DE10142465A1 - Production of an antibiotic coating on a porous body useful as an implant comprises impregnation with a solution of gentamicin dodecyl sulfate or sulfonate and evaporation of the solvent - Google Patents
Production of an antibiotic coating on a porous body useful as an implant comprises impregnation with a solution of gentamicin dodecyl sulfate or sulfonate and evaporation of the solventInfo
- Publication number
- DE10142465A1 DE10142465A1 DE10142465A DE10142465A DE10142465A1 DE 10142465 A1 DE10142465 A1 DE 10142465A1 DE 10142465 A DE10142465 A DE 10142465A DE 10142465 A DE10142465 A DE 10142465A DE 10142465 A1 DE10142465 A1 DE 10142465A1
- Authority
- DE
- Germany
- Prior art keywords
- gentamicin
- dodecyl
- sulfate
- sulfonate
- dodecyl sulfate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 title claims abstract description 61
- 229930182566 Gentamicin Natural products 0.000 title claims abstract description 55
- 229960002518 gentamicin Drugs 0.000 title claims abstract description 54
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 43
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229940043264 dodecyl sulfate Drugs 0.000 title claims abstract description 33
- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 17
- 238000000576 coating method Methods 0.000 title claims abstract description 16
- 230000008020 evaporation Effects 0.000 title claims abstract description 15
- 238000001704 evaporation Methods 0.000 title claims abstract description 15
- 239000002904 solvent Substances 0.000 title claims abstract description 14
- 239000011248 coating agent Substances 0.000 title claims abstract description 12
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 title claims abstract description 9
- 239000007943 implant Substances 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- 238000005470 impregnation Methods 0.000 title abstract 3
- 238000000034 method Methods 0.000 claims abstract description 23
- -1 tetracyline Chemical compound 0.000 claims abstract description 12
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims abstract description 11
- 229960002227 clindamycin Drugs 0.000 claims abstract description 9
- 239000011148 porous material Substances 0.000 claims abstract description 7
- KOFBVFFPLADGGO-DUSUDKPKSA-N (3r,4s,5r,6r)-6-[(1r,2r)-1-amino-2-hydroxypropyl]oxane-2,3,4,5-tetrol Chemical compound C[C@@H](O)[C@@H](N)[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O KOFBVFFPLADGGO-DUSUDKPKSA-N 0.000 claims abstract description 6
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 claims abstract description 6
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 claims abstract description 6
- 229960003722 doxycycline Drugs 0.000 claims abstract description 6
- 229960004023 minocycline Drugs 0.000 claims abstract description 6
- HMEYVGGHISAPJR-IAHYZSEUSA-N rolitetracycline Chemical compound O=C([C@@]1(O)C(O)=C2[C@@H]([C@](C3=CC=CC(O)=C3C2=O)(C)O)C[C@H]1[C@@H](C=1O)N(C)C)C=1C(=O)NCN1CCCC1 HMEYVGGHISAPJR-IAHYZSEUSA-N 0.000 claims abstract description 6
- 229960005009 rolitetracycline Drugs 0.000 claims abstract description 6
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 claims abstract description 6
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
- 229940088710 antibiotic agent Drugs 0.000 claims description 12
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 12
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229920000728 polyester Polymers 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 102000008186 Collagen Human genes 0.000 claims description 7
- 108010035532 Collagen Proteins 0.000 claims description 7
- 229920001436 collagen Polymers 0.000 claims description 7
- 108010010803 Gelatin Proteins 0.000 claims description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 6
- 239000001506 calcium phosphate Substances 0.000 claims description 6
- 239000004744 fabric Substances 0.000 claims description 6
- 239000008273 gelatin Substances 0.000 claims description 6
- 229920000159 gelatin Polymers 0.000 claims description 6
- 235000019322 gelatine Nutrition 0.000 claims description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims description 6
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 6
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 6
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 6
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 6
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 6
- VEVRNHHLCPGNDU-MUGJNUQGSA-O desmosine Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(CC[C@H](N)C(O)=O)=C(CCC[C@H](N)C(O)=O)C(CC[C@H](N)C(O)=O)=C1 VEVRNHHLCPGNDU-MUGJNUQGSA-O 0.000 claims description 5
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 claims description 4
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 claims description 4
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004100 Oxytetracycline Substances 0.000 claims description 4
- 239000004098 Tetracycline Substances 0.000 claims description 4
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 claims description 4
- 239000011521 glass Substances 0.000 claims description 4
- 238000000465 moulding Methods 0.000 claims description 4
- 229960000625 oxytetracycline Drugs 0.000 claims description 4
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 claims description 4
- 235000019366 oxytetracycline Nutrition 0.000 claims description 4
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 claims description 4
- 229960002180 tetracycline Drugs 0.000 claims description 4
- 229930101283 tetracycline Natural products 0.000 claims description 4
- 235000019364 tetracycline Nutrition 0.000 claims description 4
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 claims description 2
- ZEUUPKVZFKBXPW-TWDWGCDDSA-N (2s,3r,4s,5s,6r)-4-amino-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,5s,6r)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-6-(hydroxymethyl)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N ZEUUPKVZFKBXPW-TWDWGCDDSA-N 0.000 claims description 2
- VXPSARQTYDZXAO-CCHMMTNSSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O VXPSARQTYDZXAO-CCHMMTNSSA-N 0.000 claims description 2
- OAPVUSSHCBRCOL-KBHRXELFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O OAPVUSSHCBRCOL-KBHRXELFSA-N 0.000 claims description 2
- NAUHPSRFNVHVLD-GGLKHSNMSA-N (4s,4as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-n-(pyrrolidin-1-ylmethyl)-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.OC([C@@]1(O)C(=O)C=2C([C@](C3=CC=CC(O)=C3C=2O)(C)O)C[C@H]1[C@@H](C1=O)N(C)C)=C1C(=O)NCN1CCCC1 NAUHPSRFNVHVLD-GGLKHSNMSA-N 0.000 claims description 2
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 claims description 2
- PTNZGHXUZDHMIQ-UHFFFAOYSA-N 4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C)C(C(O)C3C(C(O)=C(C(N)=O)C(=O)C3N(C)C)(O)C3=O)C3=C(O)C2=C1O PTNZGHXUZDHMIQ-UHFFFAOYSA-N 0.000 claims description 2
