CA2138780A1 - Prophylactic and therapeutical preparation against caries - Google Patents
Prophylactic and therapeutical preparation against cariesInfo
- Publication number
- CA2138780A1 CA2138780A1 CA002138780A CA2138780A CA2138780A1 CA 2138780 A1 CA2138780 A1 CA 2138780A1 CA 002138780 A CA002138780 A CA 002138780A CA 2138780 A CA2138780 A CA 2138780A CA 2138780 A1 CA2138780 A1 CA 2138780A1
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- Prior art keywords
- preparation according
- acid
- calcium
- thc
- proportion
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Birds (AREA)
- Rheumatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Confectionery (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Dental Preparations (AREA)
- Orthopedics, Nursing, And Contraception (AREA)
Abstract
-11-A B S T R A C T Preparation for the Prophylactic and Therapeutic Treatment of Carics Propose is a preparation for the prophylactic and therapeutic treatment of carics, in the for of a chewable mass, chewable sweets, sucking sweets, toothpaste, mouth wash, mouth spray and similar, whereby a proton donor dissolved or easily soluble calcium and dissolved or easily soluble phosphate are provided. - Figure 1 -
Description
-` ` 213878~3 ~'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.
- , i: , 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 ..
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 - : `
^-:
~ ' , .
., 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 ~ . ~
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 ~` -~{ ~
~' ' .,,. ' ' .
..
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.
- , i: , 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 ..
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 - : `
^-:
~ ' , .
., 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 ~ . ~
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 ~` -~{ ~
~' ' .,,. ' ' .
..
2~3~78i, 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 ' ' "
,, 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~
~, .
. ~`.: . . .
-., ` , ` , ~... . . .
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 '-"''-~ ' :
~ : -. ~.
~.. ..
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.
'-. . - ,, , , ` ' `
~;. - ~ . ~. . .
`` .. . ,.
.~.. ~ ., .
Z`" '~' '~ '' '" ' ' ` ,` "' ` " , ~
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:
........ ~f .
~ `
- 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 ~ . ....... . .
~., -,; ' 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 ~,~_ . ,, .
'~
~"
-.
`- 213~8~
o-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. ~ --:;'~"'.
. ~
' ' '.'.;
' '`.
~' ~, -;..~..
, .
'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 ' ' "
,, 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~
~, .
. ~`.: . . .
-., ` , ` , ~... . . .
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 '-"''-~ ' :
~ : -. ~.
~.. ..
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.
'-. . - ,, , , ` ' `
~;. - ~ . ~. . .
`` .. . ,.
.~.. ~ ., .
Z`" '~' '~ '' '" ' ' ` ,` "' ` " , ~
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:
........ ~f .
~ `
- 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 ~ . ....... . .
~., -,; ' 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 ~,~_ . ,, .
'~
~"
-.
`- 213~8~
o-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. ~ --:;'~"'.
. ~
' ' '.'.;
' '`.
~' ~, -;..~..
, .
Claims (12)
1. Preparation for the prophylactic and therapeutic treatment of carics, in the form of a chewable mass, chewable sweets, sucking sweets, toothpaste, mouth wash, mouth spray and similar, wherein a proton donor and dissolved or easily soluble calcium and dissolved or easily soluble phosphate are provided.
2. Preparation according to claim 1, wherein as a base mass sugar or sugar substitute and/or gelatine and/or gum arabic and/or chewing mass is contained.
3. Preparation according to claim 1 or 2, wherein the proton donor is an organic acid, especially an acid used to aromatise confectionery, such as citric acid, lactic acid, fruit acid, tartaric acid or their mixtures.
4. Preparation according to one of claims 1 to 3, wherein the calcium compound is a calcium fruit acid salt.
5. Preparation according to one of claims 1 to 4, wherein in a solid state the proportion of calcium is 0.9 to 3.6 weight per cent, preferably 1.35 to 2.7 weight per cent, especially 1.8 to 2.55 weight per cent and that of the phosphate is 0.47 to 3.73, especially 0.94 to 2.82 and a quantity of 400 to 1500 millival fruit acid per kilogram of solid mass.
