Areal implant with ultrasonically detectable elements

• US 20040093069A1
• Filed: 08/06/2003
• Published: 05/13/2004
• Est. Priority Date: 10/11/2000
• Status: Abandoned Application

• Current Assignee: Barbara Schuldt-Hempe, Christoph Walther, Jorg Priewe
• Original Assignee: Barbara Schuldt-Hempe, Christoph Walther, Jorg Priewe
• Inventors: Schuldt-Hempe, Barbara, Walther, Christoph, Priewe, Jorg
• Application Number:
  US10/398,639
• Publication Number:
  US 20040093069A1
• Time in Patent Office: Days
• US Class Current: 623/1.15
• CPC Class Codes: A61B 2090/3937 Visible markers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque

Abstract

An areal implant has a flexible basic structure on a polymer basis (1) and ultrasonically detectable elements (2) which contain or produce gas and which are set up for detectability for at least four weeks after implantation. The implant can be non-resorbable, partially resorbable or resorbable. Examples of ultrasonically detectable elements are foams (2) or microcapsules embedded in a matrix. The ultrasonically detectable elements are preferably designed as pre-shaped bodies (2) or linear structures such as e.g. threads.

Claims

1. Areal implant, with a flexible basic structure on a polymer basis (1;

30, 32;

40, 42;

50) and with ultrasonically detectable elements (2;

10;

20;

32;

42;

52), which contain or produce gas and which are set up for detectability for at least four weeks after implantation.

2. Implant according to claim 1, characterized in that the elements (52) detectable in ultrasound are arranged in an areal pattern.

3. Implant according to claim 1 or 2, characterized in that the basic structure (1;

30;

40) contains non-resorbable polymer.

4. Implant according to claim 3, characterized in that the basic structure (1;

30;

40) contains at least one of the substances selected from the following group;

polyalkenes, polypropylene, polyethylene, partially halogenated polyolefins, wholly halogenated polyolefins, fluorinated polyolefins, polytetrafluorethylene, polyvinylidene fluoride, polyisoprenes, polystyrenes, polysilicones, polycarbonates, polyarylether ketones, polymethacrylic acid esters, polyacrylic acid esters, polyimides, copolymers of polymerizable substances thereof.

5. Implant according to one of claims 1 to 4, characterized in that the basic structure (50) contains resorbable polymer.

6. Implant according to claim 5, characterized in that the basic structure (50) contains at least one of the substances selected from the following group:

polyhydroxy acids, polylactides, polyglycolides, polyhydroxy butyrates, polyhydroxy valeriates, polycaprolactones, polydioxanones, synthetic and natural oligo- and polyamino acids, polyphosphazenes, polyanhydrides, polyorthoesters, polyphosphates, polyphosphonates, polyalcohols, polysaccharides, polyethers, polyamides, aliphatic polyesters, aromatic polyesters, copolymers of polymerizable substances thereof, resorbable glasses.

7. Implant according to one of claims 1 to 6, characterized in that the basic structure has one of the forms selected from the following group:

meshes (1), tapes (50), films, perforated films, felts, fleeces, open-pored foam films.

8. Implant according to one of claims 1 to 7, characterized in that the elements (2) detectable in ultrasound contain at least one of the substances selected from the following group:

physiologically acceptable gases;

low-boiling-point liquids which are present in gaseous form at 38°

C.;

low-boiling-point liquids which vaporize in the ultrasound field.

9. Implant according to claim 8, characterized in that the elements (2;

10;

20;

32;

42;

52) detectable in ultrasound contain at least one of the substances selected from the following group;

non-, partially and perfluorinated n-, iso-, neo- and cycloalkanes, fluorobromoalkanes, sulfur hexafluoride, hydrogen, nitrogen, oxygen, air, carbon dioxide, helium, neon, argon, xenon, krypton.

10. Implant according to one of claims 1 to 9, characterized in that the elements (2;

10;

20;

32;

42) detectable in ultrasound contain a non-resorbable structural material.

11. Implant according to claim 10, characterized in that the structural material of the elements (2;

10;

20;

32;

42) detectable in ultrasound contains at least one of the substances selected from the following group;

polyalkenes, polypropylene, polyethylene, partially halogenated polyolefins, wholly halogenated polyolefins, fluorinated polyolefins, polytetrafluorethylene, polyvinylidene fluoride, polyisoprenes, polystyrenes, polysilicones, polycarbonates, polyarylether ketones, polymethacrylic acid esters, polyacrylic acid esters, polyimides, hydrophilic cross-linked polymers, silicones, copolymers of polymerizable substances thereof, ceramics, glasses, metals, carbon.

