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 essentially an alternating copolymer of ethylene glycol and glycolic acid and through ring-opening Polymerization from 1,4-dioxan-2-one occurs.

In addition to homopolymers , a number of random copolymers and block copolymers , mostly with other lactone monomers such as glycolide , lactide or ε-caprolactone, are described.

Poly-1,4-dioxan-2-one under the name PDS TM ( p oly d ioxanon s utures ) in the form of monofilaments absorbable as the first, i. H. biodegradable surgical sutures introduced in 1981.

synthesis

The preparation of the homopolymer poly- p -dioxanons takes place in bulk or solution at elevated temperatures (100 ° C to 175 ° C) for 3 to 48 hours at atmospheric pressure or vacuum in the presence of tin - alkoxides such. B. dibutyltin dilaurate , tin (II) -2-ethylhexanoate or the cyclic alkoxide 1-di- n -butyl-1-stanna-2,5-dioxacyclopentane, which suppresses transesterification reactions and should lead to higher intrinsic viscosities, i.e. molar masses of the polymer .

Polymerization of the PDO / depolymerization of the PPDO

The ring-opening polymerization (ROP) of p -dioxanone with aluminum alkoxides , such as. B. aluminum isopropoxide or aluminum sec-butoxide also leads to high molecular weight PPDO as with diethyl zinc or zirconyl acetylacetonate as a catalyst.

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 use of moderate polymerization temperatures are prerequisites for achieving higher molecular weight poly- p- dioxanones 110 ° C, d. H. below the solidification temperature of PPDO. Under these conditions, the solid monomer apparently reacts very quickly (within less than 30 minutes) in the amorphous areas with the active aluminum alkoxide function at the chain end to form higher molecular weight PPDO.

While in the ring-opening polymerization of similar compounds, such as. B. ε-caprolactone complete monomer conversion can be achieved, the polymer yields are p -dioxanone - even with alternative processes, such as. B. the heat supply by microwave radiation - usually below 70%.

Because of its low ceiling temperature of 235 ° C (calculated) or 265 ° C (measured), poly- p -dioxanone is inherently thermally unstable and tends to be thermally unstable when heated, i.e. when it is formed as well as during subsequent thermal deformation by e.g. B. extrusion , injection molding or spinning, for depolymerization with chain breakdown from the hydroxy chain end ( unzipping ) with the formation of the monomeric p -dioxanone.

Depolymerization of the PPDO by "unzipping" from the hydroxyl chain end

The depolymerization is achieved by endcapping , i.e. H. Closure of the active chain ends towards the end of the polymerization z. B. with pyromellitic dianhydride , by reaction with chain extenders ( chain extenders ) or by copolymerization with similar lactones, such as. B. ε-caprolactone. suppressed.

The reactive coextrusion z. B. in a twin screw extruder produces semicrystalline copolymers with randomly distributed, short PPDO and polycaprolactone blocks, whose thermal stability at melting points up to 94 ° C is significantly improved compared to the homopolymer , even with low caprolactone contents and short reaction times with complete implementation of the p- dioxanone. The efficient, one-step, continuous and rapid process of reactive coextrusion could be suitable for avoiding the weaknesses of the conventionally produced poly- p- dioxanone and for producing commercial quantities in a reproducible and cost-effective manner.

properties

Poly-1,4-dioxan-2-one is a semicrystalline polymer (crystallinity from 37 to 55%) with a melting point T m = 110 ° C and a glass transition temperature T g = −10 ° C. or −16 ° C, as well as a number average molar mass M n of approx. 28,000 to approx. 68,000 and a relatively narrow polydispersity of approx. 1.6. The modulus of elasticity and the glass transition temperature of PPDO are 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 also be used as a monofilament. Poly- p -dioxanone is tougher than polylactide and even as polyethylene having a tensile strength of 48.3 MPa and a maximum breaking elongation of 500 to 700%.

For use as an implant material, poly-1,4-dioxan-2-one can be radiation-sterilized without any significant deterioration in the mechanical properties.

Under physiological conditions, PPDO is chemically degraded, with approx. 58% of the original seam thickness remaining after four weeks. After about 180 days in the body, the polymer is completely degraded without any negative tissue reactions.

