1、Designation: F 1925 09Standard Specification forSemi-Crystalline Poly(lactide) Polymer and CopolymerResins for Surgical Implants1This standard is issued under the fixed designation F 1925; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revi
2、sion, the year 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 virgin semi-crystalline poly(L-lactide) or poly(D-lactide) homopolymer res
3、ins intended for usein surgical implants. This specification also covers semi-crystalline resins of L-lactide copolymerized with other bioab-sorbable monomers including, but not limited to, glycolide,D-lactide, and DL-lactide. The poly(L-lactide) or poly(D-lactide)based homopolymers and copolymers c
4、overed by this specifi-cation possess lactide segments of sufficient length to allowpotential for their crystallization upon annealing.1.2 Since poly(glycolide) is commonly abbreviated as PGAfor poly(glycolic acid) and poly(lactide) is commonly abbre-viated as PLA for poly(lactic acid), these polyme
5、rs are com-monly referred to as PGA, PLA, and PLA:PGA resins for thehydrolytic byproducts to which they respectively degrade. PLAis a term that carries no stereoisomeric specificity and thereforeencompasses both the amorphous atactic/syndiotactic DL-lactide based polymers and copolymers as well as t
6、he isotacticD-PLA and L-PLA moieties, each of which carries potential forcrystallization. Inclusion of stereoisomeric specificity withinthe lactic acid based acronyms results in the following:poly(L-lactide) as PLLA for poly(L-lactic acid), poly(D-lactide)as PDLA for poly(D-lactic acid), and poly(DL
7、-lactide) as PDLLAfor poly(DL-lactic acid).1.3 This specification is applicable to lactide-based poly-mers or copolymers that possess isotactic polymeric segmentssufficient in size to carry potential for lactide-based crystalli-zation. Such polymers typically possess nominal mole frac-tions that equ
8、al or exceed 50 % L-lactide. This specification isparticularly applicable to isotactic-lactide based block copoly-mers or to polymers or copolymers synthesized from combi-nations of D-lactide and L-lactide that differ by more than 1.5total mole percent (1.5 % of total moles). This specification isno
9、t applicable to lactide-co-glycolide copolymers with gly-colide mole fractions greater than or equal to 70 % (65.3 % inmass fraction), which are covered by Specification F 2313.This specification is not applicable to amorphous polymers orcopolymers synthesized from combinations of D-lactide andL-lac
10、tide that differ by less than 1.5 total mole percent (1.5 %of total moles) as covered by Specification F 2579.1.4 This specification covers virgin semi-crystallinepoly(lactide)-based resins able to be fully solvated at 30C byeither methylene chloride (dichloromethane) or chloroform(trichloromethane)
11、. This specification is not applicable tolactide:glycolide copolymers that possess glycolide segmentssufficient in size to deliver potential for glycolide-based crys-tallization, thereby requiring fluorinated solvents for completedissolution under room temperature conditions (see Specifica-tion F 23
12、13).1.5 Within this specification, semi-crystallinity within theresin is defined by the presence of a DSC (differential scanningcalorimetry) crystalline endotherm after annealing above theglass transition temperature. While other copolymeric seg-ments may also crystallize upon annealing (for example
13、,glycolide), specific characterization of crystalline structuresother than those formed by lactide are outside the scope of thisspecification.1.6 This specification addresses material characteristics ofthe virgin semi-crystalline poly(lactide) based resins intendedfor use in surgical implants and do
14、es not apply to packaged andsterilized finished implants fabricated from these materials.1.7 As with any material, some characteristics may bealtered by processing techniques (such as molding, extrusion,machining, assembly, sterilization, and so forth) required forthe production of a specific part o
15、r device. Therefore, proper-ties of fabricated forms of this resin should be evaluatedindependently using appropriate test methods to assure safetyand efficacy.1.8 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1This specificat
16、ion is under the jurisdiction of ASTM Committee F04 onMedical and Surgical Materials and Devices and is the direct responsibility ofSubcommittee F04.11 on Polymeric Materials.Current edition approved June 1, 2009. Published August 2009. Originallyapproved in 1998. Last previous edition approved in 2
17、005 as F 1925 99 (2005).1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.1.9 This standard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to
18、 establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D 1505 Test Method for Density of Plastics by the Density-Gradient TechniqueD 2857 Practice for Dilute Solution Viscosity of Polymers
19、D 3417 Test Method for Enthalpies of Fusion and Crystal-lization of Polymers by Differential Scanning Calorimetry(DSC)3D 3418 Test Method for Transition Temperatures and En-thalpies of Fusion and Crystallization of Polymers byDifferential Scanning CalorimetryD 3536 Test Method for Molecular Weight A