12. Implant according to one of claims 1 to 11, characterized in that the elements (52) detectable in ultrasound contain a resorbable structural material.

13. Implant according to claim 12, characterized in that the structural material of the elements (52) detectable in ultrasound contains at least one of the substances selected from the following group:

polyhydroxy acids, polylactides, polyglycolides, polyhydroxybutyrates, polyhydroxyvaleriates, polycaprolactones, polydioxanones, synthetic and natural oligo- and polyamino acids, polyphosphazenes, polyanhydrides, polyorthoesters, polyphosphates, polyphosphonates, polyalcohols, polysaccharides, polyethers, polyamides, aliphatic polyesters, aromatic polyesters, natural polyamino acids, synthetic polyamino acids, genetically produced polyamino acids, collagen, rhcollagen, silk, pseudopolyamino acids, polycyanoacrylates, polyethylene glycols, polyvinyl alcohols, derivatized cellulose, fats, waxes, fatty acids, fatty acid esters, polyphosphate esters, copolymers of polymerizable substances thereof, resorbable glasses.

14. Implant according to one of claims 1 to 13, characterized in that at least part of the ultrasonically detectable elements is formed as pre-shaped bodies (2;

10;

52) with respective length, width and height in the range from 0.1 mm to 50 mm.

15. Implant according to claim 14, characterized in that at least one pre-shaped body has one of the shapes selected from the following group:

rings (2), disks, platelets, buttons, flat ellipses, hemispheres, solid spheres, beads, cylinders, cubes, blocks, cones, rods, sleeves, tubes (10), pipes, films (52).

16. Implant according to one of claims 1 to 15, characterized in that at least part of the ultrasonically detectable elements is designed as linear structures (20;

32;

42).

17. Implant according to claim 16, characterized in that at least one linear structure is of a type selected from the following group:

tapes, cords, threads (20;

40), twines, knotted filaments, film tapes (32), covering twines.

18. Implant according to one of claims 1 to 17, characterized in that at least part of the ultrasonically detectable elements is connected to the basic structure in at least one of the ways selected from the following group:

melting on, welding (2;

10), application from solution (52), gluing, knotting, attachment to a holding device connected to the basic structure, incorporation into the basic structure using textile techniques (32;

42).

19. Implant according to one of claims 1 to 18, characterized in that at least part of the ultrasonically detectable elements has a symbol detectable in ultrasound, which is preferably provided repeatedly at uniform intervals.

20. Implant according to claim 19, characterized in that the symbol is designed in one of the forms selected from the following group:

sewn from linear structures, embroidered from linear structures, embossed from film, composed of several objects.

21. Implant according to one of claims 1 to 20, characterized in that at least part of the elements (2) detectable in ultrasound has a structure with a mono-to-multi-cell integral foam, the internal walls of which are dry or wetted by a liquid.

22. Implant according to one of claims 1 to 21, characterized in that at least part of the elements (20;

32;

42) detectable in ultrasound contains a matrix into which gas-filled microcapsules (22) are embedded.

23. Implant according to claim 22, characterized in that the microcapsules are present in at least one of the ways selected from the following group:

microcapsules surrounded by liquid which are embedded in polymer;

microcapsules surrounded by liquid which are embedded in fat;

microcapsules surrounded by liquid which are embedded in an organogel;

microcapsules surrounded by liquid which are embedded in a glass;

microcapsules (22) which are embedded in a hydrophobic polymer;

microcapsules which are embedded in a hydrophilic gel;

microcapsules which are embedded in a cross-linked polymer;

microcapsules which are embedded in a polymer gel;

microcapsules which are embedded in an open-pored polymer foam, the diameter of the microcapsules generally being greater than the pore diameter of the outer foam pores.

24. Implant according to one of claims 1 to 23, characterized in that at least part of the ultrasonically detectable elements has a structure with a composite which contains hollow threads in a polymer matrix.

25. Implant according to one of claims 1 to 24, characterized in that at least part of the ultrasonically detectable elements has a structure with open-pored pre-shaped bodies or linear structures which are surrounded by a gas-tight envelope.

26. Implant according to one of claims 1 to 25, characterized in that at least part of the ultrasonically detectable elements is composed at least partially of gas-filled microparticles, the microparticles being surface-fused, i.e. preferably thermally surface-filmed, ionically crosslinked and/or chemically crosslinked.

