WO1997027148A9 - Bioactive glass compositions and methods of treatment using bioactive glass - Google Patents
Bioactive glass compositions and methods of treatment using bioactive glassInfo
- Publication number
- WO1997027148A9 WO1997027148A9 PCT/US1997/001785 US9701785W WO9727148A9 WO 1997027148 A9 WO1997027148 A9 WO 1997027148A9 US 9701785 W US9701785 W US 9701785W WO 9727148 A9 WO9727148 A9 WO 9727148A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- tooth structure
- contacting
- tooth
- bioactive
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 109
- 239000005313 bioactive glass Substances 0.000 title claims abstract description 47
- 239000002245 particle Substances 0.000 claims abstract description 80
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 230000000395 remineralization Effects 0.000 claims abstract description 29
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 15
- 239000000606 toothpaste Substances 0.000 claims abstract description 9
- 229940034610 Toothpaste Drugs 0.000 claims abstract description 7
- 210000000515 Tooth Anatomy 0.000 claims description 91
- 239000011521 glass Substances 0.000 claims description 32
- 230000000975 bioactive Effects 0.000 claims description 17
- 239000000463 material Substances 0.000 claims description 17
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium monoxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 16
- DLYUQMMRRRQYAE-UHFFFAOYSA-N Phosphorus pentoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 10
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 10
- 229910052681 coesite Inorganic materials 0.000 claims description 9
- 229910052906 cristobalite Inorganic materials 0.000 claims description 9
- 229910052904 quartz Inorganic materials 0.000 claims description 9
- 238000007789 sealing Methods 0.000 claims description 9
- 229910052682 stishovite Inorganic materials 0.000 claims description 9
- 229910052905 tridymite Inorganic materials 0.000 claims description 9
- 210000003298 Dental Enamel Anatomy 0.000 claims description 8
- KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims description 8
- 208000002925 Dental Caries Diseases 0.000 claims description 7
- NTGONJLAOZZDJO-UHFFFAOYSA-M disodium;hydroxide Chemical compound [OH-].[Na+].[Na+] NTGONJLAOZZDJO-UHFFFAOYSA-M 0.000 claims description 7
- 230000003239 periodontal Effects 0.000 claims description 7
- WUKWITHWXAAZEY-UHFFFAOYSA-L Calcium fluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 6
- 229910001634 calcium fluoride Inorganic materials 0.000 claims description 6
- 239000006072 paste Substances 0.000 claims description 6
- 231100001004 fissure Toxicity 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 229940051866 Mouthwash Drugs 0.000 claims description 4
- -1 liner Substances 0.000 claims description 4
- 239000002324 mouth wash Substances 0.000 claims description 4
- 239000003827 pulp capping and pulpectomy agent Substances 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims 3
- 201000005794 allergic hypersensitivity disease Diseases 0.000 claims 3
- 230000009610 hypersensitivity Effects 0.000 claims 3
- 210000004268 Dentin Anatomy 0.000 abstract description 37
- 229910052791 calcium Inorganic materials 0.000 abstract description 12
- 238000006243 chemical reaction Methods 0.000 abstract description 8
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 8
- 229910052586 apatite Inorganic materials 0.000 abstract description 5
- 210000001124 Body Fluids Anatomy 0.000 abstract description 4
- 239000010839 body fluid Substances 0.000 abstract description 4
- MMCOUVMKNAHQOY-UHFFFAOYSA-M oxido hydrogen carbonate Chemical compound OOC([O-])=O MMCOUVMKNAHQOY-UHFFFAOYSA-M 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 201000002170 dentin sensitivity Diseases 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 15
- 150000002500 ions Chemical class 0.000 description 12
- 239000011575 calcium Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 210000000988 Bone and Bones Anatomy 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 229960005069 Calcium Drugs 0.000 description 5
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H Tricalcium phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 238000005115 demineralization Methods 0.000 description 5
- 230000002328 demineralizing Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 208000002599 Smear Layer Diseases 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 239000004568 cement Substances 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000036961 partial Effects 0.000 description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 229910001415 sodium ion Inorganic materials 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 238000004626 scanning electron microscopy Methods 0.000 description 3
- 239000000565 sealant Substances 0.000 description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000001519 tissues Anatomy 0.000 description 3
- 210000002540 Macrophages Anatomy 0.000 description 2
- 210000003296 Saliva Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005553 drilling Methods 0.000 description 2
- 230000002708 enhancing Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000007496 glass forming Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000002356 laser light scattering Methods 0.000 description 2
- 230000002045 lasting Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000000068 pit and fissure sealant Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002344 surface layer Substances 0.000 description 2
- 208000004434 Calcinosis Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 210000004283 Incisor Anatomy 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- JMTCDHVHZSGGJA-UHFFFAOYSA-M Potassium hydrogenoxalate Chemical compound [K+].OC(=O)C([O-])=O JMTCDHVHZSGGJA-UHFFFAOYSA-M 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N Silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 210000004746 Tooth Root Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 230000002378 acidificating Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000001464 adherent Effects 0.000 description 1
- 230000001058 adult Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940077747 antacids containing calcium compounds Drugs 0.000 description 1
- 230000000675 anti-caries Effects 0.000 description 1
- 230000001580 bacterial Effects 0.000 description 1
- 230000003385 bacteriostatic Effects 0.000 description 1
- 239000003462 bioceramic Substances 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 239000000316 bone substitute Substances 0.000 description 1
- 230000001680 brushing Effects 0.000 description 1
- 150000001674 calcium compounds Chemical class 0.000 description 1
- 229940043430 calcium compounds Drugs 0.000 description 1
- KBQXDPRNSDVNLB-UHFFFAOYSA-L calcium;carbonic acid;hydrogen phosphate Chemical compound [Ca+2].OC(O)=O.OP([O-])([O-])=O KBQXDPRNSDVNLB-UHFFFAOYSA-L 0.000 description 1
- MFLAROGHONQVRM-UHFFFAOYSA-L calcium;dihydrogen phosphate;fluoride Chemical compound [F-].[Ca+2].OP(O)([O-])=O MFLAROGHONQVRM-UHFFFAOYSA-L 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 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
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002320 enamel (paints) Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009615 fourier-transform spectroscopy Methods 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002962 histologic Effects 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 230000003522 irritant Effects 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 230000000670 limiting Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000002557 mineral fiber Substances 0.000 description 1
- 230000001264 neutralization Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000000149 penetrating Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000717 retained Effects 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- IATRAKWUXMZMIY-UHFFFAOYSA-N strontium oxide Inorganic materials [O-2].[Sr+2] IATRAKWUXMZMIY-UHFFFAOYSA-N 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000000699 topical Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Definitions
- BIOACTIVE GLASS COMPOSITIONS AND METHODS OF TREATMENT USING BIOACTIVE GLASS
- the present invention relates to bioactive glass compositions. More particularly, the present invention relates to improved compositions of bioactive glass including particles having combinations of size ranges significantly lower than previous compositions. The present invention also relates to various methods of treatment including the use of such bioactive glass compositions.
