1. A radio-opaque polymeric compound comprising:
at least one biodegradable region; and
at least one iodinated radio-opaque end-group;
wherein the biodegradable region and the iodinated radio-opaque end-group are linked by at least one biodegradable bond.
2. The compound of claim 1, wherein the biodegradable region comprises a polymer chain selected from a group consisting of linear, branch, star, and dendramer chain, wherein one or more terminal ends of the polymer chain are linked to the iodinated end group.
3. The compound of claim 1, wherein the biodegradable region is selected from a group consisting of polymers, copolymers or oligomers of: glycolide, dl-lacide, d-lactide, I-lactide, caprolactone, dioxanone, trimethylene carbonate, and combinations thereof.
4. The compound of claim 1, wherein the biodegradable region is selected from a group consisting of polymers, copolymers or oligomers of: polyhydroxyacids, polylactic acid, polyglycolic acid, polyorthocarbonates, polyanhydrides, polylactones, polyaminoacids, and polyphosphates and combinations thereof.
5. The compound of claim 1, wherein the biodegradable region is selected from a group consisting of collagen, albumin, gelatin, elastin, keratin, hyaluronic acid chitosan, dextran, fibrinogen, immunoglobins, and polyphosphates.
6. The compound of claim 1, wherein the iodinated end-group is selected from a group consisting of triiodobenzoic acid, triiodophenol, 3,5-Diacetamido-2,4,6-triiodobenzoic acid, 3,5-Bis(acetylamino)-2,4,6-triiodobenzoic acid, erythrosin, rose bengal, and derivatives thereof.
7. The compound of claim 1, wherein the biodegradable bond is selected from a group consisting of amide, urea, ester, ether bonds, and combinations thereof.
8. A biodegradable radio-opaque composition for implantation in the animal body, the composition comprising:
a. at least one biodegradable polymer; and
b. at least one iodinated organic compound, the iodinated organic compound is physically mixed with the biodegradable polymer;
wherein the iodinated organic compound in the biodegradable radio-opaque composition is 3 to 40 percent by weight.
9. The biodegradable radio-opaque composition of claim 8, wherein the biodegradable polymer is selected from group consisting of polymers, copolymers or oligomers of glycolide, dl-lactide, d-lactide, 1-lactide, caprolactone, dioxanone and trimethylene carbonate, or their copolymers
10. The biodegradable radio-opaque composition of claim 8, wherein the biodegradable polymer is selected from group consisting of polyethylene glycol-polylactone copolymers, polyhydroxyacids, polyorthocarbonates, polyanhydrides, polylactones, and their derivatives.
11. The composition of claim 8, wherein the composition is sterilized using ethylene oxide sterilization.
12. The composition of claim 8, wherein the composition is hydrophobic.
13. The composition of claim 8, wherein the composition is hydrophilic.
14. The composition of claim 8, wherein the composition melts at temperature 37\xb0 C. to 65\xb0 C.
15. The composition of claim 8, further capable of being in a liquid state between 10\xb0 C. to 45\xb0 C. temperature.
16. The composition of claim 8, wherein the composition is cross-linkable.
17. The composition of claim 8, wherein the composition is porous.
18. The composition of claim 17, wherein the porous composition is filled with a biocompatible gas.
19. The composition of claim 8 further comprising at least one bioactive compound.
20. The composition of claim 18, wherein the bioactive compound is selected from a group consisting of anti-viral agents, anti-infectives, anti-pruritics, anti-psychotics, cholesterol or lipid reducing agents, cell cycle inhibitors, anti-cancer agents, anti-parkinsonism drugs, HMG-CoA inhibitors, anti-restenosis agents, anti-inflammatory agents, anti-asthmatic agents, anti-helmintics, immunosuppressives, muscle relaxants, anti-diuretic agents, vasodilators, beta-blockers, hormones, anti-depressants, decongestants, calcium channel blockers, growth factors, wound healing agents, analgesics and analgesic combinations, local anesthetics agents, anti-histamines, sedatives, angiogenesis promoting agents, angiogenesis inhibiting agents, and tranquilizers.
21. The composition of claim 8, wherein the composition is used as a coating on a medical device.
22. The compositions of claim 8, wherein the iodinated compounds are selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid salts, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine and ioversol.
23. A biodegradable radio-opaque composition for implantation in the animal body, the composition comprising:
a. at least one biodegradable natural polymer, the biodegradable natural polymer selected from group consisting of albumin, collagen, implantable tissue, gelatin, fibrinogen, keratin, hyaluronic acid, chitosan, dextran and their derivatives;
b. at least one iodinated organic compound, the iodinated organic compound being chemically bound to the natural polymer;
wherein the iodinated organic compound in the radio-opaque composition is 3 to 40 percent by weight;
wherein the radio-opaque composition is crosslinked using zero length crosslinker.
24. The composition of claim 23, wherein the composition is sterilized using ethylene oxide.
25. The composition of claim 23, wherein the composition is crosslinked using carbodiimide derivative.
26. The composition of claim 23, wherein the composition is crosslinked using water soluble carbodiimide derivative.
27. The composition of claim 23, wherein the composition is porous.
28. The composition of claim 23 further comprising at least one bioactive compound.
29. The composition of claim 27, wherein the porous composition is filled with a biocompatible gas.
30. A radio opaque protein cross-linker having the structural formula:
(F)n\u2014X-M
n\u22671
wherein F is a functional group reactive with protein, the functional group is selected from a group consisting of anhydride, isocyanate, n-hydroxysuccinimide, n-hydroxysulfosuccinimide, epoxy, and aldehyde;
wherein M is a chromophore, the chromophore is selected from a group consisting of 2,3,5-triiodobenzoic acid, 3,4,5-triiodophenol, erythrosine, rose bengal, 3,5 -Bis(acetylamino)-2,4,6-triiodobenzoic acid, and 3,5-Diacetamido-2,4,6-triiodobenzoic acid;
wherein X is an organic molecule linking F and M, the organic molecule comprising chemical bonds selected from a group consisting of Carbon-Carbon, Carbon-Hydrogen, Carbon-Nitrogen, Carbon-Oxygen, Carbon-sulfur, Nitrogen-Hydrogen and Oxygen-Hydrogen covalent bonds.
