JPH04279520A - Pharmaceutical preparation for embedding in bone - Google Patents
Pharmaceutical preparation for embedding in boneInfo
- Publication number
- JPH04279520A JPH04279520A JP3153805A JP15380591A JPH04279520A JP H04279520 A JPH04279520 A JP H04279520A JP 3153805 A JP3153805 A JP 3153805A JP 15380591 A JP15380591 A JP 15380591A JP H04279520 A JPH04279520 A JP H04279520A
- Authority
- JP
- Japan
- Prior art keywords
- bone
- implantation
- preparation
- drug
- polymeric substance
- 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.)
- Pending
Links
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 59
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract 5
- 239000003814 drug Substances 0.000 claims abstract description 36
- 239000000126 substance Substances 0.000 claims abstract description 16
- 238000002156 mixing Methods 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract 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 abstract description 6
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 4
- 229940088710 antibiotic agent Drugs 0.000 claims abstract description 3
- 238000002844 melting Methods 0.000 claims abstract 3
- 230000008018 melting Effects 0.000 claims abstract 3
- 229940079593 drug Drugs 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 25
- 238000002513 implantation Methods 0.000 claims description 23
- 239000008187 granular material Substances 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 10
- 239000007943 implant Substances 0.000 claims description 8
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 8
- 239000004626 polylactic acid Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 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 claims description 5
- 229930182566 Gentamicin Natural products 0.000 claims description 5
- -1 canendomycin Chemical compound 0.000 claims description 5
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[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 JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 claims description 5
- 229960002518 gentamicin Drugs 0.000 claims description 5
- 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 5
- 230000003115 biocidal effect Effects 0.000 claims description 4
- 229960003807 dibekacin Drugs 0.000 claims description 4
- 238000000748 compression moulding Methods 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 3
- 229960004368 oxytetracycline hydrochloride Drugs 0.000 claims description 3
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 2
- 102000009027 Albumins Human genes 0.000 claims description 2
- 108010088751 Albumins Proteins 0.000 claims description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229930183998 Lividomycin Natural products 0.000 claims description 2
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 229920001710 Polyorthoester Polymers 0.000 claims description 2
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 claims description 2
- 229930192786 Sisomicin Natural products 0.000 claims description 2
- 108010059993 Vancomycin Proteins 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229940050528 albumin Drugs 0.000 claims description 2
- 229960004821 amikacin Drugs 0.000 claims description 2
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 2
- 229960000723 ampicillin Drugs 0.000 claims description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 2
- 229960005397 arbekacin Drugs 0.000 claims description 2
- MKKYBZZTJQGVCD-XTCKQBCOSA-N arbekacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)CC[C@H]1N MKKYBZZTJQGVCD-XTCKQBCOSA-N 0.000 claims description 2
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 claims description 2
- 229960003866 cefaloridine Drugs 0.000 claims description 2
- 229960000603 cefalotin Drugs 0.000 claims description 2
- 229960001139 cefazolin Drugs 0.000 claims description 2
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 claims description 2
- 229960004682 cefoperazone Drugs 0.000 claims description 2
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 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
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 229960005188 collagen Drugs 0.000 claims description 2
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[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[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 229950003076 lividomycin Drugs 0.000 claims description 2
- DBLVDAUGBTYDFR-SWMBIRFSSA-N lividomycin A Chemical compound O([C@@H]1[C@@H](N)C[C@@H](N)[C@H](O)[C@H]1O[C@@H]1O[C@H](CO)[C@H]([C@H]1O)O[C@H]1O[C@H]([C@H]([C@H](O)[C@H]1N)O[C@@H]1[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)CN)[C@H]1O[C@H](CO)[C@@H](O)C[C@H]1N DBLVDAUGBTYDFR-SWMBIRFSSA-N 0.000 claims description 2
