U.S. patent application number 12/605079 was filed with the patent office on 2010-02-18 for self-etching dental materials based on (meth)acrylamide phosphates.
This patent application is currently assigned to IVOCLAR VIVADENT AG. Invention is credited to Jorg ANGERMANN, Iris LAMPARTH, Norbert MOSZNER, Angela MUCKE, Volker M. RHEINBERGER, Ulrich SALZ, Frank ZEUNER, Jorg ZIMMERMANN.
Application Number | 20100041790 12/605079 |
Document ID | / |
Family ID | 36059702 |
Filed Date | 2010-02-18 |
United States Patent
Application |
20100041790 |
Kind Code |
A1 |
MOSZNER; Norbert ; et
al. |
February 18, 2010 |
SELF-ETCHING DENTAL MATERIALS BASED ON (METH)ACRYLAMIDE
PHOSPHATES
Abstract
Polymerizable dental material, characterized in that it contains
at least one (meth)acrylamide phosphate of the following general
formula (I): ##STR00001## in which R.sup.1 is H or CH.sub.3;
R.sup.2 is H or a C.sub.1-C.sub.4 alkyl radical or forms together
with the nitrogen atom to which it is bonded and one or more atoms
which belong to R.sup.3 or R.sup.3' a heterocyclic ring; R.sup.3,
R.sup.3' independently of each other are a linear or branched
aliphatic C.sub.1-C.sub.50 radical with a valency of m+n or p+n, an
aromatic C.sub.6-C.sub.18 radical with a valency of m+n or p+n, or
a cycloaliphatic, araliphatic or heterocyclic C.sub.3-C.sub.18
radical with a valency of m+n or p+n, wherein the carbon chains of
the radical or radicals can be interrupted by O, S, CONR.sup.4,
OCONH, or form together with one or more atoms which belong to
R.sup.2 and the nitrogen atom, to which the R.sup.2 is bonded a
heterocyclic ring, R.sup.3' being H if p=0, and R.sup.4 being H,
C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.12 aryl, C.sub.6-C.sub.10
aralkyl or a bicyclic C.sub.4-C.sub.12 radical; n is 1, 2, 3 or 4
if p=0, and is 1 or 2 if p.noteq.0; m is 1, 2, 3 or 4; p is 0, 1,
2, 3 or 4; x is 0 or S.
Inventors: |
MOSZNER; Norbert; (Triesen,
LI) ; LAMPARTH; Iris; (Grabs, CH) ; ZEUNER;
Frank; (Schellenberg, LI) ; SALZ; Ulrich;
(Lindau, DE) ; MUCKE; Angela; (Schlins, AT)
; ZIMMERMANN; Jorg; (Lustenau, AT) ; ANGERMANN;
Jorg; (Feldkirch, AT) ; RHEINBERGER; Volker M.;
(Vaduz, LI) |
Correspondence
Address: |
NIXON PEABODY LLP - PATENT GROUP
1100 CLINTON SQUARE
ROCHESTER
NY
14604
US
|
Assignee: |
IVOCLAR VIVADENT AG
Schaan
LI
|
Family ID: |
36059702 |
Appl. No.: |
12/605079 |
Filed: |
October 23, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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11211938 |
Aug 25, 2005 |
7622538 |
|
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12605079 |
|
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Current U.S.
Class: |
523/118 ;
526/263; 526/277; 558/170 |
Current CPC
Class: |
A61K 6/20 20200101; A61K
6/887 20200101; A61K 6/30 20200101; A61K 6/20 20200101; A61K 6/30
20200101; A61K 6/887 20200101; A61K 6/30 20200101; C08L 75/04
20130101; A61K 6/20 20200101; C08L 33/04 20130101; C08L 33/26
20130101; C08L 33/04 20130101; C08L 75/04 20130101; C08L 75/04
20130101; C08L 33/26 20130101; C08L 33/04 20130101; C08L 75/04
20130101; C08L 33/04 20130101; C08L 75/04 20130101; C08L 75/04
20130101; C08L 33/04 20130101; C08L 33/26 20130101; C08L 33/26
20130101; A61K 6/887 20200101; A61K 6/20 20200101; A61K 6/30
20200101; A61K 6/20 20200101; A61K 6/887 20200101; A61K 6/20
20200101; A61K 6/893 20200101; A61K 6/20 20200101; A61K 6/30
20200101; A61K 6/887 20200101; A61K 6/893 20200101; A61K 6/30
20200101; A61K 6/30 20200101; A61K 6/40 20200101; A61K 6/893
20200101; C08L 33/26 20130101; C08L 33/26 20130101; C08L 33/04
20130101 |
Class at
Publication: |
523/118 ;
558/170; 526/277; 526/263 |
International
Class: |
A61K 6/00 20060101
A61K006/00; C07F 9/08 20060101 C07F009/08 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 22, 2004 |
DE |
10 2004 061 925.5 |
Claims
1. Polymerizable dental material, which comprises at least one
(meth)acrylamide phosphate of the following general formula (I):
##STR00020## in which R.sup.1 is H or CH.sub.3; R.sup.2 is H or a
C.sub.1-C.sub.4 alkyl radical; R.sup.3, R.sup.3' independently of
each other are a linear or branched aliphatic C.sub.1-C.sub.50
radical with a valency of m+n or p+n, an aromatic C.sub.6-C.sub.18
radical with a valency of m+n or p+n, or a cycloaliphatic,
araliphatic or heterocyclic C.sub.3-C.sub.18 radical with a valency
of m+n or p+n, wherein the carbon chains of the radical or radicals
can be interrupted by O, S, CONR.sup.4, OCONH, R.sup.3' being H if
p=0, and wherein R.sup.4 is H, C.sub.1-C.sub.10 alkyl,
C.sub.6-C.sub.12 aryl, C.sub.6-C.sub.10 aralkyl or a bicyclic
C.sub.4-C.sub.12 radical; n is 1, 2, 3 or 4 if p=00, and is 1 or 2
if p.noteq.0; m is 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; x is 0 or
S.
2. Dental material according to claim 1, in which R.sup.2 is a
C.sub.1-C.sub.4 alkyl radical.
