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Poly-p-dioxanone

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General structural formula of poly-1,4-dioxan-2-one

Poly-p-dioxanone (poly-1,4-dioxan-2-one) – often abbreviated as PDS, PPDX or PPDO – is a poly (ether-ester) which is virtually an alternating copolymer of ethylene glycol and glycolic acid and is formed from 1,4-dioxan-2-one by ring-opening polymerization.

In addition to the homopolymer, a number of random copolymers and block copolymers,[1][2] usually with other lactone monomers, such as glycolide,[3] Lactide[4] or ε-caprolactone[5] have been described.

Poly-1,4-dioxan-2-one was introduced under the name PDSTM (polydioxanone sutures) in the form of monofilaments as the first absorbable, i.e. biodegradable, surgical suture material in 1981.[6]

Synthesis

The preparation of the homopolymeric poly-p-dioxanone is carried out in substance or solution at elevated temperatures (100 °C to 175 °C) for 3 to 48 hours at normal pressure or vacuum in the presence of tin alkoxides, such as dibutyltin dilaurate,[7] Tin(II) 2-ethylhexanoate[8] or the cyclic alkoxide 1-di-n-butyl-1-stanna-2,5-dioxacyclopentane[9]which suppresses transesterification reactions and should lead to higher intrinsic viscosities, i.e. molar masses of the polymer.

Polymerisation des PDO / Depolymerisation des PPDO

Ring-opening polymerization (ROP) of p-dioxanone with aluminum alkoxides, such as aluminum isopropoxide[10] or aluminum sec-butoxide leads to high molecular weight PPDO as well as with diethylzinc[11] or zirconyl acetylacetonate[11] as catalyst.

The prerequisites for obtaining higher molecular weight poly-p-dioxanones are, in addition to the high purity of the monomer 1,4-dioxan-2-one (>99.9%), the absence of water, moisture and compounds containing hydroxyl groups, and the application of moderate polymerization temperatures below 110 °C, i.e., below the solidification temperature of PPDO.[10] Under these conditions, the solid monomer apparently reacts very rapidly (within less than 30 minutes) in the amorphous regions with the active aluminum alkoxide function at the chain end to form higher molecular weight PPDO.

While complete monomer conversion can be achieved in the ring-opening polymerization of similar compounds, such as ε-caprolactone, the polymer yields for p-dioxanone – even with alternative methods, such as heat input by microwave radiation[12] – are generally below 70 %.

Because of its low ceiling temperature of 235 °C (calculated)[10] or 265 °C (measured)[13] poly-p-dioxanone is inherently thermally unstable and tends to depolymerize with chain degradation from the hydroxy chain end (unzipping) with formation of the monomeric p-dioxanone.

Depolymerisation des PPDO durch "unzipping" vom Hydroxylkettenende

Depolymerization is achieved by endcapping, i.e. Closure of the active chain ends towards the end of the polymerization, e.g. with pyromellitic dianhydride,[8] by reaction with chain extenders (chain extenders)[14] or by copolymerization with similar lactones, such as ε-caprolactone.[15] suppressed.

Reactive coextrusion, e.g. in a twin-screw extruder, produces semicrystalline copolymers with randomly distributed, short PPDO and polycaprolactone blocks already at low caprolactone contents and short reaction times with complete conversion of the p-dioxanone, and their thermal stability at melting points up to 94 °C is significantly improved compared to the homopolymer. The efficient, one-step, continuous and fast process of reactive coextrusion could be suitable to avoid the weaknesses of the conventional generated poly-p-dioxanone and to produce commercial quantities in a reproducible and cost-effective way.[16]

Features

Poly-1,4-dioxan-2-one is a semicrystalline polymer (crystallinity of 37 to 55%) with a melting point Tm = 110 °C and a glass transition temperature Tg =-10 °C.[15] and -16 °C[11]and a number average molecular weight Mn of approx. 28000[8] to about 68000[15] and a relatively narrow polydispersity of about 1.6.
The elastic modulus and glass transition temperature of PPDO is lower compared to the polylactones polyglycolide and polylactide; due to the ether function in the polymer backbone, PPDO is more flexible and softer than the other two polylactones and can therefore be used as a monofilament.[11] Poly-p-dioxanone is tougher than polylactide and even than polyethylene with a tensile strength of 48.3 MPa at a maximum elongation at break of 500 to 700 %.[10]

For use as an implant material, poly-1,4-dioxan-2-one can be radiation sterilized without significant degradation of mechanical properties.[11]

Under physiological conditions, PPDO is chemically degraded, with approximately 58% of the original suture strength remaining after four weeks. After approximately 180 days in the body, the polymer is completely degraded without negative tissue reactions.

Segmented copolymers or block copolymers of PPDO with other lactones lead to materials with altered property profiles, such as shorter degradation time in vivo for polyglycolide segments or higher flexibility for poly-ε-caprolactone segments.

