Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K6/00—Preparations for dentistry
  • A61K6/40—Primers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K6/00—Preparations for dentistry
  • A61K6/30—Compositions for temporarily or permanently fixing teeth or palates, e.g. primers for dental adhesives

Definitions

• the present invention relates to a one-part self-etching, self-priming dental adhesive having improved storage stability and low toxicity. Moreover, the present invention also relates to the use of a specific thermal polymerisation inhibitor in a one-part self-etching, self-priming dental adhesive having a pH of at most 2.
• One-part self-etching, self-priming dental adhesive compositions known from the prior art typically contain a mixture of an acid, a polymerizable monomer and an initiator system in a suitable solvent.
• the acidity of the mixture must be adapted to provide sufficient etching activity on dentin and enamel surfaces.
• an increased acidity leads to a complex stability problem due to the activation of chemical bonds of the functional components of the mixture.
• ester bonds present in the polymerizable monomers may be solved under acid catalysis.
• the initiator system may be activated in the acidic medium leading to premature polymerization of the mixture.
• the storage stability at room temperature of commercial one-part self-etching, self-priming dental adhesive compositions known from the prior art may be insufficient. Accordingly, conventional commercial one-part self-etching, self-priming dental adhesive compositions must be stored in a refrigerator in order to avoid deterioration by solvolysis or polymerization.
• the commercial composition “iBond Gluma inside” may be mentioned, which has a low thermal stability when stored at temperatures of 37° C. or 50° C. due to premature polymerization within less than two weeks, which is indicative of an insufficient thermal stability at room temperature for all practical purposes.
• EP-A 1 548 021 suggests hydrolysis stable one-part self-etching, self-priming dental adhesive compositions containing specific monomers having improved resistance against hydrolysis under acidic conditions.
• EP-A 1 548 021 suggests a stabilizer such as hydroquinone monomethylether, 2,6-di-tert.-butyl-p-cresol, tetramethyl piperidine N-oxyl radical and galvanoxyl radical.
• generic one-part self-etching, self-priming dental adhesive composition known from EP-A 1 548 021 still require improvement of the thermal stability at storage for attaining a stability of at least 10 days at 60° C. required.
• hydroquinone is an allergenic compound imparting undesirable toxic properties to a dental adhesive composition.
• the present invention provides a one-part self-etching, self-priming dental adhesive having a pH of at most 2, which comprises an aqueous mixture containing
• the present invention is based on the recognition that an aqueous mixture containing one or more polymerizable monomers optionally containing an acidic group, one or more organic or inorganic acids, and a polymerization initiator is particularity problematic with regard to polymerization whereby conventional stabilizers such as hydroquinone monomethylether, 2,6-di-tert.-butyl-p-cresol, tetramethyl piperidine N-oxyl radical and galvanoxyl radical provide an insufficient effect for attaining a high storage stability.
• conventional stabilizers such as hydroquinone monomethylether, 2,6-di-tert.-butyl-p-cresol, tetramethyl piperidine N-oxyl radical and galvanoxyl radical provide an insufficient effect for attaining a high storage stability.
• the present invention is furthermore based on the recognition that a specific class of water insoluble stabilizers provides a surprising stabilizing effect in an acidic aqueous mixture so that a one-part self-etching, self-priming dental adhesive having a pH of at most 2 may be provided which has an excellent storage stability due to an improved resistance against premature polymerization.
• the present invention also relates to the of a thermal polymerisation inhibitor of formula (I) in a one-part self-etching, self-priming dental adhesive having a pH of at most 2.
• the dental adhesive composition according to the present invention contains a water-insoluble thermal polymerisation inhibitor of formula (I).
• the saturated hydrocarbon group which may be present as R′ 1 or R′ 2 in formula (I) represents a straight chain or branched C 1-18 , alkyl group or a C 3-8 cycloalkyl group optionally substituted by one or more C 1-5 alkyl groups or a C 4-18 cycloalkylalkyl group optionally substituted by one or more C 1-5 alkyl groups.
• R′ 1 represents a straight chain or branched C 1-18 alkyl group.
• R′ 1 is hydrogen or a tert.-butyl group.
• R′ 2 in formula (I) is believed to provide a steric effect due to the bulky nature of the substituent in this position. Therefore, at least one R′ 2 in formula (I) is a saturated hydrocarbon group having 1 to 18 carbon atoms. Accordingly, in a specific embodiment, at least one R′ 2 in formula (I) represents a branched C 3-18 alkyl group or a C 3-18 cycloalkyl group optionally substituted by one or more C 1-5 alkyl groups or a C 4-18 cycloalkylalkyl group optionally substituted by one or more C 1-5 alkyl groups.
• At least one R′ 2 in formula (I) preferably represents a branched C 3-18 alkyl group or a C 3-18 cycloalkyl group optionally substituted by one or more C 1-5 alkyl groups. Even more specifically, at least one R′ 2 in formula (I) preferably represents a branched C 3-18 alkyl group. In a further preferred embodiment, R′ 2 is a tert.-butyl group.