- YWMSSKBMOFPBDM-UHFFFAOYSA-N 4-carbamoylbenzenesulfonyl chloride Chemical compound NC(=O)C1=CC=C(S(Cl)(=O)=O)C=C1 YWMSSKBMOFPBDM-UHFFFAOYSA-N 0.000 claims description 2
- 229960001656 amikacin sulfate Drugs 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- XMEVHPAGJVLHIG-FMZCEJRJSA-N chembl454950 Chemical compound [Cl-].C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H]([NH+](C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O XMEVHPAGJVLHIG-FMZCEJRJSA-N 0.000 claims description 2
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001229 ciprofloxacin hydrochloride Drugs 0.000 claims description 2
- 229960001200 clindamycin hydrochloride Drugs 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 2
- 238000007598 dipping method Methods 0.000 claims description 2
- 229960004082 doxycycline hydrochloride Drugs 0.000 claims description 2
- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical compound OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 claims description 2
- 229960002064 kanamycin sulfate Drugs 0.000 claims description 2
- 229940051860 methacycline hydrochloride Drugs 0.000 claims description 2
- 229960002421 minocycline hydrochloride Drugs 0.000 claims description 2
- 229960004368 oxytetracycline hydrochloride Drugs 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000005507 spraying Methods 0.000 claims description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 claims description 2
- 229960004989 tetracycline hydrochloride Drugs 0.000 claims description 2
- 229960004477 tobramycin sulfate Drugs 0.000 claims description 2
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003522 tetracyclines Chemical class 0.000 claims 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- GJPICBWGIJYLCB-UHFFFAOYSA-N dodecyl phenylmethanesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)CC1=CC=CC=C1 GJPICBWGIJYLCB-UHFFFAOYSA-N 0.000 abstract description 3
- 229940042016 methacycline Drugs 0.000 abstract description 3
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 abstract 6
- 229960003405 ciprofloxacin Drugs 0.000 abstract 3
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- 235000019365 chlortetracycline Nutrition 0.000 abstract 2
- 229960002398 demeclocycline Drugs 0.000 abstract 2
- FMTDIUIBLCQGJB-SEYHBJAFSA-N demeclocycline Chemical compound C1([C@@H](O)[C@H]2C3)=C(Cl)C=CC(O)=C1C(=O)C2=C(O)[C@@]1(O)[C@@H]3[C@H](N(C)C)C(O)=C(C(N)=O)C1=O FMTDIUIBLCQGJB-SEYHBJAFSA-N 0.000 abstract 2
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 abstract 2
- MHIGBKBJSQVXNH-IWVLMIASSA-N methacycline Chemical compound C=C([C@H]1[C@@H]2O)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O MHIGBKBJSQVXNH-IWVLMIASSA-N 0.000 abstract 2
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 abstract 2
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 abstract 2
- 229960003702 moxifloxacin Drugs 0.000 abstract 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 description 16
- 210000000988 bone and bone Anatomy 0.000 description 10
- 230000007547 defect Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 208000035143 Bacterial infection Diseases 0.000 description 4
- 208000022362 bacterial infectious disease Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000000979 retarding effect Effects 0.000 description 3
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229940126575 aminoglycoside Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
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- SATIISJKSAELDC-ZIOPZPSVSA-N 3-hydroxy-N-[(3R,6S,7R,10S,13S,16S,22R,24R)-24-hydroxy-7,11,13,17,20-pentamethyl-16-[(2S)-3-methylbutan-2-yl]-3-(2-methylpropyl)-2,5,9,12,15,18,21-heptaoxo-10-phenyl-8-oxa-1,4,11,14,17,20-hexazabicyclo[20.3.0]pentacosan-6-yl]pyridine-2-carboxamide Chemical compound CC(C)C[C@H]1NC(=O)[C@@H](NC(=O)c2ncccc2O)[C@@H](C)OC(=O)[C@@H](N(C)C(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)C(C)C)N(C)C(=O)CN(C)C(=O)[C@H]2C[C@@H](O)CN2C1=O)c1ccccc1 SATIISJKSAELDC-ZIOPZPSVSA-N 0.000 description 1
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- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- 125000002091 cationic group Chemical group 0.000 description 1
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- LBOVMDOAMWYGHK-UHFFFAOYSA-N ethanol;methylsulfinylmethane Chemical compound CCO.CS(C)=O LBOVMDOAMWYGHK-UHFFFAOYSA-N 0.000 description 1
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- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Chemical compound O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
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- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
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- 239000002609 medium Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- XMKLKZFSQXZUQU-UHFFFAOYSA-N neoviridogrisein-II Natural products CC1OC(=O)C(C=2C=CC=CC=2)N(C)C(=O)C(C)NC(=O)C(C(C)C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(CC(C)C)NC(=O)C1NC(=O)C1=NC=CC=C1O XMKLKZFSQXZUQU-UHFFFAOYSA-N 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- 239000011368 organic material Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Dispersion Chemistry (AREA)
- Neurosurgery (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Application Of Or Painting With Fluid Materials (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein Verfahren zur antibiotischen Beschichtung nichtmetallischer Körper mit interkonnektierenden Mikrohohlräumen, einen beschichteten Körper sowie seine Verwendung. The present invention relates to a method for antibiotic coating non-metallic body with interconnecting micro-cavities, a coated body as well its use.
Diese antibiotisch ausgerüsteten Körper mit interkonnektierenden Mikrohohlräumen sollen als Implantate in der Human- und Veterinärmedizin zur Behandlung von Knochendefekten und ggf. zur Behandlung von Weichteildefekten Verwendung finden. Dabei wird eine kontinuierliche Antibiotika-Freisetzung aus der auf der inneren Oberfläche der interkonnektierenden Mikrohohlräume befindlichen antibiotischen Beschichtung über einen Zeitraum von mehreren Tagen angestrebt, damit eine mikrobielle Infektion im Bereich des zu behandelnden Knochendefekts und oder Weichteildefektes wirksam verhindert oder bekämpft werden kann. These antibiotic bodies with interconnecting micro-cavities are said to be Implants in human and veterinary medicine for the treatment of bone defects and possibly for the treatment of soft tissue defects. Doing so will be a continuous Antibiotic release from the interconnect on the inner surface Microvoided antibiotic coating over a period of several days aimed for a microbial infection in the area of the bone defect to be treated and or soft tissue defects can be effectively prevented or combated.
