COATED ARTICLES FOR BLOOD COAGULATION TESTING AND METHODS OF PREPARING THE SAME
20190275515 ยท 2019-09-12
Inventors
Cpc classification
C08L77/00
CHEMISTRY; METALLURGY
B01L3/508
PERFORMING OPERATIONS; TRANSPORTING
C08L77/00
CHEMISTRY; METALLURGY
C08L33/12
CHEMISTRY; METALLURGY
C08L33/12
CHEMISTRY; METALLURGY
C09D133/20
CHEMISTRY; METALLURGY
International classification
Abstract
The present invention provides a coated article, which can be used in in-vitro diagnostics, in particular in the diagnostic testing of body fluids, such as in blood coagulation testing. The coated article is made of a polymer material and coated with a polymer material, which may be the same or different. The present invention furthermore provides a method of preparing such a coated article and a method of performing such diagnostics, e.g. coagulation analysis.
Claims
1. An article for contacting coagulating and/or coagulated blood components made of a polymer material comprising a polymer, wherein the article is at least partially coated with a coating material comprising a polymer and/or a resin.
2. The article according to claim 1, wherein the coating material comprises at least one polymer.
3. The article according to claim 2, wherein the polymer comprised by the coating material is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, alkyl monomers, vinyl monomers, allyl monomers, carbonate monomers, aromatic monomers, olefin monomers, halogenolefine monomers, methylolefine monomers, urethane monomers, amide monomers, ester monomers and ether monomers.
4. The article according to claim 2 or 3, wherein the coating material comprises at least one polymer selected from polystyrenes, polycarbonates, polymethacrylates, polyolefines, polyhalogenolefines such as polyfluorolefines, polymethylolefines, polyacetals, polyurethanes, polyamides, polyaramides, polyesters, polyethers, polyketones, or any partially substituted polymers thereof, or any co-polymers thereof.
5. The article according to any of claims 2-4, wherein the polymer comprised by the coating material is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, carbonate monomers, amide monomers, and aromatic monomers.
6. The article according to any of claims 2-5, wherein the polymer comprised by the coating material is selected from acrylonitrile butadiene styrene (ABS), methyl methacrylate acrylonitrile butadiene styrene (MABS), polystyrene (PS), high impact polystyrene (HIPS), poly(methyl methacrylate) (PMMA), polycarbonate (PC), polyamide (PA), and polyphenylene sulfide (PPS).
7. The article according to any of claims 2-6, wherein the polymer comprised by the coating material is the same as the polymer comprised by the polymer material.
8. The article according to any of claims 2-6, wherein the polymer comprised by the coating material is distinct from the polymer comprised by the polymer material.
9. The article according to any of claims 1-8, wherein the coating material comprises at least one resin.
10. The article according to claim 9, wherein the resin is selected from epoxy resin, phenol resin, polyurethane resin and/or acrylate resin.
11. The article according to any of claims 1-10, wherein the coating material comprises a dye.
12. The article according to any of claims 1-11, wherein the coating material comprises a particle enabling determination of the quality of the coating.
13. The article according to any of claims 1-12, wherein the polymer material is a mass-production compatible plastic.
14. The article according to any of claims 1-13, wherein the polymer material is selected from thermoplastics, thermoplastic elastomers, conventional elastomers, and duromers.
15. The article according to any of claims 1-14, wherein the polymer material comprises polymethylpentene (PMP) and/or methyl methacrylate acrylonitrile butadiene styrene (MABS).
16. The article according to any of claims 1-15, wherein the article made of the polymeric material is produced by injection molding, press molding, extrusion molding, milling, cutting, or swiveling, preferably by injection molding.
17. The article according to any of claims 1-16, wherein the article is a measurement cup.
18. The article according to any of claims 1-16, wherein the article is a pin or a sleeve for a pin.
19. Coating composition for coating an article for contacting coagulating and/or coagulated blood components made of a polymer material, wherein the coating composition comprises (i) a polymer and/or a resin; and (ii) a solvent, which is capable of dissolving at least 1*10.sup.?6% v/v of the coating polymer and/or the coating resin and which forms a contact angle on the polymer material surface of the article of less than 90? when containing the coating polymer and/or resin; or a first solvent, which is capable of dissolving at least 0.1% v/v of the coating polymer and/or the coating resin and which forms a contact angle on the polymer material surface of the article of 90? or higher when containing the coating polymer and/or resin, and a second solvent in an amount of at least 20% of said first solvent, which forms a contact angle on the polymer material surface of the article of less than 90? and which has an at least 10% longer drying time than said first solvent.