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

Applications

The applications discussed and implemented for poly-p-dioxanone include biodegradable films, fibers, fleeces, adhesives and coatings, but in particular biocompatible articles for wound care such as absorbable surgical suture material (PDS), ligature clips, wound clips, needles and bone pins, such as e.g. B. ethipine.

While the homopolymer poly- p- dioxanone has not found any applications as an implant material for the controlled release of active substances in the body, copolymers, such as e.g. B. from 1,4-dioxan-2-one and ω-pentadecalactone (cyclopentadecanolide) to be suitable.

Copolymer of ω-pentadecalactone and 1,4-diocxan-2-one

Individual evidence

  1. ↑ RS Bezwada, DD Jamiolkowski, K. Cooper: Poly (p-dioxane) and its copolymers, in Handbook of Biodegradable Polymers . Ed .: AJ Domb, J. Kost, DM Wiseman. Harwood Academic Publishers, 1997, ISBN 90-5702-153-6 , chap. 2 , p. 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. Band 42 , no. 3 , 2002, p. 373-398 , doi : 10.1081 / MC-120006453 .
  3. ↑ Patent US4653497 : Crystalline p-dioxanone / glycolide copolymers and surgical devices made therefrom. Filed on Nov. 29, 1985 , published on March 31, 1987 , Applicant: Ethicon, Inc., inventors RS Bezwada, SW Shalaby, HD Newman, Jr
  4. ↑ Patent US4643191 : Crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom. Applied November 29, 1985 , published February 17, 1987 , Applicant: Ethicon, Inc., Inventors: RS Bezwada, SW Shalaby, H. Newman, Jr., A. Kafrawy. ‌
  5. ↑ Patent US5047048 : Crystalline copolymers of p-dioxanone and ε-caprolactone. Applied November 29, 1985 , published February 17, 1987 , Applicant: Ethicon, Inc., Inventor: RS Bezwada, SW Shalaby, M. Erneta. ‌
  6. ^ JA Ray, N. Doddi, D. Regula, JA Williams, A. Melveger: Polydioxanone (PDS), a novel monofilament synthetic absorbable suture . In: Surgery, Gynecology & Obstetrics . tape 151 , no. 4 , 1981, p. 497-507 ( [1] ).
  7. ↑ Patent US3645941 : Method of preparing 2-p-dioxanone polymers. Filed April 1, 1970 , published February 29, 1972 , applicant: Eastman Kodak Co., inventor: TC Snapp, AE Blood. ‌
  8. ↑ a b c Patent US5652331 : Method for preparing poly-p-dioxanone polymer. Applied on August 30, 1996 , published July 29, 1997 , Applicant: Shell Oil Co., Inventor: TC Forschner, DE Gwyn, CA 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 . tape 45 , no. 23 , 2007, p. 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 (O i Pr) 3 in bulk: thermodynamics, kinetics and mechanism . ( PDF ). PDF ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / morris.umh.ac.be
  11. ↑ a b c d e Patent US4032988 : Synthetic absorbable surgical devices of poly-dioxanone. Filed June 12, 1976 , published October 11, 1977 , Applicant: Ethicon, Inc., Inventor: N. Doddi, CC 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. Band 57 , no. 6 , 2006, p. 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-ones in bulk . In: Macromolecules . tape 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 . tape 9 , 2009, p. 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. Closely. Sci. tape 45 , no. 4 , 2005, p. 622-629 , doi : 10.1002 / pen.20312 .
  16. ↑ Patent WO2006020544 : Copolymerization of 1,4-dioxan-2-one and a cyclic ester monomer producing thermal stabilized 1,4-dioxan-2-one (co) polymers. Filed August 8, 2005 , published February 23, 2006 , Applicant: Michigan State University, Inventor: 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 . tape 53 , no. 3 , 2009, p. 165-178 .
  18. ^ J. Liu, Z. Jiang, C. Liu, RA Gross, TR Kyriakides, WM Saltzman: Biodegradation, biocompatibility, and drug delivery in poly (ω-pentadecalactone- co -p-dioxanone) copolyesters . In: Biomaterials . tape 32 , no. 27 , 2011, p. 6646–6654 , doi : 10.1016 / j.biomaterials.2011.05.046 .