Knochendefekte treten in der Human- und Veterinärmedizin relativ häufig auf und werden insbesondere durch Knochenfisteln, Trümmerfrakturen und Tumoren verursacht. Bei offenen Trümmerfrakturen werden vielfach zusätzlich Infektionen des Knochengewebes beobachtet. Die Behandlung von Knochendefekten kann durch Auffüllung mit geeigneten Implantaten erfolgen. In den letzten Jahren haben insbesondere poröse Implantate Interesse gefunden, die aufgrund ihrer chemischen Zusammensetzung und ihrer Porosität eine osteokonduktive Wirkung aufweisen und ein Einwachsen des umgebenden Knochengewebes begünstigen. Problematisch ist die Behandlung von Knochendefekten immer dann, wenn zusätzlich mikrobielle Infektionen des Knochengewebes vorhanden sind. Infektionen des Knochengewebes können durch systemische oder lokale Applikation von geeigneten Antibiotika bekämpft werden. Die systemische Anwendung von Antibiotika ist aufgrund der mitunter nicht unbeträchtlichen Toxizität der Antibiotika problematisch. Die lokale Applikation direkt im oder am infizierten Gewebe bietet dagegen den Vorteil, dass hohe lokale Antibiotika-Konzentrationen erreicht werden können unter Vermeidung von schädigenden Antibiotika-Konzentrationen im übrigen Organismus. Durch diese hohen lokalen Antibiotika-Konzentrationen am Ort der bakteriellen Infektion ist eine fast vollständige Abtötung der Mikroorganismen möglich, so dass die bakteriellen Infektionen sehr wirksam behandelt werden. Besonders vorteilhaft ist es, wenn am Ort der bakteriellen Infektionen eine wirksame Antibiotikum-Konzentration über einen Zeitraum von mehreren Tagen bis Wochen aufrechterhalten wird, damit das Antibiotikum möglichst tief in das infizierte Gewebe eindringen kann und dadurch auch schwer zugängliche Keime vernichtet werden. Weichteildefekte mit bakteriellen Infektionen sind in der Human- und Veterinärmedizin ebenfalls häufig zu finden. Zur Behandlung dieser Infektionen ist daher auch die lokale Antibiotika-Behandlung von Interesse. Bone defects occur and become relatively common in human and veterinary medicine especially caused by bone fistulas, comminuted fractures and tumors. With open Rubble fractures are also often observed as infections of the bone tissue. The Bone defects can be treated by filling them with suitable implants. In recent years, porous implants have been of particular interest because of their chemical composition and their porosity have an osteoconductive effect exhibit and promote ingrowth of the surrounding bone tissue. Is problematic the treatment of bone defects whenever additional microbial infections of the Bone tissue are present. Bone tissue infections can be caused by systemic or local application of suitable antibiotics can be combated. The systemic The use of antibiotics is due to the sometimes not inconsiderable toxicity of the Antibiotics problematic. On the other hand, local application directly in or on the infected tissue offers the advantage that high local antibiotic concentrations can be reached under Avoidance of harmful antibiotic concentrations in the rest of the organism. Through this high local antibiotic concentrations at the site of the bacterial infection is almost a complete killing of the microorganisms possible, so that the bacterial infections very be treated effectively. It is particularly advantageous if the site of the bacterial infections an effective antibiotic concentration over a period of several days to Weeks are maintained so the antibiotic is as deep as possible in the infected tissue can penetrate and thereby destroy even difficult to access germs. Soft tissue defects with bacterial infections are also common in human and veterinary medicine. Local antibiotic treatment is therefore also necessary to treat these infections Interest.
Bisher fanden in Wasser gering lösliche Salze der Aminoglykosid-Antibiotika relativ wenig Beachtung für die Herstellung von Depotpräparaten und von antibiotisch wirksamen Implantaten. Es sind eine Reihe von geringlöslichen Salzen bekannt. So wurde beim Gentamicin die Darstellung geringlöslicher Salze basierend auf höheren Fettsäuren und Arylalkylcarbonsäuren publiziert (G. M. Luedemann, M. J. Weinstein: Gentamycin and method of production. 16.07.1962, US 3,091,572). Exemplarisch sind dafür Gentamicin-Salze der Laurinsäure, der Stearinsäure, der Palmitinsäure, der Ölsäure, der Phenylbuttersäure, der Naphthalen-1- carbonsäure. Die Synthese der Dodecylsulfate des Gentamicins in wässriger bzw. wässrigmethanolischer Lösung sind von Jurado Soler et al. beschrieben worden (A. Jurado Soler, J. A. Ortiz Hernandez, C. Ciuro Bertran: Neue Gentamicinderivate, Verfahren zur Herstellung derselben und diese enthaltende antibiotisch wirksame Zusammensetzung. 30.09.1974, DE 24 46 640). Diese Salze erwiesen sich jedoch vielfach als unvorteilhaft, weil sie wachsartige, hydrophobe Substanzen darstellen, die eine galenische Verwendung behindern. Jurado Soler et al. fanden, dass Gentamicin-pentakis-dodecylsulfat in Lösungsmitteln wie Methanol, Ethanol und Dimethylsulfoxid löslich ist. Sie setzten das Gentamicin-pentakis-dodecylsulfat zur Herstellung von Injektionspräparaten, Salben und Cremes ein. Weitere Verwendungsmöglichkeiten von Gentamicin-pentakis-dodecylsulfat-Lösungen wurden nicht betrachtet. Festtsäuresalze und aliphatische Sulfate von Gentamicin und von Etamycin wurden aus der freien Base bzw. aus ihren Salzen in Wasser bei 50 bis 80°C synthetisiert (H. Voege, P. Stadler, H. J. Zeiler, S. Samaan, K. G. Metzger: Schwerlösliche Salze von Aminoglykosiden sowie diese enthaltende Formulierungen mit verzögerter Wirkstoff-Freigabe. 28.12.1982, DE 32 48 328). Diese Antibiotika-Fettsäuresalze sollen als Injektionspräparate geeignet sein. Eine neuere Entwicklung stellen schwerlösliche Aminoglykosid-Flavonoid-Phosphate dar (H. Wahlig, E. Dingeldein, R. Kirchlechner, D. Orth, W. Rogalski: Flavonoid phosphate salts of aminoglycoside antibiotics. 13.10.1986, US 4,617,293). Es werden die Salze der Phosphorsäuremonoester von Derivaten der Hydroxyflavane, Hydroxyflavene, Hydroxyflavanone, Hydroxyflavone und Hydroxyflavylium beschrieben. Besonders bevorzugt sind dabei die Derivate der Flavanone und der Flavone. Diese schwerlöslichen Salze sollen als Depotpräparate Verwendung finden. So werden zum Beispiel diese Salze in Kollagenyliese eingebracht (H. Wahlig, E. Dingeldein, D. Braun: Medicinally useful, shaped mass of collagen resorbable in the body. 22.09.1981, US 4,291,013). So far, sparingly soluble salts of the aminoglycoside antibiotics have been found in water Attention for the manufacture of depot preparations and antibiotic implants. A number of poorly soluble salts are known. So with Gentamicin the Presentation of slightly soluble salts based on higher fatty acids and arylalkyl carboxylic acids published (G. M. Luedemann, M. J. Weinstein: Gentamycin and method of production. July 16, 1962, US 3,091,572). Examples of this are gentamicin salts of lauric acid, the Stearic acid, palmitic acid, oleic acid, phenylbutyric acid, naphthalene-1- carboxylic acid. The synthesis of the dodecyl sulfates of gentamicin in aqueous or aqueous methanolic solution are from Jurado Soler et al. (A. Jurado Soler, J.A. Ortiz Hernandez, C. Ciuro Bertran: New gentamicin derivatives, process for their preparation the same and containing antibiotic composition. 30.09.1974, DE 24 46 640). However, these salts have often proven to be disadvantageous because they are waxy, Represent hydrophobic substances that hinder galenical use. Jurado Soler et al. found that gentamicin pentakis dodecyl sulfate in solvents such as methanol, ethanol and Dimethyl sulfoxide is soluble. They used the gentamicin pentakis dodecyl sulfate for the production of injectables, ointments and creams. Other uses of Gentamicin pentakis dodecyl sulfate solutions were not considered. Solid acid salts and Aliphatic sulfates of gentamicin and of etamycin were derived from the free base and from, respectively their salts in water at 50 to 80 ° C (H. Voege, P. Stadler, H. J. Zeiler, S. Samaan, K.G. Metzger: Poorly soluble salts of aminoglycosides and those containing them Delayed release formulations. December 28, 1982, DE 32 48 328). This Antibiotic fatty acid salts are said to be suitable as injectables. Ask a newer development sparingly soluble aminoglycoside flavonoid phosphates (H. Wahlig, E. Dingeldein, R. Kirchlechner, D. Orth, W. Rogalski: Flavonoid phosphate salts of aminoglycoside antibiotics. October 13, 1986, US 4,617,293). There are the salts of phosphoric acid monoesters of derivatives the Hydroxyflavane, Hydroxyflavene, Hydroxyflavanone, Hydroxyflavone and Hydroxyflavylium described. The derivatives of flavanones and flavones are particularly preferred. These poorly soluble salts are said to be used as depot preparations. So become Example of these salts introduced into collagenyliese (H. Wahlig, E. Dingeldein, D. Braun: Medicinally useful, shaped mass of collagen resorbable in the body. September 22, 1981, US 4,291,013).