20. The coating composition according to claim 19, wherein the coating composition comprises at least one polymer.
21. The coating composition according to claim 20, wherein the polymer comprised by the coating composition is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, alkyl monomers, vinyl monomers, allyl monomers, carbonate monomers, aromatic monomers, olefin monomers, halogenolefine monomers, methylolefine monomers, urethane monomers, amide monomers, ester monomers and ether monomers.
22. The coating composition according to claim 20 or 21, wherein the coating composition comprises at least one polymer or copolymer selected from polystyrenes, polycarbonates, polymethacrylates, polyolefines, polyhalogenolefines, polymethylolefines, polyurethanes, polyamides, polyesters, polyethers, any partially substituted polymers thereof, or any co-polymers thereof.
23. The coating composition according to any of claims 20-22, wherein the polymer comprised by the coating composition is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, carbonate monomers, amide monomers, and aromatic monomers.
24. The coating composition according to any of claims 20-23, wherein the polymer comprised by the coating composition is selected from acrylonitrile butadiene styrene (ABS), methyl methacrylate acrylonitrile butadiene styrene (MABS), polystyrene (PS), high impact polystyrene (HIPS), poly(methyl methacrylate) (PMMA), polycarbonate (PC), polyamide (PA), and polyphenylene sulfide (PPS).
25. The coating composition according to any of claims 20-24, wherein the coating composition comprises at least one resin.
26. The coating composition according to claim 25, wherein the resin is selected from epoxy resin, phenol resin, polyurethane resin and/or acrylate resin.
27. The coating composition according to any of claims 19-26, wherein the coating composition comprises at least one solvent selected from benzene or benzene derivatives (e.g., alkyl or polyalkyl benzenes); acetate or acetate derivatives (e.g., alkyl or polyalkyl acetates); alkanols or alkanol derivatives (e.g., alkandiols or cyclo alkanols); or naphtha or naphtha components.
28. The coating composition according to any of claims 19-26, wherein the solvent is a lower-risk solvent.
29. A method for treating a surface of an article for contacting coagulating and/or coagulated blood components made of a polymer material, comprising the step of applying a coating composition, which comprises (i) a polymer and/or a resin and (ii) a solvent, to at least a part of the surface of the article.
30. The method according to claim 29, wherein the coating composition comprises at least one polymer.
31. The method according to claim 30, wherein the polymer comprised by the coating composition is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, alkyl monomers, vinyl monomers, allyl monomers, carbonate monomers, aromatic monomers, olefin monomers, halogenolefine monomers, methylolefine monomers, urethane monomers, amide monomers, ester monomers and ether monomers.
32. The method according to claim 30 or 31, wherein the coating composition comprises at least one polymer or copolymer selected from polystyrenes, polycarbonates, polymethacrylates, polyolefines, polyhalogenolefines, polymethylolefines, polyurethanes, polyamides, polyesters, polyethers, any partially substituted polymers thereof, or any co-polymers thereof.
33. The method according to any of claims 30-32, wherein the polymer comprised by the coating composition is a polymer or a copolymer comprising one or more monomers selected from styrene monomers, (meth)acrylate monomers, (meth)acrylamide monomers, carbonate monomers, amide monomers, and aromatic monomers.
34. The method according to any of claims 30-33, wherein the polymer comprised by the coating composition is selected from acrylonitrile butadiene styrene (ABS), methyl methacrylate acrylonitrile butadiene styrene (MABS), polystyrene (PS), high impact polystyrene (HIPS), poly(methyl methacrylate) (PMMA), polycarbonate (PC), polyamide (PA), and polyphenylene sulfide (PPS).
35. The method according to any of claims 30-34, wherein the polymer comprised by the coating composition is the same as the polymer comprised by the polymer material.
36. The method according to any of claims 30-34, wherein the polymer comprised by the coating composition is distinct from the polymer comprised by the polymer material.