- U.S. Patent No. 5,427,768 discloses calcium phosphate solutions which are supersaturated with respect to calcium phosphate solids and carbon dioxide. The solutions deposit calcium phosphate compounds with or without fluoride on and in the tooth weaknesses such as dental caries, exposed root, or dentin.
- U.S. Patent Nos. 5,268,167 and 5,037,639 disclose the use of amo ⁇ hous calcium compounds such as amo ⁇ hous calcium phosphate, amo ⁇ hous calcium phosphate fluoride and amo ⁇ hous calcium carbonate phosphate for use in remineralizing teeth. These amo ⁇ hous compounds, when applied to dental tissue prevent and/or repair dental weaknesses.
- Demineralization eventually leads to cavitation of enamel coating such that there is exposure of the underlying tooth structure.
- this type of decay is treated by drilling out the decayed region and inserting a semi-permanent filling material.
- a semi-permanent filling material there is a need for a less invasive means of arresting and reversing decay.
- Prophylactic pit and fissure sealants have become widely used in preventing decay in areas that are particularly at risk for decay. These sealants have included polymer or other cements that require a dry application and the use of a fixing agent These sealants are temporary and do not provide for an optimal seal.
- Liners and bases are materials that are used to treat newly exposed tooth surfaces such as those surfaces exposed by drilling. After a cavity is prepared, it is common practice to apply a liner or base before filling the cavity with a filling material.
- a liner is a thin coating of material and a base is a thicker coating.
- Liner and base materials are designed to decrease permeability of dentin at the tooth material interface and protect against microleakage around and through the fill material and to seal dentin tubules.
- Earlier liners or "cavity varnishes” include materials such as organic "gums" dissolved in organic solvents. Upon evaporation of the organic solvent, the gum is left behind.
- 5,296,026 discloses glass phosphate cement compositions and methods for their use as surgical implant materials to fill cavities in bone and canals in teeth.
- the cement compositions include P 2 O 5 , CaO, SrO and Na 2 O in combination with an aqueous liquid with or without therapeutic agents. Mixing the powder and liquid results in a hardening reactions.
- the cement When the cement is implanted into hard tissue, it serves as a filler/graft material and along with the release of leachable constituents it can assist in the healing and maintenance of healthy bone.
- the glass has been reported to be bacteriostatic or bacteriocidal most likely related to the change in pH induced by the dissolution of the ions from the surface of the glass and lack of bacterial adherence to the glass surface.
- the bonding of the glass to bone begins with the exposure of the glass to aqueous solutions. Na + in the glass exchanges with H+ from the body fluids causing the pH to increase. Ca and P migrate from the glass forming a Ca-P rich surface layer. Underlying this
- Ca-P rich is a layer which becomes increasingly silica rich due to the loss of Na, Ca and P ions (U.S. Patent No. 4,851,046).
- the 90-710 ⁇ m size range was determined to be the most effective for periodontal applications when in direct contact with bone. However, size ranges smaller than 90 ⁇ m were ineffective due to their high rate of reactivity and rapid reso ⁇ tion at the bony site. Moreover, size ranges smaller than 90 ⁇ m were determined to be ineffective in soft tissue sites also due to the presumption that the smaller particles were removed by macrophages
- None of the foregoing methods or compositions provide for the combined advantages of both easy application and adherence to tooth structure including penetration into very small tooth structure defects and the opportunity for continued chemical and physical interaction with tooth structure after application.
- the present invention relates to, for example, a bioactive glass composition including particulate bioactive and biocompatible glass including by weight percentage:
- the particulate bioactive and biocompatible glass including particles less than 90 ⁇ m and an effective remineralizing amount of particles less than about 10 ⁇ m.
- the present invention also relates to various methods of dental treatment including remineralization, sealing fissures and/or pits, lining tooth structure, treating decay, capping pulp, treating sensitive post surgical tooth structure, sealing dentinal tubules, and surface for tissue regeneration.
- Figure 1 is a dentin control surface that has been treated with 37% phosphoric acid for 30 seconds to remove any smear layer after sectioning and grinding to emulate clinical sensitivity.
- the surface has not been treated with bioactive glass in accordance with the present invention (2000X magnification).
- Figure 2 is a dentin control surface that has been treated with 37% Phosphoric acid for 30 seconds to remove any smear layer after sectioning and grinding to emulate clinical sensitivity. The surface has not been treated with bioactive glass in accordance with the present invention (3000X magnification).
- Figure 3 is a dentin surface that has been treated with an acid etch and treated with a bioactive glass composition in accordance with the present invention in water and glycerin for 2 minutes (Particle size range submicron to 90 ⁇ m, 1000X magnification).
- Figure 4 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention in water and glycerin for 2 minutes. The surfaces were subsequently agitated and water rinsed for 2 minutes (Particle size range submicron to 20 ⁇ m, 2000X magnification).
- Figure 5 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention and placed in water for 3 days. There was no subsequent agitation, but the surface was water rinsed for 2 minutes
- Figure 6 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention in water and toothpaste for 2 minutes with agitation and a subsequent 2 minute water rinse (Particle size range submicron to 3 ⁇ m, 3000X magnification).
- Figure 7 is a dentin surface that has been acid etched and treated with a bioactive glass composition in accordance with the present invention in water and toothpaste for 2 minutes with agitation and water rinse for 2 minutes (Particle size range submicron to 3 ⁇ m, 3500X magnification).
- Figures 8 and 9 each include a dentin surface which has been acid etched with phosphoric acid, treated with a bioactive glass in accordance with the present invention for 2 minutes and immersed in a phosphate buffered saline for 5 days (Particle size range submicron).
- Figure 10 depicts a dentin surface that has been acid etched and subsequently treated with a single application of a bioactive glass composition in accordance with the present invention.
- Figure 11 depicts a dentin surface that has been acid etched and treated with three separate applications of a bioactive glass composition in accordance with the present invention.
- Figure 12 is a Fourier Transform Spectroscopy (FTIR) performed on samples treated with optimal sizes and shaped particulate bioactive glass.
- FTIR Fourier Transform Spectroscopy
- the present invention provides a bioactive glass composition which is useful in, for example, enamel remineralization, incipient caries remineralization, carious dentin remineralization, caries prevention, arresting decay, reversing decay, anti-caries, pit and fissure sealants, prophylactic pastes, fluoride treatments, dentinal sealants, etc. It can also be included in toothpastes, liners, bases, gels, and restorative material e.g. packing, indirect pulp capping agent, etc. Compositions in accordance with the present invention are also useful in the treatment of surfaces after periodontal surgery to decrease dentinal sensitivity and enhance tissue attachment. The compositions are active in treating various defects associated with a variety of dental and other conditions and actually chemically and physically bond to the tooth thereby remineralizing tooth structure.
- remineralization is the formation of hydroxyapatite.
