WO2014203279A2 - Formulations composites dentaires - Google Patents

Formulations composites dentaires Download PDF

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Publication number
WO2014203279A2
WO2014203279A2 PCT/IN2014/000408 IN2014000408W WO2014203279A2 WO 2014203279 A2 WO2014203279 A2 WO 2014203279A2 IN 2014000408 W IN2014000408 W IN 2014000408W WO 2014203279 A2 WO2014203279 A2 WO 2014203279A2
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WO
WIPO (PCT)
Prior art keywords
composite
matrix
dental
experimental
composition
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Application number
PCT/IN2014/000408
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English (en)
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WO2014203279A3 (fr
Inventor
V. Susila ANAND
Venkatesh Balasubramanian
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Indian Institute Of Technology Madras
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Publication of WO2014203279A2 publication Critical patent/WO2014203279A2/fr
Publication of WO2014203279A3 publication Critical patent/WO2014203279A3/fr

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    • 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

  • the embodiments herein relate to polymeric biomaterials more specifically for restorative dentistry, broadly to a composition for an organic resin matrix which can be used for cementation of implants, endodontic sealers, root repair materials, root end filling materials and luting cements.
  • Polymeric biomaterials are used in Dental composites as restorative material or adhesives.
  • the dental composites are widely used for filling cavity preparations, filling gaps between teeth, minor reshaping of teeth, and as inlays or onlays.
  • amalgam was the preferred choice as a dental restorative material owing to its low cost, ease of application, strength, durability, and longevity.
  • amalgam is no more the preferred choice as it poses many disadvantages. Problems associated with the amalgam include environmental pollution, toxicity of mercury, and aesthetic concerns.
  • the dental composites are used as an alternative to the amalgam.
  • the dental composites consists of organic resin based matrix and a filler.
  • the organic resin based matrix mostly includes a bisphenol A-glycidyl methacrylate (Bis-GMA) or urethane dimethacrylate (UDMA). Most commonly used fillers are silica-based.
  • the organic resin matrix further includes lower viscosity polymerizable component ( "fluid izer"), a methacrylate monomer, such as a tetraethylene glycol dimethacrylate (TEGDMA) or a docecanediol dimethacrylate.
  • TEGDMA tetraethylene glycol dimethacrylate
  • docecanediol dimethacrylate a methacrylate monomer
  • lower viscosity components generally low molecular weight monomers
  • the shrinkage can lead to gaps between the filling and the tooth thereby allowing bacteria to enter and may cause secondary caries or pulpitis.
  • dental conposites are bonded to the teeth using intermediary low filled or unfilled diluents containing bonding agents. These diluents may contribute to a greater elution and cytotoxicity and increases the potential interfaces in a tooth-restoration unit. These interfaces may leak leading to bacterial ingress into dental soft tissues like pulp and the aforementioned effects.
  • the principal object of the embodiments herein is to provide a composition for organic resin matrix and filler modification for polymeric biomaterials.
  • Another object of the embodiments herein is to provide a composition for dental composites.
  • the embodiments herein provide a composition for dental composites.
  • the dental composites includes an organic resin matrix, wherein the organic resin matrix includes silicone macromer resins, polymerizable monomers, adhesive monomers, photo initiators, accelerators, and photoacid catalysts.
  • the organic resin matrix includes a hybrid of two Macromer resins "a” and "c".
  • the Macromer resin "a” also referred as first silicone macromer includes at least one of polysiloxane having Methacrylate terminal group.
  • Macromer resin "c” also referred as second silicone macromer includes at least one ofpolysiloxane having cyclic epoxy group.
  • FIGS. 1A and I B are block diagrams representing generally, among other things, constituents of an organic resin matrix, according to an embodiment as disclosed herein;
  • FIGS. 2A to 2D are example graph depicting rate of elution of experimental dental organic matrix and conventional dental organic matrix stored in an artificial saliva medium for 24 hours, according to an embodiment as disclosed herein;
  • FIGS. 2E to 2G are example graph depicting rate of elution of experimental dental organic matrix and conventional dental organic matrix stored in an absolute alcohol medium for 24 hours, according to an embodiment as disclosed herein;
  • FIG. 3A is a example graph depicting cytotoxicity levels in experimental dental organic resin matrix and conventional dental organic resin matrix, according to an embodiment as disclosed herein;
  • FIG. 3B is a example graph depicting cytotoxicity levels in experimental dental composites and conventional dental composites, according to an embodiment as disclosed herein;
  • FIG. 4A represents absorption mode FTIR recorded with ATR of conventional resin based matrix N5 (BT) after polymerization, according to an embodiment as disclosed herein;
