Title of Invention

METHOD FOR THE PRODUCTION OF A CHEWABLE COMPOUND FOR THE REMINERALISATION OF TOOTH ENAMEL

Abstract Method for the production of a chewable compound for the remineralisation of tooth enamel comprising the following steps: a. preparation of an aqueous solution of at least one acidifying agent suitable for foodstuff such as herein described; b. addition of a reactive calcium source to the aqueous solution to obtain a solution; c. addition of the solution to a thickener, wherein the thickener is gelatine; d. thorough mixing of the components into a compound; e. forming of the compound and drying; whereby phosphoric acid is added in at least one of steps a, b or c.
Full Text Chewable compound for the remineralisa'bion of tiooth enamel
The. present. inv?ent±on relates to a chewabie compound Lcr '¦ he-
remine ra I i.sat. ion ot tooth enamel as wel.l as a metl-iod .:¦;;- ¦ tie-
production ol such a chewabie compound.
Up till, today the use of fluoride applies as m€5thod ol
choice to prevent caries, since other options such as rriouvh
hygiene or nutritional guidance generally fail due '.o turriari
slackness. Nevcrt,heless fluoride is only useful to -a 1 .rnj-.tid
extent for healthy maintenance of teeth, since its mail
protection me(;:hanism, promotion of the reminer a.l isat. i C5..n c;
tooi.h cnanie.i is only possible in the presence of free
calcium- and phosphate-ions.
[yui i.nq pel iods, .i.n which the tooth enamel is decalcif.ied t)y
the acids separated from micro organisms in thie oral ';.;a.v,ty,
sma.l 1 porcjs lorm on its surface. From these the calc.-;um
salts migrate from the bottom of the enamel into tliC Loc !".
lining and then to the oral cavity. Deep pores, ir; wl. ici.
the minerals (..:a Icium and phosphate are deficient, ttie re J c r c
remain betiind. If this deca.l cif icati.on is not., stoppcn, i.hey
then c;ave5 in later with the actual caries formation .
En the case of naturally occurring remineralisation of tno
tooth enamel such pores are very quickly closed by the
calcium- and phosphate-ions near the neutral point exisf. ;riq
i.n l..he; sa.1 i va just as with a cork. Deeper ly.ing enamel
layers riowever remain impoverished of m.inera.l .
At. t.h.i s point, i.he so-called "forced dynamic
remlnerai i sat: ; on" begins. By reducing the pH level wirh
simultaneous increase of the mineral concentration by meai'.s
of an acidic remineralisation solution enriched with ca.l c i urr;
and phosphate.-;.:.; or a chewable or suckable compound p.repare i
ac:c;("jrdinq.; y t.or. example, the concentration o£ miner,-i.s i:.
t..ht: ora.: cav':;..y environment can be increased several i. mc;.->,
without the sat:uration point being substantial.! y exceeded.
As a result of a measure the porous, decalcified tooth
enamel .is impregnated with mineral. In this way a ..arge
quantity of dissolved mineral is transported into a 1 .[ aroa. of the i es i on.
After the application, the pH level in the environment of
the tooth again rises through saliva clearance, but at. the;
same time the ni.Lneral concentration there fal.ls drastica; .y.
Both protons and some of the mineral inwardly dispersed
during the application again diffuse back into the mou::h
cavity out of the porous enamel area. Because of trie
greater mobility of the hydronium ions and the non-linear
correlation between diffusion time and extent, the aro}a n^^ar
the surface oecomes impoverished of mineral faster t.ha..i >.:i::
deeper lying layers. The mineral is trapped in these beca...ise
of tfie greater mobility of the hydronium ions and after
their removal - on account of the rise in pH caused as a
result - is deposited on the pore walls. In this way both
place and quantity of the mineral entrapment are influenced
positively tiirough the temporary concentration profile,
which is predefined by the appli.cation.
Kruit gum, which contains an addition of calcium in the
range of 3 mMol/kg, is well known from practice. This
concent.ration is too low for preventing the formation of
cari es .
A possible way '."..o produce the aforementioned temporary
concent.rai:. i en profile in the oral cavity is through cnewabi'^
compounds partjcularly in the form of fruit gum, which )-s
enriched vj 1 [.h ca.l.cium and phosphate. Such chewable
compourios are .aoscribed m European Patent EP 0 64 8 108 Bl
in a general, way regarding the concentrations of calcJurr aiiO
phosphate toget:her with other exemplary embodiments. There
It IS proposeci a concentration of calcium m the chewabi.e
compound is adjusted between 200 mMol/kg and 800 mMoi/kq and
that, of phospnate in the range of 50 mMol/kg and 400mMo.;/kq.
A produce i.on process for such a chewable compound is not
disclosed.
US Pal:en!-. US ;:001/0033831 AI proposes the addit.ion of o t : i -
calcium phospriate in remineralising chewing gum. AlthoLigh; c
tri-calcium phosphate is more soluble than the other neutral
and basic calcium phosphates, an effective remineraLisatLon
effect exceeding that of saliva is not to be expected.
The implementation of calcium and phosphate from the caicijiti
salts oi; 1:he fruit- or carboxylic acids and phosphates d;-es
not provide ttie desired results. Although a product, in
which calcium phosphate is added, is known from US Fai.en^ US
5 015 628, tne necessary concentration of calcium, whrcri is
available .for the remineralisation process, is too lev;.
A similar product is also not on the market. The problem^s in
production are not solved by the state of the art, ir-
particular not for chewable compound on a gelatine basi.",.
As IS weL.i Known Ca-ions affect the thickening reaction of
gelatine in a negative way. Calcium can lead to turbidity
of the gelat.ine used for fruit gum even as far as its