3. Dental material according to claim 1, comprising at least one
(meth)acrylamide phosphate of formula (I'): ##STR00021## wherein
R.sup.1=H or CH.sub.3; R.sup.2=H or a C.sub.1-C.sub.4 alkyl
radical; R.sup.3=a linear or branched aliphatic C.sub.1-C.sub.12
radical, a cycloaliphatic or a heterocyclic C.sub.3-C.sub.18,
wherein the carbon chain of the radical can be interrupted by O, S,
CONH, or OCONH; m=1, 2, 3 or 4; X=O or S.
4. Dental material according to claim 1, wherein at least one of
the variables has one of the following meanings: R.sup.1=H or
CH.sub.3; R.sup.2=H or a C.sub.1-C.sub.3 alkyl radical; R.sup.3=a
linear or branched aliphatic C.sub.1-C.sub.3 radical with a valency
of m+n; R.sup.3'=H; R.sup.4=H, C.sub.1-C.sub.3 alkyl; n=1; m=1 or
2; p=0; x=O.
5. Dental material according to claim 1, which additionally
contains a solvent.
6. Dental material according to claim 5, which contains as solvent
water or a mixture of water and a solvent miscible with water.
7. Dental material according to claim 1, which additionally
contains at least one non-acid, radically polymerizable
monomer.
8. Dental material according to claim 7, which contains as non-acid
monomer one or more monomers from the following group:
mono(meth)acryl compounds, mesityl(meth)acrylate,
2-(alkoxymethyl)acrylic acids, 2-(ethoxymethyl)acrylic acid,
2-(hydroxymethyl)acrylic acid, N-mono and N-disubstituted
acrylamides, N-ethylacrylamide, N,N-dimethylacrylamide,
N-(2-hydroxyethyl)acrylamide,
N-methyl-N-(2-hydroxyethyl)acrylamide, N-monosubstituted
methacrylamide, N-ethylmethacrylamide,
N-(2-hydroxyethyl)methacrylamide, N-vinylpyrrolidone and allyl
ethers.
9. Dental material according to claim 7, which contains as non-acid
monomer one or more monomers from the following group: urethanes
from 2-(hydroxymethyl)acrylic acid and diisocyanates,
2,2,4-trimethylhexamethylene diisocyanate, isophorone diisocyanate,
cross-linking pyrrolidones, 1,6-bis(3-vinyl-2-pyrrolidonyl)-hexane,
bisacrylamides, methylene and ethylene bisacrylamide,
bis(meth)acrylamides, N,N'-diethyl-1,3-bis(acrylamido)propane,
1,3-bis(methacrylamido)-propane, 1,4-bis(acrylamido)-butane and
1,4-bis(acryloyl)-piperazine.
10. Dental material according to claim 1, which additionally
contains at least one initiator for the radical polymerization.
11. Dental material according to claim 1, which additionally
contains at least one filler.
12. Dental material according to claim 1, which contains the
following components: a) 0.5 to 95 wt.-% (meth)acrylamide phosphate
according to Formula (I), b) 0.01 to 15 wt.-% initiator, c) 0 to 80
wt.-% non-acid radically polymerizable monomer, d) 0 to 95 wt.-%
solvent, e) 0 to 20 wt.-% filler.
13. Dental material according to claim 12, which additionally
contains f) 0.01 to 10 wt.-% of one or more further additives.
14. Dental material comprising a) 0.5 to 95 wt.-% of at least one
(meth)acrylamide phosphate of the following general formula (I):
##STR00022## in which R.sup.1 is H or CH.sub.3; R.sup.2 is H or a
C.sub.1-C.sub.3 alkyl radical; R.sup.3, R.sup.3' independently of
each other are a linear or branched aliphatic C.sub.1-C.sub.50
radical with a valency of m+n or p+n, an aromatic C.sub.6-C.sub.18
radical with a valency of m+n or p+n, or a cycloaliphatic,
araliphatic or heterocyclic C.sub.3-C.sub.18 radical with a valency
of m+n or p+n, wherein the carbon chains of the radical or radicals
can be interrupted by O, S, CONH, OCONH, R.sup.3' being H if p=0,
and wherein n is 1, 2, 3 or 4 if p=0, and is 1 or 2 if p.noteq.0; m
is 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; X is O or S b) 0.01 to 8
wt.-% initiator, c) 0 to 80 wt.-% non-acid radically polymerizable
monomer, d) 0 to 80 wt.-% solvent, e) 0 to 20 wt.-% filler.
15. Dental material comprising a) 0.5 to 95 wt.-% of at least one
(meth)acrylamide phosphate of the following general formula (I'):
##STR00023## wherein R.sup.1=H or CH.sub.3; R.sup.2=H or a
C.sub.1-C.sub.4 alkyl radical; R.sup.3=a linear or branched
aliphatic C.sub.1-C.sub.50 radical, a cycloaliphatic or a
heterocyclic C.sub.3-C.sub.18, wherein the carbon chain of the
radical can be interrupted by O, S, CONH, or OCONH; m=1, 2, 3 or 4;
X=O or S b) 0.01 to 8 wt.-% initiator, c) 0 to 80 wt.-% non-acid
radically polymerizable monomer, d) 0 to 80 wt.-% solvent, e) 0 to
20 wt.-% filler.
16. Dental material according to claim 14, wherein the non-acid
radically polymerizable monomer is a (meth)acrylamide monomer.
17. Dental material according to claim 15, wherein the non-acid
radically polymerizable monomer is a (meth)acrylamide monomer.
Description
[0001] This application is a continuation of U.S. patent
application Ser. No. 11/211,938, filed Aug. 25, 2005, which claims
priority to German Patent Application Serial No. 10 2004 061 925.5,
filed Dec. 22, 2004, which are hereby incorporated by reference in
their entirety.
[0002] The present invention relates to (meth)acrylamide phosphates
with a high hydrolysis resistance which are suitable in particular
as adhesion component for self-etching dental materials such as
adhesives, coating materials and composites.
