1、Designation: F 1581 08Standard Specification forComposition of Anorganic Bone for Surgical Implants1This standard is issued under the fixed designation F 1581; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revisi
2、on. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) 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 forsurgical impl
3、ants. 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, with organicc
4、omponents 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 synthetic hy-droxylapa
5、tite, hydroxylapatite coatings, ceramic glasses, triba-sic calcium phosphate, whitlockite, and alpha- and beta-tricalcium phosphate.1.4 This standard does not pruport to address all of thesafety concerns, such as health concerns due to the presence oftransmissible disease, associated with its use. I
6、t is the respon-sibility of the user of this standard to establish appropriatesafety and health practices and determine the applicability ofregulatory limitations prior to use. (See Appendix X2).2. Referenced Documents2.1 ASTM Standards:3D 513 Test Methods for Total and Dissolved Carbon Diox-ide in
7、WaterD 1688 Test Methods for Copper in WaterD 2972 Test Methods for Arsenic in WaterD 3557 Test Methods for Cadmium in WaterD 3559 Test Methods for Lead in WaterD 3919 Practice for Measuring Trace Elements in Water byGraphite Furnace Atomic Absorption SpectrophotometryD 4129 Test Method for Total an
8、d Organic Carbon in Waterby High Temperature Oxidation and by Coulometric De-tectionE 1184 Practice for Electrothermal (Graphite Furnace)Atomic Absorption AnalysisF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 1185 Specification for Composition of Hydroxylap
9、atitefor Surgical Implants2.2 Code of Federal Regulations:4Title 21, Part 8202.3 National Formulary:5Tribasic Calcium Phosphate2.4 United States Pharmocopeia:6Identification Tests for Calcium and Phosphate Lead Mercury Cadmium Arsenic Heavy Metals Method 1Nitrogen Determination 2.5 U.S. Geological S
10、urvey Method: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-a
11、ted.1This specification is under the jurisdiction of ASTM Committee F04 onMedical and Surgical Materials and Devices and is under the direct responsibility ofSubcommittee F04.13 Ceramic Materials.Current edition approved Feb. 1, 2008. Published March 2008. Originallyapproved in 1995. Last previous e
12、dition approved in 1999 as F 1581 99.2The 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 Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume
13、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.access.gpo.gov.5National Formulary 25. Available from U.S. Pharmacopeia (US
14、P), 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, MD 20852-1790, http:/www.usp.org. Succeed-ing USP editions may altern
15、atively be referenced.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,
16、 pp. 335340.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.3.1.3 apatite, nthe mineral substance having the molecu-lar formula Ca10(X)2(PO4)6where X = OH (hydroxyapatite orhydroxylapatite), CO3(carbonated apatite), F (fluorine), or
17、Cl(chlorine) (8).3.1.4 xenogeneic, adjderived from individuals of a differ-ent, specified species. For example, bovine bone, when used asan implant material in humans, is xenogeneic.4. Chemical Requirements4.1 Elemental analysis for calcium and phosphorus will beconsistent with the expected composit
18、ion of the source of thebiologically-derived bone mineral (9).4.2 An X-ray diffraction analysis of the material shall beconsistent with PDF card #9-432 for hydroxyapatite (10) orPDF card #35-180 for calcium phosphate carbonate (carbon-ated apatite). Analysis of relative peak intensities shall becons
19、istent with published data.84.3 The crystal size of the anorganic bone shall be deter-mined from the X-ray diffraction data using the well-knownScherrer formula (11).4.4 The concentration of trace elements in the anorganicbone shall be limited as follows:Element ppm, maxarsenic 3cadmium 5mercury 5le
20、ad 30total heavy metals (as lead) 50For referee purposes, use either inductively coupled plasma/mass spectroscopy (ICP/MS) (12) or the USP methods , , , Method 1, ; and forcadmium, use either or the U.S. Geological SurveyMethod on cadmium. (See 2.4 and 2.5). Graphite furnaceatomic absorption spectro
21、photometry may also be used foranalysis of trace elements using for arsenic (Test MethodsD 2972), copper (Test Methods D 1688), cadmium (Test Meth-ods D 3557), lead (Test Methods D 3559) with 1 g anorganicbone/100mL water samples. General guides for the applicationof the graphite furnace are given i
22、n Practices D 3919 andE 1184.4.5 The maximum allowable limit of all heavy metalsdetermined as lead shall be 50 ppm as described in 2.4 orequivalent. Sample preparation shall be identical to that fortribasic calcium phosphate as specified in the National Formu-lary (see 2.3), except that approximatel
23、y1gofmaterial shallbe dissolved in approximately 30 mL of 5 % HCl and boiled.4.6 It is recommended that all minor constituents such asmetals or 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
24、either as total carbonor nitrogen (see Note 1) or total protein by amino acid analyses(13). For all methods, a synthetic hydroxylapatite control thatconforms to Specification F 1185 or an established NationalInstitute of Standards and Technology (NIST) standard shall beused. The maximum allowable li
25、mit of either nitrogen, carbon,or protein shall be within two standard deviations of the meanvalue established for the control.NOTE 1The Kjeldahl process for nitrogen determination (USP) is set forth by the Association of Official Analytical Chemists (14)as an appropriate measure of proteins. Altern
26、atively, organic material(carbon) can be measured by the coulometric method (Test MethodD 4129). Subtract from this value the carbonate content, which can bedetermined by Test Methods D 513.4.8 The carbonate content of the anorganic bone shall bedetermined. Carbonate content is typically 5 to6%inbon