- the formation of hydroxyapatite begins with exposure of a bioactive glass composition to aqueous solutions. It is believed that the sodium ions (Na+) in the bioactive glass exchanges with H+ ions in body fluids causing pH to increase. Calcium and phosphorus then migrate from the bioactive glass forming a calcium-phosphorous rich surface layer. An underlying silica rich zone slowly increases as the sodium ion in the bioactive glass continues to exchange with the hydrogen ion of the solution. After time, the calcium-phosphorous rich layer crystallizes into a hydroxyapatite material. Collagen can become structurally integrated with the apatite agglomerates.
- an effective remineralizing amount is any amount capable of forming hydroxyapatite.
- a tooth structure is used herein, it is intended to refer to any feature or features of a tooth including but not limited to enamel, dentin, pulp, tooth root structure, cementum, root dentin, coronal dentin, any dental manufacture, etc.
- a bioactive glass in accordance with the present invention is a glass composition that will form a layer of hydroxycarbonate apatite in vitro when placed in a simulated body fluid.
- the following composition by weight will provide a bioactive glass: SiO 2 40-60
- Bioactive glasses with these properties provide a more efficacious material for interaction with the tooth structure.
- a biocompatible glass in accordance with the present invention is one that does not trigger an overwhelmingly adverse immune response.
- bioactive glasses of specified particle sizes are particularly useful in treating the above-mentioned conditions.
- su ⁇ rising results are obtained by the present invention where small and very small particles are combined.
- the larger of these particles adhere to tooth structure and act as ionic reservoirs while the smaller are capable of entering and lodging inside of various tooth structure surface irregularities.
- the larger of these particles provide a reservoir of additional calcium and phosphorous so that the mineralization, or depositing of the calcium phosphate layer begun by the small particles can continue.
- Additional calcium and phosphorous can be leached to all tooth structure as well as to particles which have become attached to the inside or at the openings of surface irregularities of tooth structure such as dentinal tubules. This in turn provides for continuation of the entire reaction and continued growth of the smaller of these particles which have lodged inside or over the openings of such surface irregularities and can result in effectively coating or filling the surface irregularity.
- This excess concentration of ions of calcium and phosphorous is necessary for continued reaction of the smaller of these particles to take place because the smaller particles quickly exhaust their ions as a result of their relatively high surface area.
- the larger of these particles will react and release their ions more slowly as a longer term effect.
- the larger of these particles will mechanically abrade the tooth surface opening various surface irregularities allowing small particles to enter and react with the surface irregularity.
- the composition of the present invention is capable of penetrating into the depths of the smallest of surface irregularities and receiving a continued supply of ions from larger nearby particles so that it is able to grow after exhausting its stored ion supply. This is also very useful in sealing pits and fissures and a much more effective and long lasting seal is obtained.
- extremely small particles are used.
- the occlusion of these tubules leads to a significant reduction in the amount of sensitivity after, for example, periodontal surgery.
- a mixture of particles less than two microns and larger than 45 microns in diameter are ' used. It has been found that this combination yields a particularly effective composition.
- Compositions in accordance with the present invention generally do not require time to set. Previous compositions were easily washed away by mechanical abrasion caused by brushing, exposure to mild acids in food, salivary flow or other liquids which normally come in contact with the teeth.
- compositions in accordance with the present invention have been able to generally withstand significant agitation, rinsing with water and long term soaking in simulated saliva for five days. Moreover, many of the small particles of the present invention do not require a set time because they begin to chemically react and adhere to tooth structure as soon as they come into contact with these surfaces and fluids naturally present in the mouth. Although compositions in accordance with the present invention are effective with a single application, it is likely that multiple applications will be more efficacious.
- the relatively small bioactive particulate glass of the present invention does not generate a significant immune response. Moreover, it is generally not engulfed by macrophages and rendered inactive in this application.
- composition of the present invention is capable of providing a bioactive layer that will form a new structural layer which is a lasting remineralization of tooth structure. This has been verified by the reformation of a hydroxycarbonate apatite layer on dentin surfaces after treatment with compositions in accordance with the present invention with Fourier Transform Infrared spectroscopy (FTIR).
- FTIR Fourier Transform Infrared spectroscopy
- the particles have a particle size of about 20 microns with about 30 percent of the particles less than 10 microns. In another embodiment in accordance with the present invention the particles have an average particle size of 10 microns with at least 25% smaller than 2 microns.
- compositions of the present invention may be formulated into toothpaste.
- the particles may replace the silica currently used in toothpastes.
- fluoride in the glass composition will enhance and strengthen the tooth structure.
- the bioactive glass composition of the present invention can also be applied in a saline or distilled water based medium.
- compositions of the present invention may also be formulated into mouthwash, gel or they may be applied by a dentist as a paste.
- the starting product was a mixture containing (% by weight)
- the mixture was melted in a covered platinum crucible at 1350° C for 2 hours to achieve homogenization.
- the mixture was later quenched in deionized water at 0°C. Fritted glass was placed in an appropriate milling apparatus including ball mill, impact mill. The glass is milled for 2 hours and separated into appropriate size ranges.
- the particle size range less than 90 ⁇ m was obtained using this process and confirmed by scanning electron microscopy and laser light scattering technique (Coulter LS 100). These mixtures were placed on the dentin slabs previously described. The exposure times to the dentin varied between two minutes with scrubbing to 3 days with no agitation. The occlusion of the tubules is depicted in Figures 3-7. Visible in Figures 3-7 are total and partial occlusion of the dentin tubules with multiple size of small (1- 5 ⁇ m) particles present. In addition, larger particles that are visible that will act as reservoirs for the chemical composition. Early formation of hydroxyapatite crystals is beginning on the dentin surface confirmed by FTIR.
- Figures 8 and 9 indicate the results obtainable by using submicron particles made in accordance with Example 1.
- the samples of figures 8 and 9 are dentin surfaces which have been acid etched with phosphoric acid, treated with a bioactive glass for 2 minutes and immersed in a phosphate buffered saline for 5 days. With the lack of large particles for reservoir activity, there was less complete regeneration as confirmed by FTIR.
- Example 3 was conducted to illustrate the benefits associated with multiple applications of compositions in accordance with the present invention.
- an acid etched dentin surface was treated with a single treatment of bioactive particulate glass for two minutes and is depicted in Figure 10.
- a dentin surface which has been acid etched and treated three times for two minutes is depicted in Figure 11.
- Figure 10 shows significant penetration and occlusion of the tubules with a bonding over the surface of the dentin. There are not many large particles visible in Figure 10. In Figure 11, there is even more significant penetration and occlusion of the tubules and a greater number of particles present. This demonstrates the benefits associated with multiple application including the tubules as well as increased presence of larger reservoirs of Ca and P ions. This also demonstrates inte ⁇ article welding of the larger particles to the smaller particles already bound to the surface.
- Example 4 further illustrates the benefits associated with the use of particles less than 2 microns in combination particles greater than 45 microns in size.