[0003] Nowadays self-etching, self-conditioning dentine-enamel
adhesives are increasingly used in restorative dentistry. These
adhesives are mostly constructed such that they contain an adhesion
monomer with acid function, one or more non-acid comonomers,
solvent, a polymerization initiator and optionally further
additives. Suitable as polymerizable adhesion monomers are above
all acid monomers which on the one hand exhibit a high reactivity
during radical polymerization and on the other hand are capable of
conditioning the hard tooth substance sufficiently rapidly. Known
examples of such acid monomers are carboxylic acid methacrylates,
such as 4-MET (4-methacryloyloxyethyloxycarbonyl phthalic acid),
MAC-10 (10-methacryloyloxydecyl malonic acid) or acid methacrylate
phosphates, such as MDP (10-methacryloyloxydecyl dihydrogen
phosphate) or MEP (2-methacryloyloxyethyl dihydrogen
phosphate):
##STR00002##
[0004] In this connection acid dimethacrylates are also known
which, like PMDM (addition product of 1 mol of pyromellitic acid
anhydride with 2 mol of 2-hydroxyethyl methacrylate) or GDMP
[(1,3-dimethacryloyloxy)-prop-2-yl-dihydrogen phosphate], are
characterized, because of their cross-linking properties, by a high
polymerization activity:
##STR00003##
[0005] Water is used in most cases as solvent or co-solvent in
enamel-dentine adhesives, as it promotes the wetting of the hard
tooth substance. The ester bonds of the methacrylates are however
known to be hydrolyzed under acid, aqueous conditions. Through the
hydrolysis of the monomers, the corresponding adhesive loses its
function, and the adhesion effect clearly decreases over time.
Therefore the acid monomers are stored water-free and mostly
separate from the other adhesive constituents. They are either
mixed shortly before use with the aqueous part or applied
separately to the tooth surface. It would be of great advantage if
hydrolysis-stable adhesives could be prepared which combine all the
components in one composition.
[0006] Hydrolysis-stable acryl phosphonic acids are known from EP 0
909 761 A1 and DE 102 34 326 in which polymerizable (meth)acryl
groups are bonded to the radical of the molecule via ether-,
thioether-, or via carbon-carbon bonds.
[0007] EP 1 169 996 A1 discloses dental materials based on
(meth)acrylamide phosphonic acids which, because of a relatively
long-chain bridge between phosphonic acid group and reactive double
bond, are said to have a high hydrolysis stability and improved
adhesion properties.
[0008] WO 03/035013 and WO 03/013444 disclose self-etching,
self-conditioning dental adhesives based on (meth)acrylamides
containing acid groups, with monomers containing sulfonic acid and
phosphonic acid groups being preferred. These compounds can be
obtained synthetically only with difficulty.
[0009] Curable compositions are known from DE 0 333 503 A2 which
contain filler which has been treated with polymerizable organic
phosphoric- or phosphonic acid compounds. The compositions can
additionally contain acid monomers.
[0010] The object of the invention is to provide a dental material
which can be cured by means of radical polymerization, at the same
time showing a high polymerization tendency, which is insensitive
to hydrolysis in the presence of water at room temperature and is
thus storage-stable and capable of etching the hard tooth
substance.
[0011] The object is achieved according to the invention by
polymerizable dental materials which contain at least one
(meth)acrylamide phosphate of the following general formula (I) or
a pyrophosphate thereof:
##STR00004##
in which [0012] R.sup.1 is H or CH.sub.3; [0013] R.sup.2 is H or a
C.sub.1-C.sub.4 alkyl radical or forms together with the nitrogen
atom to which it is bonded and one or more atoms which belong to
R.sup.3 or R.sup.3' a heterocyclic ring; [0014] R.sup.3, R.sup.3'
independently of each other are a linear or branched aliphatic
C.sub.1-C.sub.50 radical with a valency of m+n or p+n, an aromatic
C.sub.6-C.sub.18 radical with a valency of m+n or p+n, or a
cycloaliphatic, araliphatic or heterocyclic C.sub.3-C.sub.18
radical with a valency of m+n or p+n, wherein the carbon chains of
the radical or radicals can be interrupted by O, S, CONR.sup.4,
OCONH, or form together with one or more atoms which belong to
R.sup.2 and the nitrogen atom to which R.sup.2 is bonded a
heterocyclic ring, R.sup.3' being H if p=0, and wherein [0015]
R.sup.4 is H, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.12 aryl,
C.sub.6-C.sub.10 aralkyl or a bicyclic C.sub.4-C.sub.12 radical;
[0016] n is 1, 2, 3 or 4 if p=00, and [0017] is 1 or 2 if
p.noteq.0; [0018] m is 1, 2, 3 or 4; [0019] p is 0, 1, 2, 3 or 4;
[0020] x is 0 or S. [0021] R.sup.2 is preferably different from
H.
[0022] By araliphatic or aralkyl radicals is meant groups which
contain both aromatic and aliphatic radicals. A typical example of
an araliphatic radical is the benzylene radical -Ph-CH.sub.2--
which comprises an aromatic phenylene group and an aliphatic
methylene radical.
[0023] By carbon chain which is interrupted by other groups and/or
atoms is to be understood that these other groups or atoms are
inserted into the carbon chain, i.e. are bonded by carbon atoms on
both sides. These groups or atoms cannot therefore assume a
terminal position. If several groups or atoms are integrated into a
carbon chain, they must in each case be separated from one another
by at least one carbon atom. "Carbon chain" does not mean cyclic
molecule groups. The total number of groups and/or atoms which are
integrated into the carbon chain is smaller by at least the value 1
than the number of carbon atoms in the chain.
