WO2004056325A1 - Dental formulation - Google Patents
Dental formulation Download PDFInfo
- Publication number
- WO2004056325A1 WO2004056325A1 PCT/AU2003/001713 AU0301713W WO2004056325A1 WO 2004056325 A1 WO2004056325 A1 WO 2004056325A1 AU 0301713 W AU0301713 W AU 0301713W WO 2004056325 A1 WO2004056325 A1 WO 2004056325A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formulation
- weight
- polymer
- gel
- acid
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 58
- 238000009472 formulation Methods 0.000 title claims abstract description 53
- 229920000642 polymer Polymers 0.000 claims abstract description 33
- 210000005239 tubule Anatomy 0.000 claims abstract description 29
- 239000000178 monomer Substances 0.000 claims abstract description 16
- 201000002170 dentin sensitivity Diseases 0.000 claims abstract description 13
- 210000000214 mouth Anatomy 0.000 claims abstract description 11
- 239000003975 dentin desensitizing agent Substances 0.000 claims abstract description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 13
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 13
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical group CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 13
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 13
- VNQXSTWCDUXYEZ-UHFFFAOYSA-N 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione Chemical compound C1CC2(C)C(=O)C(=O)C1C2(C)C VNQXSTWCDUXYEZ-UHFFFAOYSA-N 0.000 claims description 11
- 229930006711 bornane-2,3-dione Natural products 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 9
- HYXIJVZYRWWFOO-UHFFFAOYSA-N n,n,2,3-tetramethylaniline Chemical compound CN(C)C1=CC=CC(C)=C1C HYXIJVZYRWWFOO-UHFFFAOYSA-N 0.000 claims description 9
- 229940044192 2-hydroxyethyl methacrylate Drugs 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 239000003999 initiator Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- -1 poly(ethylene glycol) Polymers 0.000 claims description 8
- 230000035945 sensitivity Effects 0.000 claims description 7
- 239000000470 constituent Substances 0.000 claims description 6
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Chemical compound CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- PHZSUOPYLUNLDX-UHFFFAOYSA-N 2,2-bis(prop-2-enoxy)acetic acid Chemical compound C=CCOC(C(=O)O)OCC=C PHZSUOPYLUNLDX-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- CNHDIAIOKMXOLK-UHFFFAOYSA-N toluquinol Chemical compound CC1=CC(O)=CC=C1O CNHDIAIOKMXOLK-UHFFFAOYSA-N 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- NEYTXADIGVEHQD-UHFFFAOYSA-N 2-hydroxy-2-(prop-2-enoylamino)acetic acid Chemical compound OC(=O)C(O)NC(=O)C=C NEYTXADIGVEHQD-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 2
- 229920002873 Polyethylenimine Polymers 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N hydroquinone methyl ether Natural products COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 2
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 claims description 2
- 230000005012 migration Effects 0.000 claims description 2
- 238000013508 migration Methods 0.000 claims description 2
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 claims description 2
- NBFRQCOZERNGEX-UHFFFAOYSA-N n,n,3,5-tetramethylaniline Chemical compound CN(C)C1=CC(C)=CC(C)=C1 NBFRQCOZERNGEX-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 150000004059 quinone derivatives Chemical group 0.000 claims description 2
- 210000004268 dentin Anatomy 0.000 abstract description 9
- 230000001680 brushing effect Effects 0.000 abstract description 3
- 238000004140 cleaning Methods 0.000 abstract description 3
- 230000007794 irritation Effects 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 230000004888 barrier function Effects 0.000 description 4
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 102100026735 Coagulation factor VIII Human genes 0.000 description 3
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000002985 plastic film Substances 0.000 description 2
- 229920006255 plastic film Polymers 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000002966 varnish Substances 0.000 description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229920005603 alternating copolymer Polymers 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 239000007863 gel particle Substances 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 239000003178 glass ionomer cement Substances 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/60—Preparations for dentistry comprising organic or organo-metallic additives
- A61K6/69—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/884—Preparations for artificial teeth, for filling teeth or for capping teeth comprising natural or synthetic resins
- A61K6/887—Compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds
Definitions
- This invention relates to formulations for treating or reducing dentine hypersensitivity that causes pain arising from exposed dentine in the oral cavity.