Die Erzeugung von einfachen Antibiotikum-/Antibiotka-Depots in den Porensystemen von porösen Körpern durch Tränken von porösen Körpern mit wässrigen Antibiotika-Lösungen ist allgemeiner Kenntnisstand (R. Reiner, W. Kißing, H. Döring, K. Köster, H. Heide: Implantierbares Pharmaka-Depot. 20.02.1978, DE 28 07 132). Hierbei kann eine retardierende Wirkstofffreisetzung der in Wasser leicht löslichen Antibiotika durch Adsorptions- und oder durch Diffusionsprozesse erreicht werden, die vom verwendeten Material, dem Porenvolumen und der Porosität abhängt. Daneben ist es auch möglich, in Wasser gering lösliche Antibiotika-Salze in geeigneten organischen Lösungsmitteln zu lösen und mit diesen Lösungen die Formkörper zu tränken. Dadurch entstehen Wirkstoffdepots in den Formkörpern, die eine retardierende Wirkstofffreisetzung zeigen. Ein Beispiel dafür ist die von Cimbollek und Nies beschriebene Methode zur Lösung eines in Wasser gering löslichen Gentamicin-Salzes und deren Verwendung zur Beschichtung (M. Cimbollek, B. Nies: Solvent for a sparingly soluble gentamicin salt. 04.05.1994, US 5,679,646). Diese Gentamicinsalz wurde auf Basis von 3-p-Methoxybezylidene-6-hydroxy- 4'-methoxyflavanone-6-phosphat synthetisiert. Von Kurtz wird eine sehr interessantes Verfahren beschrieben, bei dem in Wasser gering lösliche Antibiotika-Salze, die aus Gentamicin oder Polymycin und Penicillin oder Cephalosporin aufgebaut sind, in einem organischen Lösungsmittel gelöst werden und mit diesen Lösungen nicht näher spezifizierte Unterlagen getränkt werden (L. D. Kurtz: Wasserunlösliche biocide Antibiotikasalze. 13.11.1973, DE 23 01 633). Die Penicillin- bzw. Cephalosporinreste bilden die anionische Komponente der Salze und die Aminoglukosid-Reste die kationische Komponente. The creation of simple antibiotic / antibiotka depots in the pore systems of porous bodies by soaking porous bodies with aqueous antibiotic solutions general state of knowledge (R. Reiner, W. Kißing, H. Döring, K. Köster, H. Heide: Implantables Pharmaceuticals depot. 20.02.1978, DE 28 07 132). Here, a retarding Active ingredient release of the easily soluble antibiotics in water by adsorption or or Diffusion processes can be achieved by the material used, the pore volume and the porosity depends. In addition, it is also possible to use antibiotic salts that are sparingly soluble in water dissolve suitable organic solvents and soak the moldings with these solutions. This creates drug depots in the moldings, which is a retarding Show drug release. An example of this is the method used by Cimbollek and Nies Solution of a slightly soluble gentamicin salt in water and its use for Coating (M. Cimbollek, B. Nies: Solvent for a sparingly soluble gentamicin salt. 04.05.1994, US 5,679,646). This gentamicin salt was based on 3-p-methoxybezylidene-6-hydroxy- 4'-methoxyflavanone-6-phosphate synthesized. Kurtz will be a very interesting one Process described in which sparingly water-soluble antibiotic salts, which from Gentamicin or Polymycin and penicillin or cephalosporin are built up in an organic Solvents are dissolved and soaked with these solutions unspecified documents (L. D. Kurtz: Water-insoluble biocidal antibiotic salts. November 13, 1973, DE 23 01 633). The Penicillin or cephalosporin residues form the anionic component of the salts and Aminoglucoside residues the cationic component.
Zusammenfassend kann festgestellt werden, dass bisher keine Verfahren bekannt sind, bei denen antibiotische Beschichtungen auf der Oberfläche von interkonnektierenden Mikrohohlräumen aufgebracht werden, die aus in Wasser gering löslichen Salzen des Gentamicins bestehen, welche einen anionischen Rest aus der Gruppe der Alkylsulfate und oder Alkylsulfonate enthalten. Die Schichtbildungseigenschaften von in Wasser gering löslichen Antibiotika-Salzen auf Basis von organischen Sulfaten und Sulfonaten fanden bisher keine Beachtung. In summary, it can be stated that no methods are known so far for which antibiotic coatings on the surface of interconnecting Micro-cavities are applied, which consist of salts of gentamicin that are sparingly soluble in water consist of an anionic radical from the group of alkyl sulfates and or alkyl sulfonates contain. The layering properties of antibiotics salts that are sparingly soluble in water based on organic sulfates and sulfonates have so far been ignored.
Der vorliegenden Erfindung liegt die Aufgabe zugrunde, verbesserte nichtmetallische Körper mit antibiotischer Beschichtung, sowie ein einfaches, kostengünstiges Herstellungsverfahren zur antibiotischen Beschichtung von nichtmetallischen Körpern mit interkonnektierenden Mikrohohlräumen zu entwickeln. Diese antibiotisch ausgerüsteten, Körper mit interkonnektierenden Mikrohohlräumen sollen als Implantate zur Behandlung von Knochen- und Weichteildefekten in der Human- und Veterinärmedizin Verwendung finden. Mit diesem Verfahren sollen in einfacher Weise, unter Verzicht auf polymere Bindemittel, antibiotische Beschichtungen erzeugt werden, die eine Antibiotika-Freisetzung über einen Zeitraum von mehreren Tagen ermöglichen. Die antibiotische Beschichtung soll auf der inneren Oberfläche von nichtmetallischen Körpern mit interkonnektierenden Mikrohohlräumen gut haften und darf die innterkonnektierenden Mikrohohlräume nicht verschließen. The present invention has for its object to provide improved non-metallic body antibiotic coating, as well as a simple, inexpensive manufacturing process for antibiotic coating of non-metallic bodies with interconnecting To develop micro cavities. These antibiotic-endowed, interconnecting bodies Microcavities are said to be implants for the treatment of bone and soft tissue defects in the Find human and veterinary medicine. This procedure is said to be easier in Way, without using polymeric binders, antibiotic coatings are produced, that allow antibiotics to be released over a period of several days. The Antibiotic coating is said to have on the inner surface of non-metallic bodies interconnecting microvoids adhere well and the interconnecting Do not close micro-cavities.