- FTIR spectra for the following samples are included in figure 12 to illustrate remineralization:
- 15% were in the range of 20 to 38 microns and 15% were in the range of 38-90 microns.
- the control sample provides a representative view of the spectrum of hydroxycarbonate apatite (HCA).
- HCA hydroxycarbonate apatite
- the shape of the peaks between wave number 1 150 to 500 are very characteristic of HCA.
- the peaks are disrupted after treatment with the acid etchant, especially in the 1150 to 900 range. This indicates a loss of the mineral components of the tooth structure, Calcium and Phosphorous.
- Sample 3 shows a partial remineralization of the Ca and P on the tooth structure.
- Sample 4 was treated with the optimal size and shape mixture of bioactive glass and shows an almost complete remineralization.
- a photomicrograph of Sample 4 is included as Figure 11.
- Comparative Example 5 shows the benefits associated with the use of particles less than 10 microns in combination with particles greater than 45 microns in size over the use of just particles less than 2 microns or 53-90 ⁇ .
- a control sample of untreated dentin surface was used in addition to treated surfaces as described below:
- composition of the starting product for the following examples was the same as
- Example 1 except the level of SiO 2 was 45%, 55%, and 60%. Also, the method of preparation was different. The mixture was melted in a covered platinum crucible at 1350°C for 2 hours to achieve homogenization. The mixture was poured into a slab, allowed to cool to room temperature and crushed with a hammer. Crushed glass fractions were then separated by sieving through a standard screen. Fractions were then separated and retained.
- the particle size range less than 90 ⁇ m was obtained using this process and confirmed by scanning electron microscopy and laser light scattering technique (Coulter LS 100). These mixtures were placed on the dentin slabs previously described.
Abstract
A novel silica-based bioactive glass composition that can be used in conjunction with a delivery agent such as a toothpaste, gel, etc., having a particle size range < 90 νm which will form a rapid and continuous reaction with body fluids due to the immediate and long-term ionic release of Ca and P from the core silica particles, to produce a stable crystalline hydroxy carbonate apatite layer deposited onto and into the dentin tubules for the immediate and long-term reduction of dentin hypersensitivity and tooth surface remineralization.
Description
BIOACTIVE GLASS COMPOSITIONS AND METHODS OF TREATMENT USING BIOACTIVE GLASS
This application is a continuation-in-part application of copending U.S. Application Serial No. 08/597,936 filed February 7, 1996, the disclosure of which is hereby incoφorated by reference. This application is further a continuation-in-part application of copending U.S. Provisional Application Serial No. 60/010,795 filed January 29, 1996, the disclosure of which is hereby incoφorated by reference.
FIELD OF THE INVENTION
The present invention relates to bioactive glass compositions. More particularly, the present invention relates to improved compositions of bioactive glass including particles having combinations of size ranges significantly lower than previous compositions. The present invention also relates to various methods of treatment including the use of such bioactive glass compositions.
BACKGROUND OF THE INVENTION
Human tooth enamel naturally undergoes a process of demineralization. Exposure of enamel to saliva and food slowly leaches minerals from teeth and eventually leads to increased susceptibility to decay. This process of demineralization results in incipient caries which are typically very small defects in the enamel surface that are thus far usually left untreated. Carious dentin demineralization also may occur in patients that have exposed regions of dentin resulting from decay below the cementum-enamel junction. Accordingly, there has been much work associated with slowing this natural process of demineralization including the application of fluoride and other topical treatments.
For example, U.S. Patent No. 5,427,768 discloses calcium phosphate solutions which are supersaturated with respect to calcium phosphate solids and carbon dioxide. The solutions deposit calcium phosphate compounds with or without fluoride on and in the tooth weaknesses such as dental caries, exposed root, or dentin. U.S. Patent Nos. 5,268,167 and 5,037,639 disclose the use of amoφhous calcium compounds such as amoφhous calcium phosphate, amoφhous calcium phosphate fluoride and amoφhous calcium carbonate
phosphate for use in remineralizing teeth. These amoφhous compounds, when applied to dental tissue prevent and/or repair dental weaknesses. The disadvantages of these methods include (1) a low pH necessary for the application which can be an irritant, (2) rapid reaction results in a very short term effect, (3) since these methods use solutions, the actual reactions are difficult to control from patient to patient, and (4) since the reactions are rapid and of short duration, the procedure must be repeated to maintain the effect. Also, both methods require maintaining at least one solution with pressurized CO2 prior to mixing delivery which makes the method difficult to incoφorate into an over-the-counter procedure.
Demineralization eventually leads to cavitation of enamel coating such that there is exposure of the underlying tooth structure. Typically, this type of decay is treated by drilling out the decayed region and inserting a semi-permanent filling material. However, there is a need for a less invasive means of arresting and reversing decay.
Prophylactic pit and fissure sealants have become widely used in preventing decay in areas that are particularly at risk for decay. These sealants have included polymer or other cements that require a dry application and the use of a fixing agent These sealants are temporary and do not provide for an optimal seal.
Liners and bases are materials that are used to treat newly exposed tooth surfaces such as those surfaces exposed by drilling. After a cavity is prepared, it is common practice to apply a liner or base before filling the cavity with a filling material. A liner is a thin coating of material and a base is a thicker coating. Liner and base materials are designed to decrease permeability of dentin at the tooth material interface and protect against microleakage around and through the fill material and to seal dentin tubules. Earlier liners or "cavity varnishes" include materials such as organic "gums" dissolved in organic solvents. Upon evaporation of the organic solvent, the gum is left behind. Disadvantages associated with these organic gums are well documented and include leaky junctions, lack of adherence, acid vulnerability, etc. Another method of lining is disclosed in U.S. Patent No. 4,538,990 which describes applying a 1 to 30% w/v neutral oxalate salt solution, such as dipotassium oxalate to the smear layer and then applying a 0.5 to 3% w/v of an acidic oxalate salt solution such as monopotassium monohydrogen oxalate to the layer. Research has shown poor seal occlusion of the tubules with this method.
U.S. Patent No. 5,296,026 discloses glass phosphate cement compositions and methods for their use as surgical implant materials to fill cavities in bone and canals in teeth. The cement compositions include P2O5, CaO, SrO and Na2O in combination with an aqueous liquid with or without therapeutic agents. Mixing the powder and liquid results in a hardening reactions. When the cement is implanted into hard tissue, it serves as a filler/graft material and along with the release of leachable constituents it can assist in the healing and maintenance of healthy bone.
Various bioactive and biocompatible glasses have been developed as bone replacement materials. Studies have shown that these glasses will induce or aid osteogenesis in a physiologic systems. Hench et al, J. Biomed. Mater. Res. 5:117-141 (1971). The bond developed between the bone and the glass has been demonstrated to be extremely strong and stable. Piotrowski et al., J. Biomed. Mater. Res. 9:47-61 (1975). Toxicology evaluation of the glasses has shown no toxic effects in bone or soft tissue in numerous in vitro and'in vivo models. Wilson et al., J. Biomed. Mater. Res. 805-817 (1981). The glass has been reported to be bacteriostatic or bacteriocidal most likely related to the change in pH induced by the dissolution of the ions from the surface of the glass and lack of bacterial adherence to the glass surface. Stoor et al, Bioceramics Vol. 8 p. 253-258 Wilson et al (1 95).