- Dentine sensitivity (or hypersensitivity, both terms being used in clinical dental practice interchangeably) is believed to be caused by rapid shifts, in either direction, of the fluids contained within dentinal tubules of teeth, following stimulus application, resulting in activation of sensory nerves in the pulp / inner dentine region of a tooth.
- the pain producing stimuli can be thermal, tactile, osmotic, chemical or evaporative, but the cold stimulus appears to be the greatest problem.
- Dentine hypersensitivity is characterized by short, sharp pain arising from the exposed dentine.
- Physical materials and compounds which have been used for treating or preventing sensitivity in the oral cavity and which aim to block the sensitivity mechanism through tubule occlusion include compounds that interact with proteins of the tooth structure and block the ends of the dentinal tubules, light curable composites and resins, varnishes, glass ionomer cements, sealants and others.
- Prior art formulations comprising physical "barrier” compounds are generally hard materials that often exhibit poor adhesion to tooth enamel by themselves and may require dentine bonding agents or surface primers. Also, some of the varnishes and resins employed will be brushed off in time with normal teeth cleaning regimes, resulting in re-opening of the dentinal tubules previously sealed off by the resin.
- Preferred formulations should be easy to apply, be immediately effective and maintain dentinal tubule occlusion under normal teeth cleaning regimes that include regular tooth brushing.
- Another aim is to provide a method of treating dentine sensitivity using physical (barrier) formulations that may be brushed (or otherwise applied) onto exposed dentine and provide longer term sensitivity reduction.
- a formulation for reducing dentine sensitivity in the oral cavity which incorporates at least one physical desensitising agent in form of a light curable monomer that forms a resilient polymer gel upon curing.
- a dentine sensitivity reducing formulation that includes a light-cured, form-stable, resilient gel polymer.
- a formulation for topical application on dentine may include or be formed from (1 ) at least one multifunctional polymer or (2) at least one multifunctional polymer and at least one monomer or (3) more than one monomer.
- a light sensitive polymerisation initiator is mixed with the multifunctional polymer(s) and/or monomer (s) to form a polymer premix in a suitable carrier liquid.
- This premix can be stored in suitable, light-protected containers, and on demand then applied in the oral cavity to the surface of a painful or sensitive tooth, or to exposed dentine.
- the premix and carrier liquid mixture should advantageously have a sufficiently low viscosity to allow fluid migration into exposed dentinal tubules by capillary action, where it forms a liquid plug within the tubule and seals off the tubule opening at the toot surface area.
- Light in the wavelength range of 300 to 650nm which is the wave length at which most commercially available polymerisation initiators react to initiate polymerisation of suitable, gel-forming monomers employed in the invention, is then directed onto the area to which the mixture has been applied, which causes polymerisation of the monomer into a gel, thereby setting the desensitising polymer formulation within the tubules and forming relatively soft gel plugs that occlude access to the tubules.
- the use of light-curing, gel-forming formulations for desensitising teeth has a number of advantages over known methods of physical desensitising.
- the formulation once cured, forms a resilient, relatively soft gel plug within the dentinal tubules.
- the gel plugs which undergo slight expansion during curing, form a slight resilient press fit within the tubules and thus act as an effective physical barrier to stimulus agents, including liquid ingress from the oral cavity and thermal stimuli.
- the gel blocks the dentinal tubules and prevents fluid movement within the dentinal tubules. The result is a prevention or reduction of sensitivity or pain.
- the resiliency and softness of the gel plug avoids creation of strains that are typically encountered with hard setting compounds previously used.
- the formulation may include a hydrogel that swells in the presence of moisture in the mouth, causing the gel to resiliently tighten, i.e. form an improved press fit within the tubules compared to the press fit achieved upon curing of the mixture.
- the gel polymer is advantageously selected such as to remain permeable to oxygen and electrolytes, just as would be the case with normal tubules.
- a method of preventing or reducing sensitivity or pain in at least one tooth which method includes applying to said tooth a polymer premix of the invention and curing said premix by application of light.
- Desensitising is to be taken as meaning reducing sensitivity or pain by physically blocking access to the interior of the dentinal tubules .
- Cured/curing and grammatical variations thereof refers to the polymerisation process whereby the desensitising polymer plug is formed within the dentinal tubules.
