CLINICAL EVALUATION OF UREA-AMMONIATED DENTIFRICES* By CEsxEP, J. HENscheL, D.D.S. Research Director, Eastern Graduate Research Foundation, New York 33, N.Y. AN IMPORTANT change has occurred in the armamentarium for oral hygiene: urea-ammoniated dentifrices have been established as one possible means of reducing the rate of cavity formation in human teeth. In a litde less than four years since the first of these urea dentifrices appeared on the market, "ammoniated" has become a magic word to millions of people. Those more closely associated with the development of these denti- frices have been aware of factions with opposing technical opinions. Studious scrutiny, however, will disclose no important disparity be- tween the schools of thought there exist only a few minor differences stemming from, on one side, con- centration upon laboratory experi- ment, and on the other, upon clini- cal application and results. Actu- ally it is fundamentally agreed prin- ciples which have resulted in proved caries reduction from nearly four years of clinical triall The development of urea-am- * Presented at the Dec. 8, 1949, Meeting, New York City. 57 moniated dentifrices could have been accidental and romantic. An efficient bacteriological laboratory in Jersey, interested in Lactobacillus acidophilus, was doing salivary counts on plant workers in its own building. Everything was progress- ing in an orthodox fashion until one day subjects previously laden with Lactobacilli began to show none at all. This was explained only when it was realized that the plant workers were packaging and han- dling a high urea dentifrice powder and that the air they breathed bore a considerable amount of the active ingredient. However, the dentifrice with which the subjects were work- ing was not an empiric formula but was based upon considerable prior research. With adequate perspec- tive let us briefly review the mile- stones in the history of our topic. In ancient times physicians pre- scribed and used a 3 to $ per cent urea solution for preventing dental caries and as an antibiotic and anti- septic in wounds. Their supply of urea was freshly voided urine in this century urea is easily and

58 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS cheaply synthetized as white, slightly saline crystals immensely soluble in water and capable of ex- tremely rapid diffusion. Since 1902 the literature has contained many articles on the therapeutic proper- ties of urea for general surgery. The papers of Ramsden, P•ju and Rajat, Symmers and Kirk, Foulger and Foshay, and Holder and MacKay are especially notable. Carl T. Grove and Carl J. Grove, of St. Paul, wrote of the biochemical a•tack of ammonia on dental caries in 1934 (1). They believed natural immunity traceable to salivary am- monia derived from urea and sug- gested an ammonia mouth rinse. Hill found the saliva of caries-im- mune to have inhibi.tory properties upon Lactobacilli but did not de- termine the active factor (2). In 1940 Stephan proposed a strong solution of urea instead of ammonia solution since a similar end result came from the hydrolysis of urea by the enzyme urease in addition to its now well-known antibiotic proper- ties (3). It is probable that all the present activity in this field is based upon the fundamental work of the Groves and Stephan (3a). The latter's research may be considered classic, although his interest waned and his clinical experience with urea, while excellent, was limited to a few subjects and to a two-year test period. UREA Synthetic urea, known as carbam- ide, dissolves in an equal weight of water with little change in the vis- cosity of the solvent. This property accounts for the ease with which urea diffuses, and its virtual non- toxicity allows for high concentra- tions. It is a protein denaturant, at least partly digests the filamentous strands of food plaques and mini- mizes the retention of carbohydrates and micro-organisms. Urea is easily hydrolyzed to ammonium carbonate by urease-producing organisms of the mouth. The carbonate buffers and alkalizes acidulated food debris, and since the supply of urease is limited but continuous, this process goes on as long as urea is retained in stagnant areas. Stephan showed the effect lasted for twenty-odd hours provided enough urea was employed for a long enough time. Our group at Sydenham Hospital became interested in Stephan's find- ings and our early formulas were imitations of his in an attempt to prevent decalcification accompany- ing orthodontic treatment (4). As clinicians, we were deeply aware of the difficulty of therapeutically af- fecting the "working" under-side of tenacious food plaques beneath which caries begins. Caries almost never occurs wherever saliva can freely circulate, and food plaques, meshes of filamentous protein strands of hyphae and mycelia, are nearly impervjous devices creating stagnant areas and confining carbo- hydrates and bacteria against vul- nerable tooth surface. The word "nearly" is the chink in the insidious armor of the caries susceptible area. The effect of any therapy upon free-flowing saliva has little