Applications

The applications discussed and realized for poly-p-dioxanone include biodegradable films, fibers, nonwovens, adhesives, and coatings, but especially biocompatible articles for wound care such as absorbable surgical sutures (PDS), ligature clips, wound clips, needles, and bone pins, such as ethipin.[17]

While the homopolymer poly-p-dioxanone has not found applications as an implant material for controlled drug release in the body, copolymers such as those made from 1,4-dioxan-2-one and ω-pentadecalactone (cyclopentadecanolide) appear to be suitable for this purpose.[18]

Copolymer aus ω-Pentadecalacton und 1,4-Diocxan-2-on

Individual references

  1. R.S. Bezwada, D.D. Jamiolkowski, K. Cooper: Poly(p-dioxane) and its copolymers, in Handbook of Biodegradable Polymers. Eds: A.J. Domb, J. Kost, D.M. Wiseman. Harwood Academic Publishers, 1997, ISBN 90-5702-153-6, ch. 2, pp. 29-61.
  2. K.-K. Yang, X.-L. Wang, Y.-Z. Wang: Poly(p-dioxanone) and its copolymers. In: J. Macromol. Sci., Part C Polym. Rev. vol. 42, no. 3, 2002, pp. 373-398 , doi:10.1081/MC-120006453.
  3. Patent US4653497 : Crystallinep-dioxanone/glycolide copolymers and surgical devices made therefrom. Filed November 29, 1985, published March 31, 1987, Applicant:Ethicon, Inc, Inventors: R.S. Bezwada, S.W. Shalaby, H.D. Newman, Jr.
  4. Patent US4643191 : Crystallinecopolymers of p-dioxanone and lactide and surgical devices made therefrom. Filed November 29, 1985, published February 17, 1987, Applicant:Ethicon, Inc., Inventors: R.S. Bezwada, S.W. Shalaby, H. Newman, Jr, A. Kafrawy.
  5. Patent US5047048 : Crystallinecopolymers of p-dioxanone and ε-caprolactone. Filed 29 November1985, published 17 February 1987, applicant:Ethicon, Inc, inventors: R.S. Bezwada, S.W. Shalaby, M. Erneta.
  6. J.A. Ray, N. Doddi, D. Regula, J.A. Williams, A. Melveger: Polydioxanone (PDS), a novel monofilament synthetic absorbable suture. In: Surgery, Gynecology & Obstetrics. Vol. 151, No. 4, 1981, pp. 497-507 ([ 1]).
  7. Patent US3645941 : Method ofpreparing 2-p-dioxanone polymers. Filed April 1, 1970, published February 29, 1972, applicant:Eastman Kodak Co, inventors: T.C. Snapp, A.E. Blood.
  8. a b c Patent US5652331 : Methodfor preparing poly-p-dioxanone polymer. Filed August 30, 1996, published July 29, 1997, applicant:Shell Oil Co, inventors: T.C. Forschner, D.E. Gwyn, C.A. Veith.
  9. T. Redin, A. Finne-Wistrand, T. Mathisen, A.-C. Albertsson: Bulk polymerization of p-dioxanone using a cyclic tin alkoxide as initiator. In: J. Polym. Sci., Part A. vol. 45, no. 23, 2007, pp. 5552-5558 , doi:10.1002/pola.22301.
  10. a b c d J.-M. Raquez, Ph. Degée, Ph. Dubois: ROP of 1,4-dioxan-2-one initiated by Al(OiPr)3 in bulk: thermodynamics, kinetics and mechanism.(PDF).ofOriginals march 4, 2016 on the Internet Archive) Info:The archive linkwas inserted automatically and has not yet been checked. Please check original and archive link according to instructions and then remove this note.@1@2Template:Webachiv/IABot/morris.umh.ac.be
  11. a b c d e Patent US4032988 : Syntheticabsorbable surgical devices of poly-dioxanone. Filed June 12, 1976, published October 11, 1977, applicant:Ethicon, Inc, inventors: N. Doddi, C.C. Versfelt, D. Wasserman.
  12. Y. Li, X.-L. Wang, K.-K. Yang, Y.-Z. Wang: A rapid synthesis of poly (p-dioxanone) by ring-opening polymerization under microwave irradiation. In: Polym. Bull. Vol. 57, No. 6, 2006, pp. 873-880 , doi:10.1007/s00289-006-0668-2.
  13. H. Nishida, M. Yamashita, T. Endo, Y. Tokiwa: Equilibrium polymerization behavior of 1,4-dioxan-2-one in bulk. In: Macromolecules. Vol. 33, No. 19, 2000, pp. 6982-6986 , doi:10.1021/ma000457t.
  14. X.-L. Wang, S.-C. Chen, Y.-H. Zhang, K.-K. Yang, Y.-Z. Wang: A biodegradable copolymer from coupling poly(p-dioxanone) with poly(ethylene succinate) via toluene-2,4-diisocyanate. In: e-Polymers. Vol. 9, 2009, pp. 133-144, doi:10.1515/epoly.2009.9.1.133.
  15. a b c J.-M. Raquez, P. Degée, P. Dubois, S. Balakrishnan, R. Narayan: Melt-stable poly(1,4-dioxan-2-one) (co)polymers by ring-opening polymerization via continuous reactive extrusion. In: Polym. Eng. Sci. vol. 45, no. 4, 2005, pp. 622-629 , doi:10.1002/pen.20312.
  16. Patent WO2006020544 : Copolymerization of1,4-dioxan-2-one and a cyclic ester monomer producing thermally stabilized 1,4-dioxan-2-one (co)polymers. Filed August 8, 2005, published February 23, 2006, Applicant:Michigan State University, Inventors: R. Narayan, J.-M. Raquez, S. Balakrishnan, P. Dubois, P. Degee.
  17. J.-M. Raquez, O. Coulombier, A. Duda, R. Narayan, P. Dubois: Recent advances in the synthesis and applications of poly(1,4-dioxan-2-one) based copolymers. In: Polymery. Vol. 53, No. 3, 2009, pp. 165-178 .
  18. J. Liu, Z. Jiang, C. Liu, R.A. Gross, T.R. Kyriakides, W.M. Saltzman: Biodegradation, biocompatibility, and drug delivery in poly(ω-pentadecalactone-co-p-dioxanone) copolyesters. In: Biomaterials. Vol. 32, No. 27, 2011, pp. 6646-6654 , doi:10.1016/j.biomaterials.2011.05.046.