¦,;oaquiat:,j on. l( the caJ.cium usually m the form of sails ; .-;
ridded toqetfier v;lth sugar, colouring, flavouring ager^^'cs
etc, >:he thrc^shold for turbidj ty of the gelatjne is
approx.imav.el V :> mMol/kg. For saleable products however a
highly transparent, homogeneous consistency of the geLaiJri.'
J s a 1 ways p re f e r red.
The object to be achieved now consists of introducing
cai.cium ancd phosphate in suitable modification as well as
sufficient quantity into the production process of cnewabie
compound (in particular fruit gum) so that the finished
product-, corresponds to the requirements in effectiveness,
without the Laste and transparency of the gum compound or
the "tactile fee] between the teeth", that is to say tne
bite or ctievj i r'\g feel of the finished product, being
impaired. It is also an object of the invention to creaie a
chewabJ.e compound having good effect with reduced
concentrations of calcium and phosphate.
Those objeccs are achieved by a method comprising the
features of Claim 1 and by a chewable compound comprisirg
the features of Claim 6.
Because wi r.h the inventive method for the production of a
chewabie compound for the remineralisation of tooth enamel
the foiJowinq steps are proposed:
a. preparation of an aqueous solution of at least one
acidifying agent, for example from the group of.
carboxyLic acids, certified according to the food-stuTf:
law, m particular fruit acids, and phosphoric ac.ci;
b. addition of a reactive calcium source, for (.ixampl',;
calcium hydroxide;
c. add It...or: ol. thickener, for example gelatine prescr;L '. ri
d. ground or pre-swollen state, to the solution;
a. thiorough mixing of the components;
e. forming of the compound and drying m corn starch
moulds for example.
a transfjarent. and homogeneous chewable compound witii tr.e
desirable properties as regards caries prevention and for
j nf I ucnc:ing i.nitial caries is obtained. The produci. made by
this method is distinguished by particularly good
transparency and homogeneity.
'i'he thicken.ing agent: can contain some of the flavourings arid
adjuncts. These however can also be added separately t,o I'lo
soluLion .
The phosphoric acid can also be added between steps (b) anc.
(c). Likewise it is possible to add the coarsely grouno
thickening agent to the solution and allow it to swel i
there .
Because with a chewable compound according to Claim 7 ii is
proposed ohat. the calcium content is between 30 mMol/kg 190 mMoi/Kg ¦1.4 g/kg to 9.0 g/kg) related to the lin i shc-.c;
product, a long-term stable product which can be produce'i
simply, but which exhibits a good effect in vivo i;;
avai.lable. I'his effect is achieved due to the fad. trial t.hc
local concentration is particularly high through trie
chewable compound adhering on the tooth surface and sal.i/a-
condiLioncd removal of calcium and phosphate ions docs no;
take place to a significant degree in the contact area
between the chewab.le compound and the tooth. J.n particuior
the phosphor lis content can lie between 15 mMol/kg and
500 mMo"L/kq wit.h this calcium concentration.
Part Lcu I ar.,. y good properties result in the case of a
chewabie compound adhering on the upper surface of t nc to:H.h.
i£ the calc:,jum content is between 50 mMol/kg and 150 mMo.i .¦ K.q
(2.3 g/kq to ..0 g/kg) related to the finished product.
For the iorced remineralisation to function well, the
calcium and the phosphate should be present in the iruj.t (Jurn
as fully dissolved as possible, that is to say it should i present as tar as possible in ion or colloidal form bu>. r^ i
crystal]ine as salt.
The method is designed to be incorporated as optimally as
possi.ble into the conventional process for the production of
fruit gum. In this case the respective thickener, ior
example qclat. Lne, is allowed to swell m some of the-.' 1 ...qi; , c;,
which can aJso contain some of the adjuncts and additive;;..
The swollen thickening agent, designated below as "part. 1",
is then careiully mixed, avoiding bubbles, with the
remainder of the ingredients (the residual water, sugar,
acid, flavouring and colouring agents as well as the cil-'ium
and phosphate), designated below as "part 2", to form .he
fruit gum, dried in corn starch moulds and then further
processed, waxed etc. for example.
If calcium and phosphate are mixed in the conventional Wciy
I from salts into the solution part 2 for example, the
gelatine always becomes lumpy, particularly severely .in !.->.(:;
case of the t.-alcium lactic acid phosphate buffer.