- 229960002292 piperacillin Drugs 0.000 claims description 2
- 239000002745 poly(ortho ester) Substances 0.000 claims description 2
- 239000004633 polyglycolic acid Substances 0.000 claims description 2
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 claims description 2
- 229960001225 rifampicin Drugs 0.000 claims description 2
- 229960005456 sisomicin Drugs 0.000 claims description 2
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound 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(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 claims description 2
- 229960004989 tetracycline hydrochloride Drugs 0.000 claims description 2
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 claims description 2
- 229960004659 ticarcillin Drugs 0.000 claims description 2
- 229960003165 vancomycin Drugs 0.000 claims description 2
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 claims 1
- QYQDKDWGWDOFFU-IUODEOHRSA-N Cefotiam Chemical compound CN(C)CCN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC=3N=C(N)SC=3)[C@H]2SC1 QYQDKDWGWDOFFU-IUODEOHRSA-N 0.000 claims 1
- 229920001651 Cyanoacrylate Polymers 0.000 claims 1
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 claims 1
- 229960001242 cefotiam Drugs 0.000 claims 1
- IVBHGBMCVLDMKU-GXNBUGAJSA-N piperacillin Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 IVBHGBMCVLDMKU-GXNBUGAJSA-N 0.000 claims 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 230000017423 tissue regeneration Effects 0.000 abstract description 2
- 229940034982 antineoplastic agent Drugs 0.000 abstract 1
- 230000008023 solidification Effects 0.000 abstract 1
- 238000007711 solidification Methods 0.000 abstract 1
- 230000001502 supplementing effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 25
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000004570 mortar (masonry) Substances 0.000 description 11
- 229960000448 lactic acid Drugs 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 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 description 6
- 239000000945 filler Substances 0.000 description 6
- 238000000227 grinding Methods 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- 206010005940 Bone and joint infections Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 208000002565 Open Fractures Diseases 0.000 description 1
- 206010031256 Osteomyelitis chronic Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000004154 testing of material Methods 0.000 description 1
- UPPMZCXMQRVMME-UHFFFAOYSA-N valethamate Chemical compound CC[N+](C)(CC)CCOC(=O)C(C(C)CC)C1=CC=CC=C1 UPPMZCXMQRVMME-UHFFFAOYSA-N 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 description 1
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は徐放化された薬物を含む
人工骨成分含有の骨内部埋め込み用製剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a preparation for implantation into bone containing an artificial bone component containing a sustained-release drug.
【０００２】0002
【従来の技術】難治性疾患である慢性骨髄炎や開放骨折
の術後感染の治療として、アミノグリコシド系抗生物質
を徐放化させた高分子ビーズ（ゲンタマイシン含有ポリ
メチルメタクリレート）を骨内部に外科的に埋め込む治
療が欧米では実用化されている。[Prior Art] Polymer beads (polymethyl methacrylate containing gentamicin) containing sustained release aminoglycoside antibiotics are surgically inserted into the bone as a treatment for chronic osteomyelitis, which is an intractable disease, and postoperative infection of open fractures. In Europe and the United States, treatment in which patients are implanted has been put into practical use.
【０００３】0003
【発明が解決しようとする課題】しかしながら、用いた
高分子が、生体内で殆ど分解しないため、骨組織修復に
伴って徐々に除去していく必要がある。従って、手術後
に取り出す必要がなく、かつ、ハイドロキシアパタイト
、β−トリカルシウムホスフェートなどの人工骨成分を
含有して、骨組織修復を補填出来るような埋め込み剤が
、骨・関節感染症領域で望まれている。このような埋め
込み剤としては、ジャ−ナル オブ コントロ−ル
ドリリ−ズ 第２巻 １７９〜１８６頁１９８５年
（Ｊ．Ｃｏｎｔｒｏｌｌｅｄ Ｒｅｌｅａｓｅ Ｖ
ｏｌ．２ １７９〜１８６（１９８５））に、ジベカ
シン、ハイドロキシアパタイトをポリ乳酸中に分散固化
したものが見られる。しかし、埋め込み剤からのジベカ
シンの放出は、初期放出量が比較的高い挙動を示した。
手術後に取り出す必要がない埋め込み剤を調製するには
、上記のようにポリ乳酸等の生体内分解性高分子を用い
るのが適しているが、薬物の放出速度を調節するという
点では必ずしも十分とは言えない。[Problems to be Solved by the Invention] However, since the polymer used hardly decomposes in vivo, it is necessary to gradually remove it as bone tissue is repaired. Therefore, an implant that does not need to be taken out after surgery and that can supplement bone tissue repair by containing artificial bone components such as hydroxyapatite and β-tricalcium phosphate is desired in the field of bone and joint infections. ing. Such an implant is described in J. Controlled Release V, Journal of Controlled Releases, Vol. 2, pp. 179-186, 1985.