The bonding of the glass to bone begins with the exposure of the glass to aqueous solutions. Na+ in the glass exchanges with H+ from the body fluids causing the pH to increase. Ca and P migrate from the glass forming a Ca-P rich surface layer. Underlying this
Ca-P rich is a layer which becomes increasingly silica rich due to the loss of Na, Ca and P ions (U.S. Patent No. 4,851,046).
The behavior of the bioactive glass as solid implants in a dental application was reported by Stanley et al., Journal of Prostetic Dentistry, Vol. 58, pp. 607-613 (1987). Replicate tooth forms were fabricated and implanted into extracted incisor sockets of adult baboons. Successful attachment of the implants to surrounding bone was seen after histologic examination at six months. Clinical application of this technique is presently available for human use. Endosseous Ridge Maintenance Implant ERMI®. Particulate bioactive glass has been used for periodontal osseous defect repair (US Patent No. 4,851 ,046) utilizing a size range of 90-710 μm and a compositional range described in the following chart.
Component Weight Percentage SiO2 40-55
CaO 10-30
Na2O 10-35 P205 2-8
CaF2 0-25
B203 0-10
Previously described data has shown that 60% silica is beyond the limit of bioactive melt derived glasses. Okasuki et al. Nippon Seramikbusu Kyokai Gakijutsu Konbuski, Vol. 99, pp. 1-6 (1991).
The 90-710 μm size range was determined to be the most effective for periodontal applications when in direct contact with bone. However, size ranges smaller than 90 μm were ineffective due to their high rate of reactivity and rapid resoφtion at the bony site. Moreover, size ranges smaller than 90 μm were determined to be ineffective in soft tissue sites also due to the presumption that the smaller particles were removed by macrophages
(see U.S. Patent No. 4,851,046). A size range of less than 200 μm was also found to be ineffective in certain bone defects (see U.S. Patent No. 5,204,106) due to the high rate of reactivity.
U.S. Patent No. 4,239,113 ("the '113 patent") also describes the use of a bone cement. The '113 patent only discloses bioactive glass ceramic powder having a particle size of 10-
200 microns. Moreover, the '113 patent also requires the use of methylmethacrylate (co)polymers and vitreous mineral fibers.
None of the foregoing methods or compositions provide for the combined advantages of both easy application and adherence to tooth structure including penetration into very small tooth structure defects and the opportunity for continued chemical and physical interaction with tooth structure after application.
Accordingly, it is an object of the present invention to provide a composition capable of chemical and physical interaction with tooth structure that is easily applied and readily adherent to tooth structure. It is a further object of the invention to provide a method of using such a bioactive glass composition to treat a variety of dental and other conditions.
SUMMARY OF THE INVENTION
The present invention relates to, for example, a bioactive glass composition including particulate bioactive and biocompatible glass including by weight percentage:
SiO2 40-60
CaO 10-30
Na20 10-35
P20s 2-8
CaF2 0-25
B203 0-10
K2O 0-8
MgO 0-5, the particulate bioactive and biocompatible glass including particles less than 90 μm and an effective remineralizing amount of particles less than about 10 μm. The present invention also relates to various methods of dental treatment including remineralization, sealing fissures and/or pits, lining tooth structure, treating decay, capping pulp, treating sensitive post surgical tooth structure, sealing dentinal tubules, and surface for tissue regeneration.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a dentin control surface that has been treated with 37% phosphoric acid for 30 seconds to remove any smear layer after sectioning and grinding to emulate clinical sensitivity. The surface has not been treated with bioactive glass in accordance with the present invention (2000X magnification).
Figure 2 is a dentin control surface that has been treated with 37% Phosphoric acid for 30 seconds to remove any smear layer after sectioning and grinding to emulate clinical sensitivity. The surface has not been treated with bioactive glass in accordance with the present invention (3000X magnification).
Figure 3 is a dentin surface that has been treated with an acid etch and treated with a bioactive glass composition in accordance with the present invention in water and glycerin for 2 minutes (Particle size range submicron to 90 μm, 1000X magnification).
Figure 4 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention in water and glycerin for 2 minutes. The surfaces were subsequently agitated and water rinsed for 2 minutes (Particle size range submicron to 20 μm, 2000X magnification).
Figure 5 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention and placed in water for 3 days. There was no subsequent agitation, but the surface was water rinsed for 2 minutes
(Particle size range submicron to 90 μm, 2000X magnification).
Figure 6 is a dentin surface that has been acid etched and subsequently treated with a bioactive glass composition in accordance with the present invention in water and toothpaste for 2 minutes with agitation and a subsequent 2 minute water rinse (Particle size range submicron to 3 μm, 3000X magnification).
Figure 7 is a dentin surface that has been acid etched and treated with a bioactive glass composition in accordance with the present invention in water and toothpaste for 2 minutes with agitation and water rinse for 2 minutes (Particle size range submicron to 3 μm, 3500X magnification). Figures 8 and 9 each include a dentin surface which has been acid etched with phosphoric acid, treated with a bioactive glass in accordance with the present invention for 2 minutes and immersed in a phosphate buffered saline for 5 days (Particle size range submicron).
Figure 10 depicts a dentin surface that has been acid etched and subsequently treated with a single application of a bioactive glass composition in accordance with the present invention.
Figure 11 depicts a dentin surface that has been acid etched and treated with three separate applications of a bioactive glass composition in accordance with the present invention. Figure 12 is a Fourier Transform Spectroscopy (FTIR) performed on samples treated with optimal sizes and shaped particulate bioactive glass.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a bioactive glass composition which is useful in, for example, enamel remineralization, incipient caries remineralization, carious dentin remineralization, caries prevention, arresting decay, reversing decay, anti-caries, pit and fissure sealants, prophylactic pastes, fluoride treatments, dentinal sealants, etc. It can also be included in toothpastes, liners, bases, gels, and restorative material e.g. packing, indirect pulp capping agent, etc. Compositions in accordance with the present invention are also useful in the treatment of surfaces after periodontal surgery to decrease dentinal sensitivity and enhance tissue attachment. The compositions are active in treating various defects associated with a variety of dental and other conditions and actually chemically and physically bond to the tooth thereby remineralizing tooth structure.
As referred to herein, remineralization is the formation of hydroxyapatite. The formation of hydroxyapatite begins with exposure of a bioactive glass composition to aqueous solutions. It is believed that the sodium ions (Na+) in the bioactive glass exchanges with H+ ions in body fluids causing pH to increase. Calcium and phosphorus then migrate from the bioactive glass forming a calcium-phosphorous rich surface layer. An underlying silica rich zone slowly increases as the sodium ion in the bioactive glass continues to exchange with the hydrogen ion of the solution. After time, the calcium-phosphorous rich layer crystallizes into a hydroxyapatite material. Collagen can become structurally integrated with the apatite agglomerates. As hereinafter referred to, an effective remineralizing amount is any amount capable of forming hydroxyapatite.
