BS ISO 13175-3-2013 Implants for surgery Calcium phosphates Hydroxyapatite and beta-tricalcium phosphate bone substitute《外科植入物 磷酸钙 羟磷灰石和β-磷酸三钙骨骼替代品》.pdf

1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS ISO 13175-3:2012Implants for surgery Calcium phosphatesPart 3: Hydroxyapatite and beta-tricalcium phosphate bone substitutesBS ISO 13175-3:2012 BRITISH STANDARDNational forewo

2、rdThis British Standard is the UK implementation of ISO 13175-3:2012.The UK participation in its preparation was entrusted to Technical Committee CH/150/1, Materials for surgical implants.A list of organizations represented on this committee can be obtained on request to its secretary.This publicati

3、on does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. The British Standards Institution 2013. Published by BSI Standards Limited 2013 ISBN 978 0 580 71183 1 ICS 11.040.40 Compliance with a British Standard cannot confer immunity

4、 from legal obligationsThis British Standard was published under the authority of the Standards Policy and Strategy Committee on 30 April 2013.Amendments issued since publicationDate Text affectedBS ISO 13175-3:2012 ISO 2012Implants for surgery Calcium phosphates Part 3: Hydroxyapatite and beta-tric

5、alcium phosphate bone substitutesImplants chirurgicaux Phosphates de calcium Partie 3: Substituts osseux base dhydroxyapatite et de phosphate tricalcique btaINTERNATIONAL STANDARDISO13175-3First edition2012-10-01Reference numberISO 13175-3:2012(E)BS ISO 13175-3:2012ISO 13175-3:2012(E)ii ISO 2012 All

6、 rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2012All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO a

7、t the address below or ISOs member body in the country of the requester.ISO copyright officeCase postale 56 CH-1211 Geneva 20Tel. + 41 22 749 01 11Fax + 41 22 749 09 47E-mail copyrightiso.orgWeb www.iso.orgPublished in SwitzerlandBS ISO 13175-3:2012ISO 13175-3:2012(E) ISO 2012 All rights reserved ii

8、iContents PageForeword ivIntroduction v1 Scope . 12 Normative references 13 Terms, definitions and symbols 13.1 Terms and definitions . 13.2 Symbols . 34 Requirements 34.1 Trace elements 34.2 Qualitative and quantitative determination of crystalline phases . 44.3 Form and shape 54.4 Porosity . 54.5

9、Dissolution and pH change . 64.6 Measurement of material mechanical strength 74.7 Test report 11Bibliography .13BS ISO 13175-3:2012ISO 13175-3:2012(E)ForewordISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work

10、of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-government

11、al, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.The main

12、task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.Attent

13、ion is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights.ISO 13175-3 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 1, Materia

14、ls.ISO 13175 consists of the following parts, under the general title Implants for surgery Calcium phosphates: Part 3: Hydroxyapatite and beta-tricalcium phosphate bone substitutesiv ISO 2012 All rights reservedBS ISO 13175-3:2012ISO 13175-3:2012(E)IntroductionHydroxyapatite and -tricalcium phosphat

15、e synthetic bone substitutes are now considered as an adequate alternative to autografts and allografts. Indeed, the synthetic origin of these devices guarantees that no transmittable disease will contaminate the patient. Moreover, hydroxyapatite and -tricalcium phosphate have been shown to be osteo

16、conductive which means that they will promote bone healing at the surface of the material if implanted in a bone site (see References 6 and 7). Biocompatibility of hydroxyapatite and -tricalcium phosphate is demonstrated by extensive literature (see Reference 8).The devices referred to in this part

17、of ISO 13175 are of three types: synthetic monophasic hydroxyapatite or -tricalcium phosphate bone substitutes and biphasic hydroxyapatite/-tricalcium phosphate bone substitutes. The hydroxyapatite/-tricalcium phosphate ratio influence the dissolution rate of the material: the higher the -tricalcium

18、 phosphate content, the higher the dissolution rate (see References 9 to 11).The healing process into the bone substitutes is not only related to the material osteoconductive potential, it is also related to the porosity structure (see References 12 to 16). It is necessary that macroporosities are l

19、arge enough and interconnected for bone ingrowth to take place into the whole volume of the implant. Porosities have also an influence on the resorption rate of the ceramic: the higher the number of microporosities, the higher the dissolution rate (see Reference 14).As bone substitutes are not inten

20、ded for bearing heavy loads, their mechanical properties are not essential. However, most of the time blocks have to be reshaped by the surgeon to fit the shape of the bone cavity. The bone substitute shall have sufficient mechanical properties to be machined. ISO 2012 All rights reserved vBS ISO 13

