Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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~'rcp~ration for th~ rrophylati~ and
_ . . .
l~herapcutic Tre~tn~cnl orCa~ics
l`hc invention et)nce1ns a preparation fr.~r the l~rophylalic and thcraT-eutic
~reatment of oaries, in thc form of a chowable mass, chcw~ble swcct~,
sucking swe~ls1 toothpastct mollth wnsh, moul1l Spl ay and ~imilar.
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Witll c~ries, poillt-b~-point de~tructioll ~f th~ looth cnalllcl a~ld, fron
lime to time, also orthe dentine underneattl, causcs Icsion~. As ~
pleparativc mcasurc to save the t~th, tbe dama~cd rcgion o~th~ dent~l
enamcl and the dentille is fir~l removed with thc aid of a ~rsll so thnt a
ca~ity is formed. A~ter di.sinfccting, the ~/ity iS fi11cd through the
insertio1l of ceItnin m~leria1s in the form of amal~am, ~lastic, cement,
~old or similar in order to prev~l1t dirt, bactcria from cnlerin~. Fin~lly, thc
~ .- - - ~
surface of thc fillin~ material and cspccially thc ~urface of the tr~sition r
zonc is l~olished to prevent thc rcoccurrence of carics. ~ )
,
It i~ 1t) be seen 8S disadvanta~cous that t!lc priur ~n method is costly and
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under circumstallces re~u;re~ mor~ thalt onc ~isit to thc physici~n.
It is the ~biCct of this invenlion to prt)vide a prcparRtion for . ~:
reminer~1isation~ the use of which crcalc~ optimum conditions - : `
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213878 ~3
in tho ora1 eavity al~d/or dir~o~ly at the tooth~
This object is solva~ th~r~in that it is prop~ d lo provido a r)rol(~n donor
flS well as dissolved ()r easily s~11ublc calcium ~nd dissolve<l or ea~ily
sotuble })h( æphRtc~ The prel aration is l~cd or~lly, e.~ in the fi)rm of a
suckin~ or ~;hGwa~le sweet c~r n d~ ble mn~. 'I`onth~as~e, mouth w~sh,
mmlth ~pr~y ~)r olher pr~paration~ ~r daily dent~l and ~r~l hy~iene ean
also be viewed a~ vehicles.
l`h~ invention is b~scd on llle recognition thntthe } rocess eausing ~aries -;
is rever~ible. Results f~om both ex,~rimenlal tests ~s woll a~; a
mathematica~ diff`usiotl-r~action model ~how that the non-station~ry
marginal condilions fo~ the n1inera~ axchange pr~eesses at the tee~h are
ospccially imporl~nt: only adequa~ly varying eoneentrations of dissolved
min~ral (essentially ealcium and phosphate) ~nd tho pH value and - ~ -
inaetive ingr~di~nts sueh as ~quo~de in ~dle oral cavity envir~ nt~ whieh
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rinse me Icsinn, facilil~ a coml~lctc and dccp rcmin~ra~isabon ~)fthc
: :.
le~ion~ The samc procc8~c~ play an im~rt~nt role in the prophylactic -
saturation of the h~rd clental substanee with mineral~
. :.
The mineralisntion proces~ des~ribed is lar~el~ dcfincd b~ physieo~
c.hemical values such as ~he de~o~ilion ~ate of minernl from t~e ~ isol~
pl~ase, the saturatic)n concenlration at the resl ective pll val~lc, ()t the ~` -
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difl`u~ion oons~ants of thc different diss~lved components. Thc.sc
parameters and thc ~ubstratc surrace, i.e. the sctivc surf~ce in the cn~mel,
il~flncnce the quantily, type nnd struct1lrc of tl1e depositcd mineral.
'I'he9e pro~Gs~ vicwed ini~ially in vitro also filn(;tit)n in vivu.