[0024] The variables of the above formula (I) can have the
following preferred meanings independently of one another: [0025]
R.sup.1=H and/or CH.sub.3, wherein in the case m>1 the R.sup.1
radicals can have different meanings; [0026] R.sup.2=H or a
C.sub.1-C.sub.20 alkyl radical or R.sup.2 forms together with the
nitrogen atom to which it is bonded and one or more atoms which
belong to R.sup.3 or R.sup.3' a heterocyclic ring, preferably a
ring with one nitrogen atom and 4 to 7 carbon atoms, in particular
a piperidinyl ring; [0027] R.sup.3, R.sup.3'=independently of each
other a linear or branched aliphatic C.sub.1-C.sub.10 radical with
a valency of m+n or n+p, an aromatic C.sub.6-C.sub.10 radical with
a valency of m+n or n+p, or a cycloaliphatic C.sub.5-C.sub.8
radical or a araliphatic C.sub.6-C.sub.12 radical with a valency of
m+n or n+p, wherein the carbon chains of the radical or radicals
can be interrupted by 0, or R.sup.3 and/or R.sup.3' form together
with one or more atoms which belong to R.sup.2 and the nitrogen
atom to which R.sup.2 is bonded a heterocyclic ring, preferably a
ring with one nitrogen atom and 4 to 7 carbon atoms, in particular
a piperidinyl ring, R.sup.3' being H if p=0; [0028] R.sup.4=H,
C.sub.1-C.sub.6 alkyl, C.sub.6 aryl; [0029] n=1 or 2 if p=0, and
[0030] =1 if p 0; [0031] m=1 or 2; [0032] p=0, 1 or 2; [0033]
x=O.
[0034] Quite particularly preferred meanings of the variables of
the above formula (I) are: [0035] R.sup.1=H or CH.sub.3; [0036]
R.sup.2=H or a C.sub.1-C.sub.3 alkyl radical or R.sup.2 forms
together with the nitrogen atom to which it is bonded and one or
more atoms which belong to R.sup.3 a piperidinyl ring; [0037]
R.sup.3=a linear or branched aliphatic C.sub.1-C.sub.3 radical with
a valency of m+n, or R.sup.3 forms together with one or more atoms
which belong to R.sup.2 and the nitrogen atom to which R.sup.2 is
bonded a piperidinyl ring, quite particularly preferably a C.sub.3
alkylene radical; [0038] R.sup.3'=H; [0039] R.sup.4=H,
C.sub.1-C.sub.3 alkyl; [0040] n=1; [0041] m=1 or 2; [0042] p=0;
[0043] x=O.
[0044] Compounds of formula (I), in which several and in particular
all variables have one of the preferred and in particular of the
particularly preferred meanings are particularly suitable according
to the invention.
[0045] The (meth)acrylamide phosphates according to the invention
of general formula (I) (p=0; R.sup.3'=H; n=1) can for example be
prepared in 3 stages starting from reactive (meth)acrylic acid
derivatives (chloride, anhydride, ester, acid) and aminoalkanols.
Reactive (meth)acrylic acid derivatives and monoaminoalkanols are
commercially available. Polyaminoalcohols (m>1, R.sup.2=alkyl,
aryl etc.) are obtained e.g. by reaction of polyhalogen alcohols
with a large excess of an aliphatic or aromatic amine (B. J. Gaj
and D. R. Moore, Tetrahedron Lett. 23 (1967) 2155).
##STR00005##
Specific example:
##STR00006##
[0046] Moreover, diaminoalcohols (m=2, n=1, R.sup.2=alkyl, aryl
etc.) can be obtained by reaction of aliphatic or aromatic amines
with epichlorohydrin (B. J. Gaj and D. R. Moore, Tetrahedron Lett.
23 (1967) 2155).
Specific example:
##STR00007##
[0047] A possibility for the preparation of polyaminopolyols
(m,n>1) is the reaction of polyamines with epoxides.
Specific example:
##STR00008##
[0048] In the 1st reaction stage a reactive (meth)acrylic acid
derivative (R.sup.1.dbd.H, CH.sub.3; R'=Hal,
O--CO--CR.sup.1.dbd.CH.sub.2, Oalkyl, OH) is reacted with
aminoalkanols using the methods known from organic chemistry for
the linking of amide bonds (cf. Methoden der Organischen Chemie,
HOUBEN-WEYL Volume E5 1985, Georg Thieme Verlag pages 941 ff.) to
produce (meth)acrylamidoalcohols.
##STR00009##
[0049] For this purpose in the case m=n=1 the reactive
(meth)acrylic acid derivative is reacted with primary
(R.sup.2.dbd.H) or secondary (R.sup.2=alkyl, aryl)
monoaminoalkanols, in the case m>1, n=1 with primary
(R.sup.2.dbd.H) or secondary (R.sup.2=alkyl, aryl)
polyaminoalkanols, in the case m=1, n>1 with primary
(R.sup.2.dbd.H) or secondary (R.sup.2=alkyl, aryl)aminopolyols and
in the case m>1, n>1 with primary (R.sup.2.dbd.H) or
secondary (R.sup.2=alkyl, aryl) polyaminopolyols.
[0050] The corresponding acid chlorides are preferably used in the
presence of equimolar quantities of base.
Specific example:
##STR00010##
[0051] In the 2nd stage the (meth)acrylamidoalcohols are reacted
with n equivalents of a phosphoryl compound, preferably dimethyl
chlorophosphate (R.sup.5.dbd.CH.sub.3) (Y. Xu., G. D. Prestwich, J.
Org. Chem. 67 (2002) 7158).
##STR00011##
Specific example:
##STR00012##
[0052] In the 3rd stage the selective hydrolysis of the alkoxy
groups OR.sup.5 takes place, a dimethyl phosphate
(R.sup.5.dbd.CH.sub.3) preferably being used in which the
splitting-off is carried out with bromotrimethylsilane (Y. Xu., G.
D. Prestwich, J. Org. Chem. 67 (2002) 7158).
##STR00013##
Specific example:
##STR00014##
[0053] Preferred examples of the (meth)acrylamide phosphates
according to the invention of the formula (I) are:
##STR00015## ##STR00016## ##STR00017##
[0054] The (meth)acrylamide phosphates according to the invention
of formula (I) are strongly acid and very well soluble in water or
mixtures of water with polar solvents, such as acetone, ethanol,
acetonitrile or tetrahydrofuran (THF). They are capable of etching
enamel and dentine comparably with phosphoric acid.
[0055] The (meth)acrylamide phosphates of formula (I) are
hydrolysis-stable under aqueously acid conditions at room
temperature over a long period. In the context of the present
invention compounds are described as hydrolysis-stable which are
stable in water or in mixtures of water and water-miscible solvents
at a concentration of approximately 20 wt.-% and a pH value of
approximately 2.0 at 37.degree. C. for at least 6 weeks, i.e.
hydrolyze less than 10%, preferably less than 5%.
