WO2012117218A1 - Biomatériau - Google Patents

Biomatériau Download PDF

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Publication number
WO2012117218A1
WO2012117218A1 PCT/GB2012/000197 GB2012000197W WO2012117218A1 WO 2012117218 A1 WO2012117218 A1 WO 2012117218A1 GB 2012000197 W GB2012000197 W GB 2012000197W WO 2012117218 A1 WO2012117218 A1 WO 2012117218A1
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WO
WIPO (PCT)
Prior art keywords
substituent
biomaterial according
mol
biomaterial
combination
Prior art date
Application number
PCT/GB2012/000197
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English (en)
Inventor
Benjamin Peter McCARTHY
Xiang Cheng Zhang
Anthony KINZELLA
Philip Robert Jackson
Original Assignee
Ceram Research Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ceram Research Limited filed Critical Ceram Research Limited
Publication of WO2012117218A1 publication Critical patent/WO2012117218A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite

Definitions

  • This invention concerns a biomaterial, and particularly a biomaterial comprising synthetic hydroxyapatite into which one or more substituent components has been introduced.
  • Hydroxyapatite is used in a range of applications relating to bone replacement/interface. Typical uses include coatings on bio-inert metallic implants in order to improve biocompatibility (and so new bone in-growth) and to reduce the risk of rejection. In another use porous HA granulates may be employed to encourage fresh bone growth in voids arising from disease or trauma.
  • a biomaterial comprising synthetic hydroxyapatite in which up to 10% by molar composition in total of substituent components for the phosphate are provided, with the phosphate substituent components comprising at least two of a sulphate, silicate or borate, with the total mean charge difference by virtue of the phosphate substituent components being less than 1.8 F.mol '2 .
  • the total mean charge difference by virtue of the phosphate substituent components may be less than 0.9 F.mol '2 and may be less than 0.432 F.mol '2 .
  • the substituent components for the phosphate may be derived from an element, or a compound of an element and oxygen.
  • the substituent components for the phosphate may be anions.
  • the substituent component for the phosphate may therefore also include aluminate or titanate.
  • a substituent component may also be provided for the calcium.
  • the substituent component for the calcium may be an element.
  • the substituent component for the calcium may be a cation.
  • the substituent component for the calcium may be any of magnesium, silver, barium, strontium, zinc, sodium, potassium, aluminium, titanium, yttrium, lanthanum, Iron, a lanthanide, an actinide, a transition metal, or copper
  • a substituent component may also be provided for the hydroxyl.
  • the substituent component for the hydroxyl may be an anion.
  • the substituent component for the hydroxyl may be any of fluorine, chlorine, bromine, iodine or carbonate.
  • the synthetic hydroxyapatite may comprise up to 10% by molar composition in total of substituent components for the calcium.
  • the synthetic hydroxyapatite may comprise up to 10% by molar composition in total of a substituent components for the hydroxyl.
  • the synthetic hydroxyapatite may comprise up to 10% by molar composition in total of substituent components for phosphate, calcium and hydroxyl.
  • the substituent components may comprise a combination of silicate, sulphate and strontium.
  • the substituent components may comprise a combination of silicate and sulphate.
  • the substituent components may comprise a combination of silicate, borate and strontium.
  • the substituent components may comprise a combination of sulphate, borate and strontium.
  • the substituent components may comprise a combination of silicate, borate and Magnesium.
  • the substituent components may comprise a combination of sulphate, borate and magnesium
  • the substituent components may comprise a combination of silicate, sulphate and Magnesium
  • the substituent components may comprise a combination of sulphate, silicate and borate.
  • the substituent components may comprise a combination of sulphate, silicate, borate and sodium.
  • the substituent components may comprise a combination of sulphate, borate and sodium.
  • the substituent components may comprise a combination of silicate, borate, sodium and yttrium.
  • the substituent components may comprise a combination of sulphate, borate and chlorine.
  • the biomaterial may be made by a precipitation method, and may be made so as to produce crystallites of less than 250 nanometres. Following precipitation the material may be filtered, dried and sintered.
  • Examples 1 and 2 show a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate and silicate substituent components.
  • Example 1 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate and silicate substituent components.
  • Example 1 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate and silicate substituent components.
  • Example 1 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate and silicate substituent components.
  • Pre-calcination XRD showed a large amount of amorphous material (40-50%), with a HA phase evident.
