1、Designation: F1581 08 (Reapproved 2016)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、ductSafety Data Sheet (DS) for details and EPAs website (http:/www.epa.gov/mercury/faq.htm) for additional information.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 address all of
8、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 use. (See App
9、endix 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 for Measuring Tr
10、ace 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 Practice for
11、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:6Identification Tests for C
12、alcium 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 F04.13 on Ceramic Materials.Current edition approved Oct. 1, 2016. Published October 2016. Original
13、lyapproved in 1995. Last previous edition approved in 2012 as F1581 08 (2012).DOI: 10.1520/F1581-08R16.2The 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 Se
14、rvice 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.access.gp
15、o.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, MD
16、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:7Cad
17、mium3. 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 apatite
18、, 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 an im
19、plant 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 PDF c
20、ard #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 well-kn
21、ownScherrer 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 USP me
22、thods , , , 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 (Test M
23、eth-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 orequivalent
24、. 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 oxi
25、des 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 acid analyses(13). For all methods, a synthetic hydroxylapatite control th
26、atconforms to Specification F1185 or an established NationalInstitute of Standards and Technology (NIST) standard shall beused. The maximum allowable limit of either nitrogen, carbon,or protein shall be within two standard deviations of the meanvalue established for the control.NOTE 1The Kjeldahl pr
27、ocess 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, which
28、 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 various
29、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 bone min
30、eral (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 Analysis
31、 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 device.7
32、Crock, 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 Joint C
33、ommittee 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 and i
34、s available from the Joint Committee on Powder Diffraction Standards,1600 Park Lane, Swarthmore, PA 19801.F1581 08 (2016)26. Quality Program Requirements6.1 The manufacturer shall conform to Quality SystemsRegulations (see Title 21, Part 820, of the Code of FederalRegulations4) or its equivalent.7.
35、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 preclini
36、cal 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 changes i
37、n 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 forthe
38、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 allogeneic; a
39、norganic; 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, anor
40、ganic 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 not e
41、xist 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. BIOCOMPATIBILITYX2.1 No
42、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 is us
43、ed 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 Biomaterials
44、 , 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 Bone
45、 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.,“Com
46、parative 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,” Journ
47、al 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 (2016)3(9) LeGeros, R. Z., LeGeros, J. P., Daculsi, G., and Kijkows
48、ka, 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 Reliable
49、 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 Enzymology, Vol
