1、Designation: F1581 08 (Reapproved 2012)Standard Specification forComposition of Anorganic Bone for Surgical Implants1This standard is issued under the fixed designation F1581; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the yea
2、r of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This specification covers material requirements for an-organic xenogeneic or allogeneic bone (apatite) intended f
3、orsurgical implants. For a material to be called anorganic ordeorganified bone, it must conform to this specification (seeAppendix X1).1.2 The biological response to apatite in soft tissue and bonehas been characterized by a history of clinical use and bylaboratory studies (1, 2, 3).2Xenogeneic bone
4、, with organiccomponents present, has been shown to be antigenic in thehuman host (4) whereas the same material that has beencompletely deorganified has been shown to elicit no inflam-matory or foreign body reactions in human clinical use (5, 6,7).1.3 This specification specifically excludes synthet
5、ichydroxylapatite, hydroxylapatite coatings, ceramic glasses,tribasic calcium phosphate, whitlockite, and alpha- and beta-tricalcium phosphate.1.4 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.5 WarningMercury has been desig
6、nated by EPA andmany state agencies as a hazardous material that can causecentral nervous system, kidney, and liver damage. Mercury, orits vapor, may be hazardous to health and corrosive tomaterials. Caution should be taken when handling mercury andmercury-containing products. See the applicable pro
7、duct Ma-terial Safety Data Sheet (MSDS) for details and EPAs website(http:/www.epa.gov/mercury/faq.htm) for additional informa-tion. Users should be aware that selling mercury or mercury-containing products, or both, in your state may be prohibited bystate law.1.6 This standard does not purport to a
8、ddress all of thesafety concerns, such as health concerns due to the presence oftransmissible disease, associated with its use. It is the respon-sibility of the user of this standard to establish appropriatesafety and health practices and determine the applicability ofregulatory limitations prior to
9、 use. (See Appendix X2).2. Referenced Documents2.1 ASTM Standards:3D513 Test Methods for Total and Dissolved Carbon Dioxidein WaterD1688 Test Methods for Copper in WaterD2972 Test Methods for Arsenic in WaterD3557 Test Methods for Cadmium in WaterD3559 Test Methods for Lead in WaterD3919 Practice fo
10、r Measuring Trace Elements in Water byGraphite Furnace Atomic Absorption SpectrophotometryD4129 Test Method for Total and Organic Carbon in Waterby High Temperature Oxidation and by CoulometricDetectionE1184 Practice for Determination of Elements by GraphiteFurnace Atomic Absorption SpectrometryF748
11、 Practice for Selecting Generic Biological Test Methodsfor Materials and DevicesF1185 Specification for Composition of Hydroxylapatite forSurgical Implants2.2 Code of Federal Regulations:4Title 21, Part 8202.3 National Formulary:5Tribasic Calcium Phosphate2.4 United States Pharmocopeia:6Identificati
12、on Tests for Calcium and Phosphate Lead Mercury 1This specification is under the jurisdiction of ASTM Committee F04 onMedical and Surgical Materials and Devices and is under the direct responsibility ofSubcommittee F04.13Ceramic Materials.Current edition approved Oct. 1, 2012. Published October 2012
13、. Originallyapproved in 1995. Last previous edition approved in 2008 as F1581 081. DOI:10.1520/F1581-08R12.2The boldface numbers in parentheses refer to the list of references at the end ofthis specification.3For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Custome
14、r Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.4Available from U.S. Government Printing Office Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.acces
15、s.gpo.gov.5National Formulary 25. Available from U.S. Pharmacopeia (USP), 12601Twinbrook Pkwy., Rockville, MD 20852-1790, http:/www.usp.org. SucceedingUSP editions may alternatively be referenced.6United States Pharmacopeia 30. Available from U.S. Pharmacopeia (USP),12601 Twinbrook Pkwy., Rockville,
16、 MD 20852-1790, http:/www.usp.org. Succeed-ing USP editions may alternatively be referenced.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States1Cadmium Arsenic Heavy Metals Method 1Nitrogen Determination 2.5 U.S. Geological Survey Method:
17、7Cadmium3. Terminology3.1 Definitions:3.1.1 allogeneic, adjderived from different individuals ofthe same species.3.1.2 anorganic, adjdenoting tissue (for example, bone)from which the organic material has been totally removed.Also referred to as deorganified, deproteinized or deprotein-ated.3.1.3 apa
18、tite, nthe mineral substance having the molecu-lar formula Ca10(X)2(PO4)6where X = OH (hydroxyapatite orhydroxylapatite), CO3(carbonated apatite), F (fluorine), or Cl(chlorine) (8).3.1.4 xenogeneic, adjderived from individuals of adifferent, specified species. For example, bovine bone, whenused as a