As the term "a tooth structure" is used herein, it is intended to refer to any feature or features of a tooth including but not limited to enamel, dentin, pulp, tooth root structure, cementum, root dentin, coronal dentin, any dental manufacture, etc.
A bioactive glass in accordance with the present invention is a glass composition that will form a layer of hydroxycarbonate apatite in vitro when placed in a simulated body fluid. For example, the following composition by weight will provide a bioactive glass:
SiO2 40-60
CaO 10-30
Na2O 10-35
P205 2-8
CaF2 0-25
B203 0-10
K2O 0-8
MgO 0-5
Bioactive glasses with these properties provide a more efficacious material for interaction with the tooth structure. A biocompatible glass in accordance with the present invention is one that does not trigger an overwhelmingly adverse immune response.
In accordance with the present invention, it has been found that bioactive glasses of specified particle sizes are particularly useful in treating the above-mentioned conditions. Specifically, suφrising results are obtained by the present invention where small and very small particles are combined. For example, when compositions including small particles that are capable of bonding with tooth structure (e.g. less than about 90 microns) as well smaller particles (e.g. less than about 10) are used in combination, the larger of these particles adhere to tooth structure and act as ionic reservoirs while the smaller are capable of entering and lodging inside of various tooth structure surface irregularities. The larger of these particles provide a reservoir of additional calcium and phosphorous so that the mineralization, or depositing of the calcium phosphate layer begun by the small particles can continue. Additional calcium and phosphorous can be leached to all tooth structure as well as to particles which have become attached to the inside or at the openings of surface irregularities of tooth structure such as dentinal tubules. This in turn provides for continuation of the entire reaction and continued growth of the smaller of these particles which have lodged inside or over the openings of such surface irregularities and can result in effectively coating or filling the surface irregularity. This excess concentration of ions of calcium and phosphorous is necessary for continued reaction of the smaller of these particles to take place because the smaller particles quickly exhaust their ions as a result of their relatively high surface area. The larger of these particles will react and release their ions more slowly as a longer term effect. Furthermore, the larger of these particles will mechanically abrade the tooth surface
opening various surface irregularities allowing small particles to enter and react with the surface irregularity.
This effect is very beneficial in a variety of applications. For example, in preventing caries or decay, the composition of the present invention is capable of penetrating into the depths of the smallest of surface irregularities and receiving a continued supply of ions from larger nearby particles so that it is able to grow after exhausting its stored ion supply. This is also very useful in sealing pits and fissures and a much more effective and long lasting seal is obtained.
In some embodiments of the present invention, extremely small particles are used. For example, particles that are in the range of 2 μm to submicron fit inside dentin tubules that are approximately 1-2 μm in diameter. The occlusion of these tubules leads to a significant reduction in the amount of sensitivity after, for example, periodontal surgery. Preferably, a mixture of particles less than two microns and larger than 45 microns in diameter are'used. It has been found that this combination yields a particularly effective composition. Compositions in accordance with the present invention generally do not require time to set. Previous compositions were easily washed away by mechanical abrasion caused by brushing, exposure to mild acids in food, salivary flow or other liquids which normally come in contact with the teeth. However, some compositions in accordance with the present invention have been able to generally withstand significant agitation, rinsing with water and long term soaking in simulated saliva for five days. Moreover, many of the small particles of the present invention do not require a set time because they begin to chemically react and adhere to tooth structure as soon as they come into contact with these surfaces and fluids naturally present in the mouth. Although compositions in accordance with the present invention are effective with a single application, it is likely that multiple applications will be more efficacious.
Suφrisingly, the relatively small bioactive particulate glass of the present invention does not generate a significant immune response. Moreover, it is generally not engulfed by macrophages and rendered inactive in this application.
The composition of the present invention is capable of providing a bioactive layer that will form a new structural layer which is a lasting remineralization of tooth structure. This has been verified by the reformation of a hydroxycarbonate apatite layer on dentin surfaces
after treatment with compositions in accordance with the present invention with Fourier Transform Infrared spectroscopy (FTIR).
In one embodiment in accordance with the present invention, the particles have a particle size of about 20 microns with about 30 percent of the particles less than 10 microns. In another embodiment in accordance with the present invention the particles have an average particle size of 10 microns with at least 25% smaller than 2 microns.
The compositions of the present invention may be formulated into toothpaste. In fact, the particles may replace the silica currently used in toothpastes. The addition of fluoride in the glass composition will enhance and strengthen the tooth structure. In addition to direct application of the bioactive glass to the teeth, the bioactive glass composition of the present invention can also be applied in a saline or distilled water based medium.
The compositions of the present invention may also be formulated into mouthwash, gel or they may be applied by a dentist as a paste.
Examples
The following working examples are non-limiting:
In vitro experiments were performed using a standardized slab of human tooth dentin from extracted teeth. These discs were cut from the extracted teeth using an Isomet diamond saw (Buchler Ltd.). The discs were 1.0 mm thick and the size of the tooth. The occlusal surfaces were ground on a series of wet silicon-carbide papers ranging from 320 to 600 grit.
This was done to standardize the test surfaces. The surfaces were treated with 37% phosphoric acid for 60 seconds to remove the smear layer created during the grinding process and open and enlarge all the dentin tubules (See Figures 1 and 2). The surface was rinsed with distilled water for 20 seconds and dried with a stream of oil free air. Each slab was split in half and the experimental material placed on one-half of the specimen as described in the examples. An untreated slab with open and enlarged tubules is shown in Figures 1 and 2.
Scanning electron microscopy was performed on the slab surface in each group. The slabs were mounted on scanning electron microscope stubs using sliver paste. AU specimens were vacuum dried, sputter coated and examined in a JEOL-T200 scanning electron microscope.
EXAMPLE I
The starting product was a mixture containing (% by weight)
SiO2 45 CaO 24.5
Na2O 24.5
P2O5 6
The mixture was melted in a covered platinum crucible at 1350° C for 2 hours to achieve homogenization. The mixture was later quenched in deionized water at 0°C. Fritted glass was placed in an appropriate milling apparatus including ball mill, impact mill. The glass is milled for 2 hours and separated into appropriate size ranges.
The particle size range less than 90 μm was obtained using this process and confirmed by scanning electron microscopy and laser light scattering technique (Coulter LS 100). These mixtures were placed on the dentin slabs previously described. The exposure times to the dentin varied between two minutes with scrubbing to 3 days with no agitation. The occlusion of the tubules is depicted in Figures 3-7. Visible in Figures 3-7 are total and partial occlusion of the dentin tubules with multiple size of small (1- 5 μm) particles present. In addition, larger particles that are visible that will act as reservoirs for the chemical composition. Early formation of hydroxyapatite crystals is beginning on the dentin surface confirmed by FTIR.