ol. 2 179-186 (1985)), dibekacin and hydroxyapatite are dispersed and solidified in polylactic acid. However, the release of dibekacin from the implant exhibited a relatively high initial release behavior. To prepare implants that do not need to be taken out after surgery, it is suitable to use biodegradable polymers such as polylactic acid as described above, but this is not always sufficient in terms of controlling the drug release rate. I can't say that.
【０００４】そこで、本発明者らは薬物を含有する骨内
部埋め込み用製剤において、薬物の放出速度を調節し、
徐放化できる製剤について鋭意検討を長年にわたってお
こなった。その結果、次に示す方法を採用することによ
り上記の問題点を解決できることを見い出し、本発明を
完成した。[0004] Therefore, the present inventors adjusted the release rate of the drug in a drug-containing preparation for implantation into the bone.
For many years, we have conducted extensive research into formulations that can be released in a sustained manner. As a result, the inventors discovered that the above problems could be solved by employing the following method, and completed the present invention.
【０００５】[0005]
【課題を解決するための手段】すなわち、本発明は、薬
物、高分子物質、人工骨成分からなる薬物を含有する骨
内部用埋め込み剤において、薬物と高分子物質をあらか
じめ圧縮若しくは溶融した後固化した成型物を用いるこ
とを特徴とする薬物を含有する骨内部埋め込み用製剤で
ある。更に、本発明は薬物と高分子物質を混合し、圧縮
若しくは溶融固化せしめて成型物とした後、これを顆粒
状に解砕し、次いで人工骨成分を混合し、更に圧縮成型
することを特徴とする薬物を含有する骨内部用埋め込み
用製剤の製造方法である。[Means for Solving the Problems] That is, the present invention provides a bone implant containing a drug, a polymeric substance, and an artificial bone component, in which the drug and the polymeric substance are compressed or melted in advance, and then solidified. This is a drug-containing preparation for implantation into bone, which is characterized by using a molded product. Furthermore, the present invention is characterized in that the drug and the polymeric substance are mixed and compressed or melted and solidified to form a molded product, which is then crushed into granules, and then an artificial bone component is mixed and further compression molded. This is a method for producing a preparation for implantation into bone containing a drug.
【０００６】本発明によって得られた薬物を含有する骨
内部用埋め込み用製剤は、薬物が生体内で適度な速さで
放出されるように制御された製剤であり、各種疾患に適
した徐放化された骨内部埋め込み用製剤を得ることがで
きる。したがって、本発明の目的は、薬物の放出速度が
制御された新規な薬物を含有する骨内部埋め込み用製剤
を提供するにある。本発明における薬物は骨内部に埋め
込む必要があるものであれば、いかなるものでも使用可
能である。通常は抗生物質が用いられるが、必要に応じ
て抗ガン剤等の薬物も用いることができる。[0006] The intraosseous implant preparation containing the drug obtained according to the present invention is a preparation that is controlled so that the drug is released at an appropriate rate in the body, and is a controlled release drug suitable for various diseases. A formulated preparation for implantation into bone can be obtained. Therefore, an object of the present invention is to provide a preparation for implantation into bone containing a novel drug with a controlled drug release rate. Any drug can be used in the present invention as long as it needs to be implanted inside the bone. Antibiotics are usually used, but drugs such as anticancer agents can also be used if necessary.