[0056] Because of the high hydrolysis stability of the
(meth)acrylamide phosphates according to the invention, mixtures
with water and other hydrolysis-stable components can be prepared
therefrom which are storage-stable at room temperature. These
mixtures show, depending on the structure and concentration of the
(meth)acrylamide phosphates of formula (I), a pH value which lies
between approximately 0.5 and 3.0 and are therefore capable of
etching the surface of the hard tooth substance (enamel and
dentine). These mixtures are therefore suitable in particular as
adhesives or cements for the dental field, quite particularly as
self-etching enamel-dentine adhesives. (Meth)acrylamide phosphates
which contain three (m+p=3) and quite particularly preferably two
polymerizable (meth)acrylamide groups (m+p=2) are particularly
advantageous.
[0057] The dental materials according to the invention preferably
also contain in addition to the (meth)acrylamide phosphates of
formula (I) a solvent, particularly preferably water or a mixture
of water and a water-miscible solvent. Preferred water-miscible
solvents are polar solvents such as acetone, ethanol, acetonitrile,
tetrahydrofuran (THF) and mixtures thereof.
[0058] Moreover, the dental materials according to the invention
can also contain one or more non-acid, radically polymerizable
monomers, such as mono- or preferably multi-functional (meth)acryl
compounds. By mono-functional (meth)acryl compounds is meant
compounds with one, by multi-functional (meth)acryl compounds,
compounds with two or more, preferably 2 to 3 (meth)acryl
groups.
[0059] Preferred monofunctional (meth)acryl compounds are
hydrolysis-stable mono(meth)acrylates, e.g. mesityl(meth)acrylate,
or 2-(alkoxymethyl)acrylic acids, e.g. 2-(ethoxymethyl)acrylic
acid, 2-(hydroxymethyl)acrylic acid, N-mono or N-disubstituted
acrylamides, such as e.g. N-ethylacrylamide,
N,N-dimethylacrylamide, N-(2-hydroxyethyl)acrylamide or
N-methyl-N-(2-hydroxyethyl)acrylamide, N-monosubstituted
methacrylamides, such as e.g. N-ethylmethacrylamide or
N-(2-hydroxyethyl)methacrylamide, and also N-vinylpyrrolidone or
allyl ethers and mixtures of these substances. The above-named
monomers are liquid at room temperature or low-melting, i.e. they
have a melting point of less than 60.degree. C., and can therefore
be used as diluents.
[0060] Preferred multi-functional (meth)acrylates are e.g.
hydrolysis-stable urethanes from 2-(hydroxymethyl)acrylic acid and
diisocyanates, such as 2,2,4-trimethylhexamethylene diisocyanate or
isophorone diisocyanate, cross-linking pyrrolidones, such as e.g.
1,6-bis(3-vinyl-2-pyrrolidonyl)-hexane, or bisacrylamides, such as
methylene or ethylene bisacrylamide, or bis(meth)acrylamides, such
as e.g. N,N'-diethyl-1,3-bis(acrylamido)-propane,
1,3-bis(methacrylamido)-propane, 1,4-bis(acrylamido)-butane or
1,4-bis(acryloyl)-piperazine, which can be synthesized by reaction
from the corresponding diamines with (meth)acrylic acid chloride.
The remaining compounds are mostly commercially available.
Multi-functional (meth)acrylates act as cross-linkers during
polymerization because of the number of polymerizable groups.
Mixtures of these substances and mixtures with monofunctional
(meth)acrylates are also suitable.
[0061] In order to initiate the radical polymerization the dental
materials preferably contain an initiator, particularly preferably
a photoinitiator.
[0062] Benzophenone, benzoin and their derivatives or
.alpha.-diketones or their derivatives such as
9,10-phenanthrenequinone, 1-phenyl-propan-1,2-dione, diacetyl or
4,4-dichlorobenzil are preferably used as photoinitiators.
Camphorquinone and 2,2-methoxy-2-phenyl-acetophenone and in
particular .alpha.-diketones are particularly preferably used in
combination with amines as reductants, such as e.g.
4-(dimethylamino)-benzoic acid esters,
N,N-dimethylaminoethylmethacrylate, N,N-dimethyl-sym.-xylidine or
triethanolamine.
[0063] Redox-initiator combinations, such as e.g. combinations of
benzoylperoxide with N,N-dimethylsym.-xylidine or
N,N-dimethyl-p-toluidine are used as initiators for a
polymerization carried out at room temperature. In addition, redox
systems consisting of peroxides and reductants such as e.g.
ascorbic acid, barbiturates or sulfinic acids are also particularly
suitable.
[0064] Moreover, the dental materials according to the invention
can be filled with organic or inorganic particles in order to
improve the mechanical properties or adjust the viscosity.
Preferred inorganic particulate fillers are amorphous spherical
oxide-based materials, such as ZrO.sub.2 and TiO.sub.2 as well as
mixed oxides of SiO.sub.2, ZrO.sub.2 and/or TiO.sub.2,
nanoparticulate or microfine fillers, such as pyrogenic silicic
acid or precipitation silicic acid as well as minifillers, such as
quartz, glass ceramic or glass powder with an average particle size
of 0.01 to 1 .mu.m and X-ray-opaque fillers, such as ytterbium
trifluoride or nanoparticulate tantalum(V)-oxide or barium
sulfate.
[0065] Dental materials for use as enamel-dentine adhesives
preferably contain as fillers nanoparticulate (primary particle
diameters from 1 to 100 nm) amorphous spherical materials based on
oxides, such as ZrO.sub.2 and TiO.sub.2 or mixed oxides of
SiO.sub.2, pyrogenic silicic acid or precipitated silica, ZrO.sub.2
and/or TiO.sub.2 and also X-ray-opaque nanoparticulate fillers,
such as ytterbium trifluoride, tantalum(V)-oxide or barium
sulfate.
[0066] In order to obtain the self-conditioning effect of the
(meth)acrylamide phosphates of Formula (I) used according to the
invention, it is essential that the (meth)acrylamide phosphates are
not applied to the filler, as the phosphoric acid groups are bonded
by the filler surface in the process.