20、verages andMolecular Weight Distribution by Liquid Exclusion Chro-matography (Gel Permeation ChromatographyGPC)3D 3593 Test Method for Molecular Weight Averages andMolecular Weight Distribution of Certain Polymers byLiquid Size-Exclusion Chromatography (Gel PermeationChromatographyGPC) Using Univers
21、al Calibration3D 4603 Test Method for Determining Inherent Viscosity ofPoly(Ethylene Terephthalate) (PET) by Glass CapillaryViscometerE 386 Practice for Data Presentation Relating to High-Resolution Nuclear Magnetic Resonance (NMR) Spectros-copyE 473 Terminology Relating to Thermal Analysis and Rhe-
22、ologyE 793 Test Method for Enthalpies of Fusion and Crystalli-zation by Differential Scanning CalorimetryE 794 Test Method for Melting And Crystallization Tem-peratures By Thermal AnalysisE 967 Test Method for Temperature Calibration of Differ-ential Scanning Calorimeters and Differential ThermalAna
23、lyzersE 968 Practice for Heat Flow Calibration of DifferentialScanning CalorimetersE 1142 Terminology Relating to Thermophysical PropertiesE 1252 Practice for General Techniques for Obtaining In-frared Spectra for Qualitative AnalysisE 1356 Test Method for Assignment of the Glass TransitionTemperatu
24、res by Differential Scanning CalorimetryE 1994 Practice for Use of Process Oriented AOQL andLTPD Sampling PlansF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and DevicesF 2313 Specification for Poly(glycolide) andPoly(glycolide-co-lactide) Resins for Surgical Implantswit
25、h Mole Fractions Greater Than or Equal to 70 %GlycolideF 2579 Specification for Amorphous Poly(lactide) andPoly(lactide-co-glycolide) Resins for Surgical Implants2.2 ANSI Standards:ANSI/ISO/ASQ Q9000-2000 Quality Management Sys-tems; Fundamentals and Vocabulary4ANSI/ISO/ASQ Q9001-2000 Quality Manage
26、ment Sys-tems; Requirements42.3 Other Documents:ICH Q3C(R3) International Conference on Harmonisationof Technical Requirements for Registration of Pharmaceu-ticals for Human Use, Quality Guideline: Impurities:Residual Solvents5ISO 31-8 Physical Chemistry and Molecular PhysicsPart8: Quantities and Un
27、its4ISO 10993 Biological Evaluation of Medical Devices4ISO 11357 PlasticsDifferential Scanning Calorimetry(DSC)421 CFR 820 United States Code of Federal Regulations,Title 21Food and Drugs Services, Part 820QualitySystem Regulation6USP United States Pharmacopeia, Edition 267NIST Special Publication S
28、P811 Guide for the Use of theInternational System of Units (SI)83. Terminology3.1 Definitions:3.1.1 virgin polymer, nthe initially delivered form of apolymer as synthesized from its monomers and prior to anyprocessing or fabrication into a medical device.4. Materials and Manufacture4.1 All raw monom
29、er components and other materialscontacting either the raw monomer(s) or resin product shall beof a quality suitable to allow use of such resin in themanufacture of an implantable medical product. Such qualityincludes adequate control of particles and other potentialcontaminants that may affect eith
30、er the toxicity of or the cellresponse to the as-implanted or degrading final product.4.2 All polymer manufacturing (including monomer han-dling, synthesis, pelletization/grinding and all subsequent han-dling) shall be undertaken under conditions suitable to allowuse of such resin in the manufacture
31、 of an implantable medicalproduct.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3Withdrawn.4Available from
32、American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.5Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758,1211 Geneva 13, Switzerland. Available online at http:/www.ich.org/LOB/media/MEDIA423.pdf.6Available from U.S. Go
33、vernment Printing Office Superintendent of Documents,732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:/www.access.gpo.gov.7Available from U.S. Pharmacopeia, 12601 Twinbrook Pkwy., Rockville, MD20852 or through http:/www.usp.org/products/USPNF/. The standards will be listedby approp
34、riate USP citation number. Succeeding USP editions alternately may bereferenced.8Available from National Institute of Standards and Technology (NIST), 100Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, at http:/physics.nist.gov/cuu/Units/bibliography.html.F19250925. Chemical Composition5.1 The s
35、emi-crystalline poly(lactide) polymers and copoly-mers covered by this specification shall be composed of eitherD-lactide or L-lactide in segments of sufficient length to allowcrystallization. Copolymers covered by this specification canbe of variable copolymer ratios and shall be composed ofcrystal
36、lizable lengths of D-lactide and/or L-lactide in combina-tion with glycolide or other monomers where the glycolidemole fraction is less than 70 % (65.3 % in mass fraction). Toassure such composition and the attainment of the desiredproperties, the following tests shall be conducted.5.2 Chemical Iden
37、tification:5.2.1 The identity of the virgin polymer shall be confirmedeither by infrared,1H-NMR, or13C-NMR spectroscopy.5.2.2 Infrared Identification:5.2.2.1 Identity of semi-crystalline poly(lactide) homopoly-mer or poly(lactide)-based copolymer may be confirmedthrough an infrared spectrum exhibiti
38、ng major absorptionbands only at the wavelengths that appear in a suitablereference spectrum. Analysis shall be conducted using infraredspectroscopy practices similar to those described in PracticeE 1252. A typical infrared transmission reference spectrum foran L-PLA homopolymer is shown in Fig. 1.