Tht, exploitation Oî this rccognitit)n in ordcr to dev~lop a carics
prop}~ lactic ()r therapy i~ lurgely dcf'1ncd b) tlle possibility c f creatin~ thc -
op~imum conditioll~ in the oral cavit;y or directly at the too~h~ This ~Iso
includ~s the ~;r~aliurl of optil1lum condilions for remincr~ tion, which
l;e in Ihe acidic ran~,c 'l hc additio1l of n prcton don~r servcs to gcncralc
(initially from a neulral conditio1l~ a low p~ lae~ ~)nly thcn nrc tho
calcium and phosphatc bonds diss~ciated. ; - `-
~`or a suclcinE~ sweet~ sugar or sug~r subslitutcs such as xylitc, ~orbi1 or
isomalt can be used the as bas~ mass. l~ulthcr possibilities consist of - . -`. -;
sugar subst:itutcs and/or gelatine and/c)r Rum ~rslbi~ and~or chewablc
mass ``~
In the formuIati~n of a re~iip~ for`an application, the bullèr AC1ioll oft~lc
rcsidual phospll~e and that ~f the saliva mu~ be ~)nsidcrcd~ An -
importan~ point of view for the compc~sitioll is also thc saliva clcarancc,
i.e. lhe qu~ntity of introduccd agcnl~ ~ hich are diluted and swnllowed via
thc salivu 1`his pr(~portion is ~r¢~tl~ innuel~ced ~y the forl~l of
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21387,~
application Isucking s~veel, chcwshlc swcc~l, to~)lhrtaste ...). ln thc cai~ of
an initial pll valuc of ,n~ 44.5, which Is rcqllired for ~ controllcd
rcmillcralisfl~ion~ one part of the ph~n;phatc is providcd ~fi H2rO4 ion, i~c.
only sitnTlly diss~iatcd in solu~i<)n~ The undissoci~ d l~rotons, fixed to
~he phosphatc, must bc addition~ly addcd~ This can b~ donc, c.~, in the
10ml of citrate or anotller acid uscd in conreGlit)ncry nlaking for
aromali~;in~ (e~g lactic acid~ malic acid, tar~ri~ acid, gcncral rruit acid).
The usc of calciltm ctlloride nS a Galciu1n donor is also concei-~ablc.
'~`o dclay the clearance of the substan~es dcriving irom the dcvicc ~nd
tl-erefore to control ~he eoncentl~ation profiles~ substnnccs can also ~c : :
added to thc dcvicc~;, especially thc tonthpaste, thc mouth wa~;h and 1he ~ :
n~ollt}l spray, ~vhich~ ~n ~h~ onc hand, phystcally bind caloium and/or
. . .
phosphate in lar~c ~uantilies9 on the other hand, are t}t~m~ielYc~ ad~orbcd ~ m ~;
on thc tooth surface alld/or or~l ca~ly mucous mcmbranc. Such .~SU~ allCeS are most~y of organic nature, and bipolnr mtd ~e usod as ` - -iluoride carriers in caries therQpy, such y~; amine fluoridc~ Substanccs
*om thc class of th~ clllorhexidine digluconnte and the quarl~rnary
ammonium ba.~s ~r~ al~o u~icd for silltilar purpose~" e~g. to prolong thc
disinfècling ef~ect (e.g. ui1h ehlorllexidine ~nd bcnzoxonium chloride~
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21387~ij
But ~Iso additions of highcr vigoo~ily whioh flre de~o~ited On the tooth
and the mllcoll~q mcmhrane and wllicll c~n contain adsorbod calcium nnd -;
pbosphatc adsurbed, C~l1 be con~idored k~ delay tllc clcar~ncc. NAIIJre
forms such substanccs, c.g., in tho d~ntal plaquc ~n the form of
e~tracclllllar polysaccharides. Therefor~ such an a~3di~i~ n can, c.g., he a
suhstancc from lhe class of thc r~oly~,luc~ns. ~ -
In ~n ~scidic envir()nmcnt, Ca-PO4 o~en docs nnt ~rccipitate in u solid ~ -
îorm ur in thc tnost f~vourable encrgctio form, hydroxylapatito. Ther~rc,
~sGort sul)slances ara to bc ~dded tn the forrnulation, which act ns : ~
cat~lysls ror ~hc foM~lation of solid hydroxylnpa1i1e and to avoid fractional ~ :
dcposition ~:or cxample, fluorid~ is ~;no~n as ~leh a substnncc.