【０００７】本発明における骨内部埋め込み用製剤の製
造法は一般に知られている方法を用いることができる。
例えば薬物と高分子を混合し、材料試験機あるいは圧延
機等で圧縮後、得られた成形物を乳バチあるいは解砕機
で解砕し、篩により必要な粒度のものを分取し、さらに
、ハイドロキシアパタイト等の人工骨成分を混合して打
錠機等を用いて錠剤あるいは適切な形態に圧縮加工すれ
ばよい。[0007] Generally known methods can be used to produce the preparation for implantation into bone according to the present invention. For example, a drug and a polymer are mixed, compressed using a material testing machine or a rolling machine, the resulting molded product is crushed using a pestle or a crusher, and the required particle size is separated using a sieve. An artificial bone component such as hydroxyapatite may be mixed and compressed into a tablet or other appropriate form using a tablet machine or the like.
【０００８】本発明における高分子物質とは、主として
生体内分解性高分子を指すが、合成又は天然起源のいず
れも用いることができる。例えば、合成高分子重合物の
例としては、ポリ乳酸、ポリグリコール酸、ポリ−α−
シアノアクリル酸エステル、ポリ−β−ヒドロキシ酪酸
、ポリオルソエステル、ポリアミノ酸等があげられる。
これらの高分子重合物は、一種でも、二種以上の共重合
物あるいは単なる混合物でもよく、またこれらの塩でも
よい。又、天然高分子の例としては、アルブミン、ゼラ
チン、コラーゲン、コンドロイチン硫酸、ヒアルロン酸
等があげられる。[0008] The polymer substance in the present invention mainly refers to biodegradable polymers, but either synthetic or natural substances can be used. For example, examples of synthetic polymers include polylactic acid, polyglycolic acid, poly-α-
Examples include cyanoacrylic acid ester, poly-β-hydroxybutyric acid, polyorthoester, and polyamino acid. These polymers may be one type, a copolymer of two or more types, or a mere mixture, or a salt thereof. Further, examples of natural polymers include albumin, gelatin, collagen, chondroitin sulfate, hyaluronic acid, and the like.
【０００９】これらの高分子の中で、２週間以上の長期
間に亘る徐放性を付与するのに好ましい高分子としては
、ポリ乳酸、あるいはポリ乳酸・グリコール酸共重合物
が挙げられる。Among these polymers, polylactic acid and polylactic acid/glycolic acid copolymers are preferred for imparting sustained release over a long period of two weeks or more.
【００１０】本発明における抗生物質とは、特に限定さ
れないが、アミノグリコシド系、ペニシリン系、セファ
ロスポリン系などいずれも用いることができる。例を挙
げれば、ゲンタマイシン、ジベカシン、トプラマイシン
、アミカシン、カネンドマイシン、リビドマイシン、シ
ソマイシン、フラジオマイシン、アンピシリン、ピペラ
シリン、チカルシリン、塩酸テトラサイクリン、塩酸オ
キシテトラサイクリン、セファロチン、セファロリジン
、セファゾリン、セフォチアム、セフォペラゾン、アズ
スレオナム、ヴァンコマイシン、アルベカシン、リファ
ンピシン等である。[0010] The antibiotic used in the present invention is not particularly limited, but any of aminoglycosides, penicillins, cephalosporins, etc. can be used. Examples include gentamicin, dibekacin, topramycin, amikacin, canendomycin, lividomycin, sisomicin, fradiomycin, ampicillin, piperacillin, ticarcillin, tetracycline hydrochloride, oxytetracycline hydrochloride, cephalothin, cephaloridine, cefazolin, cefothiam, cefoperazone, These include azureonam, vancomycin, arbekacin, and rifampicin.
