BIOCOMPATIBLE X-RAY OPAQUE POLYMERS FOR MEDICAL DEVICE
The present application relates to a radio opaque material and a method of producing the same. The material is a hybrid material comprising two phases, an inorganic phase comprising a radio opaque substance and a polymer phase.
1 . A sol-gel method of producing a hybrid material comprising two phases; a first and a second phase wherein the first phase comprises an inorganic compound and the second phase comprises a biodegradable polymer, where the method comprises the steps of:
providing a first solution comprising an inorganic precursor comprising at least one metal alkoxide compound that is radio opaque, and a first solvent;
providing a second solution comprising a biodegradable polyether polymer and a second solvent miscible with the first solvent;
forming a mixture by mixing the first and the second solutions;
bringing the mixture in contact with liquid water or water in vapor phase;
letting the liquid water or water in vapor phase react with the metal alkoxide to form a sol;
letting the liquid water or water in vapor phase react further with the metal alkoxide to form a gel; and
removing the solvents to form a solid material.
2 . The method of claim 1 , wherein the biodegradable polymer is a co-polymer of a polyether and a polyester.
3 . The method of claim 1 , wherein the polyether is based on polyethylene glycol, polypropylene glycol or co-polymers of polyethylene glycol and polypropylene glycol.
4 . The method of claim 2 , wherein the co-polymer is a PEG-co-polyester polymer.
5 . The method of claim 2 , wherein the polyester is based on lactic acid, glycolic acid, caprolactone, trimethylene carbonate, paradioxanone, β-butyrolactone, valerolactone, or a mixture of two or more of said polyesters.
6 . The method of claim 1 , wherein the polymer is a multiarmed polymer with 2, 3, 4, 5, 6 or 7 or more arms.
7 . The method of claim 1 , wherein the molecular weight of the polymer is more than 1000 g/mol, such as 2000 g/mol, preferably more than 5000 g/mol.
8 . The method of claim 1 , wherein the inorganic precursor comprises tantalum alkoxide, titanium alkoxide, gold alkoxide, bismuth alkoxide or zirconium alkoxide.
9 . The method of claim 1 , wherein the weight ratio of inorganic precursor to polymer is at least 1:1, or preferably 5:1, or even more preferred 10:1.
10 . The method of claim 1 , wherein the polymer further contains a radio opaque substance.
11 . The method of claim 10 , wherein the content of the radio opaque substance in the polymer is more than 0.5 wt %, such as more than 5 wt %, or more than 10 wt %, or more than 15 wt %, or more than 25 wt %, or more than 35 wt %.
12 . The method of claim 10 , wherein the radio opaque substance contained in the co-polymer is iodine, bromine or any other halogen or combinations thereof.
13 . The method of claim 12 , wherein the radio opaque substance is iodine, which is incorporated in the polymer backbone by initiation of ring-opening polymerization by an initiator containing iodine and hydroxyl groups, and optionally further by end group functionalization of the iodinated polyester with triiodobenzonic acid.
14 . The method of claim 1 , wherein the concentration of inorganic precursor in the first solution is 0.8-15 weight % and the concentration of the biodegradable polyether polymer in the second solution is 15-30 weight %.
15 . The method of claim 1 , wherein an acid is added to the first or the second solution or to the mixture of the first and the second solution.
16 . The method of claim 1 , wherein the weight ratio of metal oxide is between 30 wt % and 95 wt % of the total weight of the material.
17 . A hybrid material obtainable by a sol-gel method of producing a hybrid material comprising two phases; a first and a second phase wherein the first phase comprises an inorganic compound and the second phase comprises a biodegradable polymer, where the method comprises the steps of:
providing a first solution comprising an inorganic precursor comprising at least one metal alkoxide compound that is radio opaque, and a first solvent;
providing a second solution comprising a biodegradable polyether polymer and a second solvent miscible with the first solvent;
forming a mixture by mixing the first and the second solutions;
bringing the mixture in contact with liquid water or water in vapor phase;
letting the liquid water or water in vapor phase react with the metal alkoxide to form a sol;
letting the liquid water or water in vapor phase react further with the metal alkoxide to form a gel; and
removing the solvents to form a solid material.
18 . A hybrid material obtainable by a sol-gel method of producing a hybrid material according to claim 1 .
19 . A hybrid material comprising two phases; a first and a second phase wherein the first phase comprises an inorganic radio opaque compound and the second phase comprises a biodegradable co-polymer of a polyether and a polyester.
20 . The hybrid material of claim 19 , wherein the first phase comprises a radio opaque metal oxide selected from tantalum oxide, titanium oxide, bismuth oxide, zirconium oxide or gold oxide.
21 . The hybrid material of claim 20 , wherein the metal oxide has a weight ratio of 40 to 90 wt % of the total weight of the hybrid material.
22 . The hybrid material of claim 19 , wherein the polyester is based on lactic acid, glycolic acid, caprolactone, trimethylene carbonate, paradioxanone, β-butyrolactone, valerolactone, or a mixture of two or more of said polyesters.
23 . The hybrid material of claim 19 , wherein the co-polymer comprises a radio opaque substance.
24 . The hybrid material of claim 23 , wherein the content of the radio opaque substance in the polymer is more than 0.5 wt %, such as more than 5 wt %, or more than 10 wt %, or more than 15 wt %, or more than 25 wt %, or more than 35 wt %.
25 . The hybrid material of claim 23 , wherein the radio opaque substance contained in the co-polymer is iodine, bromine or any other halogen or combinations thereof.
26 . The hybrid material of claim 19 , wherein the co-polymer is a multiarmed co-polymer with 2, 3, 4, 5, 6 or 7 or more arms.
27 . The hybrid material of claim 19 , wherein the molecular weight of the co-polymer is more than 1000 g/mol, such as 2000 g/mol, preferably more than 5000 g/mol.
28 . The hybrid material of claim 19 , wherein the material comprises a PEG-co-polyester polymer having a molecular weight of at least 20000 g/mol and with a radio opaque substance content of at least 5 wt % and where the polyester is derived from lactic acid, caprolactone and glycolic acid and the inorganic phase comprising tantalum oxide or titanium oxide is present in a molar ratio of 25:1 to 75:1 to the polymer.
29 . The hybrid material of claim 19 , wherein the material comprises a PEG-co-polyester in which the polyester part comprises 33 wt % each of glycolic acid, DL-lactic acid and caprolactone and the inorganic phase consists of tantalum oxide or titanium oxide having a weight ratio of 60 to 90 wt % of the total weight of the material.
30 . Use of a hybrid material of claim 19 for coating closure devices, catheters, guide wires, stents, sutures, light scattering material, or as a membrane.