- DETAILED DESCRIPTION OF THE INVENTION a description of preferred embodiments of the invention will be provided. Whilst specific chemical compounds are used in the preferred embodiments, it will be appreciated that other polymer compounds may be employed that form a resilient gel body once cured, in contrast with hard curing polymers.
- a preferred multifunctional polymer used in a desensitising formulation according to the invention is a polycarboxylic acid polymer. The monomer is preferably an acrylate or allyl derivative.
- the monomer is selected from hydroxy ethylmethacrylate, glycol dimethacrylate, diallyloxyacetic acid, poly(ethylene glycol) dimethacrylate, 2-acrylamidoglycolic acid, acrylic acid, methacrylic acid, and itaconic acid.
- the light sensitive polymerisation initiator is a quinone derivative in combination with a quaternary amine derivative.
- a preferred formulation uses camphorquinone.
- the quaternary amine derivative may be selected from N,N,3,5-tetramethyl aniline, poly(ethyleneimine), N,N,N,N- tetraethyldiethylenetriamine, and N,N-diethylethylenediamine, tetramethyl aniline being the most preferred quaternary amine.
- the light sensitive initiator initiates the polymerisation of the monomer to form the desensitising polymer.
- a ready to use formulation is prepared by dissolving the polymer(s) and/or monomer(s) and polymerisation initiator in water, together with a preservative (to improve shelf life).
- a preservative to improve shelf life.
- a typically used preservative is butylated hydroxy toluene, although other preservatives such as hydroquinone, and methyl hydroquinone may be used.
- the relative amounts of the constituents of the formulation may vary within certain ranges. Broadly, the constituents may be present as follows:
- Polycarboxylic acid polymer about 1 to about 50% by weight
- Glycol dimethacrylate about 1 to about 50% by weight
- Camphorquinone about 0.01 to about 5% by weight Tetramethyl aniline about 0.01 to about 5% by weight Butylated hydroxy toluene about 0.01 to about 5% by weight
- Polycarboxylic acid polymer about 5 to about 15% by weight
- Glycol dimethacrylate about 3 to about 9% by weight
- Camphorquinone about 0.1 to about 1% by weight Tetramethyl aniline about 0.1 to about 1% by weight Butylated hydroxy toluene about 0.01 to about 0.1%byweight Excellent results in creating a soft, resilient gel after curing have been obtained with a formulation that comprises Polycarboxylic acid polymer about 7.5% by weight 2-Hydroxy ethylmethacrylate about 74.5% by weight Diallyloxyacetic acid, sodium salt about 6% by weight
- a desensitising hydrogel formulation in accordance with the invention was prepared as follows: Ingredients
- Tetramethyl aniline 0.22 grams Gantrez AN119BF is an alternating copolymer of vinyl methyl ether and maleic anhydride, HEMA is 2-hydroxy ethyl methacrylate and BHT is butylated hydroxy toluene.
- a clean glass beaker was placed on the balance and the balance tared.
- To the glass beaker was added 7.5 grams of Gantrez AN119BF, 12.0 grams of deionised water, 74.5 grams of HEMA, and 6.0 grams of diallyloxyacetic acid sodium salt.
- the mixture was stirred with a plastic spatula and then the beaker covered with plastic film.
- Water was poured into the ultrasonic bath to a depth of about one centimeter, and then the beaker placed in the ultrasonic bath.
- the ultrasonic bath was turned on to agitate the contents of the beaker until the mixture became clear, and there were no gel particles.
- This premix can then be applied to a painful or sensitive tooth, or to exposed dentine. Naturally, the premix can also be applied to a tooth which has no pain, but in anticipation of pain, for example before a surgical procedure. Light is directed onto the area to which the premix is applied to cause polymerisation. The desensitising polymer so formed reduces or prevents pain.
Landscapes
- Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plastic & Reconstructive Surgery (AREA)
- Dental Preparations (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
This invention relates to formulations for treating or reducing dentine hypersensitivity that causes pain arising from exposed dentine in the oral cavity. The present invention seeks to provide formulations for physical blockage of dentinal tubules that have long term effectiveness and cause minimal irritation (if any at all) to the tissues of the oral cavity. Preferred formulations should be easy to apply, be immediately effective and maintain dentinal tubule occlusion under normal teeth cleaning regimes that include regular tooth brushing. The invention provides a formulation for reducing dentine sensitivity in the oral cavity, which incorporates at least one physical desensitising agent in form of a light curable monomer that forms a resilient polymer gel upon curing.
