of prostaglandins and thereby exacerbates the inflammatory response in gingivitis and periodontitis. The present invention is a method for preventing dental caries by administering a fluoride salt into the oral cavity while at the same time controlling periodontal bone loss by administering, in addition to the fluoride salt, an amount of an NSAID sufficient to inhibit the production of prostaglandins induced by the fluoride." NSAID = Non-steroidal aniti-inflammatory drug)