Die Aufgabe wird durch die Merkmale der unabhängigen Ansprüche gelöst. Vorteilhafte Ausgestaltungen sind in den Unteransprüchen angegeben. The object is solved by the features of the independent claims. advantageous Refinements are specified in the subclaims.
Der Erfindung liegt der überraschende Befund zugrunde, dass antibiotische Beschichtungen mit retardierender Wirkstofffreisetzung in den Mikrohohlräumen von nichtmetallischen Körpern mit interkonnektierenden Mikrohohlräumen insbesondere dadurch gebildet werden, dass in die Mikrohohlräume eine Lösung von Gentamicin-pentakis-dodecylsulfat oder von Gentamicinpentakis-dodecylsulfonat in einem geeigneten organischen Lösungsmittel - beispielsweise aus der Gruppe der Alkohole - durch geeignete Maßnahmen wie Tauchen, Sprühen oder Tropfen, eingebracht wird und nach Entfernen (wie etwa durch Verdampfung oder Verdunstung) des organischen Lösungsmittels eine Schicht aus Gentamicin-pentakis-dodecylsulfat oder von Gentamicin-pentakis-dodecylsulfonat auf der Oberfläche der Mikrohohlräume zurückbleibt. Die Mikrohohlräume können als Poren ausgebildet sein. The invention is based on the surprising finding that antibiotic coatings with retarding drug release in the micro-cavities of non-metallic bodies with interconnecting microvoids are formed in particular by the fact that in the Micro voids a solution of gentamicin pentakis dodecyl sulfate or Gentamicin pentakis dodecyl sulfonate in a suitable organic solvent - for example the group of alcohols - by suitable measures such as dipping, spraying or dripping, is introduced and after removal (such as by evaporation or evaporation) of the organic solvent, a layer of gentamicin pentakis dodecyl sulfate or Gentamicin pentakis dodecyl sulfonate remains on the surface of the microcavities. The Micro voids can be designed as pores.
Die nichtmetallischen Körper können organischer oder anorganischer Natur sein oder auch sogenannte Composites aus anorganischem und organischem Material. Sie sind z. B. aus Kollagen, Gelatine, Polyestern, Calciumcarbonat, Calciumsulfat, Tricalciumphosphat oder Hydroxylapatit aufgebaut. Es versteht sich, dass die benutzten Lösungen möglichst homogen sind. Als Lösungsmittel kommen vor allem niedere Alkohole sowie N,N-Dimethylformamid (DMF) oder Dimethylsulfoxid (DMSO) in Frage. Bevorzugte Lösungsmittel sind Methanol oder Ethanol. The non-metallic bodies can be organic or inorganic in nature or else so-called composites made of inorganic and organic material. You are e.g. B. from Collagen, gelatin, polyester, calcium carbonate, calcium sulfate, tricalcium phosphate or Hydroxyapatite built up. It goes without saying that the solutions used are as homogeneous as possible. As Solvents come mainly from lower alcohols and N, N-dimethylformamide (DMF) or Dimethyl sulfoxide (DMSO) in question. Preferred solvents are methanol or ethanol.
Gentamicin-pentakis-dodecylsulfat, Gentamicin-tetrakis-dodecylsulfat Gentamicin-tetrakisdodecylsulfonat und auch Gentamicin-pentakis-dodecylsulfonat sind nichtkristalline, wachsartige Substanzen, die bei der Abdampfung bzw. bei der Verdunstung des organischen Lösungsmittels einen gewissen Verlauf zeigen und sich dabei als Schicht auf Oberflächen auflagern. Sie haften überraschenderweise gut auf Glas-, Keramik- und Kunststoffoberflächen. Gentamicin pentakis dodecyl sulfate, Gentamicin tetrakis dodecyl sulfate Gentamicin tetrakis dodecyl sulfonate and also gentamicin pentakis dodecyl sulfonate are non-crystalline, wax-like substances that are present in the evaporation or in the evaporation of the organic Solvent show a certain course and thereby deposit as a layer on surfaces. she adhere surprisingly well to glass, ceramic and plastic surfaces.
Überraschenderweise lösen sich auch Clindamycin-dodecylsulfat, Clindamycin-dodecylsulfonat, Lincosamin-dodecylsulfat, Lincosamin-dodecylsulfonat in Methanol, Ethanol Dimethylsulfoxid und N,N-Dimethylformamid. Diese Stoffe können somit ohne weiteres den Gantamicin- Lösungen zugefügt werden. Es ist auch möglich Tetracyclin-dodecylsulfat oder Tetracylindodecylsulfonat in den Lösungen einzusetzen. Man kann auch anstelle des Tetracyclindodecylsulfates die Dodecylsulfate und oder die Dodecylsulfonate des Chlortetracyclins, des Oxytetracylins, des Demethylchlortetracyclins, des Methacyclins, des Doxycyclins, des Rolitetracyclins und des Minocyclins verwenden. Es kann auch Coprofloxacindodecylbenzylsulfonat zugesetzt werden. Entsprechend entstehen an den Oberflächen der Mikrohohlräume Beschichtungen enthaltend die Gentamicinkomponenten und mindestens eine der genannten weiteren Antibiotika-Komponenten. Im Sinne der Erfindung ist auch die Herstellung von antibiotischen Schichten nur mit den in Methanol, Ethanol, Dimethylsulfoxid und N,N-Dimethylformamid gelösten Dodecylsulfaten, Dodecylsulfonaten und Dodecylbenzylsulfonaten der aufgeführten Antibiotika ohne eine Gentamicin enthaltende antibiotische Komponente. Surprisingly, clindamycin dodecyl sulfate, clindamycin dodecyl sulfonate, Lincosamine dodecyl sulfate, lincosamine dodecyl sulfonate in methanol, ethanol dimethyl sulfoxide and N, N-dimethylformamide. These substances can therefore easily be the gantamicin Solutions are added. It is also possible to use tetracycline dodecyl sulfate or Use tetracylindodecyl sulfonate in the solutions. You can also replace the Tetracyclinedodecyl sulfates the dodecyl sulfates and or the dodecyl sulfonates of chlorotetracycline, des Oxytetracycline, demethylchlorotetracycline, methacycline, doxycycline, des Use rolitetracycline and minocycline. It can also coprofloxacindodecylbenzylsulfonate be added. Correspondingly, micro-cavities are created on the surfaces Coatings containing the gentamicin components and at least one of the named other antibiotic components. The production of antibiotic layers only with those in methanol, ethanol, dimethyl sulfoxide and N, N-dimethylformamide dissolved dodecyl sulfates, dodecyl sulfonates and dodecylbenzyl sulfonates listed antibiotics without an antibiotic component containing gentamicin.