Description
DENTAL FORMULATION FIELD OF THE INVENTION
This invention relates to formulations for treating or reducing dentine hypersensitivity that causes pain arising from exposed dentine in the oral cavity. BACKGROUND OF THE INVENTION
Dentine sensitivity (or hypersensitivity, both terms being used in clinical dental practice interchangeably) is believed to be caused by rapid shifts, in either direction, of the fluids contained within dentinal tubules of teeth, following stimulus application, resulting in activation of sensory nerves in the pulp / inner dentine region of a tooth. The pain producing stimuli can be thermal, tactile, osmotic, chemical or evaporative, but the cold stimulus appears to be the greatest problem. Dentine hypersensitivity is characterized by short, sharp pain arising from the exposed dentine.
Conventional therapies for dentine hypersensitivity are based on using topical applied "desensitising" agents and formulations. These agents can be classified on the basis of their chemical and physical properties, ie there are chemical agents such as corticosteroids, benzalkonium chloride in hydroxy ethyl methacrylate, chlorhexidine, glutaraldehyde, potassium oxalate, fluorides and others that use chemical interaction with the sensory nerves, there are physical agents that act as a barrier to prevent dential tubule fluid contact with stimulus agents, and mixed chemical/physical agents. Physical materials and compounds which have been used for treating or preventing sensitivity in the oral cavity and which aim to block the sensitivity mechanism through tubule occlusion include compounds that interact with proteins of the tooth structure and block the ends of the dentinal tubules, light curable composites and resins, varnishes, glass ionomer cements, sealants and others.
For a more in depth look at the epidemiology, mechanisms of pain reduction and aetiological factors of dentine hypersensitivity reference should be had to the article by R.H. Dababneh, AT. Khouri and M. Addy, "Dentine hypersensitivity - an enigma? A review of terminology, epidemiology, mechanisms and management, in British Dental Journal, Vol.187, No.11 , Dec
Prior art formulations comprising chemically active compounds have the disadvantage that they are generally short lived in effectiveness, and can cause irritation of the soft tissues, such as the gum line. Some active compounds, such as glutaraldehyde, can burn the skin or eyes. Prior art formulations comprising physical "barrier" compounds are generally hard materials that often exhibit poor adhesion to tooth enamel by themselves and may require dentine bonding agents or surface primers. Also, some of the varnishes and resins employed will be brushed off in time with normal teeth cleaning regimes, resulting in re-opening of the dentinal tubules previously sealed off by the resin.
It is an aim of the present invention to provide formulations for physical blockage of dentinal tubules that have long term effectiveness and cause minimal irritation (if any at all) to the tissues of the oral cavity. Preferred formulations should be easy to apply, be immediately effective and maintain dentinal tubule occlusion under normal teeth cleaning regimes that include regular tooth brushing.
Another aim is to provide a method of treating dentine sensitivity using physical (barrier) formulations that may be brushed (or otherwise applied) onto exposed dentine and provide longer term sensitivity reduction. SUMMARY OF THE INVENTION
According to a broad form of the invention there is provided a formulation for reducing dentine sensitivity in the oral cavity, which incorporates at least one physical desensitising agent in form of a light curable monomer that forms a resilient polymer gel upon curing. According to a further aspect of the invention there is provided a dentine sensitivity reducing formulation that includes a light-cured, form-stable, resilient gel polymer.
A formulation for topical application on dentine may include or be formed from (1 ) at least one multifunctional polymer or (2) at least one multifunctional polymer and at least one monomer or (3) more than one monomer. A light sensitive polymerisation initiator is mixed with the multifunctional polymer(s) and/or monomer (s) to form a polymer premix in a suitable carrier liquid. This premix can be stored in suitable, light-protected containers, and on demand then
applied in the oral cavity to the surface of a painful or sensitive tooth, or to exposed dentine.