37. The method according to any of claims 29-36, wherein the coating composition comprises at least one resin.
38. The method according to claim 37, wherein the resin is selected from epoxy resin, phenol resin, polyurethane resin and/or acrylate resin.
39. The method according to any of claims 29-38, wherein the coating composition comprises a dye.
40. The method according to any of claims 29-39, wherein the coating composition comprises a particle enabling determination of the quality of the coating.
41. The method according to any of claims 29-40, wherein the polymer material is a mass-production compatible plastic.
42. The method according to any of claims 29-41, wherein the polymer material is selected from thermoplastics, thermoplastic elastomers, conventional elastomers, and duromers.
43. The method according to any of claims 29-42, wherein the polymer material comprises polymethylpentene (PMP) and/or methyl methacrylate acrylonitrile butadiene styrene (MABS).
44. The method according to any of claims 29-43, wherein the article made of the polymeric material is produced by injection molding, press molding, extrusion molding, milling, cutting, or swiveling, preferably by injection molding.
45. The method according to any of claims 29-44, wherein the article is a measurement cup (cuvette).
46. The method according to any of claims 29-45, wherein the article is a pin or a sleeve for a pin.
47. The method according to any of claims 29-46, wherein the coating composition comprises at least one solvent selected from benzene or benzene derivatives (e.g., alkyl or polyalkyl benzenes); acetate or acetate derivatives (e.g., alkyl or polyalkyl acetates); alkanols or alkanol derivatives (e.g., alkandiols or cyclo alkanols); or naphtha or naphtha components.
48. The method according to any of claims 29-47, wherein the solvent comprised by the coating composition is a lower-risk solvent.
49. The method according to any of claims 29-48, wherein the coating composition is according to any of claims 19-28.
50. The method according to any of claims 29-49, wherein the method further comprises a step of drying the coating, which follows (directly) after the step of applying the coating composition.
51. The method according to claim 50, wherein the step of drying is performed at room temperature (about 22? C.).
52. The method according to any of claims 29-51, wherein the method further comprises a step of quality control of the coating, which follows (directly) after the step of applying the coating composition.
53. The method according to claim 52, wherein the step of quality control is performed before, during or after the step of drying the coating.
54. The method according to claim 52 or 53, wherein the step of quality control is performed by detection by optical, electrical, and/or magnetic fields, for example by light reflection, color changes, light image changes, X-ray image changes, fluorescence image changes, light emission wavelength changes, and/or magnetic field changes.
55. The method according to any of claims 29-54, wherein the coating composition is applied to at least a part of the surface of the article by spraying the coating composition onto the article, by filling the article with the coating composition, by dipping the article into the coating composition, by spin coating, by dip-tumbling, by spray-tumbling, by screen printing, by inkjet printing, by microcontact printing, by sputter deposition, by thermal evaporation, or by vapor deposition.
56. The method according to claim 55, wherein the coating composition is applied to at least a part of the surface of the article by spraying the coating composition onto the article, by filling the article with the coating composition, by dipping the article into the coating composition, by dip-tumbling, or by spray-tumbling.
57. The method according to any of claims 29-56, wherein the method comprises a step of removing excess coating composition, which directly follows after the step of applying the coating composition.
58. An article for contacting coagulating and/or coagulated blood components obtainable by the method according to any of claims 29-57.
59. Use of the article according to any of claims 1-18 and 58 for contacting coagulating and/or coagulated blood components.
60. Use of the article according to any of claims 1-18 and 58 for blood coagulation testing.
61. Use of the article according to any of claims 1-18 and 58 for viscoelastic measurements of clotting blood.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0131] In the following a brief description of the appended figures will be given. The figures are intended to illustrate the present invention in more detail. However, they are not intended to limit the subject matter of the invention in any way.
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EXAMPLES
[0145] In the following, particular examples illustrating various embodiments and aspects of the invention are presented. However, the present invention shall not to be limited in scope by the specific embodiments described herein. The following preparations and examples are given to enable those skilled in the art to more clearly understand and to practice the present invention. The present invention, however, is not limited in scope by the exemplified embodiments, which are intended as illustrations of single aspects of the invention only, and methods which are functionally equivalent are within the scope of the invention. Indeed, various modifications of the invention in addition to those described herein will become readily apparent to those skilled in the art from the foregoing description, accompanying figures and the examples below. All such modifications fall within the scope of the appended claims.