[0067] In addition, the compounds according to the invention can
contain further additives, such as e.g. stabilizers, flavours,
microbiocidal agents, fluoride ion-releasing additives, optical
whitening agents, plasticizers or UV absorbers.
[0068] The (meth)acrylamide phosphates of Formula (I) are
particularly suitable for the preparation of dental materials, in
particular adhesives, coating materials and composites for dental
purposes.
[0069] The (meth)acrylamide phosphates of Formula (I) are quite
particularly suitable for the preparation of dental adhesives and
self-adhesive fixing cements, in particular for the preparation of
enamel-dentine adhesives. Such adhesives and cements are
characterized by a very good adhesion to the hard tooth substance
and are hydrolysis-stable under moist conditions.
[0070] According to the invention, dental materials which contain
the following components are particularly preferred: [0071] a) 0.5
to 95 wt.-%, preferably 10 to 60 wt.-% and particularly preferably
15 to 50 wt.-% (meth)acrylamide phosphate according to Formula (I),
[0072] b) 0.01 to 15 wt.-%, particularly preferably 0.1 to 8.0
wt.-% initiator for the radical polymerization, [0073] c) 0 to 80
wt.-%, preferably 0 to 60 wt.-% and particularly preferably 10 to
50 wt.-% non-acid monomer, [0074] d) 0 to 95 wt.-%, preferably 0 to
80 wt.-% and particularly preferably 20 to 60 wt.-% solvent, [0075]
e) 0 to 20 wt.-% filler.
[0076] The quantity of filler depends particularly on the desired
application of the dental material. For the application as
adhesive, 0 to 20 wt.-%, and for the application as cement 20 to 75
wt.-%, filler is preferred.
[0077] Other additives and adjuvants are optionally used in a
quantity of 0.01 to 10 wt.-%.
[0078] Unless otherwise indicated all percentages relate to the
total mass of the material.
[0079] The invention is explained in more detail below with
reference to examples.
EXAMPLES
Example 1
Phosphoric acid mono-(1-acryloyl-piperidin-4-yl)-ester (APP)
##STR00018##
[0080] 1st Stage: 1-(4-hydroxy-piperidin-1-yl)-propenone
[0081] 10.11 g (0.10 mol) of 4-hydroxypiperidine was dissolved in
60 ml of 2M NaOH. The solution was stirred at room temperature for
10 minutes and then cooled to 0.degree. C. A solution of 9.96 g
(0.11 mol) of acrylic acid chloride and 20 mg of
2,6-di-tert.-butyl-4-methylphenol (BHT) in 60 ml of chloroform was
added dropwise within 2 hours at 0.degree. C. After the addition
was completed, the clear, yellow reaction mixture was stirred at
0.degree. C. for 1 hour, then the ice bath was removed and the
mixture stirred at room temperature for another 3 hours. Organic
and aqueous phases were separated. The aqueous phase was saturated
with NaCl and extracted with 5.times.100 ml of chloroform. The
combined organic phases were dried over Na.sub.2SO.sub.4, filtered,
concentrated in a rotary evaporator after addition of 20 mg of BHT
and dried in a fine vacuum. The yellowish oil was taken up in 5 ml
of ethyl acetate and purified by means of column chromatography
(silica gel 60, 0.035-0.070 mm, ethyl acetate). The solvent was
concentrated in a rotary evaporator after addition of 25 mg of BHT
and dried in a fine vacuum. 4.35 g (28.0 mmol, 28%) of a yellowish
oil was obtained which set to form a yellowish solid when stored in
a refrigerator.
[0082] .sup.1H NMR (CDCl.sub.3, 400 MHz): .delta.=1.47-1.63 (m; 2H;
CH.sub.2), 1-82-1.96 (m; 2H; CH.sub.2), 3.22-3.88 (m; 2H;
CH.sub.2), 3.77-3.88 (m; 1; CH), 3.88-3.98 (m; 2H; CH.sub.2),
3.98-4.16 (m; 1; OH), 5.68-5.70 (dd, J=1.7 Hz, 10.8 Hz; 1H;
.dbd.CH), 6.20-6.24 (dd, J=2.0 Hz, 16.6 Hz; 1H; .dbd.CH), 6.56-6.63
(dd, J=10.6 Hz, 16.8 Hz; 1H; .dbd.CH).
[0083] .sup.13C NMR (CDCl.sub.3, 100 MHz): .delta.=33.7 (CH.sub.2),
34.5 (CH.sub.2), 39.5 (CH.sub.2), 43.2 (CH.sub.2), 66.5 (CH), 127.7
(CH.sub.2), 127.8 (CH), 165.5 (C).
2nd Stage: Phosphoric
acid(1-acryloyl-piperidin-4-yl)ester-dimethylester
[0084] 2.60 g (18.0 mmol) of dimethyl chlorophosphate, 2.33 g (15.0
mmol) of 1-(4-hydroxy-piperidin-1-yl)-propenone, 10 mg of
hydroquinone monomethyl ether (MEHQ) and 10 mg of BHT were
dissolved under argon in 50 ml of dichloromethane and cooled to
-5.degree. C. in an ice bath. 2.36 g (21.0 mmol) of
potassium-tert.-butylate was added accompanied by stirring.
Stirring was carried out for 30 minutes accompanied by cooling in
ice, the solution turning a brownish colour, then the ice bath was
removed and the mixture stirred at room temperature for 4 hours. 50
ml of a saturated aqueous NH.sub.4Cl solution was then added. The
mixture was stirred for 10 minutes, then the phases were separated.
The aqueous phase was extracted with 2.times.50 ml of
dichloromethane. The combined organic phases were dried over
Na.sub.2SO.sub.4, filtered, concentrated in a rotary evaporator
after addition of 20 mg of BHT and dried in a fine vacuum. The
brown oil was taken up in 5 ml of dichloromethane and purified by
means of column chromatography (silica gel 60, 0.035-0.070 mm,
methylene chloride/ethanol 98:2). The eluent was concentrated in a
rotary evaporator after addition of 20 mg of BHT and dried in a
fine vacuum. 3.02 g (11.5 mmol, 76%) of a red-brown oil was
obtained.