19、n implant material in humans, is xenogeneic.4. Chemical Requirements4.1 Elemental analysis for calcium and phosphorus shall beconsistent with the expected composition of the source of thebiologically-derived bone mineral (9).4.2 An X-ray diffraction analysis of the material shall beconsistent with P
20、DF card #9-432 for hydroxyapatite (10) orPDF card #35-180 for calcium phosphate carbonate (carbon-ated apatite). Analysis of relative peak intensities shall beconsistent with published data.84.3 The crystal size of the anorganic bone shall be deter-mined from the X-ray diffraction data using the wel
21、l-knownScherrer formula (11).4.4 The concentration of trace elements in the anorganicbone shall be limited as follows:Element ppm, maxarsenic 3cadmium 5mercury 5lead 30total heavy metals (as lead) 50For referee purposes, use either inductively coupled plasma/mass spectroscopy (ICP/MS) (12) or the US
22、P methods , , , Method 1, ; and forcadmium, use either or the U.S. Geological SurveyMethod on cadmium. (See 2.4 and 2.5.) Graphite furnaceatomic absorption spectrophotometry may also be used foranalysis of trace elements using for arsenic (Test MethodsD2972), copper (Test Methods D1688), cadmium (Te
23、st Meth-ods D3557), lead (Test Methods D3559) with 1 g anorganicbone/100mL water samples. General guides for the applicationof the graphite furnace are given in Practices D3919 andE1184.4.5 The maximum allowable limit of all heavy metalsdetermined as lead shall be 50 ppm as described in 2.4 orequiva
24、lent. Sample preparation shall be identical to that fortribasic calcium phosphate as specified in the National Formu-lary (see 2.3), except that approximately1gofmaterial shallbe dissolved in approximately 30 mL of 5 % HCl and boiled.4.6 It is recommended that all minor constituents such asmetals or
25、 oxides not detected as lead and present in concen-trations equal to or greater than 0.1 % be identified andquantified.4.7 Organic content shall be measured either as total carbonor nitrogen (see Note 1) or total protein by amino acidanalyses(13). For all methods, a synthetic hydroxylapatitecontrol
26、that conforms to Specification F1185 or an establishedNational Institute of Standards and Technology (NIST) stan-dard shall be used. The maximum allowable limit of eithernitrogen, carbon, or protein shall be within two standarddeviations of the mean value established for the control.NOTE 1The Kjelda
27、hl process for nitrogen determination (USP)is set forth by the Association of Official Analytical Chemists (14) as anappropriate measure of proteins. Alternatively, organic material (carbon)can be measured by the coulometric method (Test Method D4129).Subtract from this value the carbonate content,
28、which can be determinedby Test Methods D513.4.8 The carbonate content of the anorganic bone shall bedetermined. Carbonate content is typically 5 to6%inbonemineral prior to removal of the organic phase. Residualcarbonate content remaining after processing is one means ofdistinguishing between the var
29、ious processing methods utilizedto process bone powder into anorganic bone. Carbonate con-tent is linked to dissolution and resorbability characteristics ofanorganic bone products and should be kept within1%ofprevious lots in order to assure consistent performance. Lowcarbonate content anorganic bon
30、e mineral (2 % or less) isbarely soluble in dilute acids as compared to anorganic bonecontaining 5 to 6 % carbonate.4.9 Functional groups will be identified by infrared analysis.Typical functional groups of apatites have been described byElliott (8), LeGeros et al (15), and Rey(16, 17, 18).4.10 Anal
31、ysis of additional elements or ionic species asso-ciated with the source or with processing conditions should bespecified for this material.5. Test Specimen Fabrication5.1 Prepare test specimens from the same batch of materialand by the same processes as those employed in fabricating theimplant devi
32、ce.7Crock, J. G., Felichte, F. E., and Briggs, P. H., “Determination of Elements inNational Bureau of Standards Geological Reference Materials SRM 278 Obsidianand SRM 688 Basalt by Inductively Coupled Argon PlasmaAtomic EmissionSpectrometry,” Geostandards Newsletter , Vol 7, 1983, pp. 335340.8The Jo
33、int Committee on Powdered Diffraction Standards has established aPowder Diffraction File. The Committee operates on an international basis andcooperates closely with the Data Commission of the International Union ofCrystallography and ASTM. Hydroxylapatite data can be found on file card number9-432
34、and is available from the Joint Committee on Powder Diffraction Standards,1600 Park Lane, Swarthmore, PA 19801.F1581 08 (2012)26. Quality Program Requirements6.1 The manufacturer shall conform to Quality SystemsRegulations (see Title 21, Part 820, of the Code of FederalRegulations4) or its equivalen