  • FIG. 4B represents absorption mode FTIR recorded with ATR of conventional resin based matrix N5 (BT) before polymerization, according to an embodiment as disclosed herein;
  • FIG. 4C represents absorption mode FTIR recorded with ATR of experimental resin based matrix N4 (E) after polymerization, according to an embodiment as disclosed herein;
  • FIG. 4D represents absorption mode FTIR recorded with ATR of experimental resin based matrix N4 (E) before polymerization, according to an embodiment as disclosed ; herein;
  • FIG. 4E represents absorption mode FTIR recorded with ATR of experimental resin based matrix N3 (G) after polymerization, according to an embodiment as disclosed herein;
  • FIG. 4F represents absorption mode FTIR recorded with ATR of experimental resin based matrix N3 (G) before polymerization, according to an embodiment as discfosed herein;
  • FIG. 4G represents absorption mode FTIR recorded with ATR of experimental resin based matri 2 (T) after polymerization, according to an embodiment as disclosed herein;
  • FIG. 4H represents absorption mode FTTR recorded with ATR of experimental resin based matrix N2 (T) before polymerization, according to an embodiment as disclosed herein;
  • FIG. 41 represents absorption mode FTIR recorded with ATR of Experimental resin based matrixNl (U) after polymerization, according to an embodiment as disclosed herein;
  • FIG. 4J represents absorption mode F ⁇ R recorded with ATR of Experimental resin based matrix Nl (U) before polymerization, according to an embodiment as disclosed herein;
  • FIG. 5D is an example FTIR-ATR graph of un-polymerized materials showing the peak area under 880 oxirane vibration for the organic matrix based composite 1U and control commercial composite 6S, according to an embodiment as disclosed;
  • FIG. 6 is a graph depicting micro-tensile bond strength of the experimental organic matrix based four composites U, G, E, T and conventional dental composite bonded without any adhesive and two commercial composites bonded with known adhesives and a control commercial self-adhesive restorative cement on human teeth, according to an embodiment as disclosed herein;
  • FIG. 7 is an example graph depicting dimensional change of composites during polymerization measured at different instants showing expansion and shrinkage of the experimental and conventional dental composites, according to an embodiment as discbsed herein;
  • FIG. 8 A is an example ⁇ - ⁇ graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 1U unlike internal standard control composite 5BT at 2mm thickness, according to an embodiment as disclosed herein;
  • FIG. 8B is an example ⁇ - ⁇ graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 1U unlike control commercial composite 8C at 4 mm thickness, acco rd ing to an e mbod ime nt as d isc lo sed here in;
  • FIG. 8C is an example FTIR-ATR graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 1U unlike internal standard control composite 5BT at 4mm thickness, according to an embodiment as disclosed herein;
  • FIG. 8D is an example F R-ATR graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 1 U unlike control commercial composite 7R at 2mm thickness, according to an embodiment as disclosed herein;
  • FIG. 8E is an example F ⁇ R-ATR graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 2G unlike control commercial composite 8C at 2mm thickness, according to an embodiment as discbsed herein;
  • FIG. 8F is an example FHR-ATR graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 3E unlike control commercial composite 8C at 2mm thickness, according to an embodiment as disclosed herein;
  • FIG. 8G is an example ⁇ -ATR graph showing lack of oxygen inhibition in the experimental organic matrix containing composite 3E unlike internal standard control composite 5BT at 2mm thickness, according to an embodiment as disclosed herein;
  • FIG. 8H is an example ⁇ -ATR graph showing lack of oxygen inhibition in the organic experimental matrix containing composite 3E unlike control commercial composite 7R at 2mm thickness, according to an embodiment as discbsed herein.
  • inventions herein provide a composition of an organic resin matrix for polymeric biomaterials. Further, embodiments herein provide a composition for dental composites.
  • the properties of said dental composites include lo w elution, low cytotoxicity, high degree of conversion, no shrinkage, low-post operative sensitivity, no oxygen inhibition, and self-adhesive ability.
  • the embodiments herein provide a composition for organic resin matrix, wherein the organic resin matrix includes Silicone macromer resins, polymerizable monomers, adhesive monomers, photo initiators, accelerators, and photoacid catalysts.
  • Macromer resins [0045] The organic resin matrix includes two Macromer resins "a” and "c" as shown in FIG 1.
  • Macromer resin "a” also referred as first silicone macromer includes at least one of polysiloxane having Methacrylate group.
  • Macromer resin "c” also referred as second silicone macromer includes at least one of polysiloxane having cyclic Epoxy group.
  • any other cyclic ring opening polymerizable group can be substituted for the Epoxy cycto hexyl ethyl terminated polysiloxane described.
  • the Macromer resin "a” has a first functional moiety "b” and Macromer resin “c” has a second functional moiety “d” as shown in the FIG. 1.