Überraschenderweise können in Schichten aus Gentamicin-pentakis-dodecylsulfat oder Gentamicin-tetrakis-dodecylsulfat und Gentamicin-pentakis-dodecylsulfonat oder Gentamicintetrakis-dodecylsulfonat andere Antibiotika durch Einschluss oder Überdeckung mechanisch fixiert werden. Es ist daher möglich, dass in interkonnektierende Mikrohohlräume von nichtmetallischen Körpern zuerst eine wässrige Lösung, die mindestens eine in Wasser leicht lösliche antibiotische Komponente aus den Gruppen der Aminoglykosid-Antibiotika, der Tetracyclin- Antibiotika, der Lincosamid-Antibiotika und der 4-Chinolon-Antibiotika enthält, und anschließend nach Verdampfung und oder Verdunstung des Wassers eine Lösung, die aus Gentamicinpentakis-dodecylsulfat und oder Gentamicin-tetrakis-dodecylsulfat und oder Gentamicinpentakis-dodecylsulfonat und oder Gentamicin-tetrakis-dodecylsulfonat und dem Lösungsmittel Methanol oder Ethanol oder Dimethylsulfoxid oder N,N-Dimethylformamid besteht, durch Tauchen oder Sprühen oder Tropfen eingebracht wird. Es entsteht im Ergebnis eine Doppelschicht. Bei der Anwendung in Implantaten wird dann das zweite Antibiotikum erst freigesetzt, wenn die Gentamicin-Schicht zumindest teilweise gelöst ist. Als in Wasser leicht lösliche antibiotische Komponente werden in dieser Ausführungsform der Erfindung Gentamicinsulfat, Clindamycinhydrochlorid, Clindamycindihydrogenphosphat, Lincosaminhydrochlorid, Kanamycinsulfat, Amikacinsulfat, Tobramycinsulfat, Tetracyclinhydrochlorid, Chlortetracylinhydrochlorid, Oxytetracyclinhydrochlorid, Demethylchlortetracyclin-hydrochlorid, Methacyclinhydrochlorid, Doxycyclinhydrochlorid, Rolitetracyclinhydrochlorid, Minocyclinhydrochlorid und oder Ciprofloxacinhydrochlorid, bevorzugt eingesetzt. Surprisingly, layers of gentamicin or pentakis dodecyl sulfate Gentamicin tetrakis dodecyl sulfate and Gentamicin pentakis dodecyl sulfonate or Gentamicintetrakis dodecylsulfonate other antibiotics mechanically by inclusion or coverage be fixed. It is therefore possible that in interconnecting micro cavities of non-metallic bodies first an aqueous solution that has at least one easily soluble in water antibiotic component from the groups of aminoglycoside antibiotics, tetracycline Antibiotics containing lincosamide antibiotics and 4-quinolone antibiotics, and then after evaporation and or evaporation of the water a solution that comes from Gentamicin pentakis dodecyl sulfate and or Gentamicin tetrakis dodecyl sulfate and or Gentamicin pentakis dodecyl sulfonate and or gentamicin tetrakis dodecyl sulfonate and the solvent Methanol or ethanol or dimethyl sulfoxide or N, N-dimethylformamide, by Dip or spray or drop is introduced. The result is a double layer. When used in implants, the second antibiotic is only released when the Gentamicin layer is at least partially dissolved. As a readily soluble antibiotic in water Components in this embodiment of the invention are gentamicin sulfate, Clindamycin hydrochloride, clindamycin dihydrogen phosphate, lincosamine hydrochloride, kanamycin sulfate, Amikacin sulfate, tobramycin sulfate, tetracycline hydrochloride, chlorotetracylin hydrochloride, Oxytetracycline hydrochloride, demethylchlorotetracycline hydrochloride, methacycline hydrochloride, Doxycycline hydrochloride, rolitetracycline hydrochloride, minocycline hydrochloride and or Ciprofloxacin hydrochloride, preferably used.
Erfindungsgemäß ist ferner, dass bevorzugt Vliese, Filze, Gewirke oder Gestricke aus Polyestern, Kollagen und Gelatine beschichtet werden. It is also according to the invention that preferably nonwovens, felts, knitted fabrics or knitted fabrics Polyesters, collagen and gelatin can be coated.
Das jeweilige Dodecylsulfat oder -sulfonat wird bevorzugt in einer Konzentration von 0,1 bis 20,0 Masseprozent, bezogen auf das Lösungsmittel verwendet. The respective dodecyl sulfate or sulfonate is preferably in a concentration of 0.1 to 20.0 mass percent, based on the solvent used.
Erfindungsgemäß ist auch, dass bevorzugt poröse Formkörper aus Polyestern, Calciumcarbonat, Calciumsulfat, Tricalciumphosphat, Hydroxylapatit und resorbierbaren Glas beschichtet werden. It is also according to the invention that preferably porous molded articles made of polyesters, Calcium carbonate, calcium sulfate, tricalcium phosphate, hydroxyapatite and absorbable glass coated become.
Im Sinne der Erfindung ist, dass die antibiotisch beschichteten Körper mit interkonnektierenden Mikrohohlräumen als Implantate verwendet werden. In the sense of the invention is that the antibiotic-coated body with interconnecting Micro cavities can be used as implants.
Die nachfolgenden Beispiele erklären die Erfindung ohne sie einzuschränken. The following examples explain the invention without restricting it.
Die Erfindung soll durch die nachstehenden Beispiele 1 und 2 erläutert werden. The invention is illustrated by Examples 1 and 2 below.
Als nichtmetallische Körper mit interkonnektierenden Mikrohohlräumen wurden quaderförmige, resorbierbare Phosphatgläser mit den Abmessungen von 20 × 20 × 10 mm für die Beispiele 1 und 2 verwendet. Sie hatten eine Gesamt-Porosität von 65 Volumenprozent. As non-metallic bodies with interconnecting micro-cavities, cuboid, Resorbable phosphate glasses with dimensions of 20 × 20 × 10 mm for Examples 1 and 2 used. They had a total porosity of 65 percent by volume.