EXAMPLE 2
Figures 8 and 9 indicate the results obtainable by using submicron particles made in accordance with Example 1. The samples of figures 8 and 9 are dentin surfaces which have been acid etched with phosphoric acid, treated with a bioactive glass for 2 minutes and immersed in a phosphate buffered saline for 5 days. With the lack of large particles for reservoir activity, there was less complete regeneration as confirmed by FTIR.
EXAMPLE 3
Example 3 was conducted to illustrate the benefits associated with multiple applications of compositions in accordance with the present invention. First, an acid etched dentin surface was treated with a single treatment of bioactive particulate glass for two minutes and is depicted in Figure 10. A dentin surface which has been acid etched and treated three times for two minutes is depicted in Figure 11.
Figure 10 shows significant penetration and occlusion of the tubules with a bonding over the surface of the dentin. There are not many large particles visible in Figure 10. In Figure 11, there is even more significant penetration and occlusion of the tubules and a greater number of particles present. This demonstrates the benefits associated with multiple application including the tubules as well as increased presence of larger reservoirs of Ca and P ions. This also demonstrates inteφarticle welding of the larger particles to the smaller particles already bound to the surface.
EXAMPLE 4
Example 4 further illustrates the benefits associated with the use of particles less than 2 microns in combination particles greater than 45 microns in size. FTIR spectra for the following samples are included in figure 12 to illustrate remineralization:
Sample No. 1 Control (untreated dentin surface)
Sample No. 2 Acid etched dentin surface
Sample No. 3 Treated with particles of bioactive glass less than 2 microns in particle size for two minutes
Sample No. 4 Treated with particles of bioactive glass wherein 40% were less than 2 microns, 15% were in the range of 8 to 2 microns, 15% were in the range of 8 to 20 microns,
15% were in the range of 20 to 38 microns and 15% were in the range of 38-90 microns.
As illustrated in Figure 12, the control sample provides a representative view of the spectrum of hydroxycarbonate apatite (HCA). The shape of the peaks between wave number
1 150 to 500 are very characteristic of HCA. In sample 2, the peaks are disrupted after treatment with the acid etchant, especially in the 1150 to 900 range. This indicates a loss of the mineral components of the tooth structure, Calcium and Phosphorous. Sample 3 shows a partial remineralization of the Ca and P on the tooth structure. Sample 4 was treated with the optimal size and shape mixture of bioactive glass and shows an almost complete remineralization. A photomicrograph of Sample 4 is included as Figure 11.
EXAMPLE 5
Comparative Example 5 shows the benefits associated with the use of particles less than 10 microns in combination with particles greater than 45 microns in size over the use of just particles less than 2 microns or 53-90μ. A control sample of untreated dentin surface was used in addition to treated surfaces as described below:
Number of Sample Score Observations Applications Composition
Single 53-90μ 2 About 50% occluded tubules with large particles present
Control 0 No particles present
Single <2μ 2 Above 50% closure, no large particles seen
Control 0 Open tubules
Single 50% 53-90μ +3 75%+ tubules occluded 50% <2μ
Control 0 Open tubules
Multiple 53-90μ 2 Partial closure of tubules with large particles present
Control 0 Minimal occlusion seen
Multiple <2μ 2 Partial closure of tubules with small particles present
Control 0 Minimal occlusion seen
Multiple 50% 53-90μ +3 Best results— tubules closed; difficult to
50% <2μ find open tubules
Control 0 Minimal occlusion seen
All samples in the above Table were subjected to a moist environment for 24 hours and then dried for 48 hours.
As seen above, the combination of particles less than 2 microns and 53-90μ provided the best results. It is believed that the presence of both size ranges permits the smaller particles which have lodged in the tubules to continue growth after they have exhausted their own Ca and P ions and are able to make use of such ions from other nearby larger particles acting as reservoirs of Ca and P ions.
OTHER EXAMPLES
The composition of the starting product for the following examples was the same as
Example 1 except the level of SiO2 was 45%, 55%, and 60%. Also, the method of preparation was different. The mixture was melted in a covered platinum crucible at 1350°C for 2 hours to achieve homogenization. The mixture was poured into a slab, allowed to cool to room temperature and crushed with a hammer. Crushed glass fractions were then separated by sieving through a standard screen. Fractions were then separated and retained.
The particle size range less than 90 μm was obtained using this process and confirmed by scanning electron microscopy and laser light scattering technique (Coulter LS 100). These mixtures were placed on the dentin slabs previously described.
Samples containing 45%, 55%, and 60% SiO2 were utilized in the preparations with the same results seen in Example 1. Again, the key to this data was the presence of the size range of particles. Present in these examples are ranges up to 60% silica with a size range in
particles from submicron to 90 micron showing like reactions to Example 1 on the dentin surfaces.
Although the present invention has been described in one or more embodiments, this description is not intended to in any way limit the scope of the claims.
Claims
1. A bioactive glass composition comprising particulate bioactive and biocompatible glass including by weight percentage:
SiO2 40-60
CaO 10-30
Na2O 10-35
P2O5 2-8
CaF2 0-25
B203 0-10
K2O 0-8
MgO 0-5, the particulate bioactive and biocompatible glass including particles less than 90 μm and an effective remineralizing amount of particles less than about 10 μm.
2. A method for preventing tooth decay comprising contacting a tooth structure with the composition of claim 1.
3. A method for treating tooth decay comprising contacting a tooth structure with the composition of claim 1.
4. A method for preventing incipient carries comprising contacting a tooth structure with the composition of claim 1.
5. A method for remineralizing enamel comprising contacting a tooth structure with the composition of claim 1.
6. A method for incipient caries remineralization comprising contacting a tooth structure with the composition of claim 1.
7. A method for sealing fissures in tooth structure comprising contacting a tooth structure with the composition of claim 1.
8. A method for sealing pits in tooth structure comprising contacting a tooth structure with the composition of claim 1.
9. A method for lining tooth structure comprising contacting a tooth structure with the composition of claim 1.
10. A method for capping pulp comprising contacting a tooth structure with the composition of claim 1.
1 1. A method for treating tooth hypersensitivity comprising contacting a tooth structure with the composition of claim 1.
12. A method for treating tooth structure after periodontal surgery comprising contacting a tooth structure with the composition of claim 1.
13. A composition for treating teeth comprising the composition of claim 1 and a toothpaste, liner, base, gel, restorative material, glycerin gel, mouthwash, prophylactic paste, or indirect pulp capping agent, or mixture thereof.
14. A bioactive glass composition comprising particulate bioactive and biocompatible glass including by weight percentage:
SiO2 40-60
CaO 10-30
Na2O 10-35
P205 2-8
CaF2 0-25
B203 0-10
K2O 0-8
MgO 0-5, the particulate bioactive and biocompatible glass including particles between 45 μ and 90 μm and an effective remineralizing amount of particles less than about 10 μm.