【００１１】本発明における人工骨成分とは、整形外科
領域で骨充填剤として用いられている例えばハイドロキ
シアパタイト、β−トリカルシウムフォスフェート等の
無機塩をいうが、人工骨成分として用いられうるもので
あればよい。また、本発明における圧縮若しくは溶融後
固化した成型物とは固化した後何らかの方法で解砕した
ものを意味し、具体的に好ましい解砕物としては例えば
約１２メッシュ篩を通過し、約４２メッシュ篩に残存す
る解砕物をあげることができる。[0011] The artificial bone component in the present invention refers to inorganic salts such as hydroxyapatite and β-tricalcium phosphate, which are used as bone fillers in the field of orthopedics, and those which can be used as artificial bone components. That's fine. In addition, in the present invention, a molded product that has been solidified after being compressed or melted means a product that has been solidified and then crushed by some method, and specifically preferred crushed products include, for example, those that have passed through an approximately 12-mesh sieve, and have passed through an approximately 42-mesh sieve. The remaining crushed material can be mentioned.
【００１２】解砕物の粒度は２５０μ以上が好ましく、
さらに好ましくは３５０μ〜１４００μとすることが好
ましい。本発明において高分子と薬物の配合率は特に限
定されず、適切な徐放性が得られるように自由に変える
ことができる。また、圧縮成形に際して必要ならばステ
アリン酸カルシウムあるいはタルク等の滑沢剤を配合す
ることができる。さらに、解砕した成形物と人工骨成分
の配合率も特に限定されず、適用疾患に適した比率にす
ればよく、圧縮成形に際しては必要ならば滑沢剤等の添
加剤を使用することができる。[0012] The particle size of the crushed material is preferably 250μ or more,
More preferably, it is 350μ to 1400μ. In the present invention, the blending ratio of the polymer and drug is not particularly limited and can be freely changed so as to obtain appropriate sustained release properties. Furthermore, a lubricant such as calcium stearate or talc may be added if necessary during compression molding. Furthermore, the blending ratio of the crushed molded product and the artificial bone component is not particularly limited, and may be adjusted to a ratio appropriate for the disease to be treated, and additives such as lubricants may be used if necessary during compression molding. can.
【００１３】本発明により得られた薬物を含有する骨内
部埋め込み用製剤は、含有する薬物の放出を制御するこ
とが可能であるが、必要により加熱あるいはコーティン
グなどの処理によって、更に放出速度の調節をすること
ができる。以下に本発明の具体的な実施例を示し、本発
明を更に詳細に説明するが、本発明はこれらの例に限定
されるものではない。[0013] The drug-containing preparation for implantation into bone obtained according to the present invention can control the release of the drug contained therein, but if necessary, the release rate can be further adjusted by treatment such as heating or coating. can do. The present invention will be explained in more detail by showing specific examples of the present invention below, but the present invention is not limited to these examples.
【００１４】[0014]
【実施例】実施例１
硫酸ゲンタマイシン１０ｍｇ、ポリｄｌ乳酸（数平均分
子量２０００、２００メッシュ篩通過粉末）９０ｍｇを
メノウ乳鉢で均一に混合磨砕した後、オートグラフＡＧ
−５０００Ａ（島津製作所）で荷重３００ｋｇで圧縮し
て直径５ｍｍ、長さ５ｍｍの成型物を得た。この成型物
をメノウ乳鉢で砕き、顆粒状となし、１２メッシュ篩通
過、３２メッシュ篩残存の顆粒２５ｍｇを骨充填剤ボー
ンセラムＰＧ−１（０．１−０．３ｍｍ、住友製薬）２
５ｍｇと混合し、オートグラフＡＧ−５０００Ａで荷重
３００ｋｇにて圧縮して、重量５０ｍｇ、直径３ｍｍ、
長さ５ｍｍの成型物を得た。[Example] Example 1 After uniformly mixing and grinding 10 mg of gentamicin sulfate and 90 mg of poly DL lactic acid (number average molecular weight 2000, powder passed through a 200 mesh sieve) in an agate mortar, Autograph AG
-5000A (Shimadzu Corporation) under a load of 300 kg to obtain a molded product with a diameter of 5 mm and a length of 5 mm. This molded product was crushed in an agate mortar to form granules, passed through a 12-mesh sieve, and 25 mg of the granules remaining on the 32-mesh sieve were added to the bone filler Bone Ceram PG-1 (0.1-0.3 mm, Sumitomo Pharmaceuticals) 2
5mg, compressed with Autograph AG-5000A under a load of 300kg, weight 50mg, diameter 3mm,
A molded article with a length of 5 mm was obtained.
