f o r teachers
WILLIAM E. COOLEY The procter a Gomble company Winmn ~ i T i le c h n i d Center Cincinnati, Ohio 4 5 2 2 4
T h e best way for academic scientists to understand how industrial applied research operates is to visit industry and do research. A summer or sabbatical year spent working in an applied-research organization can be rewarding to both guest and host. Until more scientists from colleges and universities have gained personal experience with industrial research, articles such as this one will provide some introductory glimpses. What follows is first a viewpoint of the concept of specialization as it applies to industrial work. Second, several examples of applied research are cited in moderate detail, all of them related to the development of anticaries dentifrices. A number of testing methods developed by basic and applied researchers are discussed in this section, toget.her with some chemical relation..hips. Third, the ways in which applied research joins with other efforts in developing therapeutic products are briefly sketched at the end of the article. The Applied Research Chemist in Industry
If the newly hired industrial chemist has just finished a research project at his university, he may feel more comfortable doing a fundamental rat,herthan an applied research job at first. He will usually think of himself as a specialist in one of the chemical disciplines, and often a problem removed from direct application to a commercial product gives him a smoother transition to industrial research. His new associates, though, may look on him as a generalist. His specialty helps solve problems in several product areas, and he has not yet been identified with any one of them. On the other hand, t,he established applied-research chemist, whet,her or not he began his indust,rialcareer in applied research, oft,en becomes an expert on a certain class of products, a type of ingredient in produck, or a chemical process. He is now just as much n specialist as t,he new graduate, but in a different framework. In graspiug t,he det,ails of, say, a thcrapeutic dentifrice he has bccorne a pra~t~itioner of several kinds of chemical art and an authorit,y on several branches of science as they apply to dentifrices. He is a product specialist, but t,o the basic researcher he looks like a supreme generalist,. He is an inorganic chemist, organic chemist,, biochemist,, microbiologist, physical chemist, engineer, biometrician, computer progr;Lmmer, and, tying all these together, project manager and expediter.
Applied Research in the Development of Anficaries Dentifrices The kind of industry in which the applied-research chemist works will certainly influence how far he departs from his former type of specialization and becomes a product or process specialist. In discussing several aspects of research applied to dentifrices, this article deals with one of the more t.horough transformations of a discipline-oriented specialization to a product-oriented specialization. Therapeutic Dentifrices
Brushing the teeth has long been recommended by dentists as a simple and extremely rewarding contribution to good oral health. Admonitions from the dental profession have been reinforced in more recent years through two kinds of progress by makers of dentifrices. First, the notion that a dentifrice should have appealing flavor, texture, and color has been widely accepted. The satisfying taste and feel of a favorite dentifrice do much to encourage frequent toothbrushing. Second, dentifrices have come to be regarded as vehicles for amelioration or prevention of undesirable conditions in the mouth. Reduction of the rate of incidence of dental caries has been achieved by dentifrices containing fluorides, as is now generally known. Other oral diseases are now the targets for development of new and beneficial dentifrice product,^. The traditional cleaning function of a dentifrice is even being considered in a therapeutic sense, since cleaner teeth may well offer a less hospitable surface for the adhesion of undesirable accumulations of dental plaque and calculus. This alliance of product development with professional therapeutic goals has provided opportunity for a variety of effective projects in applied research. The examples to be discussed here are mostly related to development, testing, and improvement of fluoride dentifrices. They typify the work of a product. specialist. Fluoride Dentifrices