The premix and carrier liquid mixture should advantageously have a sufficiently low viscosity to allow fluid migration into exposed dentinal tubules by capillary action, where it forms a liquid plug within the tubule and seals off the tubule opening at the toot surface area.
Light in the wavelength range of 300 to 650nm, which is the wave length at which most commercially available polymerisation initiators react to initiate polymerisation of suitable, gel-forming monomers employed in the invention, is then directed onto the area to which the mixture has been applied, which causes polymerisation of the monomer into a gel, thereby setting the desensitising polymer formulation within the tubules and forming relatively soft gel plugs that occlude access to the tubules.
The use of light-curing, gel-forming formulations for desensitising teeth has a number of advantages over known methods of physical desensitising. The formulation, once cured, forms a resilient, relatively soft gel plug within the dentinal tubules. The gel plugs, which undergo slight expansion during curing, form a slight resilient press fit within the tubules and thus act as an effective physical barrier to stimulus agents, including liquid ingress from the oral cavity and thermal stimuli. The gel blocks the dentinal tubules and prevents fluid movement within the dentinal tubules. The result is a prevention or reduction of sensitivity or pain. The resiliency and softness of the gel plug avoids creation of strains that are typically encountered with hard setting compounds previously used. Whilst the polymer gel film that is also formed on the tooth surface will eventually be worn away as consequence of tooth brushing, the gel plugs will remain embedded within the tubules, as their resilient nature make them difficult to dislodge and extract from the tubule. Hence, desensitising formulations according to the invention have longer term effectiveness when compared with prior art formulations. Advantageously, the formulation may include a hydrogel that swells in the presence of moisture in the mouth, causing the gel to resiliently tighten, i.e. form an improved press fit within the tubules compared to the press fit achieved upon curing of the mixture.
The gel polymer is advantageously selected such as to remain permeable to oxygen and electrolytes, just as would be the case with normal tubules.
In another aspect of the invention there is provided a method of preventing or reducing sensitivity or pain in at least one tooth, which method includes applying to said tooth a polymer premix of the invention and curing said premix by application of light.
There is further provided according to the invention the use of at least one multifunctional polymer and/or at least one monomer, together with a light sensitive polymerisation initiator, for the preparation of a formulation for desensitising a tooth.
As employed above and throughout this disclosure (including the claims), the following terms, unless otherwise indicated, shall be understood to have the following meanings:
"Desensitising" is to be taken as meaning reducing sensitivity or pain by physically blocking access to the interior of the dentinal tubules .
"Cured/curing" and grammatical variations thereof refers to the polymerisation process whereby the desensitising polymer plug is formed within the dentinal tubules. DETAILED DESCRIPTION OF THE INVENTION In the following, a description of preferred embodiments of the invention will be provided. Whilst specific chemical compounds are used in the preferred embodiments, it will be appreciated that other polymer compounds may be employed that form a resilient gel body once cured, in contrast with hard curing polymers. A preferred multifunctional polymer used in a desensitising formulation according to the invention is a polycarboxylic acid polymer. The monomer is preferably an acrylate or allyl derivative. The monomer is selected from hydroxy ethylmethacrylate, glycol dimethacrylate, diallyloxyacetic acid, poly(ethylene glycol) dimethacrylate, 2-acrylamidoglycolic acid, acrylic acid, methacrylic acid, and itaconic acid.
The light sensitive polymerisation initiator is a quinone derivative in combination with a quaternary amine derivative. A preferred formulation uses camphorquinone. The quaternary amine derivative may be selected from
N,N,3,5-tetramethyl aniline, poly(ethyleneimine), N,N,N,N- tetraethyldiethylenetriamine, and N,N-diethylethylenediamine, tetramethyl aniline being the most preferred quaternary amine. On application of light in the wavelength range 300 to 650nm, the light sensitive initiator initiates the polymerisation of the monomer to form the desensitising polymer.
A ready to use formulation is prepared by dissolving the polymer(s) and/or monomer(s) and polymerisation initiator in water, together with a preservative (to improve shelf life). A typically used preservative is butylated hydroxy toluene, although other preservatives such as hydroquinone, and methyl hydroquinone may be used.