Für die Beispiele kam Gentamicin-pentakis-dodecylsulfat zur Anwendung, dessen Herstellung
entsprechend der Vorschrift von Jurado Soler et al. (A. Jurado Soler, J. A. Ortiz Hernandez,
C. Ciuro Bertran: Neue Gentamicinderivate, Verfahren zur Herstellung derselben und diese
enthaltende antibiotisch wirksame Zusammensetzung. 30.09.1974 DE 24 46 640) erfolgte. Es
wurden 135 mg bzw. 270 mg Gentamicin-pentakis-dodecylsulfat in 1 g Methanol gelöst. In die
Poren jeweils eines quaderförmigen Phosphatglases wurde die zuvor hergestellte
methanolische Lösung getropft. Die Probekörper saugten die Lösung auf und wurden anschließend bei
Raumtemperatur bis zur Massekonstanz getrocknet.
Tabelle 1
Zusammensetzungen der verwendeten Lösungen sowie Auswaagen der
unbeschichteten und beschichteten Probekörper der Beispiele 1 und 2
Gentamicin pentakis dodecyl sulfate was used for the examples, the preparation of which according to the specification by Jurado Soler et al. (A. Jurado Soler, JA Ortiz Hernandez, C. Ciuro Bertran: New gentamicin derivatives, process for their preparation and antibiotic active composition containing them. 09/30/1974 DE 24 46 640). 135 mg and 270 mg of gentamicin pentakis dodecyl sulfate were dissolved in 1 g of methanol. The previously prepared methanolic solution was dripped into the pores of a rectangular phosphate glass. The test specimens soaked up the solution and were then dried to constant weight at room temperature. Table 1 Compositions of the solutions used and weighed out of the uncoated and coated test specimens of Examples 1 and 2
Die in den Beispielen 1 und 2 hergestellten Formkörper wurden in jeweils 20 ml physiologische
Kochsalzlösung eingebracht und in dieser bei 37°C über einen Zeitraum von 28 Tagen
gelagert. Die Probennahme erfolgte nach 1, 2, 3, 6, 9, 13, 15, 21 und 28 Tagen Lagerungszeit.
Nach jeder Probennahme wurde das Freisetzungsmedium vollständig durch frisches Medium,
ersetzt. Die Antibiotika-Wertbestimmung wurde mit einem Agardiffusionstest unter Verwendung
von Bacillus subtilis ATCC 6633 als Testkeim durchgeführt. Die Ergebnisse sind in Tab. 2
dargestellt.
Tabelle 2
Ergebnisse der mikrobiellen Bestimmung der Gentamicin-Freisetzung der
beschichteten Probekörper der Beispiele 1 und 2 in Abhängigkeit von der Lagerungszeit der
Probekörper in physiologischer Kochsalzlösung bei 37°C
The moldings produced in Examples 1 and 2 were each introduced into 20 ml of physiological saline and stored in this at 37 ° C. for a period of 28 days. Samples were taken after 1, 2, 3, 6, 9, 13, 15, 21 and 28 days of storage. After each sampling, the release medium was completely replaced by fresh medium. The antibiotic value determination was carried out with an agar diffusion test using Bacillus subtilis ATCC 6633 as test germ. The results are shown in Tab. 2. Table 2 Results of the microbial determination of the gentamicin release of the coated test specimens of Examples 1 and 2 as a function of the storage time of the test specimens in physiological saline at 37 ° C.
Claims (22)
Priority Applications (32)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10142465A DE10142465A1 (en) | 2001-08-31 | 2001-08-31 | Production of an antibiotic coating on a porous body useful as an implant comprises impregnation with a solution of gentamicin dodecyl sulfate or sulfonate and evaporation of the solvent |
| IS6390A IS6390A (en) | 2001-08-31 | 2002-05-17 | Experiences of antibiotic coating of carcasses containing microspheres, thus coated carcasses and also of their use |
| MDA20020153A MD2633C2 (en) | 2001-08-31 | 2002-06-03 | Process for applying an antibiotic coating on bodies with interconnected microcavities (variants), body with interconnected microcavities with antibiotic coating (variants) and use thereof |
| BG106881A BG65774B1 (en) | 2001-08-31 | 2002-06-27 | Method for obtaining antibiotic coating of elements with interconnecting microcavities, coated elements, and use thereof |
| CZ20022322A CZ301740B6 (en) | 2001-08-31 | 2002-07-02 | Process for antibiotic coating of elements with interconnected microcavities |
| SK985-2002A SK9852002A3 (en) | 2001-08-31 | 2002-07-04 | Methods of antibiotic coating of objects having interconnected microcavities and the uses thereof |
| YUP51902 YU51902A (en) | 2001-08-31 | 2002-07-05 | Method for antibiotic layer coating onto dies with interconnecting free microspaces, so layer coated bodies and application thereof |
| CA 2396146 CA2396146C (en) | 2001-08-31 | 2002-07-29 | Process for antibiotic coating of elements with interconnecting microcavities, elements thus coated as well as their usage |
| IL15099902A IL150999A0 (en) | 2001-08-31 | 2002-07-31 | Process for antibiotic coating of elements with ineroconnecting microcavities, elements thus coated as well as their usage |
| GEAP2002004867 GEP20043333B (en) | 2001-08-31 | 2002-08-12 | Process for Antibiotic Coating of Elements with Interconnecting Microcavities, Elements Thus Coated as Well as Their Usage |
| US10/217,788 US6984410B2 (en) | 2001-08-31 | 2002-08-13 | Process for antibiotic coating of elements with interconnecting microcavities, elements thus coated as well as their usage |
| DK02018322T DK1287818T3 (en) | 2001-08-31 | 2002-08-14 | Methods for antibiotic coating of bodies with interconnecting micro cavities, thus coated bodies and their use |
| ES02018322T ES2295268T3 (en) | 2001-08-31 | 2002-08-14 | PROCEDURE FOR ANTIBIOTIC COATING OF BODIES WITH INTERCONNECTED MICROCAVITIES, BODIES AS WELL COVERED, AS WELL AS THEIR USE. |
| DE50211246T DE50211246D1 (en) | 2001-08-31 | 2002-08-14 | Process for the antibiotic coating of bodies with interconnecting microcavities, so coated bodies and their use |
| PT02018322T PT1287818E (en) | 2001-08-31 | 2002-08-14 | Methods of antibiotic coating of objects having interconnected microcavities and the uses thereof |
| EP20020018322 EP1287818B1 (en) | 2001-08-31 | 2002-08-14 | Methods of antibiotic coating of objects having interconnected microcavities and the uses thereof |
| AU2002300656A AU2002300656B2 (en) | 2001-08-31 | 2002-08-19 | Process for Antibiotic Coating of Elements with Interconnecting Microcavities, Elements Thus Coated as Well as Their Usage |
| HR20020680A HRP20020680B1 (en) | 2001-08-31 | 2002-08-20 | Process for antibiotic coating of bodies having interconnected micro-cavities, the bodies thus coated, and the application thereof |
| MXPA02008326A MXPA02008326A (en) | 2001-08-31 | 2002-08-27 | Process for antibiotic coating of elements with interconnecting microcavities, elements thus coated, as well as their usage. |