TABLE-US-00001 C.sub.10H.sub.18NO.sub.5P Calc. C 45.63 H 6.89 N
5.32 (263.23) Found 43.12 7.19 4.96
[0085] IR: 3475 (w), 2956 (w, C--H), 1642 (s, C.dbd.O), 1608 (s,
C.dbd.C), 1441 (s, C--H), 1366 (w), 1258 (s, P.dbd.O), 1219 (m),
1188 (m), 1000 (vs), 893 (m), 847 (s), 791 (m), 766 (m).
[0086] .sup.1H NMR (CDCl.sub.3, 400 MHz): .delta.=1.73-1.87 (m; 2H;
CH.sub.2), 1-92-2.03 (m; 2H; CH.sub.2), 3.40-3.64 (m; 2H;
CH.sub.2), 3.78 (d, J=11.1 Hz; 6H; O--CH.sub.3), 3.81-3.94 (m; 2H;
CH.sub.2), 4.59-4.70 (m; 1; CH), 5.59 (dd, J=2.0 Hz, 10.6 Hz; 1H;
.dbd.CH), 6.25 (dd, J=2.0 Hz, 16.6 Hz; 1H; .dbd.CH), 6.61 (dd,
J=10.6 Hz, 16.9 Hz; 1H; .dbd.CH).
[0087] .sup.13C NMR (CDCl.sub.3, 100 MHz): .delta.=31.8, 32.8
(CH.sub.2), 38.6 (CH.sub.2), 42.4 (CH.sub.2), 54.3, 54.3
(CH.sub.2), 73.7, 73.7 (CH), 127.6 (CH), 127.8 (CH.sub.2), 165.4
(C).
[0088] .sup.31P NMR (CDCl.sub.3, 162 MHz): .delta.=1.4.
3rd Stage: Phosphoric acid
mono-(1-acryloyl-piperidin-4-yl)ester
[0089] 1.32 g (5.0 mmol) of phosphoric acid
dimethyl-[4-(N-acryloyl-piperidyl]ester and 10 mg of BHT were
dissolved under argon in 5 ml of dichloromethane. 1.68 g (11.0
mmol) of bromotrimethylsilane was added dropwise. The clear
yellowish solution was stirred for 4 hours at room temperature
after the addition was completed. For the removal of volatile
components, the solution was evacuated at 45.degree. C. for 45
minutes. The oily yellow residue was mixed with 5 ml of methanol.
The clear yellowish solution was stirred for 18 hours at room
temperature and then concentrated in a rotary evaporator and dried
in a fine vacuum. The highly viscous yellowish oil was mixed with
10 ml of dichloromethane and stirred at room temperature. A light
yellowish solid formed. This was filtered off and dried in a vacuum
drying cabinet. The process was repeated with 10 ml each of ethyl
acetate and acetone. The white solid was mixed with 5 ml of
i-propanol and stirred at room temperature for 18 hours. The
suspension was filtered, and the filtrate was concentrated in a
rotary evaporator and dried in a fine vacuum. 0.31 g (1.3 mmol;
26%) of a white solid was obtained.
[0090] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): .delta.=1.46-1.64 (m;
2H; CH.sub.2), 1.77-1.95 (m; 2H; CH.sub.2), 3.24-3.47 (m; 2H;
CH.sub.2), 3.69-3.87 (m; 2H; N--CH.sub.2), 4.31-4.43 (m; 1H;
O--CH), 5.66 (dd, J=2.5 Hz, 10.5 Hz; 1H; .dbd.CH), 6.09 (dd, J=2.5
Hz, 16.7 Hz; 1H; .dbd.CH), 6.80 (dd, J=10.6 Hz, 16.7 Hz; 1H;
.dbd.CH).
[0091] .sup.31P NMR (DMSO-d.sub.6, 162 MHz): .delta.=-0.6.
Example 2
1,3-bis-(N-acryloyl-N-propyl-amino)-propan-2-yl-dihydrogen
phosphate (BAPAPP)
##STR00019##
[0092] 1st Stage:
1,3-bis-(N-acryloyl-N-propyl-amino)-2-hydroxypropane
[0093] 17.43 g (0.100 mol) of 1,3-bis-(propylamino-propan-2-ol was
mixed with 110 ml (0.220 mol) of 2N caustic soda solution and
stirred at room temperature for 10 minutes. The mixture was cooled
to 0.degree. C. A solution of 19.46 g (0.215 mol) of acrylic acid
chloride and 20 mg of BHT in 120 ml of chloroform was added
dropwise at 0.degree. C. within 3 hours 30 minutes. After the
addition was completed the reaction mixture was stirred at
0.degree. C. for 2 hours 30 minutes. Organic and aqueous phases
were separated. The aqueous phase was saturated with NaCl and
extracted with 5.times.80 ml of methylene chloride. The combined
organic phases were dried over Na.sub.2SO.sub.4, filtered,
concentrated in a rotary evaporator after addition of 20 mg of BHT
and dried in a fine vacuum. The raw product was purified by means
of two-fold column chromatography (silica gel 60, 0.035-0.070 mm,
ethyl acetate). 11.92 g (42.2 mmol; 42%) of the pure product was
obtained as a yellowish oil.
TABLE-US-00002 C.sub.15H.sub.26N.sub.2O.sub.3 Calc. C 63.80 H 9.28
N 9.92 (282.39) Found 63.54 9.16 9.67
[0094] IR: 3349 (m, --OH), 2963 (m), 2933 (m), 2875 (m, C--H), 1641
(vs, C.dbd.O), 1603 (vs, C.dbd.C), 1427 (vs, C--H), 1370 (m,
--O--H), 1271 (w), 1229 (s), 1132 (m, --C--OH), 1059 (m), 977 (s),
957 (m), 895 (w), 794 (s), 745 (m).
[0095] .sup.1H NMR (CDCl.sub.3, 400 MHz): .delta.=0.86-0.93 (m; 6H;
CH.sub.3), 1.57-1.68 (m; 4H; CH.sub.2--CH.sub.3), 3.25-3.53 (m; 8H;
CH.sub.2--N), 4.06-4.09 (m; 1H; CH), 4.96-4.99 (m; 1H; OH),
5.62-5.74 (m; 2H; .dbd.CH), 6.25-6.38 (m; 2H; .dbd.CH), 6.54-7.00
(m; 2H; .dbd.CH).