  • the first functional moiety "b” includes at least one of a free-radical polymerizable Methacrylate group and the second functional moiety "d” includes at least one of a ring-opening polymerizable cyclic Epoxy group.
  • polymerizable monomers are represented as “e”, “f ' and “g” as shown in the FIG. 1.
  • “e” is any one of the many dimethacrylates available
  • "f is BisGMA
  • "g” is TEGDMA.
  • polymerizable monomers are in the range of 10% to 18%.
  • the adhesive is used to impart self-adhesive property.
  • acidic ester, aliphatic tetra carboxylic acid, and a hydrophilic monomer in a tertiary butanol vehicle are included to impart self-adhesive property.
  • the adhesive can be used within a range of 2% to 4%.
  • the photoinitiators, accelerators, and photo acid catalysts are used to facilitate polymerization.
  • the photoinitiator includes dketone.
  • the accelerator includes hydrogen donor.
  • the photoacid catalysts include a photoacid.
  • the photoinitiator, accelerator, and photoacid catalyst group can be within a range o f 1 % to 2%.
  • the experimental dental composite includes the composition of Silicone Macromer "c” ranging between 7-15%, Silicone Macromer “a” ranging between 5-10%, at least one Dimethacrylate “e” ranging between 1-3%, BisGMA "f ranging between 7-9%, TEGDMA “g” ranging between 3-5%, Aliphatic tetra carboxylic acid ranging between 0.32-0.4%, Hydrophilic monomer ranging between 0.32-0:4%, Acidic ester ranging between 0.12-0.24%, Photosensitizer ranging between 0.2 -0.4%, Photoinitiator ranging between 0.2 -0.4%, Photoacid generator ranging between 0.12-0.24%, Hydrogen donor ranging between 0.2 -0.4%, Vehicle/solvent ranging between 0.32-0.4%, and Filler ranging between 65- 75%.
  • the resin matrix undergoes polymerization by free radical induced addition polymerization and cationic ring opening polymerization concurrently.
  • the terminal groups of hybridized silicone macromers resin react with the monomers as shown in the FIG. 1A.
  • the constituents are mixed in a cyclic mixer to obtain a homogeneous product.
  • 1 % to 2% dftcetone, photoacid and a hydrogen donor are added and mixed in a cyclic mixer and stored in a brown/black container.
  • PENTA dipentaerythritol pentaacrylate phosphoric acid ester
  • HEMA hydrophilic monomer like hydro xyethyl methacrylate
  • the embodiments herein provide a composition for dental composites, wherein the organic resin matrix is combined with unsilanized filler.
  • the composition includes 20-35% of organic resin matrix and 65-80% of unsilanized filler.
  • the unsilanized filler includes Quartz, silica, and glass.
  • the dental composite comprised 30% of the prepared organic resin matrix and 70% unsilanized Quartz filler.
  • the dental composites including the aforementioned composition exhibit enhanced physical properties and biological response such as low elution, low cytotoxicity, high degree of conversion, no shrinkage, low-post operative sensitivity, and self-adhesive ability.
  • the low elution of undesirable substances such as Bisphenol A (BP A), BADGE, Bis DMA, Bis GMA corresponds to a better matrix and composite as shown in the FIGS. 2A, 2B, and 2C (in artificial saliva medium) and FIGS. 2E, 2F (in alcohol medium).
  • undesirable substance such as Bisphenol A (BPA) corresponds to an undesirable matrix as shown in the FIG. 2D (in artificial saliva medium) and the FIG. 2G (in alcohol medium).
  • the low cytotoxicity of the dental composite is a resultant of low elution of undesirable substances.
  • the low cytotoxicity is observed in experimental dental composite and relatively high cytotoxicity is observed in conventional dental composites as shown in the FIG. 3B.
  • Degree of conversion refers to degree of polymerization. It refers to the percentage of monomer units being converted to polymers. The degree of conversion was highest in experimental resin matrix N4 as shown in the FIG. 4C and least in conventional resin matrix N5 as shown in the FIG 4 A.
  • the shrinkage upon polymerization can cause high internal stress.
  • the conventional matrix may undergoes only free radical polymerizati n wherein, linear molecules come together during polymerization, by pulling the mass together, thus occupying less space post-polymerization than pre-polymerization and causes significant volumetric shrinkage.
  • Conventional matrix monomers have low molar volume and more number of reactive double bonds that converts to single bonds during polymerization.
  • the experimental hybrid macromer-dimethacrylate copolymerized matrix has very high molar volume and fewer double bonds that convert to single bonds during polymerization.
  • the molar volume of one typical embodiment explained hereinabove is approximately 30 times more than the conventional matrix. However the viscosity is much less compared to the conventional matrix monomers.
  • the experimental matrix undergoes cationic ring opening addition polymerization in addition to free radical polymerization, wherein the ring molecule opens up for polymerization reaction, it occupies more space post-polymerization than pre-polymerization. Since the free radical polymerizable monomers are used in less quantity as the macromer hybrid has low viscosity and easy to handle, the shrinkage would be much lower. Further, polymerizatbn stress is reduced in the experimental materials as the matrix is uncoupled from the unyielding fillers and thus is more free to move. Unlike conventional materials, whose matrices are bound tightly to fillers through coupling agents.