• c represents an integer of from 1 to 4, preferably 1 or 2. In a specific embodiment, c is 1.
• the inhibitor is tert.-butyl hydroquinone (TBHQ) or tert.-butyl hydroxyanisole (BHA).
• TBHQ tert.-butyl hydroquinone
• BHA tert.-butyl hydroxyanisole
• the inhibitor is contained in the dental adhesive composition in an amount of from 0.01 to 0.5 mol %, more preferably in an amount of from 0.05 to 0.3 mol %.
• the present invention provides a one-part self-etching, self-priming dental adhesive having a pH of at most 2, which comprises an aqueous mixture containing
• the dental adhesive composition according to the present invention contains a polymerizable monomers optionally containing an acidic group.
• the polymerizable monomer is a polymerizable acidic phosphoric acid ester monomer of the following formula (A):
• Z 1 is COOR 10 , COSR 20 , CON(R 10 ) 2 , CONR 10 R 20 , or CONHR 10 , wherein R 10 and R 20 independently represent a hydrogen atom, a C 1-18 alkyl group optionally substituted by a C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 4-18 , aryl or heteroaryl group, an optionally substituted C 5-18 alkylaryl or alkylheteroaryl group, or an optionally substituted C 7-30 aralkyl group, whereby two R 1 residues may form together with the adjacent nitrogen atom to which they are bound a 5- to 7-membered heterocyclic ring which may contain further nitrogen atoms or an oxygen atoms, and whereby the optionally substituted groups may be substituted by 1 to 5 C 1-5 alkyl group(s);
• L represents an (a+b)-valent organic residue (whereby b is 1 when Y in formula
• the dental adhesive may also contain polymerisable acidic monomers selected from the group consisting of
• R 1 and R 2 independently represent a hydrogen atom, an optionally substituted C 1-18 alkyl group, an optionally substituted C 3-18 cycloalkyl group, an optionally substituted C 5-18 aryl or heteroaryl group, an optionally substituted C 5-18 alkylaryl or alkylh3eteroaryl group, an optionally substituted C 7-30 aralkyl group, whereby the optionally substituted groups may be substituted by 1 to 5 C 1-5 alkyl group(s);
• L 1 represents a (c+d) valent organic residue containing 2 to 45 carbon atoms and optionally heteroatoms such as oxygen, nitrogen and sulfur, the carbon atoms including c+d carbon atoms selected from primary and secondary aliphatic carbon atoms, secondary alicyclic carbon atoms, and aromatic carbon atoms, each of said c+d carbon atoms linking a phosphonate or optionally substituted acrylamido group; and
• L 2 represents an (e+f) valent organic residue containing 2 to 45 carbon atoms and optionally heteroatoms such as oxygen, nitrogen and sulfur-atoms, the carbon atoms including e+f carbon atoms selected from primary and secondary aliphatic carbon atoms, secondary alicyclic carbon atoms, and aromatic carbon atoms, each of said e+f carbon atoms linking a sulphonate or optionally substituted 2-(oxa-ethyl)acryl derivative group; and e and f independently represent an integer of from 1 to 10; (b3) acidic monomers of the following formula (D):
• R 3 and R 4 independently represent a hydrogen atom, an optionally substituted C 1-18 alkyl group, an optionally substituted C 3-18 cycloalkyl group, an optionally substituted C 5-18 aryl or heteroaryl group, an optionally substituted C 5-18 alkylaryl or alkylheteroaryl group, an optionally substituted C 7-30 aralkyl group, whereby the optionally substituted groups may be substituted by 1 to 5 C 1-5 alkyl group(s)
• L 3 represents a (g+h) valent valent organic residue containing 2 to 45 carbon atoms and optionally heteroatoms such as oxygen, nitrogen and sulfur atoms, the carbon atoms including g+h carbon atoms selected from primary and secondary aliphatic carbon atoms, secondary alicyclic carbon atoms, and aromatic carbon atoms, each of said g+h carbon atoms linking a sulphonate or optionally substituted acrylamido group; and g and h independently represent integers of
• the dental adhesive contains a polymerizable monomer characterized by one of the following formulas:
• n is an integer.