【００１５】実施例２
実施例１と同様の方法で、硫酸ゲンタマイシン、ポリｄ
ｌ乳酸（数平均分子量２０００、２００メッシュ篩通過
粉末）、ボーンセラムＰから成る、重量５０ｍｇ、直径
３ｍｍ、長さ５ｍｍの成型物を得た。この成型物をさら
に８０℃の恒温槽で５時間加熱処理した。Example 2 In the same manner as in Example 1, gentamicin sulfate, poly-d
A molded article having a weight of 50 mg, a diameter of 3 mm, and a length of 5 mm was obtained, consisting of lactic acid (number average molecular weight 2000, powder passed through a 200 mesh sieve) and Bone Ceram P. This molded product was further heat-treated in a constant temperature bath at 80° C. for 5 hours.
【００１６】実施例３
硫酸ジベカシン１５ｍｇ、ポリｄｌ乳酸（数平均分子量
４０００、２００メッシュ篩通過粉末）８５ｍｇをメノ
ウ乳鉢で均一に混合磨砕した後、オートグラフＡＧ−５
０００Ａ（島津製作所）で荷重３００ｋｇで圧縮して直
径５ｍｍ、長さ５ｍｍの成型物を得た。この成型物をメ
ノウ乳鉢で砕き、顆粒状となし、１２メッシュ篩通過、
３２メッシュ篩残存の顆粒２５ｍｇを骨充填剤ボーンセ
ラムＰＧ−１（０．１−０．３ｍｍ、住友製薬）２５ｍ
ｇと混合し、オートグラフＡＧ−５０００Ａで荷重３０
０ｋｇにて圧縮して、直径３ｍｍ、長さ５ｍｍの成型物
を得た。Example 3 15 mg of dibekacin sulfate and 85 mg of poly dl lactic acid (number average molecular weight 4000, powder passed through a 200 mesh sieve) were uniformly mixed and ground in an agate mortar, and then mixed and ground using an Autograph AG-5.
000A (Shimadzu Corporation) under a load of 300 kg to obtain a molded product having a diameter of 5 mm and a length of 5 mm. This molded product was crushed in an agate mortar to form granules, passed through a 12 mesh sieve,
25 mg of the granules remaining on a 32 mesh sieve were added to the bone filler Bone Serum PG-1 (0.1-0.3 mm, Sumitomo Pharmaceuticals) 25 m
g and load 30 with Autograph AG-5000A.
It was compressed at 0 kg to obtain a molded product with a diameter of 3 mm and a length of 5 mm.