  • the dental composites showed self adhesive ability due to addition of adhesives such as acidic ester, acid, and a hydrophilic monomer in a tertiary butanol vehicle. Also, the absence of strong dehydrating agent such as acetone reduces the post-operative sensitivity.
  • x-axis indicates time taken for elution (in minutes) and y- axis indicates magnitude of elution in microabsorbence units.
  • the experimental composite matrix (N2) showed the least elution as shown in the FIG. 2B and the conventional resin matrix (OBT) showed the highest elution as shown in FIG. 2D.
  • the elution rate in the artificial saliva medium is as follows:
  • the experimental organic matrix (Nl) showed the least elution as shown in the FIG. 2E and the conventional matrix (OBT) showed the most elution as shown in the FIG. 2G.
  • the elution rate in the absolute alcohol medium is as follows:
  • FIG. 3A represents cytotoxicity levels in the experimental dental organic matrix and the conventional organic matrix.
  • the experiment was conducted in BH 21 and MG 63 cell lines.
  • x- axis indicates different groups of organic resin matrices and y- axis indicates cell- viability in percentage.
  • the experimental organic resin matrix showed optimum cell viability in both BHK21 and MG63 cell lines.
  • the conventional organic resin matrix showed excessive proliferation of cells leading to abnormal growth of cells which could translate to undesirable hyperplasia greater than the negative control which could probably be due to expression of proliferating cellular nuclear antigen (PCNA) as a result of elution of BisPhenol A.
  • PCNA proliferating cellular nuclear antigen
  • x- axis indicates different group of experimental composites (organic matrix and filler) and the conventional composite (organic matrix and filler) and y-axis indicates cell- viability in percentage.
  • the experiment was conducted on a primary Mes (Mes is a code used in the experiment for Human mesenchymal stem cells) and a permanent cell line BHK 21 using Trypan Blue exclusion dye staining Flow cytometric counting (TB) and mitochondrial assay (MTT) respectively.
  • the experimental composite showed greater cell viability compared to the conventional composites SN (silorane based composite Filtek P90), RF (BisGMA-TEGDMA based composite Restofill) and CX (Polysiloxane-Dimethacrylate based composite Ceram X) in both the cell lines. Thus, greater cell viability corresponds to lower cytotoxicity.
  • x-axis indicates the wave number (cm "1 ) and the y-axis indicates the absorbance.
  • the degree of conversion of the sample was estimated using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy.
  • Nl (U) represents Urethane dimethacrylate (UDMA)
  • N2 (T) represents Triethylene glycol dimethacrylate (TEGDMA)
  • N3 (G) represents Bisphenol A glycidyl methacrylate (Bis-GMA)
  • N4 (E) represents Ethoxylatedbisphenol A dimethacrylate (BisEMA)
  • BT represnts conventional matrix (Bis GMA- TEGDMA)
  • FIG. 5A represents concentration levels of polymerizable components in the experimental dental composites and the conventional composites.
  • x-axis indicates wave number in (cm "1 ) and y- axis indicates absorbance.
  • the experimental composite matrix (1 U) showed the least concentration of 0.025 while the control commercial composite 6S showed the highest concentration of 0.273 for ⁇ -ATR of un- polymerized materials under the peak area under 880 oxirane vibration as shown in the FIG. 5D.
  • the area under peak indicates the concentration of a. particular group in the compound tested. From the above FIGS it is evident that the experimental composite occupies lesser area under the peak. Lesser is the area under the peak, lesser is the concentration.
  • FIG. 6 represents the micro- tensile bond strength levels in the experimerititl dental composites and the conventional composites.
  • x-axis indicates stress applied in Pa and y- axis indicates the experimental dental composites and the conventional composites.
  • FIG. 7 represents the rate of dimensional change in the experimental dental composites and the conventional composites.
  • x-axis indicates dimensional change in percentage and y- axis indicates time taken for the change.
  • the experimental dental composites U and T showed no shrinkage at all the time intervals tested. A mild expansion, having not more than 1.2% was noted for U and T, which is within the standard recommended by ADA for dental materials. Further, the experimental composites G and E showed mild shrinkage till 1 h which was less than commercial composites R and C and initially not different from the low-shrink commercial composite S.
  • FIG. 8A to 8H x-axis indicates wave number in cm-1 and y- axis indicate absorbance.
  • Dental composites available currently are prone to inhibition of polymerization reaction in the presence of oxygen. Unless special precautions are taken like covering the surface of polymerizing material with light-transmitting films, this cannot be prevented.
  • the experimental dental composites 1U, 2G 3E and 4T were found to undergo un- inhibited polymerization in the presence of oxygen as evidenced by the significant reduction in peak areas under their respective polymerizing groups.
  • the area under peak indicates that the oxygen inhibition is not there.