27. Implant according to one of claims 1 to 26, characterized in that at least part of the elements (52) detectable in ultrasound comprises a structure with blister films.

28. Implant according to one of claims 1 to 27, characterized in that the implant is also detectable in magnetic resonance tomography.

29. Implant according to claim 28, characterized by pre-shaped bodies or linear structures which favour a magnetic resonance contrast, the pre-shaped bodies or linear structures preferably comprising tubes filled with water, magnetic resonance contrast agents and/or fat.

30. Implant according to one of claims 1 to 29, characterized by at least one biologically active ingredient which preferably comprises at least one of the substances selected from the following group:

natural ingredients, synthetic ingredients, antibiotics, chemotherapeutics, cytostatics, metastasis inhibitors, antidiabetics, antimycotics, gynaecological agents, urological agents, anti-allergic agents, sexual hormones, sexual hormone inhibitors, haemostyptics, hormones, peptide hormones, antidepressants, anti-histamines, naked DNA, plasmid DNA, cationic DNA complexes, RNA, cell constituents, vaccines, cells occurring naturally in the body, genetically modified cells.

31. Implant according to claim 30, characterized in that the active ingredient is present in at least one of the forms selected from the following group:

in encapsulated form, in adsorbed form, in the basic structure, at the basic structure, in ultrasonically detectable elements, at ultrasonically detectable elements.

32. Process for producing an implant according to claim 1, characterized in that, during preparation of the ultrasonically detectable elements, structural material of the ultrasonically detectable elements is extruded and, in doing so, a gas is introduced into the structural material by direct gassing or under supercritical conditions, the gas preferably containing at least one of the substances selected from the following group:

air, carbon dioxide, nitrogen, mixtures of nitrogen and carbon dioxide;

sulfur hexafluoride;

inert gases;

alkanes, partially fluorinated alkanes, perfluoroalkanes, bromofluoroalkanes in linear, branched, cyclic form;

physiologically acceptable nitrogen oxides such as NO.

33. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, structural material of the ultrasonically detectable elements is expanded with the addition of a chemical or physical blowing agent, the blowing agent preferably containing at least one of the substances selected from the following group:

water;

non-, partially and perfluorinated n-, iso-, neo- and cycloalkanes;

hydrogen phosphate/hydrogen carbonate/starch mixtures;

ammonium nitrite;

calcium carbonate;

ammonium carbonate;

mixtures of carbonate and solid acids;

readily gas-eliminating monomers, oligomers and polymers, in particular maleic acid as well as its esters and anhydrides, oxocarboxylic acids, aceto acetic acid and its derivatives, á

-ketopropionic acid, acetondicarboxylic acid, tartaric acid as well as the esters and salts thereof, oxalates, Diels-Alder adduct analogs from dienes with carbon dioxide or nitrogen, 3,6-dihydro-2H-pyran-2-on [26677-08-7], homo and copolymers of itaconic acid and the esters thereof, copolymers of azobisisobutyric acid with diols, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, oligoethylene glycol, polyethylene glycol, propanediol, butanediol, hexanediol;

azo compounds, in particular azodicarbonamide and modified azodicarbonamide;

hydrazine derivatives, in particular 4,4′

-oxybis[benzol]sulfonhydrazide, diphenylsulfon-3,3′

-disulfonhydrazide, diphenylene oxide-4,4-disulfonhydrazide, trihydrazinotriazine;

semicarbazides, in particular p-toluylenesulfonyl semicarbazide;

tetrazoles, in particular 5-phenyltetrazole;

benzooxazines, in particular isatoic acid anhydride.

34. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, an open-pored foam is gassed and then closed by thermal filming at the surface, gases with a poor blood and polymer solubility preferably being used, in particular at least one of the gases selected from the following group:

perfluoromethane, perfluoroethane, perfluoropropanes, perfluorobutanes, perfluoropentanes.

35. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, an open-pored foam is gassed and then sealed by coating with a biocompatible soft powder, the powder preferably containing at least one of the substances selected from the following group:

fats, waxes, readily-melting polymers, and a thermal filming preferably then being carried out.

36. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, an open-pored foam is gassed and sealed with a coating material dissolved in a solvent, the solvent then being evaporated.