The transparency and homogeneity of the product as well a>:
its r.erni ne; ra ! ¦ .sing power can be additionaliy controlled bthe suitable nv.xture of various acidifying agents as
component, lor part 2. In particular the relevant proper!.. : os
of t.he chewabie compound can be controlled by varyirig ; ho
acio proportions with differing calcium compLexing power.
Mixing of malic acid or citric acid into a fruit gum, wh.i^iri
is conceived on pyruvic acid for example, leads to
particular Jy clear fruit gum mixtures having a pleasant
level of acidity with good effectiveness.
Rec if)e s anci i3xamp 1 e s
In tfie following examples pure water is used lor thlcloniiiq.
The thickening time of the sheet gelatine varies between 1
hour and 'A A hours at temperatures between 37 °C and 60'C
(part 1) .
Components from part 2, which do not disrupt the thicken., r:q
reaction of :. lie gelatine, can also be added to part .1 .
Ease materials are the carboxylic acids and phosphor! r; a ;;d
ciissolved in the .liquid phase of part 2 in a concet;trat i on
suitable for forced remineralisation and as reactive ca.i'.;ium
source: calcium oxide, calcium hydroxide, calcium carbonate
or a mixture thereof. The quantity of phosphoric acid
depends on Lhe desired phosphate concentration of the
finished product and lies in the range of 15 mMol/Kg to
bOO mMoL/kg (1.4 g/kg to 48 q/kg) related to the finished
product. In the examples cited a content of 70 mMol/kg
phosphate is r\ot exceeded, although a higher phosphate
c;ontent would additionallv reinforce the effect. 'I'h : s
res L r i.(:t:..i oil t.dkes Into consideration the German foodstuff
Law valid at t.he time of the patent application. The Jtk.t.
or carboxyiic- acid concentration depends on the desj rec
caic.i.uni c:;o:;l.o:i;.,, pH level and the taste of the chewabie
compound.
Related !..o tnc finished product the calcium content 1. icis
between 30 mMoi/kg and 600 mMol/kg (1.2 g/kg and 24 q/K.gr.
The neutral .1 zaLion reaction shows a strong positive heat
tone so that '.ne usual additional hearing up to accolerar-
the reacniion process can be dispensed with. In the
concentrations of acidifying agent, phosphate and calc;..um,
cited in the examples, these solutions are stable over a
long time.
The examples detailed in the following are possible
embodiments of the i.nvention.
The following materials were used as additives:
Gelatine: Sheet gelatine from Dr.
Oetker;
Ca (OH) >;: Merck 2 047;
Ortho-phosphoric acid 85%: Merck 1.00563;
Citric acid: Merck 8.18707;
Malic acid: Merck 1.00382;
F^yruvic acid: Merck 8.20170
The following recipes give a yield of approx. 65 g.
The entire qe.l.atine is always pre-swollen in 15 ml distJ.iod
water lor 1/ liours at approx. 50°C.