The expl~nalions show that thcre ~re differcnt formulations for Ihe
com~)~ ion ofthc prcparation depending ~n the l;ind of appliofltion~
n) l~`or ~;u~;king sw&cts or chewable sw~ts with an ~vor~c rctcntion time
of 5-8 minutcs in the mouth, thc mcchanism described ~bovc, while ~ -
considcrill~ salivation, c~n ~c realis~d ~hro~gh thc f~llowilll compc-sition.
'I he c~ns~ant loss of millcral componellts tllro~ swsllowing oi`thc
~lutions is tsken into acc~unt:
l'er k~ oi swcct mass~ 200 to 800 mM, prcforahly ~sûO to 600 mM.
espccially 400 lo 500 mM of calcium or calci(lm com~ nd~ mu~t he
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213~7,~
addcd, which corres~ onds to m()re or loss ().9 to 3.6 weight l-er cent, 1.35
to 2.7 wei~ht pcr aent nnd ] .8 to 2.25 weight per ceIIt rcspcchvcly of
calcium ~cum~unds).
Psecausc o~ lhe existing hi~h phOS}~llatC contcltt (contcnl of phosphate
ions) of thc saliva, thc SU~ y of phos~llate (ion.~) through tho describcd
devicc cnn b~ nitcd to betweell ~0 and 400 IIIM, es~ecially 100 to 300
mM. Fx~rcssed in wei~,ht per c~nt: 0.47 to 3.73 or 0.~4 to 2.82 per ccnt : : -
OnC p~ ofthc pl'OtOllS required for nci~lifying i~ bu~crcd by phosphatc
ns3. For this re~son and throu~h the ~ncomplete dissociation nf thc
different fruit acids, it is lost for the acidification ofthe oral cavity
cnvironment. The addition of acid i~ gc)~erllcd by thcse conditions.
Required to acidif~r thc oral cavity are 290 mM H~- per kg of swcct ma~s - - -
(th;s value is bascd on mcasurements taken in the mouth).
T~lcing into account thc aforcmcnlioned conditions, if a calcium fruit acid
salt is u8cd as a c~loium donor, a fiuit acid content of 400 to 1500
milli~al is requircd. Convcrtcd to thc tribusic critic acids, this mu~n~,
dcl cnditlg nll the d~grc~ of dissociation~ a contcnt of al)prox. 2.8 to 11 .-
wcight I-er cent orcitrate. To catalysc thc solid disposi~ion Or
hydroxyla~-atite, the su~eet should also contain 0.7 tc ~.4 mM ~f
fluoridc/kg of swe<;t.
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213~ ~8 i3
b~ ~)r an ~pplication A~; to~llhp~xle, considcring thc dilulic n e~ect
throu~h lh~ ~aliYa and its bu~cr cap~city, ~ formul4ti~m in the following
limits must bc considered: :
~ ' '
160 to 660 mM Ca, prefcr~bly ~40 to ~0 mM, e~pecially 320 to 440 ; .
n~M CA And 40 tO 330 1~1M, prcfcrably sn to 250 mM Pt)4. Of acid, onc
requires bclwccll 300 and 1~0~) milli~al All data apr)lies to 1 kg of
toothpastc.
Onc pan of the calcium alld phosphatc oan, RS desc~ibcd, ~e gi~ren in an
adso~ptive carr~cr. ;
The appliculion form as to~hpAste hns ~he grcat adv~n~ag~. that, ~ also
describcd below, it is distribut~d eYenly in ~he mouth and creates vcry
homog~nous condition~. The cR~rier is espccially irnpo~ant bcc~use ofthc
relativcly ~hort retcntion time ofthe nctuul to(>thpastc in the mo~
c) 'l'hc con~entrations in the nn~)uth wash are lower thnn in the case of ~ho
other two fi)nnulations ~ccaust; ~tho relative-lar~c quan~itics of liquid - - -~
h~t arc ~kcn up during rinsin~ o creale thc most favollrable condition~
ossiblc in the oral cavity for hardening thc tooth cnAmel~ fl mouth rin~e
SOIlltiOll can bc ~mposed as follows:
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- 213878~J
~ to 22 mM (~A, I-reIèrably 8 to 16 mM, cspecially 10 t~ 15 mM Ca and I
to 10, prcferably 3 to ~¢ mM PO~ and 10 to 14 millivfll of aeid/kg of
mOllth wa~h. Those valucs rc~cr to a rc~ldy-for-usc ~olution wilh 3~
ml/arT~lication. The fortnulalions in c?~m~les b and c are also to be
,: ~
augmcnted witl1 low doscs of ~l1oridc. During a cer~ain timc all of tl1ese
formulntions create fln cnvironment in thc (>ral cavity ill whioh the tooth
... .
enamcl is impr~gna~ed with dissol~ed mincrals from a sahlrntcd ~ ion
at a lo~crcd pH vallle. l`hrough the use ofthc acidic sweet or thc washing
out ofthc ca~clun1 flnd phosph~tc ~dx~rptivc carricr in toolhpastes or
m~ th washcs, thcrc is an increase in thc F)l ~ ~alue on thc surfac~ and a
- - ~
concentrat10n gradienl belwec~1 th~ surfacc of Ihe enamel and its interior. -~
. . .
I his causes n diflu~ion c~rrent of protons, calcium and phosphatc ion~ in ~ . `
th~ direction of ~c cxtcrior environment. Bccause ofthe greater mobility ~ -
of the protons com~ared with the ca~cium and phusphate ions, thcrc is n
f~ster incrcasc in thc p~ valu~ inside t:he enamcL This for ;as the calcium
~nd phosph~tc iO~ under the enam~l surf~ce to J~r~ ate and thcY arc
dcpositcd as a solid materiAI.
,ure 1 shows n n~easuten~enl oftht; mas~i ( mincral) gto~th in a ~or~us ::
hydmxlapatite san~plo. Such sam~lcs beh~ve like t~ ~)th enamcl as
concerns delninera1isation and rcmil1cralis~tiol~, and a~ is kn~ wn t~oth
~ . ....... . .
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21~8~8~
cn~n~el oonsist~ primarjly of this matori~l I`he s~mp1es were w~lrn in the
m~utll on a d~ntal pl~te Qnd inscrted throe timc~ dAily during ornl hygicne
(5 minutes) in a solllti~m with pH34.5 ~Jtich ~as s~l;uratod with cslciuîn
and pho~phatG.
~s n ~ntrol, in a secolld sta~c, thc xamo ~mplc WflS ~1aced in ~lis1il1c~1
w~ler snd in a third expcrimental round again in thc acidic calcium -
pho~ ate s()lution. I11c points on the dlagram show tho weighl of thc
sam~le at the bcginn;n~ of th~ les~ aI~r thc f1rsl day wilh thc acidic
ca~cium l)hosph~t~ solution, after on~ day wilh distilled watcr and thcn
an~;r a fillthcr day with an acidic calcium pho~hatc solution.
C)b~ious is a mineral incrcasc of 1.4 mg ~liler the two experimcr)tal s~agcs
with rominera~isation sol;ition, while thc cxpcrin~el1taI st:~g~ with distilled
water r~sultcd in a mincr~l los~ of 1 mg.
'
In th~ case of sucking a swcct with. c.g., 0.44 molc~ C~ ~nd n.27
molc/kg ro4, with a acid ~ontent of 3.S% citric acid in thc buccal cavity~
e resuit is the tcmporal ~H l~rofile reptcscnted jll Figurc 2. Afler
introduo~iun of thc swcct int~ ~h~ oral c~vity, the ~H valuc in thc saliva
fiRtlS within 1 minu~e to p~I 4. l)uc ~ the cuboid do~ign of the s~eet, thc
disintc~ration of i~s surf~ce is tc~mpor~lly csscntially oonstnnt, so that ~r
time lh~ same qllantit~ of acid always det~chcs~ l`hererote, a l latca~l
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formsntnboutl7114.AftrrdiDsolutionorrcmovr,lof~heswrot,thcpll
value in the saliva of tht~ molnr nr~ again incre~scs due to saliv~ ~
clcnrance withill 3.2 minut~ Corrcsponding curves with a higher pl7 ~ ~:
platcnu cnn bc achievr~d wilh othcr rciri contontr. ~ -
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