39、Whilepoly(lactide)-based copolymers will each have their ownrespective spectrum that will vary in response to copolymerratio, this analytic method typically lacks sensitivity sufficientfor quantification of copolymer ratio as specified in 7.1.2.5.2.2.2 Additional or variable spectral bands may be in
40、dica-tive of sample crystallinity or either known or unknownimpurities, including residual monomer, solvents, and catalysts(refer to limits specified in Table 1).5.2.2.3 Since an infrared spectrum cannot distinguish be-tween the different lactide stereoisomers that is, poly(L-lactide) versus poly(D-
41、lactide), it is utilized here only as ameans of identifying the non-stereospecific poly(lactide) com-ponent of the semi-crystalline poly(lactide)-based polymer orcopolymer.5.2.3 Proton Nuclear Magnetic Resonance (1H-NMR) Iden-tification:5.2.3.1 Identity of semi-crystalline poly(lactide) homopoly-mer
42、 or poly(lactide)-based copolymer may be confirmedthrough sample dissolution,1H-NMR spectroscopy, and theuse of a suitable reference spectrum. Sample dissolution is ineither deuterated chloroform, deuterated dichloromethane (me-thylene chloride) or other substantially proton-free solvent ableto full
43、y solvate the specimen without inducing competingspectral bands. Analysis shall be conducted using practicessimilar to those described in Practice E 386. A typical protonNMR reference spectrum for an L-PLA homopolymer (withresidual lactide monomer peak noted) is shown in Fig. 2.5.2.3.2 Additional sp
44、ectral bands may be indicative ofknown or unknown impurities, including residual monomer,solvents, and catalysts (refer to the limits specified in Table 1).5.2.4 Carbon-13 Nuclear Magnetic Resonance (13C-NMR)Identification:5.2.4.1 Identity of semi-crystalline poly(lactide) homopoly-mer or poly(lacti
45、de)-based copolymer may be confirmed in asolid state through13C-NMR spectroscopy and the use of aFIG. 1 Poly(L-lactide) Resin Infrared SpectrumF1925093suitable reference spectrum. Analysis shall be conducted usingpractices similar to those described in Practice E 386.5.2.4.2 Additional spectral band
46、s may be indicative ofknown or unknown impurities, including residual solvents andcatalysts (refer to the limits specified in Table 1).5.3 Specific Rotation:5.3.1 Virgin poly(L-lactide) or poly(D-lactide) homopoly-mers shall have a specific rotation of 155 to 160 degrees and+155 to +160 degrees resp
47、ectively when measured in eitherchloroform or methylene chloride at 20C using a polarimetrymethod equal to or equivalent to the Optical Rotation proce-dure described in USP . Block copolymers of poly(L-lactide:D-lactide) may possess a reduced level of specificrotation proportioned to the copolymeriz
48、ation ratio. In nosituation shall a resin covered by this specification possess aspecific rotation value of less than 2.5 (that is, between 2.5and +2.5), which is considered to be indicative of an amor-phous polymer covered under Specification F 2579.5.4 Molar Mass:NOTE 1The term molecular weight (a
49、bbreviated MW) is obsolete andshould be replaced by the SI (Systme Internationale) equivalent of eitherrelative molecular mass (Mr), which reflects the dimensionless ratio of themass of a single molecule to an atomic mass unit see ISO 31-8, or molarmass (M), which refers to the mass of a mole of a substance and istypically expressed as grams/mole. For polymers and other macromol-ecules, use of the symbols Mw, Mn, and Mzcontinue, referring tomass-average molar mass, number-average molar mass, and z-averagemolar mass, respectively. For more information regarding