The Ca-coriceni rati on in the product is 200 mMol/kg, the
pnosphate concentration being 70 mMol/kg.
Example 1:
Pan 1 : 6. / q gelatine in 15 ml distilled water.
Part 2: 10 ml malic acid (1.5 Mol/1) + 10 ml citric acid
(j.O Mol/1} t 0.3 ml phosphoric acid + 0.9 g calcium
hydroxide * 2 (..; g household sugar.
The tnree ac;.ds are mixed and the calcium hydroxide i. s aode^'d
wh."i le st..i r r 1 ru:) . After complete dissolving the sugar i ;¦¦
dissolved in trie solution while being gently iieatod ano. ;;:e
warm qelaL."ine solution is stirred into the solution part
If. is then piaced in the corn flour moulds and allowed to
dry for approx. 2 0 to 4 8 hours.
Example 2:
Part. 1: 6. / g gelatine in 15 ml distilled water.
Part 2: 20 mi citric acid (1.5 Mol/1) -t 0.3 ml phosphoric:
acid I 0. / g c;alcium hydroxide + 20 g househoici sugar
Processing as example i
Example 3:
Pact i: 10 g gelatine in 15 ml distilled water.
Part 2: 20 m,i pyruvic acid (1 Mol/1) + 0.3 ml phosphoric
acid t 0 . ¦/ g cralcium hydroxide + 20 g household sugar
Processjnq as example 1
Example 4:
Par:. ;: 8 q qeiatine in 15 ml distilled water.
Part 2: i i"; niJ niaj ic acid (l.b Mol/1) + 10 ml pyruvic ac; d
(1.5 Mol/1) +¦ 0.3 ml phosphoric acid + 0.7 g calcium
hydroxide i- 20 q household sugar
Processing as ^'^xample ]
Example 5:
?art 1: 8 g gelatine in 15 ml distilled water.
Part 2: 10 ml pyruvic acid (1.5 Mol/1) + 10 ml citric ac i.d
¦1.5 Mo.l / 1 ) t 0.3 ml phosphoric acid + 0.8 g caLcium
Iriydroxide i 2 0 q household sugar
l-'rocessing as example 1
P r o o r o f e f f G c t. i v e n e s s
The remine ra Lis i.ng effect of the fruit gum described was
tested in an Ln vitro experiment. To obtain an idea c>f tlie
:i..-nportanc(:; o" the resultant figures and to recognize the
rslations beUwecn in vivo and in vitro esxperiments, values
regarding m.neral entrapment from an experiment to d.isccvcr
the reminera i.i sat. ion effect of fluoride tooth pastes carried
out in situ and parallel thereto in vitro, are recorded in
the last six lines of the table.
The values measured in vitro and in situ are reciprrjca , i v
confirmejcd as a result of which transferability of i-le
experimental designs is given.
I'he results ;3now clear mineral entrapment m the specimen-',
treated with remineralising fruit gum. The amount of
entrapped mineral varied with the calcium complexinc;! oi -..lie
mdividual fruit acids.
The entrapmen:. rates found an the present experiment each
related ;..c a ".:, reatment, in the case of the rerainera i. i s . nq
fruit gum are greater by the factor of 4 than those in thf
case of denta! cleaning with a fluoride toothpaste.
Tn-vitro r emii neral i sation of decayed porous hydroxy i apat i'.(;-
sintered bodies with fruit gum m comparison to a popu.a;
Looth,paste on the market