31. A biostable radio-opaque compound having a molecular weight of at least 400 Daltons, the compound comprising:
at least one polyether region; and
at least one iodinated end-group;
wherein the polyether region and the iodinated end-group are linked by one or more biostable chemical bonds.
32. The compound of claim 31, wherein the polyether region is selected from a group consisting of polyethylene glycol (PEG), polyethylene oxide (PEO), polypropylene oxide (PPO), polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymer, and polypropylene oxide-polyethylene oxide-polypropylene oxide block copolymer, derivatives, and combinations thereof.
33. The compound of claim 31, wherein the iodinated end-group is selected from the group consisting of triiodobenzoic acid, triiodophenol, xanthene, and derivatives thereof.
34. The compound of claim 31, wherein the biostable chemical bonds are selected from a group consisting of amide, urea, ester, ether bonds, and combinations thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-25. (canceled)
26. A process comprising preparing an amino- and hydroxybenzonitrile of the formula (I)
wherein X is at least one amino or hydroxy group, by reacting an amino- or hydroxybenzoic acid of the general formula (II)
wherein R is \u2014OH, or NH2, and X is as defined above, with ammonia in the presence of a supported catalyst comprising phosphorus at a temperature between 250 and 500\xb0 C., wherein preparation step 1) is performed in a reaction gas and without an organic solvent and is then followed by an at least two-stage purification step 2) in which 2.1) the gaseous mixture or solid reaction product obtained from preparation step 1) is converted to an aqueous ammonium-containing suspension and 2.2)
a) releasing the product present in the solid as an ammonium salt with the aid of a filtration by adding acid or by driving out ammonia and subsequently introducing the acid, or
b) releasing the product present in the solid as an ammonium salt by reactive distillation, or
c) releasing the product present in the solid as an ammonium salt is performed by an elimination at temperatures of from 0 to 100\xb0 C. and in the presence of an organic solvent.
27. The process as claimed in claim 26, wherein the process is performed at temperature between 340 and 450\xb0 C.
28. The process as claimed in claims 26, wherein the catalyst has been doped with at least one compound comprising a transition metal of group 5, 6, 12 or 14 of the Periodic Table of the Elements and has specific surface area of at least 300 m2g.
29. The process as claimed in claim 26, wherein the catalyst is doped with boron.
30. The process as claimed in claim 26, wherein the catalyst is a supported boron phosphate catalyst which has been prepared by treating the support material with aqueous solutions of from 0.01 to 15% by weight of phosphoric acid, from 0.01 to 15% by weight of boric acid and from 0.01 to 5% by weight of at lest one salt of transition metal of group 5, 6, 12 or 14 of the Periodic Table of the Elements.
31. The process as claimed in claim 26, wherein the support material comprises at least one compound selected from the group consisting of silicon dioxide, silica gel, aluminum oxide, titanium oxide and zirconium oxide.
32. The process as claimed in claim 26, wherein the salt comprises at least one metal selected from the group consisting of vanadium, niobium, tantalum, chromium, molybdenum, tungsten, cadmium, mercury, germanium, tin, lead or zinc.
33. The process as claimed in claim 32, wherein the salt comprises an anion selected from the group consist of salts consisting of borate, chloride, phosphate and sulfate.
34. The process as claimed in claim 33, wherein the salt comprises ammonium.
35. The process as claimed in claim 26, wherein the specific surface area of the catalyst is >400 m 2g.
36. The process as claimed in claim 26, wherein the catalyst has a pore diameter between 0.4 and 25 nm.
37. The process as claimed in claim 26, wherein the catalyst has been dried at temperatures between 100 and 500\xb0 C. for up to 3 hours.
38. The process as claimed in claim 26, wherein the reaction gas (mixture) is oxygen-free and ammonia-containing.
39. The process as claimed in claim 26, wherein the amino- or hydroxybenzoic acid is introduced into the reaction gas (mixture) or the catalyst bed, as a melt, solid or aqueous solution of the ammonium salt.
40. The process as claimed in claim 26, wherein the purification step 2) is performed at a temperature between \u221220\xb0 C. and 100\xb0 C.
41. The process as claimed in claim 26, wherein the purification step 2) is performed under inert gas conditions.
42. The process as claimed in claim 26, wherein the aqueous ammonium-containing basic suspension is obtained by quenching with the aid of a quench which is performed with water or ammoniacal water.
43. The process as claimed in claim 26, wherein the aqueous ammonium-containing basic suspension is obtained in the purification step 2) by cooling the product obtained from preparation step 1) and a subsequent absorption with ammoniacal water.
44. The process as claimed in claim 26, wherein the aqueous ammonium-containing suspension is present in highly concentrated form and comprises the by-products in dissolved form.
45. The process as claimed in claim 26, wherein acidic conditions are established by adding an acid, preferably a mineral acid and especially hydrochloric acid, or by introducing an acidic gas.
46. The process as claimed in claim 26, wherein at least one washing step and at least one drying step are effected at the end.