The relative amounts of the constituents of the formulation may vary within certain ranges. Broadly, the constituents may be present as follows:
Polycarboxylic acid polymer about 1 to about 50% by weight
2-Hydroxy ethylmethacrylate about 10 to about 80% by weight
Glycol dimethacrylate about 1 to about 50% by weight
Water about 1 to about 70% by weight
Camphorquinone about 0.01 to about 5% by weight Tetramethyl aniline about 0.01 to about 5% by weight Butylated hydroxy toluene about 0.01 to about 5% by weight
Test batches of formulations in accordance with the invention have shown good tubule occlusion results where constituents were present in the formulation within the following ranges:
Polycarboxylic acid polymer about 5 to about 15% by weight
2-Hydroxy ethylmethacrylate about 50 to about 80% by weight
Glycol dimethacrylate about 3 to about 9% by weight
Water about 5 to about 25% by weight
Camphorquinone about 0.1 to about 1% by weight Tetramethyl aniline about 0.1 to about 1% by weight Butylated hydroxy toluene about 0.01 to about 0.1%byweight
Excellent results in creating a soft, resilient gel after curing have been obtained with a formulation that comprises Polycarboxylic acid polymer about 7.5% by weight 2-Hydroxy ethylmethacrylate about 74.5% by weight Diallyloxyacetic acid, sodium salt about 6% by weight
Water about 12% by weight
Camphorquinone about 0.2% by weight Tetramethyl aniline about 0.22% by weight Butylated hydroxy toluene about 0.05% by weight In the above formulations, water could be replaced by another, suitable solvent that provides the initial swelling agent for the formulation; after curing into the soft, resilient gel plug, the solvent will diffuse out of the gel at a slow rate and saliva will then concurrently provide the moisture that is necessary to replace the solvent as swelling agent. A desensitising hydrogel formulation in accordance with the invention was prepared as follows: Ingredients
Gantrez AN119BF 7.5 grams Deionised water 12.0 grams HEMA 74.5 grams
Diallyloxyacetic acid, sodium salt 6.0 grams Camphorquinone 0.20 grams BHT 0.05 grams
Tetramethyl aniline 0.22 grams Gantrez AN119BF is an alternating copolymer of vinyl methyl ether and maleic anhydride, HEMA is 2-hydroxy ethyl methacrylate and BHT is butylated hydroxy toluene. Method
The equipment requirements were as follows: a) Balance weighing in grams and reading to two decimal places b) Pasteur pipettes c) Two clean 500ml beakers d) Plastic spatula
e) Ultrasonic bath
A clean glass beaker was placed on the balance and the balance tared. To the glass beaker was added 7.5 grams of Gantrez AN119BF, 12.0 grams of deionised water, 74.5 grams of HEMA, and 6.0 grams of diallyloxyacetic acid sodium salt. The mixture was stirred with a plastic spatula and then the beaker covered with plastic film. Water was poured into the ultrasonic bath to a depth of about one centimeter, and then the beaker placed in the ultrasonic bath. The ultrasonic bath was turned on to agitate the contents of the beaker until the mixture became clear, and there were no gel particles. In an orange light production area, 0.20 grams of camphorquinone, 0.05 grams of BHT, and 0.22 grams of tetramethyl aniline was weighed into a clean glass beaker. Then the solution containing the Gantrez AN119BF was added to this beaker. The beaker was covered with plastic film and agitated in the ultrasonic bath until all the camphorquinone and BHT had dissolved. The resultant product (the "premix") was packaged, ready for delivery.
This premix can then be applied to a painful or sensitive tooth, or to exposed dentine. Naturally, the premix can also be applied to a tooth which has no pain, but in anticipation of pain, for example before a surgical procedure. Light is directed onto the area to which the premix is applied to cause polymerisation. The desensitising polymer so formed reduces or prevents pain.
Claims
1. Formulation for reducing dentine sensitivity in the oral cavity, which incorporates at least one physical desensitising agent in form of a light curable monomer that forms a resilient polymer gel upon curing.
2. Dentine sensitivity reducing formulation that includes a light-cured, form- stable, resilient gel polymer.
3. The formulation of claim 1 or 2, including a light sensitive polymerisation initiator and (1) at least one multifunctional polymer, or (2) at least one multifunctional polymer and at least one monomer, or (3) more than one monomer.