  • the powder was placed inside a ceramic crucible and calcined at 1100 °C for 3 hours. Ramp rate was controlled to 10 °C / hr.
  • Following calcination XRD showed a significant decrease in the amount of amorphous, and a large increase in the crystallinity (shown by a sharpening of the HA peaks).
  • the amorphous dropped to ⁇ 5%, with the primary phase remaining being HA.
  • Some CaO (aprx 1 %) was present as a result from the slightly high ratio.
  • Example 3 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with silicate, borate and strontium substituent components.
  • Examples 4 and 5 show a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, borate and strontium substituent components.
  • Example 5 Ca(OH) 2 (1 1.74 g, 15.85 x 10 '2 mol) and Sr(OH) 2 (2.216 g, 0.834 x 10 "2 mol) was dissolved in water (660 mL).
  • H 3 P0 4 (0.6M, 173.72 mL, 10.423 x 10 "2 mol)
  • H 2 S0 4 0.6M, 2.92 mL, 0.175 x 10 ⁇ 2 mol
  • H3BO3 0.M, 3.75 mL, 0.225 x 10 "2 mol
  • Example 6 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, borate and magnesium substituent components.
  • Example 7 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, silicate and borate substituent components.
  • Example 8 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, silicate, borate and sodium substituent components.
  • Example 8 Ca(OH) 2 (12.11 g, 16.35 x 10 '2 mol) and NaOH (0.133 g, 0.334 x 10 "2 mol) was dissolved in water (660 ml_). ⁇ 3 ⁇ 0 4 (0.6M, 180.29 ml_, 10.817 x 10 "2 mol), H 2 S0 4 (0.6M, 6.67 mL, 0.400 x 10 "2 mol), TEOS (0.554 ml_, 0.250 x 10 '2 mol) and ⁇ 3 ⁇ 0 3 (0.6M, 1.67 mL, 0.100 x 10 "2 mol) were added to the stirring mixture. The mixture had no external pH control. The mixture was left stirring at 45°C for 3 hours.
  • the cation to anion ratio is 1 .667, the total charge difference is -0.04 F.mol '2 , a total cation charge difference of 0.32 F.mol “2 and a total anion charge difference of -0.36 F.mol "2 .
  • Example 9 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, borate and sodium substituent components.
  • the cation to anion ratio is 1 .667, the total charge difference is - 0.336 F.mol "2 , a total cation charge difference of 0.24 F.mol '2 and a total anion charge difference of -0.576 F.mol '2 .
  • Example 10 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with silicate, borate, sodium and yttrium substituent components.
  • Example 10 Ca(OH) 2 (11 .94 g, 16.1 1 x 10 '2 mol), Y 2 0 3 (0.320 g, 0.142 x 10 "2 mol) and NaOH (0.1 13 g, 0.284 x 10 '2 mol) was dissolved in water (660 ml_).
  • H 3 P0 4 (0.6M, 177.04 mL, 10.622 x 10 '2 mol), TEOS (0.621 ml_, 0.280 x ,0" 2 mol) and H3BO3 (0.6 , 5.00 mL, 0.300 x 10 "2 mol) were added to the stirring mixture.
  • the mixture had no external pH control.
  • the mixture was left stirring at 45°C for 3 hours.
  • the cation to anion ratio is 1 .667, the total charge difference is 0,672 F.mol '2 , a total cation charge difference of 0 F.mor 2 and a total anion charge difference of 0.672 F.mol "2 .
  • Example 11 shows a wet chemical precipitation route used to prepare a synthetic hydroxyapatite biomaterial with sulphate, borate, and chlorine substituent components.
  • Table 1 provides an explanation of the terms used in table 2.
  • Table 2 provides an overview of the mean charge difference calculated at the phosphate site (P), calcium site (Ca) and hydroxyl site (OH) for each of examples 1 to 1 1 above. Substituent
  • Silicate Si TEOS Tetraethylorthosilicate
  • Table 2 Further Examples The drawing illustrates typical processing routes for such materials.
  • a granulate form of the raw powder material would be used.
  • the subsequent processing in this case would involve creating a stable suspension of the HA powder, whether calcined or uncalcined, and then using one of various process routes (e.g.) foaming of a slurry and then curing, sintering and milling; freeze or spray dry granulation and sintering; direct coagulation casting with a sacrificial organic filler - that is removed during subsequent sintering - which is then milled.
  • various process routes e.g.
  • freeze or spray dry granulation and sintering freeze or spray dry granulation and sintering
  • a typical sintering step following precipitation would be to sinter the material at 1200 °C for 3 hours, with a ramp up rate of 10 °C / hr. It is possible to sinter at higher or lower temperatures and the amount and form of the substitutions may affect the suitability of differing regimes.
  • the materia) prepared may be used as a biomaterial for use for instance as a raw powder material for bone void filler applications as a granulate.
  • the material can also be used to prepare ceramic or composite shape bone implants using conventional shaping routes such as powder pressing, extrusion or novel routes such as Additive Layer Manufacturing (ALM).
  • ALM Additive Layer Manufacturing
  • Such a material could be used as a coating for osteo- implants.
  • Other potential uses include dentistry, arterial stents or slow release drug carriers.
  • the molar percentage (M%) of a substitution (relative to the ion being replaced, not total substitution) is mult/plied by the (e ' ) count for the ion replaced, and finally multiplied by the (e ) count difference of the substituent.
  • the anion and cation are worked out separately and summed at the end. This is demonstrated by method of example below:

Abstract

La présente invention concerne un biomatériau comprenant de l'hydroxyapatite synthétique dans laquelle jusqu'à 10 % en composition molaire au total de composants substituants du phosphate sont fournis, les composants substituants du phosphate comprenant au moins deux d'un sulfate, d'un silicate ou d'un borate, la différente de charge totale moyenne en raison des composants substituants du phosphate étant inférieure à 1,8 F.mol-2.
PCT/GB2012/000197 2011-03-02 2012-02-29 Biomatériau WO2012117218A1 (fr)

Applications Claiming Priority (2)

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GBGB1103606.8A GB201103606D0 (fr) 2011-03-02 2011-03-02
GB1103606.8 2011-03-02

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2399000A1 (es) * 2012-12-12 2013-03-25 Biotechnology Institute I Mas D S.L. Método para producir una estructura porosa de polisfosfato cálcico
CN104071763A (zh) * 2013-03-28 2014-10-01 中国科学院理化技术研究所 多离子型类骨磷灰石的制备方法及多离子型类骨磷灰石

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1487181A (en) * 1974-10-30 1977-09-28 Colgate Palmolive Co Sintered ceramics
US6340648B1 (en) * 1999-04-13 2002-01-22 Toshiba Ceramics Co., Ltd. Calcium phosphate porous sintered body and production thereof
US20030099762A1 (en) * 2001-10-12 2003-05-29 Zongtao Zhang Coatings, coated articles and methods of manufacture thereof
WO2010092001A1 (fr) * 2009-02-10 2010-08-19 Azurebio, S. L. Matériaux de régénération osseuse basés sur des combinaisons de monétite et d'autre composés bioactifs de calcium et de silicium
US20100262258A1 (en) * 2007-04-11 2010-10-14 University Court Of The University Of Aberdeen Biomedical materials

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1487181A (en) * 1974-10-30 1977-09-28 Colgate Palmolive Co Sintered ceramics
US6340648B1 (en) * 1999-04-13 2002-01-22 Toshiba Ceramics Co., Ltd. Calcium phosphate porous sintered body and production thereof
US20030099762A1 (en) * 2001-10-12 2003-05-29 Zongtao Zhang Coatings, coated articles and methods of manufacture thereof
US20100262258A1 (en) * 2007-04-11 2010-10-14 University Court Of The University Of Aberdeen Biomedical materials
WO2010092001A1 (fr) * 2009-02-10 2010-08-19 Azurebio, S. L. Matériaux de régénération osseuse basés sur des combinaisons de monétite et d'autre composés bioactifs de calcium et de silicium

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SPRIO ET AL: "Physico-chemical properties and solubility behaviour of multi-substituted hydroxyapatite powders containing silicon", MATERIALS SCIENCE AND ENGINEERING C, ELSEVIER SCIENCE S.A, CH, vol. 28, no. 1, 21 December 2007 (2007-12-21), pages 179 - 187, XP022398445, ISSN: 0928-4931, DOI: 10.1016/J.MSEC.2006.11.009 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2399000A1 (es) * 2012-12-12 2013-03-25 Biotechnology Institute I Mas D S.L. Método para producir una estructura porosa de polisfosfato cálcico
WO2014091036A1 (fr) * 2012-12-12 2014-06-19 Biotechnology Institute, I Mas D, S.L. Procédé de production d'une structure poreuse en polyphosphate calcique
CN104071763A (zh) * 2013-03-28 2014-10-01 中国科学院理化技术研究所 多离子型类骨磷灰石的制备方法及多离子型类骨磷灰石
CN104071763B (zh) * 2013-03-28 2016-06-01 中国科学院理化技术研究所 多离子型类骨磷灰石的制备方法及多离子型类骨磷灰石

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