27、emineral prior to removal of the organic phase. Residualcarbonate content remaining after processing is one means ofdistinguishing between the various processing methods utilizedto process bone powder into anorganic bone. Carbonate con-tent is linked to dissolution and resorbability characteristics
28、ofanorganic bone products and should be kept within1%ofprevious lots in order to assure consistent performance. Lowcarbonate content anorganic bone mineral (2 % or less) isbarely soluble in dilute acids as compared to anorganic bonecontaining 5 to 6 % carbonate.4.9 Functional groups will be identifi
29、ed by infrared analysis.Typical functional groups of apatites have been described byElliott (8), LeGeros et al (15), and Rey (16, 17, 18).4.10 Analysis of additional elements or ionic species asso-ciated with the source or with processing conditions should bespecified for this material.5. Test Speci
30、men Fabrication5.1 Prepare test specimens from the same batch of materialand by the same processes as those employed in fabricating theimplant device.6. Quality Program Requirements6.1 The manufacturer shall conform to Quality SystemsRegulations (see Title 21, Part 820, of the Code of FederalRegulat
31、ions4) or its equivalent.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
32、by a combination of preclinical testing andprocess controls. Material derived under the desired processconditions should be tested in accordance with the recommen-dations of Practice F 748 and manufacturing controls put inplace to ensure that process variations outside of acceptabletolerances do not
33、 occur. Substantial changes 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 for
34、th by the Association for8The Joint 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
35、 found on file card number9-432 and is available from the Joint Committee on Powder Diffraction Standards,1600 Park Lane, Swarthmore, PA 19801.F1581082the Advancement of Medical Instrumentation (AAMI) andQuality Systems Regulations established by the Food and DrugAdministration (FDA).98.2 If user st
36、erilization or resterilization is intended, vali-dated instructions for sterilization shall be supplied with thepackage insert.9. Keywords9.1 allogeneic; anorganic; apatite; bone; hydroxyapatite;hydroxylapatite; implant; xenogeneicAPPENDIXES(Nonmandatory Information)X1. RATIONALEX1.1 Xenogeneic and
37、allograft bone is commercially avail-able as grafting material. To eliminate concerns about possibleimmunogenicity effects or partially purified bone, anorganic ordeorganified bone has been developed. To achieve reliablebiocompatibility as an implant material, this material must becharacterized for
38、its hydroxylapatite mineral component andtrace element content as well as for the absence of organicmaterial. At the current time, sufficient data do not exist toprovide specific limits for carbon and nitrogen values. Indi-vidual laboratories must apply statistical analysis to showequivalence with t
39、he negative control. Test results that mightprovide data to assign specific limits for carbon and nitrogenare hereby solicited.X2. BIOCOMPATIBILITYX2.1 No known surgical implant material has ever beenshown to be completely free of adverse reactions in the humanbody. However, long-term clinical exper
40、ience of the use of thematerial referred to in this standard has shown that anacceptable level of biological response can be expected, if thematerial is used in appropriate applications.REFERENCES(1) Hench, L. L., and Wilson, J., An Introduction to Bioceramics, WorldScientific, 1993, pp. 139238.(2)
41、Damien, C. J., and Parsons, J. R., “Bone Graft and Bone GraftSubstitutes: A Review of Current Technology and Applications,”Journal of Applied Biomaterials, 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 a
42、t a Bone-CeramicHydroxylapatite Interface,” Journal of Bioengineering, Vol 1, 1977,pp. 7992.(4) Salama, R., and Gazit, E., “The Antigenicity of Kiel 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., B
43、one Grafts,Derivatives and Substitutes, Butterworth-Heineman Ltd., 1994, pp.4142.(6) Begley, C. T., Doherty, M. J., Mollan, R. A., and Wilson, D. J.,“Comparative Study of the Osteoinductive Properties of Bioceramic,Coral and Processed Bone Graft Substitutes,” Biomaterials, Vol 16,1995, pp. 11811185.
44、(7) Callan, D. P., “Use of Bovine-Derived Hydroxyapatite in the Treat-ment of Endentulous Ridge Defects: A Human Clinical and HistologicCase Report,” Journal of Periodontology, Vol 64, 1993, pp. 575582.(8) Elliott, J. C., Structure and Chemistry of the Apatites and OtherCalcium Orthophosphates, Else
45、vier Science B.V., 1994, p. 4.(9) LeGeros, R. Z., LeGeros, J. P., Daculsi, G., and Kijkowska, R.,“Calcium Phosphate Biomaterials: Preparation, Properties, and Bio-degradation,” Encylopedic Handbook of Biomaterials and Bioengi-neering, Part A: Materials, Vol 2, Marcel Dekker, 1995, pp.14291463.(10) B
46、almain, N., Legeros, R., and Bonel, G., “X-Ray Diffraction ofCalcified Bone Tissue: A Reliable 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 Am
47、orphous 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 G
48、uide to Protein Purification,Methods in Enzymology, Vol 182, edited by M. P. Deutscher, 1990,pp. 587601.(14) Horwitz, W., ed., Offcial Methods of Analysis of the Association ofAnalytical Chemists, Association of Official Analytical Chemists,Washington, DC, 1980, pp. 15, 214.(15) LeGeros, R. Z., Calc
49、ium Phosphates in Oral Biology and Medicine,Karger, 1991.(16) Rey, C., Miquel, J. L., Facchini, L., Legrand, A. P., and Glimcher, M.J., “Hydroxyl Groups in Bone Mineral,” Bone, Vol 16, 1995, pp.583586.9Federal Register, Vol 43, No. 141, 21 July 1978.F1581083(17) Rey, C., Collins, B., Goehl, T., Dickson, I. R., and Glimcher, M. J.,“The Carbonate Environment in Bone Mineral: A Resolution-Enhanced Fourier Transform Infrared Spectroscopy Study,” CalcifiedTissue International, Vol 45, 1989, pp. 157164.(18) Rey, C., Shimizu, M., Collins, B., and Glimcher, M. J., “