| NZ521043A NZ521043A (en) | 2001-08-31 | 2002-08-27 | Antibiotic coating of porus materials by the introduction of solutions containing dodecyl sulphates or dodecyl sulphonates of various antibiotics |
| JP2002249580A JP3740449B2 (en) | 2001-08-31 | 2002-08-28 | Method for the coating of objects with continuous microcavities with antibiotics, thus coated objects and their use |
| UA2002087052A UA73161C2 (en) | 2001-08-31 | 2002-08-28 | Method for applying antibiotic coating onto items containing interconnected microcavities (variants) |
| BR0203427A BR0203427A (en) | 2001-08-31 | 2002-08-28 | Antibiotic coating process for bodies with interconnected empty microspaces, bodies thus coated, as well as their use |
| NO20024101A NO20024101L (en) | 2001-08-31 | 2002-08-28 | Procedure for Antibiotic Coating of Bodies with Internally Connected Microwells, Coated Bodies as well as Their Use |
| PL355778A PL206972B1 (en) | 2001-08-31 | 2002-08-29 | Method of antibiotically coating bodies with mutually interconnected microcavities, bodies coated thereby as well as their application |
| ZA200206983A ZA200206983B (en) | 2001-08-31 | 2002-08-30 | Process for antibiotic coating of elements with interconnecting microcavities, elements thus coated, as well as their usage. |
| EEP200200491A EE200200491A (en) | 2001-08-31 | 2002-08-30 | Method for antibiotic coating of interconnected micro-cavity elements, thus coated elements and their use |
| RU2002123420A RU2236261C2 (en) | 2001-08-31 | 2002-08-30 | Method of depositing antibiotic coating onto material with interconnected microhollows, material with such coating, and application thereof |
| HU0202916A HUP0202916A3 (en) | 2001-08-31 | 2002-08-30 | Process for coating joining bodies having microspaces with antibiotic, the so layered bodies and use of them |
| CNB02141503XA CN1203903C (en) | 2001-08-31 | 2002-08-30 | Method for coating antibiotic onto articles with interlinked micro-cavities, products thereby and use thereof |
| SA02230286A SA02230286B1 (en) | 2001-08-31 | 2002-09-03 | Process for antibiotic coating of micro-gap elements interconnected and items thus coated in addition to their use |
| CY081100074T CY1107271T1 (en) | 2001-08-31 | 2008-01-18 | METHOD FOR ANTIBIOTIC BODY COATING WITH COMMUNICATED MICROWELLS, BODIES COATED IN THIS WAY AND USE THIS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10142465A DE10142465A1 (en) | 2001-08-31 | 2001-08-31 | Production of an antibiotic coating on a porous body useful as an implant comprises impregnation with a solution of gentamicin dodecyl sulfate or sulfonate and evaporation of the solvent |
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|---|---|
| DE10142465A1 true DE10142465A1 (en) | 2003-07-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10142465A Withdrawn DE10142465A1 (en) | 2001-08-31 | 2001-08-31 | Production of an antibiotic coating on a porous body useful as an implant comprises impregnation with a solution of gentamicin dodecyl sulfate or sulfonate and evaporation of the solvent |
Country Status (3)
| Country | Link |
|---|---|
| DE (1) | DE10142465A1 (en) |
| UA (1) | UA73161C2 (en) |
| ZA (1) | ZA200206983B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102010020940A1 (en) | 2010-05-19 | 2011-11-24 | Heraeus Medical Gmbh | Antibiotic coating |
| EP2468317A2 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2468316A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2468315A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2468923A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2589439A1 (en) | 2011-11-03 | 2013-05-08 | Heraeus Medical GmbH | Coating method and coating apparatus for medical implants |
| DE102015214603A1 (en) | 2015-07-31 | 2017-02-02 | Mathys Ag Bettlach | Phosphorus containing aminoglycoside salts |
-
2001
- 2001-08-31 DE DE10142465A patent/DE10142465A1/en not_active Withdrawn
-
2002
- 2002-08-28 UA UA2002087052A patent/UA73161C2/en unknown
- 2002-08-30 ZA ZA200206983A patent/ZA200206983B/en unknown
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102010020940A1 (en) | 2010-05-19 | 2011-11-24 | Heraeus Medical Gmbh | Antibiotic coating |
| EP2392360A2 (en) | 2010-05-19 | 2011-12-07 | Heraeus Medical GmbH | Antibiotic coating |
| US9480778B2 (en) | 2010-12-23 | 2016-11-01 | Heraeus Medical Gmbh | Coating method and coating device |
| EP2468317A2 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2468315A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| EP2468923A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| DE102010055560A1 (en) | 2010-12-23 | 2012-06-28 | Heraeus Medical Gmbh | Coating method and coating device |
| DE102010055562A1 (en) | 2010-12-23 | 2012-06-28 | Heraeus Medical Gmbh | Coating method and coating device |
| DE102010055559A1 (en) | 2010-12-23 | 2012-06-28 | Heraeus Medical Gmbh | Coating method and coating device |
| DE102010055561A1 (en) | 2010-12-23 | 2012-06-28 | Heraeus Medical Gmbh | Coating method and coating device |
| US9878346B2 (en) | 2010-12-23 | 2018-01-30 | Heraeus Medical Gmbh | Device for coating regions of a medical implant |
| EP2468316A1 (en) | 2010-12-23 | 2012-06-27 | Heraeus Medical GmbH | Surface coating method and coating device |
| US8895098B2 (en) | 2010-12-23 | 2014-11-25 | Heraeus Medical Gmbh | Coating method and coating device |
| US8973521B2 (en) | 2010-12-23 | 2015-03-10 | Heraeus Medical Gmbh | Coating device and coating method |
| US9078959B2 (en) | 2010-12-23 | 2015-07-14 | Heraeus Medical Gmbh | Coating method and coating device |
| US8852669B2 (en) | 2011-11-03 | 2014-10-07 | Heraeus Medical Gmbh | Coating method and coating device for medical implants |
| EP2589439A1 (en) | 2011-11-03 | 2013-05-08 | Heraeus Medical GmbH | Coating method and coating apparatus for medical implants |
| DE102015214603A1 (en) | 2015-07-31 | 2017-02-02 | Mathys Ag Bettlach | Phosphorus containing aminoglycoside salts |
| EP3138849A1 (en) | 2015-07-31 | 2017-03-08 | Mathys AG Bettlach | Salts of phosphorus-containing aminoglycoside antibiotics |
| DE102015214603B4 (en) | 2015-07-31 | 2019-01-24 | Mathys Ag Bettlach | Phosphorus containing aminoglycoside salts |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200206983B (en) | 2003-05-02 |
| UA73161C2 (en) | 2005-06-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OP8 | Request for examination as to paragraph 44 patent law | ||
| 8127 | New person/name/address of the applicant |
Owner name: HERAEUS KULZER GMBH, 63450 HANAU, DE |
|
| 8130 | Withdrawal |