Example 1: Coating of Various Articles and Functionality Tests
[0146] In the following examples, several exemplary results obtained with different articles according to the present invention (summarized, e.g., in
[0147] In general, to obtain the coating compositions, the following solvents were used to dissolve 500 mg of each raw polymer material in 5 ml solvent (for detailed description see the examples below): [0148] Acrylonitrile butadiene styrene (ABS; Terluran GP-22, INEOS Styrolution Group GmbH, Germany) was dissolved in 96% xylene; [0149] Methyl methacrylate acrylonitrile butadiene styrene (MABS; TERLUX? 2802, INEOS Styrolution Group GmbH, Germany) was dissolved in 96% xylene or in ethylbutanol (Sigma-Aldrich Chemie GmbH, Germany) as indicated; [0150] High impact polystyrene (HIPS; Styrolution PS 495N, INEOS Styrolution Group GmbH, German)) was dissolved in 96% xylene; [0151] Poly(methyl methacrylate) (PMMA; Plexiglas?, EVONIK Industries AG, Germany) was dissolved in 96% acetone; [0152] Polycarbonate (PC; Lexan? 144R, Germany) was dissolved in 96% chloroform; [0153] Polyamide (PA; Trogamid? T5000, Evonik Industries AG, Germany) was dissolved in 96% DMSO, but the solution was not properly applicable as coating composition due to the high polarity of DMSO; and [0154] polyurethane (PU; Desmopan? 385 S, Bayer MaterialScience AG, Germany) was dissolved in 96% DMSO, but the solution was not properly applicable as coating composition due to the high polarity of DMSO.
[0155] In general, in the experiments explained in detail below, similar results were obtained for the solvents xylene, ethylbutanol, or a combination thereof (e.g., 50:50).
[0156] To achieve sufficient coating of all surface areas that are in blood contact during a thromboelastographic measurement, articles to be coated (cuvettes and probes) were either (i) filled with 600 ?l of the coating composition and excess coating composition was removed after about 10 s (cuvettes), or (ii) dipped into the coating composition for about 2 s (probes). Articles (cuvettes and probes) were subsequently dried in air for about 1 hour.
[0157] In general, improvements of blood adhesion to the polymeric surfaces of articles used for thrombelastographic diagnostics by applying coatings according to the present invention can be detected by comparing the initially achieved maximum clot firmness with the reduction of clot firmness at the end of the measurement (e.g., 60 min after measurement start). This ratio, also called ML parameter (maximum lysis activity, ML; % ratio between (i) clot firmness at the end of measurement, for example 60 minutes after measurement start, and (ii) maximum clot firmness), can be artificially lowered by partial ruptures of the fibrin network from the surface during measurements (see
[0158] The functionality was assessed by comparing thrombelastographic measurements performed with ROTEG? 05 devices (Pentapharm GmbH, Germany), where differently treated articles with dimensions comparable to the corresponding original measurement articles (ROTEM? Cup&Pin Pro, Tem International GmbH, Germany) were compared regarding clot firmness amplitudes after 20 minutes (A20) and maximum lysis activity (ML; % ratio between clot firmness 60 minutes after measurement start and maximum clot firmness).
[0159] Measurements were performed by pipetting 20 ?l of extrinsic activator (ex-TEM?, Tem International GmbH, Germany) and 20 ?l of 200 mM CaCl.sub.2 (star-TEM?, Tem International GmbH, Germany) to a 300 ?l citrated blood sample and transferring it to the respective article.
