Coating for Medical Devices
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Europäisches Patentamt *EP001247537A1* (19) European Patent Office Office européen des brevets (11) EP 1 247 537 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: A61L 27/34, A61L 29/08, 09.10.2002 Bulletin 2002/41 A61L 31/10 (21) Application number: 01201259.7 (22) Date of filing: 04.04.2001 (84) Designated Contracting States: (72) Inventor: The designation of the inventor has not AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU yet been filed MC NL PT SE TR Designated Extension States: (74) Representative: Prins, Adrianus Willem et al AL LT LV MK RO SI Vereenigde, Nieuwe Parklaan 97 (71) Applicant: IsoTis B.V. 2587 BN Den Haag (NL) 3723 MB Bilthoven (NL) (54) Coating for medical devices (57) The invention relates to a coating for medical leased in vivo in a controlled manner, as the degrada- devices. The coating comprises a copolymer of a poly- bility of the coating may also be adjusted to a predeter- alkylene glycol terephtalate and an aromatic polyester mined rate. The invention further relates to a process of which the composition may be adjusted such as to for applying the coating to a surface and to a medical achieve an excellent adhesion to a wide range of sur- device comprising the coating. faces. The coating may further comprise an additive, such as a biologically active agent, which may be re- EP 1 247 537 A1 Printed by Jouve, 75001 PARIS (FR) 1 EP 1 247 537 A1 2 Description tude of variations that can be used to achieve an opti- mum property profile of a coating. These parameters do [0001] The invention relates to a coating for medical not only serve to adjust the adhesion of the coating. Oth- devices. The invention further relates to a process for er properties can be optimised as well. Examples of applying a coating to a surface, e.g. a surface of a med- 5 such properties include the degradability and swelling ical device, and to a medical device comprising said behaviour of the coating and mechanical properties, like coating. elasticity and tensile strength. Other properties and ad- [0002] Great effort has been put into studies of coat- vantages will become clear form the following, more de- ings for medical devices. Materials used for the manu- tailed description of the invention. facture of medical devices are not always chosen from 10 [0009] A coating according to the invention comprises a biocompatability point of view as often other consid- a copolymer of a polyalkylene glycol terephtalate and erations, e.g. with respect to strength or tensile and an aromatic polyester. Preferably, the copolymer com- stretching properties, prevail. prises 20-90 wt.%, more preferably 40-70 wt.% of the [0003] Coatings for medical devices are, however, not polyalkylene glycol terephtalate, and 80-10 wt.%, more only interesting for enhancing the biocompatibility of a 15 preferably 60-30 wt.% of the aromatic polyester. A pre- medical device. They also provide a possibility to pro- ferred type of copolymers according to the invention is vide a controlled release of biologically active agents, in formed by the group of block copolymers. which case it is necessary that the coating is also bio- [0010] The polyalkylene glycol may have a weight av- degradable. erage molecular weight of about 150 to about 10000. [0004] Problems encountered in the design of coat- 20 Preferably, the polyalkylene glycol has a weight average ings for medical devices are many. One of the bigger molecular weight of 200 to 4000. The aromatic polyester problems concerns the adhesion of the coating to the preferably has a weight average molecular weight of material of which the medical device is made. As many from 200 to 9000, more preferably from 250 to 4000. different materials, varying from metals to ceramics and The weight average molecular weight of the copolymer polymeric materials, are used for the manufacture of 25 preferably lies between 10,000 and 300,000, more pref- medical devices, it is important that a good coating ad- erably between 40,000 and 120,000. heres sufficiently to all sorts of materials. This is, how- [0011] The weight average molecular weight may ever, often not the case. suitably be determined by gel permeation chromatogra- [0005] Another problem concerns the conditions a phy (GPC). This technique, which is known per se, may medical device is subjected to during use. Certain med- 30 for instance be performed using chloroform, hexafluoro ical devices, such as catheters, are for instance subject- isopropanol or m-cresol as a solvent and polystyrene as ed to deformation in vivo. When the device expands, it external standard. Alternatively, a measure for the is important that the coating is capable of undergoing weight average molecular weight may be obtained by the same deformation without breaking or coming loose. using