37. Process for producing an implant according to claim 1, characterized in that, during the manufacture of the ultrasonically detectable elements, an open-pored foam is gassed and then sealed with a monomer coating, the coating then being polymerized or cross-linked.

38. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, a syntactic foam is extruded, preferably made of polypropylene, gas-filled glass hollow balls preferably being embedded in the syntactic foam.

39. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, a polymer is precipitated from a solvent in the presence of gas-containing or gas-producing microcapsules.

40. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, an interfacial polymerization with gas-containing or gas-producing microcapsules is carried out.

41. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, in the presence of gas-containing or gas-producing microcapsules a polymerization or polyaddition or polycondensation of at least one hydrophilic monomer or polymer and a chemical cross-linker is carried out.

42. Process according to claim 41, characterized in that the hydrogel obtained upon the polymerization or polyaddition or polycondensation contains at least one of the substances selected from the following group:

polymerized hydroxyethyl methacrylate (HEMA);

polymerized hydroxypropyl methacrylate (HPMA);

polymerized α

-methacryloyl-ω

-methoxy polyethylene glycol;

polymerized polyethylene glycol-bisacrylate;

resorbable prepolymers of type A-B-C-B-A with A=acryl or methacryl groups, B=hydrolytically splittable and containing polymers of lactide, glycolide, 2-hydroxybutyric acid, 2-hydroxyvaleriac acid, trimethylene carbonate, polyorthoesters, polyanhydrides, polyphosphates, polyphosphazenes and/or polyamides and/or copolymers thereof, and C=hydrophilic polymers, in particular polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), poly-N-isoprolyacrylamide (PNiPAAM).

43. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, a hollow thread or a thin tube is thermally sealed at least at both ends.

44. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, a hollow thread or a thin tube is sealed by ultrasound at least at both ends and preferably then coated with a sealing made from wax and/or polymer.

45. Process according to claim 43 or 44, characterized in that, before the sealing, an agent is poured into the hollow thread or thin tube which releases a gas upon the introduction of humidity, the agent preferably containing one of the following substances:

baking powder, benzoic acid/carbonate mixtures, carbides, metal hydrides.

46. Process according to claim 43 or 44, characterized in that, before the sealing, a suspension of gas-containing or gas-producing microcapsules is poured into the hollow thread or thin tube.

47. Process according to claim 46, characterized in that decomposition inhibitors for the microcapsules are additionally poured into the hollow thread or thin tube before the sealing, the decomposition inhibitors preferably containing at least one of the following substances:

buffers, acids, bases, polymers which set the pH value by decomposition or solvation, esterase inhibitors, protease inhibitors, dextranase inhibitors, mixed-function oxidase inhibitors, cryoprotectors or enzymes which favour the decomposition of enzymes which break down microcapsules, competitively decomposable polymers not detectable in ultrasound.

48. Process according to claim 43 or 44, characterized in that, before the sealing, a suspension of gas-containing or gas-producing microcapsules in dry form is poured into the hollow thread or thin tube.

49. Process according to claim 43 or 44, characterized in that, before the sealing, an emulsion which vaporizes under diagnostic ultrasound is poured into the hollow thread or thin tube.

50. Process for producing an implant according to claim 1, characterized in that, for the gentle preparation of the ultrasonically detectable elements, gas-filled microparticles are encapsulated in a hydrogel below 50°

C. in the presence of hydrophilic mono- or bifunctional monomers and/or polymers.

51. Process for producing an implant according to claim 1, characterized in that, for the gentle preparation of the ultrasonically detectable elements, gas-filled microparticles are encapsulated below 50°

C. in the presence of a dialdehyde and a polyamine or protein.

52. Process according to claim 50 or 51, characterized in that the encapsulation is carried out directly on the implant.

53. Process according to claim 50 or 51, characterized in that the encapsulation is carried out in the form of pre-shaped bodies or linear structures, in particular threads, and the pre-shaped bodies or linear structures are attached to the flexible basic structure of the implant after the encapsulation.

54. Process for producing an implant according to claim 1, characterized in that, during the preparation of the ultrasonically detectable elements, gas-filled microcapsules or their suspensions are used as preliminary steps to the in-situ generation of bubbles in pre-shaped bodies or linear structures, in particular threads.

55. Process for producing an implant according to claim 1, characterized in that echogenic microcapsules are used as precursors for generating bubbles in the implant.

56. Process for producing ultrasonically detectable elements, characterized by the steps, resulting from one of claims 32 to 55, during the preparation of ultrasonically detectable elements.