[0096] .sup.13C NMR (CDCl.sub.3, 100 MHz): .delta.=11.1 (CH.sub.3),
11.4 (CH.sub.3), 20.6 (CH.sub.2), 22.5 (CH.sub.2), 22.6 (CH.sub.2),
48.8 (CH.sub.2), 51.4 (CH.sub.2), 51.6 (CH.sub.2), 51.9 (CH.sub.2),
52.0 (CH.sub.2), 70.0 (CH), 71.7 (CH), 127.2 (CH), 127.3 (CH),
127.6 (CH.sub.2), 128.4 (CH), 128.5 (CH.sub.2), 128.7 (CH.sub.2),
167.8 (C).
2nd Stage: 1,3-bis-(N-acryloyl-N-propyl-amino)-propan-2-yl
dimethylphosphate
[0097] 2.60 g (18.0 mmol) of dimethylchlorophosphate, 4.24 g (15.0
mmol) of 1,3-bis-(N-acryloyl-N-propyl-amino)-2-hydroxypropane, 20
mg of MEHQ and 20 mg of BHT were dissolved under argon in 80 ml of
dichloromethane and cooled to -5.degree. C. in an ice bath. 2.36 g
(21.0 mmol) of potassium-tert.-butylate was added accompanied by
stirring. The mixture was ice-cooled and stirred for 30 minutes,
the solution turning a slightly yellowish colour, then the ice bath
was removed, and the mixture was stirred at room temperature for 4
hours. Then 80 ml of saturated aqueous NH.sub.4Cl solution was
added. The mixture was stirred for 10 minutes, then the phases were
separated. The aqueous phase was extracted with 2.times.80 ml of
dichloromethane. The combined organic phases were dried over
Na.sub.2SO.sub.4, filtered, concentrated in a rotary evaporator
after addition of 30 mg BHT and dried in a fine vacuum. The raw
product was purified by means of column chromatography (silica gel
60, 0.035-0.070 mm), ethyl acetate/acetone 90:10.fwdarw.80:20).
2.74 g (11.6 mmol; 50%) of a yellowish oil was obtained.
3rd Stage: 1,3-bis-(N-acryloyl-N-propyl-amino)-propan-2-yl
dihydrogen phosphate
[0098] 1.17 g (3.0 mmol) of
1,3-bis-(N-acryloyl-N-propyl-amino)-propan-2-yl dimethylphosphate
and 10 mg of BHT were dissolved under argon in 5 ml of
dichloromethane. 1.01 g (6.6 mmol) of bromotrimethylsilane was
added dropwise. The clear yellowish solution was stirred at room
temperature for 3 hours after the addition was completed. In order
to remove volatile components the solution was evacuated for 45
minutes at 45.degree. C. The oily yellow residue was mixed with 5
ml of methanol, and the clear yellowish solution was stirred at
room temperature for 18 hours. The solution was concentrated in a
rotary evaporator and dried in a fine vacuum. 1.21 g (3.3 mmol;
111%) of a slightly yellowish foam was obtained.
Example 3
Examination of the hydrolysis stability of the phosphoric acid
mono-(1-acryloyl-piperidin-4-yl) ester
[0099] A 20% solution of the phosphoric acid
mono-(1-acryloyl-piperidin-4-yl) ester from Example 1 stabilized
with 200 ppm of 2,6-di-t-butyl-4-methylphenol in
D.sub.2O/EtOH-d.sub.6 (1:1) was prepared, this was stored at
37.degree. C. and examined by .sup.1H-NMR spectroscopy. After a
storage time of 3 months no changes in the .sup.1H-NMR spectrum
were found.
Example 4
Preparation of a Light-Curing Adhesive Based on (Meth)Acrylamide
phosphates (MAP)
[0100] In order to examine dentine adhesion to bovine teeth
dentine, adhesives with the following composition were prepared
(values in wt.-%).
TABLE-US-00003 Adhesion MAP Comonomers H.sub.2O Initiator values
[wt.-%] [wt.-%] [wt.-%] [wt.-%] [MPa] 14.6 BAPAPP.sup.1) A.sup.2):
9.7; B.sup.3): 2.1; 25.0% 1.0% 10.7 .+-. 2.6 C.sup.4): 47.6 14.3
APP.sup.5) C: 45.1; D.sup.6): 9.1; 12.8% 1.0% 11.9 .+-. 5.4
E.sup.7): 5.3; F.sup.8): 12.4 .sup.1)BAPAPP = monomer from Example
2 .sup.2)A = [1-(methacryloylamino)propyl]-phosphonic acid .sup.3)B
= 6-(N-acryloylamino)hexan-1-ol .sup.4)C =
N,N'-diethyl-1,3-propylene-bisacrylamide .sup.5)APP = monomer from
Example 1 .sup.6)D = D,L-2-(acryloylamino)succinic acid .sup.7)E =
N-(5-hydroxy-pentyl)methacrylamide .sup.8)F = Aerosil-H.sub.2O
mixture
[0101] Bovine teeth were embedded in plastic cylinders such that
the dentine and the plastic were situated at one level. After
grinding of the testpieces, a layer of adhesive of the above
formulation was rubbed into the dentine surface with a microbrush
for 30 seconds, gently blown with an air blower and lit with an
Astralis 7 photopolymerization lamp (Ivoclar Vivadent AG) for 20
seconds. A commercially available dental filling composite
(Tetric.RTM. Ceram, Ivoclar Vivadent AG) was then applied to the
adhesive layer and cured for 40 seconds with the Astralis 7 lamp.
The testpieces were then stored in water for 24 hours at 37.degree.
C. and the adhesive shear strength measured in accordance with the
ISO guideline "ISO 1994-ISO TR 11405: Dental Materials Guidance on
Testing of Adhesion to Tooth Structure".
[0102] Although preferred embodiments have been depicted and
described in detail herein, it will be apparent to those skilled in
the relevant art that various modifications, additions,
substitutions, and the like can be made without departing from the
spirit of the invention and these are therefore considered to be
within the scope of the invention as defined in the claims which
follow.
* * * * *