4. The formulation of claim 3 in a suitable carrier liquid.
5. The formulation of claim 4, wherein the carrier liquid includes water.
6. The formulation of claim 4 or 5 having a viscosity to allow fluid migration into exposed dentinal tubules by capillary action.
7. The formulation of any one of the preceding claims, including a gel polymer that swells in the presence of moisture.
8. The formulation of any one of the preceding claims, wherein the gel polymer is permeable to oxygen and electrolytes.
9. The formulation of any one of claims 3 to 8, including a polycarboxylic acid polymer.
10. The formulation of any one of claims 3 to 9, including an acrylate or allyl derivative.
11. The formulation of claim 10, wherein the monomer is selected from the group consisting of 2-hydroxy ethylmethacrylate, glycol dimethacrylate, diallyloxyacetic acid, poly(ethylene glycol) dimethacrylate, 2-acrylamidoglycolic acid, acrylic acid, methacrylic acid, and itaconic acid.
12. The formulation of any one of claims 3 to 11 , wherein the light sensitive polymerisation initiator is a quinone derivative in combination with a quaternary amine derivative.
13. The formulation of claim 12, incorporating camphorquinone and a quaternary amine derivative selected from the group consisting of N,N,3,5- tetramethyl aniline, poly(ethyleneimine), N,N,N,N-tetraethyldiethylenetriamine, and N,N-diethylethylenediamine.
14. The formulation of any one of claims 3 to 13, further including a preservative such as butylated hydroxy toluene or hydroquinone, in particular methyl hydroquinone.
15. The formulation of any one of claims 3 to 14, having the following constituents in % values by weight: Polycarboxylic acid polymer about 1 to about 50, 2-hydroxy ethylmethacrylate about 10 to about 80, Glycol dimethacrylate about 1 to about 50, Water about 1 to about 70, Camphorquinone about 0.01 to about 5, Tetramethyl aniline about 0.01 to about 5, and Butylated hydroxy toluene about 0.01 to about 5.
16. The formulation of claim 15, wherein the constituents are present in the following amount in % by weight: Polycarboxylic acid polymer about 5 to about
15. 2-hydroxy ethylmethacrylate about 50 to about 80, Glycol dimethacrylate about 3 to about 9, Water about 5 to about 25, Camphorquinone about 0.1 to about 1 , Tetramethyl aniline about 0.1 to about 1 and Butylated hydroxy toluene about 0.01 to about 0.1.
17. The formulation of claim 16, wherein the constituents are present in the following amounts:
Polycarboxylic acid polymer about 7.5% by weight 2-Hydroxy ethylmethacrylate about 74.5% by weight Diallyloxyacetic acid, sodium salt about 6% by weight Water about 12% by weight
Camphorquinone about 0.2% by weight Tetramethyl aniline about 0.22% by weight Butylated hydroxy toluene about 0.05% by weight
18. A method of preventing or reducing sensitivity or pain in teeth, which method includes applying a formulation in accordance with any one of claims 1 to 17 to exposed dentinal tubules of teeth, allowing said formulation to migrate into the tubules, and curing the formulation by application of light with a wave length in the range of 300 to 650nm, whereby soft resilient gel plugs are formed within the tubules.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/540,171 US20060127325A1 (en) | 2002-12-20 | 2003-12-22 | Dental formulation |
| AU2003289754A AU2003289754A1 (en) | 2002-12-20 | 2003-12-22 | Dental formulation |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2002953460 | 2002-12-20 | ||
| AU2002953460A AU2002953460A0 (en) | 2002-12-20 | 2002-12-20 | Dental formulation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004056325A1 true WO2004056325A1 (en) | 2004-07-08 |
Family
ID=30004545
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/AU2003/001713 WO2004056325A1 (en) | 2002-12-20 | 2003-12-22 | Dental formulation |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US20060127325A1 (en) |
| AU (1) | AU2002953460A0 (en) |
| WO (1) | WO2004056325A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8292625B2 (en) * | 2010-07-23 | 2012-10-23 | Pulpdent Corporation | Radically curable urethane dimethacrylates and compositions thereof for tougher dental prosthetics |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5133957A (en) * | 1991-09-18 | 1992-07-28 | Bisco, Inc. | Composition and method for desensitizing dentin |