Clinical trials have ~tablishedthe efficacy of fluoride dentifrices in reducing the rate of inception of new carious lesions. The bulk of the literature on t,his subject discusses trials of dentifrices containing tin (11) fluoride, SnFz (1-8). Reports have also been published of successful trials of dentifrices containing sodium fluoride, KaF (9); subst,ituted ammonium fluorides Volume 47, Number 3, March 1970
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(10); and sodium n~onofluorophosphntc, SnJ301F ( 1 I ) . Althouph the contrihutions of the vnrious e d o n s hnvr never h e n sntisfnctnrily rluciclntd, nnd 1111- role of the unclissocintnl 1'031.'?- ion is uncrrt.nin, nll thceffectivedentifricrs shnre the propcrty of contnining some concentrntion of fluoride nnion. Fluoride ion is known to renet. mith dentnl ennmel (13, I4), to net. n.. n hnct~ri0~t:lt (16), nncl tn inhihit. ncid-producing hncterinl metnlmlic pmcesses (I/;). All of these nctions cnn he significnnt in nffeeting cnries. condering the commonly nrcrptnl clescription of cnries :w :i procers of srlectivc clissnlution of clentnl ennrnel hy mctnholicnlly prnducnl :wid frnm oral hnctc rin. k t us rxan~inrjust onr nsprrt of the nrtion of fluoride, the result. of its renrtion \vit 11 ennmrl to prnduce n harrier ngninst diffusion. Later \ye shnll consiclrr t he nnture of the fluorih-rnnmrl renction itsrlf, nftcr :I cliseus&m of rlenning :md nhrwion hy fluoridc dentifrices. rffectivmcs- of vnrious fluoricles, to monitor the nctivity of fluoricle ilmtifricrs hy testing slurries or cxtrncts, nnd Dental ennmel is I n ~ e l yhydmxylnpntite, C ~ I ~ ( P O & to tlrterminc. rnluction of clis.solr~tionrnte 11s :r function (OH)?, which d i w h e s in ncicls formwl in the monthof fluoriclr concrntrntion. I;ipui-c 1 illusfrntes the such ncicls ns lnclic, ncetic, or pyruvic (17, 18). The rrlnt ionship hrt\vrrn rwluction ofclissolution rnte (ESR) slow procew of dis.wlution produces cnrious spots in nncl concrntrntion of SIII:? or SnIs' .solutions, n s clrtrrt,ecth. If ennrnel is exlmscd to an nqucnus fluoride m i n d hy (;r:ry (JQ. solution, the cnnrnel ncquires fluoride in its outer lnycr. Cleaning Agents for Dentifrices The fluoride mny hc prcsel1t n.q cnlcium fluoride, CRI:~, or fluornpntite, Cnlo(l'Or)sl:r, drpending on pH nnd The first inclusion of n fluoride snlt in n dentifrice concrntrntions of fluoride, phosphnte, nnd cnlcium in rcquirnl n drpnrturc from thr gmup of compouncls thnt the solution (15'). T h r fluoridctre:~tedtooth grnrrnlly h:ul usunlly rrrvwl as solid-phase clenning agrnts (nhrnhns n rnluced rnte of dissolution in ncid up to the point, sives). The venernhle (I:tC.OI. so long usrd in toothwhere the fluori(le-eont:~ir~i~~p. Inyer has hcen dismlvnl pnstc nncl tooth ~ l e pmvidrs , nn quilihrium nwny. The equilihrium solubility of the fluoridc IC:n:+] wrll nlmve that nllmvwl hy the K., for ('nF2 at, trented tooth in acid is also lowrr thnn thnt of a fluoridc fluoridr conerntrntions of the onlrr of 0.01-0.1.11, such frec tooth. Even though neither the rate of diswlution ns nrr prncticnl for n dmtifricr. The rwult is :I stmrly nor the equilibrium solubility is r ~ l u c e dto zero, the loss of soluhle fluoridr fmm the nqurnus phnw of :I production of n cnrious spi)t is slow nnrl usunlly interclrntifrice ns it ages. The wmewhnt. ncwrr CnHPO, mit,tent, so that rducing the rnte of the process cnn nnd CnHPO4.2H?0clenning Rpents were found to five give suhstnntinl prncticnl henefit (17,28). 1it.t.l~or no imprnvemmt in this respcct. (They were 11test hns hecn tlcvclopnl to simulnte in uilro the quite useful in mitigating nhrnsive xvmr of tooth dentin, protection which fluoride can confer on n tooth in the ho\vever, ns discusswI helow.) An ngmwntcrl pmhlem mouth (19). In this test n group of clenn humnn tecth s ax tlw fluoridc, for the \vns f n c d \\.hen SnI.'