WE CLAIM;
L Method for the production of a chewabie compound for the
remineralisation of tooth enamel comprising the following steps:
a. preparation of an aqueous solution of at least one acidifying
agent suitable for foodstuff such as herein described;
b. addition of a reactive calcium source to the aqueous solution to
obtain a solution;
c. addition of the solution to a thickener, wherein the thickener is
gelatine;
d. thorough mixing of the components into a compound;
e. forming of the compound and drying;
whereby phosphoric acid is added in at least one of steps a, b or c.
2. Method as claimed in claim 1, wherein the additional following step is
proposed:
mixing of various acidifying agents as reactant for process step a.
3. Method as claimed in claim 1, wherein the acidifying agent as pure
compound or mixture in step a) is selected from the group, which
comprises the following:
- carboxylic acids, in particular including
lactic acid
fruit-acids, in particular
pyi uvic acid
citric acid
malic acid.
4. Method as claimed in claim 1, wherein the following additional step is
provided:
mixing of a powerful calcium-complexing acid into a solution, which
is produced in process step a) with less powerful calcium-
complexing acid.
5. Method as claimed in claim 4, wherein the powerful calcium-
complexing acid is malic acid or citric acid and the less powerful
calcium-complexing acid is pyruvic acid.
6. Method as claimed in claim 1, wherein the calcium source as pure
compound or mixture is selected from the group, which comprises
the following:
- calcium oxide
- calcium hydroxide
- calcium carbonate.
7. Chewable compound for the remineralisation of tooth enamel,
a. which
i. is produced using a method as claimed in claim 1 and
ii. includes calcium and phosphor, wherein
b. the calcium content amounts to between 50 mMol/kg and 150
mMol/kg, and
c. the phosphoric content amounts to between 15 mMol/kg and
500 mMol/kg.


Method for the production of a chewable compound for the
remineralisation of tooth enamel comprising the following steps:
a. preparation of an aqueous solution of at least one acidifying
agent suitable for foodstuff such as herein described;
b. addition of a reactive calcium source to the aqueous solution to
obtain a solution;
c. addition of the solution to a thickener, wherein the thickener is
gelatine;
d. thorough mixing of the components into a compound;
e. forming of the compound and drying;
whereby phosphoric acid is added in at least one of steps a, b or c.

Documents:

00897-kolnp-2006 correspondence.pdf

00897-kolnp-2006 form-18.pdf

00897-kolnp-2006-abstract.pdf

00897-kolnp-2006-assignment.pdf

00897-kolnp-2006-claims.pdf

00897-kolnp-2006-correspondence(other).pdf

00897-kolnp-2006-correspondence-1.1.pdf

00897-kolnp-2006-description(complete).pdf

00897-kolnp-2006-form 1.pdf

00897-kolnp-2006-form 2.pdf

00897-kolnp-2006-form 3.pdf

00897-kolnp-2006-form 5.pdf

00897-kolnp-2006-form-26.pdf

00897-kolnp-2006-form-6.pdf

00897-kolnp-2006-international publication.pdf

00897-kolnp-2006-internationalsearch report.pdf

00897-kolnp-2006-pct form.pdf

00897-kolnp-2006-priority document.pdf

897-KOLNP-2006-CORRESPONDENCE.pdf

897-kolnp-2006-form-27.pdf

897-kolnp-2006-granted-abstract.pdf

897-kolnp-2006-granted-assignment.pdf

897-kolnp-2006-granted-claims.pdf

897-kolnp-2006-granted-correspondence.pdf

897-kolnp-2006-granted-description (complete).pdf

897-kolnp-2006-granted-examination report.pdf

897-kolnp-2006-granted-form 1.pdf

897-kolnp-2006-granted-form 13.pdf

897-kolnp-2006-granted-form 18.pdf

897-kolnp-2006-granted-form 2.pdf

897-kolnp-2006-granted-form 26.pdf

897-kolnp-2006-granted-form 3.pdf

897-kolnp-2006-granted-form 5.pdf

897-kolnp-2006-granted-form 6.pdf

897-kolnp-2006-granted-reply to examination report.pdf

897-kolnp-2006-granted-specification.pdf

897-kolnp-2006-granted-translated copy of priority document.pdf

897-KOLNP-2006-OTHERS.pdf


Patent Number 236061
Indian Patent Application Number 897/KOLNP/2006
PG Journal Number 38/2009
Publication Date 18-Sep-2009
Grant Date 17-Sep-2009
Date of Filing 12-Apr-2006
Name of Patentee MEDERER SÜβWARENVERTRIEBS GMBH
Applicant Address OSTSTRAβE 94, 90673 FURTH
Inventors:
# Inventor's Name Inventor's Address
1 DR. MED. DENT. JOBST LAHRSOW FROMBERGSTR. 26, D-97941 TAUBERBISCHOFSHEIM
PCT International Classification Number A61K 7/00
PCT International Application Number PCT/EP2004/010860
PCT International Filing date 2004-09-28
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 10349050.7 2003-10-17 Germany