viscometry (see NEN-EN-ISO 1628-1). This tech- This would lead to exposure of the surface of the mate- 35 nique may for instance be performed at 25°C using chlo- rial of the medical device to the surrounding tissue in roform as a solvent. Preferably, the intrinsic viscosity of vivo. In the worst case, parts of the coating might detach the copolymer lies between 0.2 and 1.5 dL/g, which cor- from the device completely. responds to a weight average molecular weight be- [0006] Accordingly, there is a need for a coating ma- tween 10,000 and 300,000. Likewise, the more pre- terial for medical devices which may be used universally 40 ferred ranges for the weight average molecular weight for different sorts of medical devices of different materi- measured by GPC mentioned above can also be ex- als. pressed in terms of the intrinsic viscosity. [0007] The invention provides a coating that fulfils this [0012] In a preferred embodiment, the polyalkylene need. A specific copolymer has been found of which the glycol terephtalate component has units of the formula properties may be adjusted to the needs and require- 45 -OLO-CO-Q-CO-, wherein O represents oxygen, C rep- ments of application on a specific medical device of a resents carbon, L is a divalent organic radical remaining specific material. Accordingly, the invention relates to a after removal of terminal hydroxyl groups from a poly coating for a medical device comprising a copolymer of (oxyalkylene)glycol, and Q is a divalent organic radical. a polyalkylene glycol terephtalate and an aromatic pol- [0013] Preferred polyalkylene glycol terephtalates are yester. 50 chosen from the group of polyethylene glycol terephta- [0008] A coating according to the invention may be late, polypropylene glycol terephtalate, and polybuty- applied to a wide range of materials. It is one of the great lene glycol terephtalate and copolymers thereof, such advantages of the invention that the composition of the as poloxamers. A highly preferred polyalkylene glycol copolymer may be adjusted such as to achieve a good terephtalate is polyethylene glycol terephtalate. adhesion to nearly any type of material. The nature and 55 [0014] The terms alkylene and polyalkylene generally molecular weights of the monomers of the copolymer, refer to any isomeric structure, i.e. propylene comprises as well as the ratio of the two monomers and the mo- both 1,2-propylene and 1,3-propylene, butylene com- lecular weight of the copolymer itself, provide a multi- prises 1,2-butylene, 1,3-butylene, 2,3-butylene, 1,2-iso- 2 3 EP 1 247 537 A1 4 butylene, 1,3-isobutylene and 1,4-isobutylene (tetram- tive agents. In addition, depending on the chosen com- ethylene) and similarly for higher alkylene homologues. position of the copolymer, a certain swelling behaviour The polyalkylene glycol terephtalate component is pref- may be set. Swelling may serve as an additional tool to erably terminated with a dicarboxylic acid residue modulate release of active agents from the coating. -CO-Q-CO-, if necessary to provide a coupling to the 5 When the coating is used on certain types of medical polyester component. Group Q may be an aromatic devices, e.g. which are subject to deformation during group having the same definition as R, or may be an use in vivo, an elastic behaviour may be very useful. aliphatic group such as ethylene, propylene, butylene [0020] Examples of materials onto the surface of and the like. which a coating according to the invention may be ap- [0015] The polyester component preferably has units 10 plied include metals and alloys, ceramics, glasses, and -O-E-O-CO-R-CO-, wherein O represents oxygen, C polymers. More specific examples of metals include represents carbon, E is a substituted or unsubstituted stainless steel, titanium, nickel, cobalt, chrome, nio- alkylene or oxydialkylene radical having from 2 to 8 car- bium, molybdenum, zirconium, tantalum, and combina- bon atoms, and R is a substituted or unsubstituted di- tions thereof. Further, ceramic materials, such as alumi- valent aromatic radical. 15 na and zirconia, glasses such as bioactive glasses [0016] In a preferred embodiment, the polyester is made of CaO-SiO2-P2O5, and calcium phosphates, chosen from the group of polyethylene terephthalate, such as hydroxyapatite and tricalcium phosphate, may polypropylene terephthalate, and polybutylene tereph- be coated in accordance with the invention. The subject thalate. A highly preferred polyester is polybutylene coatings can further be applied to various polymers and terephthalate. 20 plastics, more preferably biocompatible or bioresorba- [0017] The preparation of the copolymer will now be ble ones like polylactic acid or polyglycolic acid, but also explained by way of example for a polyethylene glycol polyolefines, such as (ultra high molecular weight) pol- terephtalate/polybutylene terephthalate copolymer.