【００１７】実施例４
硫酸ゲンタマイシン１０ｍｇ、ポリｄｌ乳酸（数平均分
子量２０００、２００メッシュ篩通過粉末）９０ｍｇを
メノウ乳鉢で均一に混合磨砕した後、オートグラフＡＧ
−５０００Ａ（島津製作所）で荷重３００ｋｇで圧縮し
て直径５ｍｍ、長さ５ｍｍの成型物を得た。この成型物
をメノウ乳鉢で砕き、顆粒状となし、１２メッシュ篩通
過、３２メッシュ篩残存の顆粒２５ｍｇを骨充填剤β−
トリカルシウムフォスフェート（０．１−０．３ｍｍ）
２５ｍｇと混合し、オートグラフＡＧ−５０００Ａで荷
重３００ｋｇにて圧縮して、直径３ｍｍ、長さ５ｍｍの
成型物を得た。この成型物をさらに、６５℃で２４時間
加熱処理を行った。Example 4 After uniformly mixing and grinding 10 mg of gentamicin sulfate and 90 mg of poly dl lactic acid (number average molecular weight 2000, powder passed through a 200 mesh sieve) in an agate mortar, Autograph AG
-5000A (Shimadzu Corporation) under a load of 300 kg to obtain a molded product with a diameter of 5 mm and a length of 5 mm. This molded product was crushed in an agate mortar to form granules, passed through a 12-mesh sieve, and 25 mg of the granules remaining on the 32-mesh sieve were added to the bone filler β-
Tricalcium phosphate (0.1-0.3mm)
25 mg and compressed with Autograph AG-5000A under a load of 300 kg to obtain a molded product with a diameter of 3 mm and a length of 5 mm. This molded product was further heat-treated at 65° C. for 24 hours.
【００１８】実施例５
塩酸オキシテトラサイクリン１０ｍｇ、ポリｄｌ乳酸（
数平均分子量２０００、２００メッシュ篩通過粉末）９
０ｍｇをメノウ乳鉢で均一に混合磨砕した後、オートグ
ラフＡＧ−５０００Ａ（島津製作所）で荷重３００ｋｇ
で圧縮して直径５ｍｍ、長さ５ｍｍの成型物を得た。こ
の成型物をメノウ乳鉢で砕き、顆粒状となし、１２メッ
シュ篩通過、３２メッシュ篩残存の顆粒２５ｍｇを骨充
填剤β−トリカルシウムフォスフェート（０．１−０．
３ｍｍ）２５ｍｇと混合し、オートグラフＡＧ−５００
０Ａで荷重３００ｋｇにて圧縮して、直径３ｍｍ、長さ
５ｍｍの成型物を得た。Example 5 10 mg of oxytetracycline hydrochloride, polydl lactic acid (
Number average molecular weight 2000, powder passed through a 200 mesh sieve) 9
After uniformly mixing and grinding 0 mg in an agate mortar, the mixture was ground using an Autograph AG-5000A (Shimadzu Corporation) under a load of 300 kg.
A molded product with a diameter of 5 mm and a length of 5 mm was obtained. This molded product was crushed in an agate mortar to form granules, passed through a 12 mesh sieve, and 25 mg of the granules remaining on a 32 mesh sieve were mixed with bone filler β-tricalcium phosphate (0.1-0.
3mm) 25mg and Autograph AG-500
It was compressed at 0 A and a load of 300 kg to obtain a molded product with a diameter of 3 mm and a length of 5 mm.
【００１９】実施例６
硫酸ゲンタマイシン１０ｍｇ、ポリｄｌ乳酸（数平均分
子量２０００、２００メッシュ篩通過粉末）９０ｍｇを
メノウ乳鉢で均一に混合磨砕した後、オートグラフＡＧ
−５０００Ａ（島津製作所）で荷重３００ｋｇで圧縮し
て直径５ｍｍ、長さ５ｍｍの成型物を得た。この成型物
をメノウ乳鉢で砕き、顆粒状となし、３２メッシュ篩通
過、４２メッシュ篩残存の顆粒２５ｍｇを骨充填剤ボー
ンセラムＰＧ−１（０．１−０．３ｍｍ、住友製薬）２
５ｍｇと混合し、オートグラフＡＧ−５０００Ａで荷重
３００ｋｇにて圧縮して、直径３ｍｍ、長さ５ｍｍの成
型物を得た。Example 6 After uniformly mixing and grinding 10 mg of gentamicin sulfate and 90 mg of poly dl lactic acid (number average molecular weight 2000, powder passed through a 200 mesh sieve) in an agate mortar,
-5000A (Shimadzu Corporation) under a load of 300 kg to obtain a molded product with a diameter of 5 mm and a length of 5 mm. This molded product was crushed in an agate mortar to form granules, passed through a 32 mesh sieve, and 25 mg of the granules remaining on the 42 mesh sieve were added to the bone filler Bone Ceram PG-1 (0.1-0.3 mm, Sumitomo Pharmaceuticals) 2
5 mg and compressed using Autograph AG-5000A under a load of 300 kg to obtain a molded product with a diameter of 3 mm and a length of 5 mm.