? ~ 1 - choren nre m o u n t d in wnx i n n glms henker. Only the cnnmel nnions from cit,hcr CnCOI or one of thr forms of Cncrowns protmcle from the wax, and nll defects in the HI'O, precipitate very slightly eoluhle Sn(I1) comennmel are c o v e r ~ lmith more wax. The rnte of dispounds. .solution of the ennmel is m e ~ u r dhy exposing i t to n h worknhlc solution to this prohlcm of incornpatihildilute aqueous lnctate huffrr solut.ion nt nciclie pH. it.? w:w found by Srhergnll (20) with t.he discovery thnt. Tempernture, time, concentrntion, solution volume, pH, cnlcium snlts of the con~lmsnlphosphnter; nre in cquililr nnd stirring rnte are nll stnn(lnrdiz~Ifor this cliffusionrium with sntisfnctorily low conceutrntions of Cn?+ so cont~rollnlrenetion. Thc nmount. of rnnmel dissolvd thnt, ncccptnhlc levels of I:- mny he mnintnind. At is found hy cleterminntion of thr phosphntc conccntr;~thr snmc time the condensed phosphnte nnions, in the tion in 1.11~huffer nftcr exposure. (Alternntirely, dilute nnd only pnrtinlly nquwus systems common to enlcium mny hc determind.) The same set of t w t h is drntifricrs, usunlly form soluhlr complrxes rnthcr thnn then exposd t o n trentingsolution containing n known precipitates with Sn(I1) ions. Calcium pymphosfluoridc concentrntion. After a sbnndnrdiznl exposure phn1.r. Cn,PrO7, which is the condensntion product o i r and rinsing, n second mensurement of mte of dissolution tninnl by hcnt inp CnHI'O. is mndc using fresh 1:rctnte buffer. Compnri~onof t h r rates of r e l r : ~of~ orthophosphntc ion fmm trrntnl teeth nnd untrentrcl tccth Irnrls hnu been espccinlly ~ewicenhlens n clenning went, to the cnleulntion of the dcgrrr of rnluction of the elkcompntihle with SnF2. Another npplienhlc mnterial is solution rnte. long-chnin condensnl sodium phosphnte, (Snl'OJn, of molrculnr weipht. high enough to rmder nqucnus solubilIM)''~" X IMI Reduction of I)i.iwl~~tionRnte = " . f I I ' ~[PO,'-l" ity low ((PI). In the course of the senrch for new, eompntihle clennThis test hnr been usnl to evnlunte tho relntivr Emmel Solubility Reduction T&
t h r h ~ ~ m nmonth n nrr n r m s n r y t o rstnhlish confidmcr in t h r :~ctrl;tl prrfnrmnncr of nny clrntifricc systcm. Typienlly, tllc rlraning nhility of n new pnrticnl:itr nntrri:d \vonld h r fin:~llyrstnhlishnl through nsr in n contrnllnl p m r l stucly. the srhjrcts' stains hcing grndnl hy n drntnl rs:~min:~tionnnd 1mssibly hy instrnnientnl mra.wrrnirnt :w wrll. Abr:~sionof tooth cnnmel during daily hrwhing often o c c ~ ~ r r ninl t h r pnst whrn pnn~icr: ~ n dothrr hnrdpnrtirlr tm1t11powlrrs w r r commonly usnl. \Iodrrn rlmning :igrnts :Ire nr:~rly :dl soft enough to :~vnicl i n i f i : n t : r : i o n of r n : ~ ~ n r I'I'hr snftrr clrntin :mcl that cc.n~cmtumof 1111. lwll:, tl~rundrrlying wl~rt.:~nces a111 l w cymsnl tlrnr t l ~gum r line. :wr nincl~niorc vulnrr:1b1r t o :~t~r:~sion th:m r11:1mr1is. T r s t i n ~in t h r month for this kind of : ~ h r n s i ois~ ~~ l r s t r n r t i w ,:lnd it, is not norni:~IIy clnnr. I.:~lmratory trstinc on cxtrnrtctl hum:m Icrth must rnrnisl~the n m l n l guiclnncr in rvdnnting niw nintrri:~lsfor :~hrnsivrnms. A usrful test, clrscrihnl by Grnhcnstettrr, rl al. (24, .%), nllows c l r t r r n ~ i ~ ~ a t of i o nnhrxsio~~ Ity counting the r:~dio:~etivrpl~osphornsh n ~ s h n lfnnn irrndintnl twth. t l w trrth :lrr c y m w l tn :L flns of ncnAftrr rstr:rrtio~~ tnlns encl thcll stnrnl for 11 few ( h y 5 to nllolv llis*ipntion of all netirity rsrrpt the 8-rmi.;rion o i "P, 11:tving n hnlf-life of 14.3 cl:~ys. Irrndiation, storngr, prrp:lrntion, : ~ n duse of the t w t h a r r :111 clone in nqrlmtw n ~ n l i n or ln~miclrnvirnnn~entsto prrserrc the n n t ~ mnioi-ilnre l r Ahnwion testing is cnrricd nut in rrp1ir:ltc of l l ~ trcth. with t h r cmss-t~rr~slting mnrhinr. T h e hrwhrs movc ovrr tlw rspnsnl clrntin (or en:\mcl, if clesirnl) of thc mocmtnl, irr:di:~lc.cl trrlh. i i f t r r the hrusl~ing, t h r slurry nround t IN. tooth i s snmplcrl, connlnl, :inel cnmp:~rrrlwith t11rknown spwilic :~rlivilyof t l ~ irr:dintnl r ly tooth. 1f11ns\vith trst s:~niplrsnrr u s ~ ~ : ~ lprccnlnl r srt nf t w t h hy st:~ncl:~nl ntnr nnd foIlo!vnI on t l ~ s:rnw with :I rle:rning npmt of kno\vn ahr;~sivrnrss. Ahr:~siwnrs*snrrrs of scvrrnl typrs of m:~terinIsare l i s t 1 in ' : h I 2. T h r srorw :Ire rrlntivc?, hring rrrtios of rrmovc~l"Pin the text slurry to thnt in thc st:~ncl:lrd slurry of (':1Hl'0,. the l:~t.lrrset. rqu:d to 1000. Toble 2.
Relative Abrasiveness Scores
~ n l l l ' ~ l ~ ~llqms~nlnliv~ 2ll~~, lfnttge ('!d':O:, I l ~ p r e s ~ n l n t ilw l~ w ~ ~ (':,(XI>, S1:,,,,I:,r,l ls:!l'l I,)., ll:>lNl