| US5797749A (en) * | 1997-03-19 | 1998-08-25 | Danville Materials | Dental composition |
| WO1999020227A1 (en) * | 1997-10-22 | 1999-04-29 | Dentsply International Inc. | Protective varnish for dentin |
| EP0976386A1 (en) * | 1998-07-28 | 2000-02-02 | Block Drug Company Inc. | Polymeric desensitizing compositions |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756559A (en) * | 1992-02-06 | 1998-05-26 | Dentsply Research & Development | Method and composition for adhering to tooth structure |
-
2002
- 2002-12-20 AU AU2002953460A patent/AU2002953460A0/en not_active Abandoned
-
2003
- 2003-12-22 WO PCT/AU2003/001713 patent/WO2004056325A1/en not_active Application Discontinuation
- 2003-12-22 US US10/540,171 patent/US20060127325A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5133957A (en) * | 1991-09-18 | 1992-07-28 | Bisco, Inc. | Composition and method for desensitizing dentin |
| US5797749A (en) * | 1997-03-19 | 1998-08-25 | Danville Materials | Dental composition |
| WO1999020227A1 (en) * | 1997-10-22 | 1999-04-29 | Dentsply International Inc. | Protective varnish for dentin |
| EP0976386A1 (en) * | 1998-07-28 | 2000-02-02 | Block Drug Company Inc. | Polymeric desensitizing compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| US20060127325A1 (en) | 2006-06-15 |
| AU2002953460A0 (en) | 2003-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Schwartz | Adhesive dentistry and endodontics. Part 2: bonding in the root canal system—the promise and the problems: a review | |
| Sanares et al. | Adverse surface interactions between one-bottle light-cured adhesives and chemical-cured composites | |
| Morphis et al. | Fluoride pit and fissure sealants: a review | |
| Perdigao et al. | Fundamental concepts of enamel and dentin adhesion | |
| Pashley | Dentin bonding: overview of the substrate with respect to adhesive material | |
| Paqué et al. | Apical sealing ability of Resilon/Epiphany versus gutta‐percha/AH Plus: immediate and 16‐months leakage | |
| Pegoraro et al. | Cements for use in esthetic dentistry | |
| US7128899B2 (en) | Bleaching device comprising a barrier layer and a bleaching composition comprising polyvinylpyrrolidone | |
| Poggio et al. | Effects of dentin surface treatments on shear bond strength of glass-ionomer cements | |
| WY et al. | Effect of home-use fluoride gels on resin-modified glass-ionomer cements | |
| EP0702948B1 (en) | Tooth surface treating agent | |
| WO2004060324A1 (en) | Free-radical initiator systems containing enzymes | |
| US9931281B2 (en) | Multi-functional self-healing dental composites, methods of synthesis and methods of use | |
| McLean | The clinical use of glass-ionomer cements | |
| Wang et al. | Effect of adhesive systems associated with resin‐modified glass ionomer cements | |
| Thirawat et al. | The sealing ability of materials used as retrograde root fillings in endodontic surgery | |
| Foley et al. | A comparison of in vitro enamel demineralization potential of 3 orthodontic cements | |
| Ling et al. | Physical, Mechanical, and Adhesive Properties of Novel Self‐Adhesive Resin Cement | |
| JP4467672B2 (en) | Curing method for dental glass ionomer cement | |
| Zidan et al. | Obturation of root canals using the single cone gutta‐percha technique and dentinal bonding agents | |
| US20060127325A1 (en) | Dental formulation | |
| US20020082317A1 (en) | Dental adhesive compositions with desensitizing agents | |
| Demarco et al. | Dyes for caries detection influence sound dentin bond strength | |
| AU2003289754A1 (en) | Dental formulation | |
| JPH08119822A (en) | Tacky root canal-fitting material for dentistry |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2003289754 Country of ref document: AU |
|
| ENP | Entry into the national phase |
Ref document number: 2006127325 Country of ref document: US Kind code of ref document: A1 |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 10540171 Country of ref document: US |
|
| 122 | Ep: pct application non-entry in european phase | ||
| WWP | Wipo information: published in national office |
Ref document number: 10540171 Country of ref document: US |
|
| NENP | Non-entry into the national phase |
Ref country code: JP |
|
| WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |