(C) Peter Meiers - http://www.fluoride-history.de
|Early Patents on Medical Preparations|
- Early dental preparations...........: http://www.fluoride-history.de/p-dentpr.htm
- Early Fluoride Dentifrices..........: http://www.fluoride-history.de/p-dentifrice.htm
Joseph WELLER, of Trexlertown (Lehigh County), Pennsylvania: "Medical Compound", US Patent 311,930; filed Aug. 15, 1884, patented Feb. 10, 1885; (medication for the relief of "functional derangements of the liver and the glandular system of the alimentary canal - such as piles, costiveness, dropsy, diarrhea, kidney disease, and all kindred affections which are the result of bile-poisoned blood, as well as the diseases of the genito-urinary mucous membranes in both sexes ..."; contains dilute fluoric acid, "acidum fluoricum".)
VALENTINER & SCHWARZ, of Leipzig-Plagwitz, Germany: "Verfahren zur Darstellung im Kern fluorirter aromatischer Verbindungen", German Patent DE 96,153; filed July 17, 1896; pat. Jan. 20, 1898 (In this patent the pharmaceutical company Valentiner & Schwarz described the preparation of organic fluorine compounds by decomposition of diazonium salts in the presence of hydrogen fluoride, whereby the fluorine becomes bound directly to the aromatic nucleus of the compound. One of the new chemicals described in this patent, 4,4´-difluordiphenyl, became the active ingredient of a composition against whooping cough ("Antitussin") through application to the skin, and of a wound disinfectant called "Epidermin"; see also: Schiemann G: "Die organischen Fluorverbindungen in ihrer Bedeutung für die Technik", Darmstadt, 1951, pp. 120-121).
VALENTINER & SCHWARZ, of Leipzig-Plagwitz, Germany: "Verfahren zur Darstellung aromatischer Fluorverbindungen aus Diazo- and Tetrazoverbindungen durch Zersetzung mit konzentrierter Flußsäure", German Patent DE 186,005; filed Oct. 1, 1905; pat. July 2, 1907; (the procedure filed in 1896 is modified, in order to give a better yield, by addition of ferric chloride as a catalyst.)
Charles Jules Henri NICOLLE, of Tunis, Tunis: "Vaccin culture and the like and the preparation thereof", US Patent 1,202,567; filed Dec. 13, 1913; patented Oct. 24, 1916 (addition of fluorides, around 0.7 per cent, to stabilize vaccines)
Guenther SCHIEMANN, Wolfgang WINKELMUELLER, Wilhelm ROSELIUS: "Verfahren zur Darstellung von Kondensationsprodukten kernfluorierter Arylaldehyde", German Patent DE 621,862; filed July 1, 1932; pat. Nov. 14, 1935 (In this patent, assigned to I. G. Farbenindustrie, Schiemann and Coworkers described a way for the preparation of fluorotyrosine which, under the names of "Pardinon" (marketed by Bayer) and "Florthyrin", then came in use for the treatment of hyperthyroidism in the clinic of Dr. Wilhelm May, of Kreuth, and his sons Richard and Heinz, as well as by Georg Litzka. see also: May W.: "Die Basedow´sche Krankheit. Jod und Fluor", Aulendorff, 1950; and Schiemann G.: "Die organischen Fluorverbindungen in ihrer Bedeutung für die Technik", Darmstadt 1951, pp. 104 and 118-120).
Before the organic fluorine compounds came in use for treatment of hyperthyroidism, the inorganic fluorides were also found effective (May 1950). In thyroid medications like "Druesensalbe Fides", "Strumadragees Fides" and "Strumetten", calcium fluoride and hydrogen fluoride are used as ingredients as listed still in the 1978 index of the German Federal Association of the Pharmaceutical Industry ("Schilddruesentherapeutika" in "Rote Liste", Bundesverband der Pharmazeutischen Industrie, e.V., Frankfurt)
Kurt KRAFT, Ferdinand DENGEL: "Verfahren zur Herstellung kernsubstituierter Phenylessigsäuren", German Patent DE 819,696; filed Feb. 3, 1943; pat. Nov. 5, 1951 (A compound similar to fluorotyrosine, i.e. 3-Fluoro-4-hydroxyphenylacetic acid, was patented by Kraft and Dengel of Knoll, pharmaceutical company of Ludwigshafen, and became known under the names of "Capacin", "Kapacin", and "Wiflucin" (marketed by Knoll) as a treatment against hyperthyroidism. -> s.a. The Merck Index, 9th edition, Merck & Co., Rahway, N.J., 1976)
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.")
Kurt KRAFT, Ferdinand DENGEL, assignors to Knoll A.G. Chemische Fabriken, Ludwigshafen: "Verfahren zur Herstellung von in der 5-Stellung bromiertem oder jodiertem 3-Fluor-tyrosin", German Patent DE 895,292; filed Dec. 6, 1944, publ. Feb. 19, 1953; patented Sept. 24, 1953
Toxic effects of fluorotyrosine, as reported after some experiments, can be diminished by the introduction into the molecule of iodine or bromine at the 5-position.
Emil BERTALANFFY, chemisch-pharmaz. Fabrik in Wien und Unterach A. A. (Oberoesterreich): "Verfahren zur Herstellung von 3-Fluor-4-oxy-phenylessigsäure", Austrian Patent AT 173,695; filed Sept. 5, 1951; pat. Jan. 10, 1953 (another way to prepare the compound described in the Kraft & Dengel Patent of 1943)