15. A method for preventing tooth decay comprising contacting a tooth structure with the composition of claim 14.
16. A method for treating tooth decay comprising contacting a tooth structure with the composition of claim 14.
17. A method for preventing incipient carries comprising contacting a tooth structure with the composition of claim 14.
18. A method for remineralizing enamel comprising contacting a tooth structure with the composition of claim 14.
19. A method for incipient caries remineralization comprising contacting a tooth structure with the composition of claim 14.
20. A method for sealing fissures in tooth structure comprising contacting a tooth structure with the composition of claim 14.
21. A method for sealing pits in tooth structure comprising contacting a tooth structure with the composition of claim 14.
22. A method for lining tooth structure comprising contacting a tooth structure with the composition of claim 14.
23. A method for capping pulp comprising contacting a tooth structure with the composition of claim 14.
24. A method for treating tooth hypersensitivity comprising contacting a tooth structure with the composition of claim 14.
25. A method for treating tooth structure after periodontal surgery comprising contacting a tooth structure with the composition of claim 14.
26. A composition for treating teeth comprising the composition of claim 14 and a toothpaste, liner, base, gel, restorative material, glycerin gel, mouthwash, prophylactic paste, or indirect pulp capping agent, or mixture thereof.
27. A bioactive glass composition comprising particulate bioactive and biocompatible glass including particles less than 90 μm and an effective remineralizing amount of particles less than about 10 μm.
28. A bioactive glass composition comprising particulate bioactive and biocompatible glass including particles less than 90 μm and an effective remineralizing amount of particles less than about 5 μm.
29. A bioactive glass composition comprising particulate bioactive and biocompatible glass including particles less than 90 μm and an effective remineralizing amount of particles less than about 2 μm.
30. A method for preventing tooth decay comprising contacting a tooth structure with the composition of claim 27.
31. A method for treating tooth decay comprising contacting a tooth structure with the composition of claim 27.
32. A method for preventing incipient carries comprising contacting a tooth structure with the composition of claim 27.
33. A method for remineralizing enamel comprising contacting a tooth structure with the composition of claim 27.
34. A method for incipient caries remineralization comprising contacting a tooth structure with the composition of claim 27.
35. A method for sealing fissures in tooth structure comprising contacting a tooth structure with the composition of claim 27.
36. A method for sealing pits in tooth structure comprising contacting a tooth structure with the composition of claim 27.
37. A method for lining tooth structure comprising contacting a tooth structure with the composition of claim 27.
38. A method for capping pulp comprising contacting a tooth structure with the composition of claim 27.
39. A method for treating tooth hypersensitivity comprising contacting a tooth structure with the composition of claim 27.
40. A method for treating tooth structure after periodontal surgery comprising contacting a tooth structure with the composition of claim 27.
41. A composition for treating teeth comprising the composition of claim 27 and a toothpaste, liner, base, gel, restorative material, glycerin gel, mouthwash, prophylactic paste, or indirect pulp capping agent, or mixture thereof.
42. A bioactive glass composition comprising particulate bioactive and biocompatible glass including particles less than 90 μm and particles less than about 2 μm.
43. A method for remineralizing tooth structure comprising contacting a tooth structure in need of remineralization with a bioactive glass composition including an effective remineralizing amount of particles less than 90 μm.
44. A bioactive glass composition comprising particulate bioactive and biocompatible glass including by weight percentage:
SiO2 40-60
CaO 10-30
Na2O 10-35
P205 2-8
CaF2 0-25
B203 0-10
K2O 0-8
MgO 0-5, the particulate bioactive and biocompatible glass including particles between 53 μ and 90 μm and an effective remineralizing amount of particles less than about 2 μm.
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT97906489T ATE279380T1 (en) | 1996-01-29 | 1997-01-29 | BIOACTIVE GLASS COMPOSITIONS FOR USE IN TREATING DENTAL STRUCTURES |
NZ331514A NZ331514A (en) | 1996-01-29 | 1997-01-29 | A silica based bioactive glass composition having a particle size range less than 90 microns that can be used in conjunction with a delivery agent e.g. toothpaste to release Ca and P from the silica particles and methods of treatment using bioactive glass |
SK1029-98A SK102998A3 (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions and methods of treatment using bioactive glass |
CA002244722A CA2244722C (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions and methods of treatment using bioactive glass |
DE69731184T DE69731184T2 (en) | 1996-01-29 | 1997-01-29 | BIOACTIVE GLASS COMPOSITIONS FOR USE FOR THE TREATMENT OF DENTAL STRUCTURES |
IL12556097A IL125560A0 (en) | 1996-01-29 | 1997-01-29 | A bioactive glass composition and a composition for treating teeth comprising the glass composition |
JP52713197A JP4180657B2 (en) | 1996-01-29 | 1997-01-29 | Bioactive glass composition |
AU21171/97A AU723659B2 (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions and methods of treatment using bioactive glass |
SI9720016A SI9720016A (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions and methods of treatment using bioactive glass |
BR9707219-2A BR9707219A (en) | 1996-01-29 | 1997-01-29 | Float glass compositions and treatment methods using bioactive glass. |
EP97906489A EP0877716B1 (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions for use in the treatment of tooth structures |
NO983490A NO983490L (en) | 1996-01-29 | 1998-07-29 | Bioactive glass compositions and treatment methods using bioactive glass |
BG102722A BG102722A (en) | 1996-01-29 | 1998-08-25 | Biologically active vitreous compositions and method for their treatment making use of biologically active glass |
HK99104392A HK1019222A1 (en) | 1996-01-29 | 1999-10-07 | Bioactive glass compositions and methods of treatment using bioactive glass |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1079596P | 1996-01-29 | 1996-01-29 | |
US60/010,795 | 1996-01-29 | ||
US59793696A | 1996-02-07 | 1996-02-07 | |
US08/597,936 | 1996-02-07 | ||
USNOTFURNISHED | 2004-06-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1997027148A1 WO1997027148A1 (en) | 1997-07-31 |
WO1997027148A9 true WO1997027148A9 (en) | 1997-10-16 |
Family
ID=26681603
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/001785 WO1997027148A1 (en) | 1996-01-29 | 1997-01-29 | Bioactive glass compositions and methods of treatment using bioactive glass |
Country Status (4)
Country | Link |
---|---|
JP (2) | JP4180657B2 (en) |
HU (1) | HUP9901760A3 (en) |
PT (1) | PT877716E (en) |
WO (1) | WO1997027148A1 (en) |
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- 1997-01-29 HU HU9901760A patent/HUP9901760A3/en unknown
- 1997-01-29 WO PCT/US1997/001785 patent/WO1997027148A1/en active IP Right Grant
- 1997-01-29 PT PT97906489T patent/PT877716E/en unknown
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2008
- 2008-01-16 JP JP2008007010A patent/JP5020833B2/en not_active Expired - Lifetime
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