• the dental adhesive contains a polymerizable monomer characterized by one of the following formulas:
• the dental adhesive contains a polymerizable monomer characterized by one of the following formulas:
• R 5 and R 6 independently represent a hydrogen atom or a substituted, a C 1 to C 18 alkyl group, an optionally substituted C 3-18 cycloalkyl group, an optionally substituted C 5-18 aryl or heteroaryl group, an optionally substituted C 5-18 alkylaryl or alkylheteroaryl group, an optionally substituted C 7-30 aralkyl group
• R 7 represents a divalent substituted or unsubstituted organic residue having from 1 to 45 carbon atoms, whereby said organic residue may contain from 1 to 14 oxygen and/or nitrogen atoms and is selected from a C 1 to C 18 alkylene group wherein from 1 to 6-CH 2 -groups may be replaced by a —N—(C ⁇ O)—CR 9 ⁇ CH 2 group
• R 1 is a hydrogen atom or a C 1 to C 18 alkyl group, a divalent substituted or unsubstituted C 3 to C 18 cycloalkyl or cycloalkylene group
• the dental adhesive may also contain a mono-, bis- or poly(meth) acrylamide characterized by one of the following formulas:
• the dental adhesive may also contain acrylic acid or methacrylic acid as polymerizable monomers containing an acidic group.
• the dental adhesive according to the present invention may contain polymerizable monomers in an amount of from 5 to 90 wt-%, preferably in an amount of from 20 to 70 wt. %.
• the aqueous mixture may further contain an organic water soluble solvent selected from the group of alcohols and ketones such as ethanol, propanol, butanol, acetone, methyl ethyl ketone.
• an organic water soluble solvent selected from the group of alcohols and ketones such as ethanol, propanol, butanol, acetone, methyl ethyl ketone.
• a dental composition according to the present invention may include further acids whereby the pH of the composition may be easily adjusted.
• suitable acids are sulfuric acid, phosphoric acid, hydrochloric acid and the like.
• a further acid which is not-polymerizable is added for adjusting the pH.
• the polymerization initiator may be a photo initiator such as camphor quinone.
• the dental adhesive may further contains an inorganic filler and/or an organic filler; preferably the filler is a nanofiller.
• a one-pack composition means that the composition of the present invention is contained in only one container which may be stored and allows application of the composition without any mixing and without any special equipment before the application.
• Self-etching means that the dental adhesive composition of the present invention may be applied to a tooth without any preliminarily etching of enamel in a separate method step.
• the polymerizable phosphoric acid ester derivative of the present invention allows the preparation of a dental composition which is hydrolysis stable for at least one week at a storage temperature of 50° C., whereby after such storage the bond strength of an adhesive prepared from such a dental composition to enamel and/or dentin is at least 10 MPa, preferably 15 MPa. Due to the high thermal stability of the composition of the present invention a one-part self-etching and self-priming system which has excellent shelf-life may be prepared.
• a series of test formulations containing different thermal polymerization inhibitors was prepared in order to illustrate the surprising thermal stability of a dental adhesive composition according to the present invention.
• the standard composition was used as follows.
• TBHQ tert-Butylhydroquinone
• BHA tert.-Butylhydroxyanisol
• Test formulations containing different inhibitors or inhibitor concentrations were stored in Prime&Bond NT bottles (Dentsply DeTrey) at 60° C. until thermal polymerization.
• the bottles were daily examined by shaking the bottle, whereby the acoustical test turned out to be rather sensitive, and by taking a sample with a pipette. When polymerization seemed to have occurred or after a certain minimum storage time (20 days) the bottles were sliced open and the solution were examined visually.
• Test Formulation containing different inhibitors in different amounts, was investigated regarding its thermal stability by storing these formulations at 60° C. The samples were daily examined. In case of polymerization a gel or a solid, polymerized body was observed.
• the dark shaded columns represent formulations with inhibitors, respectively inhibitor concentrations, which were polymerized after the depicted time at 60° C.
• the light shaded columns represent formulations, which were not polymerized until the depicted time.
• hydroquinone HQ
• hydroquinone monomethylether HQME
• BHT failed to provide a sufficient thermal stability.
• the adhesive does not polymerise after storage for 20 days at 60° C.

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• Health & Medical Sciences (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
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• 2005
  • 2005-10-20 EP EP05022930A patent/EP1776943B1/en not_active Not-in-force
  • 2005-10-20 AT AT05022930T patent/ATE536854T1/de active
• 2006
  • 2006-09-04 AU AU2006303625A patent/AU2006303625B2/en not_active Ceased
  • 2006-09-04 BR BRPI0617666-6A patent/BRPI0617666B1/pt not_active IP Right Cessation
  • 2006-09-04 JP JP2008535909A patent/JP5443758B2/ja not_active Expired - Fee Related
  • 2006-09-04 CA CA2626070A patent/CA2626070C/en active Active
  • 2006-09-04 WO PCT/EP2006/008612 patent/WO2007045303A1/en active Application Filing
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  • 2006-10-18 EP EP06806367.6A patent/EP1940340B1/en not_active Ceased
  • 2006-10-18 WO PCT/EP2006/010051 patent/WO2007045459A1/en active Application Filing
• 2008
  • 2008-04-21 US US12/148,568 patent/US20090043008A1/en not_active Abandoned
• 2014
  • 2014-12-23 US US14/580,893 patent/US9775786B2/en active Active

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