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  • Health & Medical Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dental Preparations (AREA)
  • Compositions Of Macromolecular Compounds (AREA)

Abstract

Les modes de réalisation de la présente invention concernent un composite dentaire ayant une composition de matrice de résine organique. Le composite dentaire décrit et la matrice de résine organique présentent des propriétés améliorées telles qu'une faible élution, une faible toxicité, un degré de conversion élevé, l'absence de rétraction, une faible sensibilité post-opératoire, aucune inhibition de l'oxygène, et une capacité d'auto-adhésion.
PCT/IN2014/000408 2013-06-21 2014-06-20 Formulations composites dentaires WO2014203279A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2709/CHE/2013 2013-06-21
IN2709CH2013 2013-06-21

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WO2014203279A2 true WO2014203279A2 (fr) 2014-12-24
WO2014203279A3 WO2014203279A3 (fr) 2015-02-26

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CN102327194B (zh) * 2004-11-16 2014-07-23 3M创新有限公司 包括酪蛋白酸盐的牙科组合物和制备牙科制品的方法
CA2587275A1 (fr) * 2004-11-16 2006-05-26 3M Innovative Properties Company Charges dentaires et compositions incluant des sels de phosphate
US8710114B2 (en) * 2004-11-16 2014-04-29 3M Innovative Properties Company Dental fillers including a phosphorus containing surface treatment, and compositions and methods thereof
CA2588103A1 (fr) * 2004-11-16 2006-05-26 3M Innovative Properties Company Compositions dentaires avec un verre liberant du calcium et du phosphore
US20060204452A1 (en) * 2005-03-10 2006-09-14 Velamakanni Bhaskar V Antimicrobial film-forming dental compositions and methods

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