6. Preparation according to one of claims 1 to 5, wherein with a toothpaste there is a proportion of 160 to 660 mM calcium compounds per kilogram preferably 240 to 500, especially 320 to 400 mM/kg and in the case of phosphate a proportion of 40 to 330 mM/kg preferably 80 to 250 mM/kg and the acid proportion is 300 to 1200 millival/kg of toothpaste.
7. Preparation according to one of claims 1 to 6, wherein with mouth wash the proportion of the calcium is 5 to 22 mM especially 10 to 15 mM
and the proportion of the phosphate is 1 to 10, preferably 3 to 8 mM and the proportion of acid is 10 to 40 millival/kg.
and the proportion of the phosphate is 1 to 10, preferably 3 to 8 mM and the proportion of acid is 10 to 40 millival/kg.
8. Preparation according to one of claims 1 to 7, wherein the content of a substance that inhibits fractional precipitation, especially fluoride is in a concentration of 0.7 to 2.4 mM/kg.
9. Preparation according to one of claims 1 to 8, wherein a calcium and/or phosphate adsorptive substance is added.
10. Preparation according to claim 9, wherein the adsorptive substance is a polyglucan.
11. Preparation according to claim 9, wherein the adsorptive substance is a mucin.
12. Preparation according to claim 9, wherein the adsorptive substance is bipolar.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4221054.2 | 1992-06-30 | ||
| DE4221054A DE4221054A1 (en) | 1992-06-30 | 1992-06-30 | Preparation for the prophylactic and therapeutic treatment of caries and method for producing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2138780A1 true CA2138780A1 (en) | 1994-01-06 |
Family
ID=6461920
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002138780A Abandoned CA2138780A1 (en) | 1992-06-30 | 1993-06-30 | Prophylactic and therapeutical preparation against caries |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0648108B1 (en) |
| JP (1) | JPH08501530A (en) |
| KR (1) | KR950702111A (en) |
| AT (1) | ATE145323T1 (en) |
| AU (1) | AU677202B2 (en) |
| BR (1) | BR9306642A (en) |
| CA (1) | CA2138780A1 (en) |
| DE (2) | DE4221054A1 (en) |
| DK (1) | DK0648108T3 (en) |
| ES (1) | ES2102652T3 (en) |
| FI (1) | FI945866A (en) |
| GR (1) | GR3022582T3 (en) |
| NO (1) | NO303163B1 (en) |
| WO (1) | WO1994000101A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5658554A (en) * | 1995-06-01 | 1997-08-19 | Colgate-Palmolive Company | Mouth moistener for the relief of dry mouth condition |
| DE19629167C2 (en) * | 1996-07-19 | 2000-05-04 | Einhorn Apotheke Dr Guenther H | Solid oral anti-cariogenic composition in the form of a lozenge for cleaning the oral cavity and teeth |
| US6491900B2 (en) * | 1996-08-20 | 2002-12-10 | American Dental Association Health Foundation | Anti-carious candies and confections |
| US5833954A (en) * | 1996-08-20 | 1998-11-10 | American Dental Association Health Foundation | Anti-carious chewing gums, candies, gels, toothpastes and dentifrices |
| DE10349050A1 (en) * | 2003-10-17 | 2005-05-12 | Nova Dentalia Zahnpflege Gmbh | Gum for the remineralization of tooth enamel |
| JP5633998B2 (en) * | 2006-09-27 | 2014-12-03 | 三栄源エフ・エフ・アイ株式会社 | Tooth remineralization promoter and oral or oral composition containing the same |
| JP7150823B2 (en) | 2017-09-08 | 2022-10-11 | アムジエン・インコーポレーテツド | Inhibitors of KRas G12C and methods of using same |
| US11090304B2 (en) | 2018-05-04 | 2021-08-17 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| AU2020379731A1 (en) | 2019-11-04 | 2022-05-05 | Revolution Medicines, Inc. | Ras inhibitors |
| CN114901662A (en) | 2019-11-08 | 2022-08-12 | 锐新医药公司 | Bicyclic heteroaryl compounds and uses thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE729572C (en) * | 1940-05-19 | 1942-12-21 | Leo Werke G M B H | Dentifrices |
| BE731578A (en) * | 1969-04-16 | 1969-10-01 | ||
| IE42129B1 (en) * | 1974-10-10 | 1980-06-04 | Procter & Gamble | Compositions for remineralizing tooth enamel |
| US4080440A (en) * | 1974-12-13 | 1978-03-21 | The Procter & Gamble Company | Method for remineralizing tooth enamel |
| CA1187417A (en) * | 1981-07-03 | 1985-05-21 | Jan Weststrate | Dentifrice |
| DE3213284A1 (en) * | 1982-04-08 | 1983-10-13 | Winfried 8451 Kümmersbruck Kruppa | ANTI-CARIES CHEWING GUM |
| NL8402786A (en) * | 1984-09-12 | 1986-04-01 | Stichting Biomaterials Science | PREPARATION FOR PROTECTION OF TEETH AGENTS FROM DESCALING. |
| US4902498A (en) * | 1988-06-01 | 1990-02-20 | The Procter & Gamble Company | Oral compositions |
-
1992
- 1992-06-30 DE DE4221054A patent/DE4221054A1/en not_active Withdrawn
-
1993
- 1993-06-30 ES ES93912643T patent/ES2102652T3/en not_active Expired - Lifetime
- 1993-06-30 JP JP6501959A patent/JPH08501530A/en active Pending
- 1993-06-30 BR BR9306642A patent/BR9306642A/en not_active Application Discontinuation
- 1993-06-30 AU AU43083/93A patent/AU677202B2/en not_active Ceased
- 1993-06-30 DK DK93912643.9T patent/DK0648108T3/en active
- 1993-06-30 WO PCT/DE1993/000579 patent/WO1994000101A1/en active IP Right Grant
- 1993-06-30 AT AT93912643T patent/ATE145323T1/en not_active IP Right Cessation
- 1993-06-30 CA CA002138780A patent/CA2138780A1/en not_active Abandoned
- 1993-06-30 EP EP93912643A patent/EP0648108B1/en not_active Expired - Lifetime
- 1993-06-30 DE DE59304554T patent/DE59304554D1/en not_active Expired - Fee Related
-
1994
- 1994-12-14 FI FI945866A patent/FI945866A/en unknown
- 1994-12-14 NO NO944831A patent/NO303163B1/en not_active IP Right Cessation
- 1994-12-29 KR KR1019940704811A patent/KR950702111A/en not_active Application Discontinuation
-
1997
- 1997-02-19 GR GR970400267T patent/GR3022582T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR9306642A (en) | 1998-12-08 |
| FI945866A (en) | 1994-12-30 |
| ATE145323T1 (en) | 1996-12-15 |
| FI945866A0 (en) | 1994-12-14 |
| DE59304554D1 (en) | 1997-01-02 |
| EP0648108B1 (en) | 1996-11-20 |
| JPH08501530A (en) | 1996-02-20 |
| NO944831L (en) | 1994-12-14 |
| KR950702111A (en) | 1995-06-19 |
| AU677202B2 (en) | 1997-04-17 |
| EP0648108A1 (en) | 1995-04-19 |
| ES2102652T3 (en) | 1997-08-01 |
| WO1994000101A1 (en) | 1994-01-06 |
| DK0648108T3 (en) | 1997-04-28 |
| AU4308393A (en) | 1994-01-24 |
| NO303163B1 (en) | 1998-06-08 |
| GR3022582T3 (en) | 1997-05-31 |
| DE4221054A1 (en) | 1994-01-05 |
| NO944831D0 (en) | 1994-12-14 |
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