21、175-3:2012BS ISO 13175-3:2012Implants for surgery Calcium phosphates Part 3: Hydroxyapatite and beta-tricalcium phosphate bone substitutes1 ScopeThis part of ISO 13175 specifies requirements for monophasic hydroxyapatite bone substitutes, monophasic -tricalcium phosphate bone substitutes and biphasi

22、c hydroxyapatite/-tricalcium phosphate bone substitutes in the form of blocks or granules.This part of ISO 13175 is not applicable to cell-seeded bone void fillers, calcium phosphate cements or bone void fillers containing materials other than hydroxyapatite and -tricalcium phosphate.2 Normative ref

23、erencesThe following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 2591-1, Test sieving Part 1: Methods us

24、ing test sieves of woven wire cloth and perforated metal plateISO 10993-1, Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management processISO 13320, Particle size analysis Laser diffraction methods1)ISO 13383-1, Fine ceramics (advanced ceramics, advanced tech

25、nical ceramics) Microstructural characterization Part 1: Determination of grain size and size distribution2)ISO 13779-3, Implants for surgery Hydroxyapatite Part 3: Chemical analysis and characterization of crystallinity and phase purityISO 15901-1, Pore size distribution and porosity of solid mater

26、ials by mercury porosimetry and gas adsorption Part 1: Mercury porosimetryISO 80000-1, Quantities and units Part 1: General3 Terms, definitions and symbols3.1 Terms and definitionsFor the purposes of this document, the following terms and definitions apply.1) Replaces ISO 13320-1.2) To be published.

27、INTERNATIONAL STANDARD ISO 13175-3:2012(E) ISO 2012 All rights reserved 1BS ISO 13175-3:2012ISO 13175-3:2012(E)3.1.1 tricalcium phosphate-TCPchemical compound with a crystallographic structure characterized by ICDD PDF3)09-0348NOTE 1to entry: The chemical formula is Ca3(PO4)2.3.1.2 tricalcium phosph

28、ate-TCPchemical compound with a crystallographic structure characterized by ICDD PDF 09-0169NOTE 1to entry: The chemical formula is Ca3(PO4)2.3.1.3bone substitutedevice intended to fill bony voids or gaps caused by trauma or surgery3.1.4hydroxyapatiteHAchemical compound with a crystallographic struc

29、ture characterized by ICDD PDF 09-0432 or ICDD PDF 72-1243NOTE 1to entry: The chemical formula is Ca10(PO4)6(OH)2.3.1.5interconnected porepore which communicates with one or more other pores3.1.6macroporepore with one of its dimensions larger than 10 m3.1.7microporepore with no dimension larger than

30、 10 m3.1.8porosityratio of total pore volume to apparent volume of the block or granule3.1.9tetracalcium phosphateTTCPchemical compound with a crystallographic structure characterized by ICDD PDF 25-1137 or ICDD PDF 70-1379NOTE 1to entry: The chemical formula is Ca4(PO4)2O.3.1.10osteoconductive mate

31、rialmaterial with the ability to serve as a scaffold on which bone cells can attach, migrate (meaning move or “crawl”), and grow and divideNOTE 1to entry: Osteoconductivity is a passive property.3) International Centre for Diffraction Data Powder Diffraction File.2 ISO 2012 All rights reservedBS ISO

32、 13175-3:2012ISO 13175-3:2012(E)3.1.11calcium oxideCaOchemical compound with a crystallographic structure characterized by ICDD PDF 4-0777 or ICDD PDF 82-16903.1.12-tricalcium phosphate densitydTCPtheoretical density of dense -tricalcium phosphate, equal to 3,07 g cm33.1.13hydroxyapatite densitydHAt

33、heoretical density of dense hydroxyapatite, equal to 3,15 g cm33.2 Symbolsdrbulk density of the synthetic bone substitutedththeoretical density of the synthetic bone substitutem mass of the synthetic bone substituteV volume of the synthetic bone substitute4 Requirements4.1 Trace elementsThe limits o

34、f specific trace elements for hydroxyapatite and -tricalcium phosphate bone substitutes are given in Table 1.Either inductively coupled plasma/atomic emission spectrometry (ICP/AES), inductively coupled plasma/mass spectroscopy (ICP/MS), atomic absorption spectroscopy (AAS), or the method specified