Example 2: Comparison of Uncoated Articles
[0160] In order to efficiently determine and compare the surface characteristics regarding blood adhesion of various polymer materials, untreated/uncoated articles (cups and pins) made of polymethylpentene (PMP; TPX?, Mitsui & Co. Ltd., Japan), methyl methacrylate acrylonitrile butadiene styrene (MABS; Terlux? 2802, INEOS Styrolution Group GmbH, Germany), polyamide (PA; Trogarnicl? T5000, Evonik Industries AG, Germany), polyphenylene sulfide (PPS; Ryton? R-4, SOLVAY GmbH, Germany), or polyurethane (PU; Desmopan? 385 S, Bayer MaterialScience AG, Germany) were obtained by industrial injection molding. Those untreated/uncoated articles underwent functionality testing as described above (cf. Example 1). Results are shown in
[0161] Injection-molded articles made of MABS, PA or PPS show significantly higher A20 values and significantly lower ML values as compared to injection-molded articles made of PMP or PU (
[0162] Articles made of PMP or PU without any treatment or coating show poor results regarding blood clot adhesion as indicated by comparably low A20 values and comparably high ML mean values in thromboelastometric measurements (
Example 3: Coating of an Exemplary Article Made of Polymethylpentene (PMP)
[0163] Uncoated articles (cup and pin) made of polymethylpentene (PMP; TPX?, Mitsui & Co. Ltd., Japan) was obtained by industrial injection molding. The uncoated articles were then partially coated with MABS (in ethylbutanol).
[0164] Thereafter, the article coated with MABS as well as an uncoated article (made of polymethylpentene (PMP; TPX?, Mitsui & Co. Ltd., Japan)) underwent functionality testing as described above (Example 1), whereby instead of A20 and ML parameters, typical thromboelastography traces were obtained as shown in
[0165] The thromboelastography trace of the untreated/uncoated article (cuvette and probe) made of Polymethylpentene (PMP; TPX?, Mitsui & Co. Ltd., Japan) is shown in
[0166] In summary, the uncoated (untreated) articles made of PMP shows undesired tear-offs (
Example 4: Coating of Further Articles Made of Polymethylpentene (PMP)
[0167] To determine blood clot adhesion of different coatings, uncoated articles (cups and pins) made of polymethylpentene (PMP; TPX?, Mitsui & Co. Ltd., Japan) were obtained by industrial injection molding and were partially coated with MABS (in xylene), HIPS, ABS, PMMA, or PC as described above (cf. Example 1).
[0168] Alternatively, uncoated articles were treated with a xylol/ethylbutanol solvent mixture (50 vol.-% xylol; 50 vol.-% ethylbutanol) without any polymer dissolved. Those articles served as comparative example to evaluate the effects of the coating with pure solvent (i.e., without any polymer contained therein).
[0169] Thereafter, PMP articles coated with MABS, HIPS, ABS, PMMA or PC; PMP articles treated with xylol/ethylbutanol; and uncoated PMP articles underwent functionality testing as described above (cf. Example 1). Results are shown in
[0170] In summary, uncoated (untreated) articles made of PMP show lower mean values for A20 and higher mean values for ML as compared to PMP articles coated with MABS, HIPS, ABS, PMMA, or PC. Accordingly, surface coating with MABS, HIPS, ABS, PMMA or PC resulted in considerable improvements regarding A20 and ML parameters as compared to uncoated PMP articles (
[0171] Surface treatment of PMP articles with compositions comprising the solvent only (but no polymer) resulted in A20 and ML values comparable to those of untreated/uncoated articles (
Example 5: Coating of Articles Made of Methyl Methacrylate Acrylonitrile Butadiene Styrene (MABS)
[0172] To determine whether articles made of materials, which already show good blood clot adhesion, can be further improved by applying a coating, uncoated articles (cups and pins) made of methyl methacrylate acrylonitrile butadiene styrene (MABS; Terlux? 2802, INEOS Styrolution Group GmbH, Germany) were obtained by industrial injection molding and were coated with MABS (in xylene) or ABS as described above.
[0173] Thereafter, MABS articles coated with MABS (in xylene) or ABS as well as uncoated articles underwent functionality testing as described above. Results are shown in
[0174] In summary, uncoated (untreated) articles made of MABS show lower mean values for A20 and higher mean values for ML as compared to MABS articles coated with MABS or ABS. Accordingly, surface coating with MABS or ABS resulted in improvements regarding A20 and ML when compared to uncoated MABS articles (
[0175] Surprisingly, coating of articles made of MABS (Terlux? 2802, INEOS Styrolution Group GmbH, Germany) with exactly the same MABS material dissolved in xylene (and/or ethylbutanol) also resulted in significant improvements regarding A20 and ML (see