35、t.7. Biocompatibility7.1 The biocompatibility of anorganic bone may dependupon processing conditions or source material history, or both,which may not be identified by the compositional requirementsof this specification. The biocompatibility of these productsshould be ensured by a combination of pre
36、clinical testing andprocess controls. Material derived under the desired processconditions should be tested in accordance with the recommen-dations of Practice F748 and manufacturing controls put inplace to ensure that process variations outside of acceptabletolerances do not occur. Substantial chan
37、ges in process condi-tions or source control parameters shall necessitate additionalbiocompatibility testing to ensure maintenance of an accept-able tissue response.8. Sterilization8.1 Anorganic bone may be supplied presterilized in accor-dance with current procedures set forth by the Association fo
38、rthe Advancement of Medical Instrumentation (AAMI) andQuality Systems Regulations established by the Food and DrugAdministration (FDA).98.2 If user sterilization or resterilization is intended, vali-dated instructions for sterilization shall be supplied with thepackage insert.9. Keywords9.1 allogene
39、ic; anorganic; apatite; bone; hydroxyapatite;hydroxylapatite; implant; xenogeneicAPPENDIXES(Nonmandatory Information)X1. RATIONALEX1.1 Xenogeneic and allograft bone is commercially avail-able as grafting material. To eliminate concerns about possibleimmunogenicity effects or partially purified bone,
40、 anorganic ordeorganified bone has been developed. To achieve reliablebiocompatibility as an implant material, this material must becharacterized for its hydroxylapatite mineral component andtrace element content as well as for the absence of organicmaterial. At the current time, sufficient data do
41、not exist toprovide specific limits for carbon and nitrogen values. Indi-vidual laboratories must apply statistical analysis to showequivalence with the negative control. Test results that mightprovide data to assign specific limits for carbon and nitrogenare hereby solicited.X2. BIOCOMPATIBILITYX2.
42、1 No known surgical implant material has ever beenshown to be completely free of adverse reactions in the humanbody. However, long-term clinical experience of the use of thematerial referred to in this standard has shown that anacceptable level of biological response can be expected, if thematerial
43、is used in appropriate applications.REFERENCES(1) Hench, L. L., and Wilson, J., An Introduction to Bioceramics, WorldScientific, 1993, pp. 139 238.(2) Damien, C. J., and Parsons, J. R., “Bone Graft and Bone GraftSubstitutes: A Review of Current Technology and Applications,”Journal of Applied Biomate
44、rials , Vol 2, 1991, pp. 187208.(3) Jarcho, M., Kay, J. F., Gumaer, K. I., Doremus, R. H., and Drobeck,H. P., “Tissue, Cellular and Subcellular Events at a Bone-CeramicHydroxylapatite Interface,” Journal of Bioengineering, Vol 1, 1977,pp. 7992.(4) Salama, R., and Gazit, E., “The Antigenicity of Kiel
45、 Bone in theHuman Host,” The Journal of Bone and Joint Surgery, Vol 60-B, No.2, 1978, pp. 262265.(5) Urist, M. R., OConnor, B. T., and Burwell, R. G., Bone Grafts,Derivatives and Substitutes , Butterworth-Heineman Ltd., 1994, pp.4142.(6) Begley, C. T., Doherty, M. J., Mollan, R. A., and Wilson, D. J
46、.,“Comparative Study of the Osteoinductive Properties of Bioceramic,Coral and Processed Bone Graft Substitutes,” Biomaterials, Vol 16,1995, pp. 11811185.(7) Callan, D. P., “Use of Bovine-Derived Hydroxyapatite in the Treat-ment of Endentulous Ridge Defects:AHuman Clinical and HistologicCase Report,”
47、 Journal of Periodontology, Vol 64, 1993, pp. 575582.(8) Elliott, J. C., Structure and Chemistry of the Apatites and OtherCalcium Orthophosphates , Elsevier Science B.V., 1994, p. 4.9Federal Register, Vol 43, No. 141, 21 July 1978.F1581 08 (2012)3(9) LeGeros, R. Z., LeGeros, J. P., Daculsi, G., and
48、Kijkowska, R.,“Calcium Phosphate Biomaterials: Preparation, Properties, andBiodegradation,” Encylopedic Handbook of Biomaterials andBioengineering, Part A: Materials, Vol 2, Marcel Dekker, 1995, pp.14291463.(10) Balmain, N., Legeros, R., and Bonel, G., “X-Ray Diffraction ofCalcified Bone Tissue: A R
49、eliable Method for the Determination ofBone Ca/P Molar Ratio,” Calcified Tissue International, Vol 34,1982, pp. 593594.(11) Klug, H. P., and Alexander, L. E., X-Ray Diffraction Procedures forPolycrystallite and Amorphous Materials, 2nd ed., John Wiley andSons, New York, 1974.(12) Northington, D. J., “Inductively Couples Plasma-Mass Spectrometryfor the Analysis of Metals on Membrane Filters,” American Indus-trial Hygiene Association Journal , Vol 48, 1987, pp. 977979.(13) Ozols, J., “Amino Acid Analysis,” in Guide to Protein Purification,Methods in Enzymol