35、in ISO 13779-3 shall be used to quantify trace elements. The method used shall be specified.Table 1 Limits of specific trace elementsElementMaximum limit mg/kgArsenic 3Cadmium 5Mercury 5Lead 30Heavy metals 50Method 1 of the United States Pharmacopeia “Heavy metals ” should be used to quantify heavy

36、metals. It is also possible to use one of the methods described above for the quantification of trace elements to assess the heavy metal content by considering that the total amount of heavy metals is the sum of the following elements: lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver,

37、 copper and molybdenum. The method used shall be specified.Any impurity with a ratio of more than 1 000 mg/kg shall be identified, quantified and its influence on bone healing shall be assessed. The influence of this impurity on biocompatibility shall be assessed according to ISO 10993-1. ISO 2012 A

38、ll rights reserved 3BS ISO 13175-3:2012ISO 13175-3:2012(E)Any additional additive shall be identified, quantified and its influence on bone healing and biocompatibility shall be justified or assessed in accordance with ISO 10993-1.4.2 Qualitative and quantitative determination of crystalline phases4

39、.2.1 GeneralComposition and phase purity shall be controlled by the quantification of the phases by X-ray diffraction (XRD) in accordance with ISO 13779-3.4.2.2 Hydroxyapatite monophasic bone substitutesHydroxyapatite mass fraction shall be not less than 95 % of the crystalline phases. The CaO mass

40、fraction shall be not more than 1 % of the crystalline phases.Hydroxyapatite mass fraction is calculated according to Formula (1):MF MF MF MF MFHA TCP TCP TTCPCaO= 100%(1)whereMFHAis the mass fraction of crystalline HA;MFTCPis the mass fraction of crystalline -TCP;MFTCPis the mass fraction of crysta

41、lline -TCP;MFTTCPis the mass fraction of crystalline TTCP;MFCaOis the mass fraction of crystalline CaO.The mass fraction of any phase shall be considered as zero if its value is under the detection threshold.4.2.3 Biphasic bone substitutesThe ratio between hydroxyapatite and -tricalcium phosphate sh

42、all be specified with a tolerance of 5 % (absolute) of the mass fraction of crystalline phases.EXAMPLE A composition of 60 % HA and 40 % TCP means that the composition can be (65 % HA and 35 % TCP) to (55 % HA and 45 % TCP).Qualitative determination of the mass fraction of other crystalline phases:

43、if -tricalcium phosphate (-TCP) can be detected, this information shall be indicated on the report.4.2.4 -tricalcium phosphate monophasic bone substitutesThe -tricalcium phosphate mass fraction shall be not less than 95 % of the crystalline phases.The -tricalcium phosphate mass fraction shall be cal

44、culated according to Formula (2):MF MFTCPHA=100% (2)The mass fraction of HA shall be considered as zero if its value is under the detection threshold.Qualitative determination of other crystalline phases: if -tricalcium phosphate (-TCP) can be detected, this information shall be indicated on the rep

45、ort.The presence of other phases shall be assessed by infrared spectroscopy (FTIR) in accordance with ISO 13779-3.4 ISO 2012 All rights reservedBS ISO 13175-3:2012ISO 13175-3:2012(E)4.3 Form and shapeThe physical form of the bone substitute (granules or pre-formed block) shall be specified.Dimension

46、al specifications shall be given for all device configurations as follows. Dimensions for the blocks. Dimensions of granulates: the laser diffraction method in accordance with ISO 13320 or sieving method in accordance with ISO 2591-1 shall be used to determine granule dimensions. Parameters D10, D50

47、 and D90 (for laser diffraction) or minimum and maximum dimensions (for sieving) of the granules shall be specified.The volume of the bone substitute shall be specified on the packaging.4.4 Porosity4.4.1 Total porosity ratioThe minimum and maximum porosity ratio of the bone substitute shall be speci

48、fied. It shall be calculated according to Formula (3):Pddrth= 100 100 (3)whereP is the porosity ratio in %.drshall be determined by measuring the dimensions and the mass of a parallelepiped bone substitute having a minimum volume of 2 cm3. The mass shall be measured with a balance capable of weighin

49、g to an accuracy of 0,02 g and the dimensions shall be measured with a vernier calliper capable of measuring to an accuracy of at least 0,02 mm. The volume, V, of the bone substitute shall then be calculated with the measured dimensions and drshall then be calculated according to Formula (4):dmVr= (4)dthshall be calculated according to Formula (5):dMFdMFdMFddMFdMFdMFthHAHAHAHATCPTCPHAPTCPTCPHAHA=+TCPTCPTCPdd (5)If the granules are manufac