【００２０】[0020]
【発明の効果】次に、本発明の効果を詳細に説明するた
め、実験例を示す。
実験例
（１）方法
上述の実施例１，２，６および下記の比較例１で得られ
た、成型物を用いて、３７℃ｐＨ７．４のフォスフェー
ト・バッファー中に静置した場合の放出率を経時的に測
定した。[Effects of the Invention] Next, an experimental example will be shown to explain the effects of the present invention in detail. Experimental Example (1) Method Release when the molded products obtained in Examples 1, 2, and 6 above and Comparative Example 1 below are left standing in a phosphate buffer at 37°C, pH 7.4. The rate was measured over time.
【００２１】比較例１
硫酸ゲンタマイシン２．５ｍｇ、ポリｄｌ乳酸（数平均
分子量２０００、２００メッシュ篩通過粉末）２２．５
ｍｇ、ボーンセラムＰＧ−１２５ｍｇをメノウ乳鉢で均
一に混合研和して、オートグラフＡＧ−５０００Ａで荷
重３００ｋｇで圧縮した成型物。Comparative Example 1 Gentamicin sulfate 2.5 mg, poly dl lactic acid (number average molecular weight 2000, powder passed through a 200 mesh sieve) 22.5
A molded product was obtained by uniformly mixing and grinding 125 mg of Bone Serum PG-1 in an agate mortar and compressing it with an Autograph AG-5000A under a load of 300 kg.
【００２２】（２）結果
結果を図１に示す。
図１において、縦軸はゲンタマイシンの放出率（％）を
示し、横軸は時間（日）を示す。図１から明らかな如く
、本発明によって得られた骨内部埋め込み用製剤は、比
較例に較べて、徐放性を示した。(2) Results The results are shown in FIG. In FIG. 1, the vertical axis shows the release rate (%) of gentamicin, and the horizontal axis shows time (days). As is clear from FIG. 1, the preparation for intraosseous implantation obtained according to the present invention exhibited sustained release properties compared to the comparative example.
【００２３】[0023]
【図１】硫酸ゲンタマイシンの放出率を示す。縦軸はゲ
ンタマイシンの放出率（％）を示し、横軸は時間（日）
を示す。FIG. 1 shows the release rate of gentamicin sulfate. The vertical axis shows the release rate (%) of gentamicin, and the horizontal axis shows time (days).
shows.
Claims (14)
る骨内部用埋め込み剤において、薬物と高分子物質を圧
縮した成型物若しくは溶融した後固化した成型物を用い
ることを特徴とする薬物を含有する骨内部埋め込み用製
剤。Claim 1: A bone implant comprising a drug, a polymeric substance, and an artificial bone component, characterized by using a molded product obtained by compressing the drug and the polymeric substance, or a molded product obtained by melting and solidifying the drug and the polymeric substance. Contains a preparation for implantation into the bone.
骨内部埋め込み用製剤。2. The preparation for implantation into bone according to claim 1, wherein the drug is an antibiotic.
シン、トプラマイシン、アミカシン、カネンドマイシン
、リビドマイシン、シソマイシン、フラジオマイシン、
アンピシリン、ピペラシリン、チカルシリン、塩酸テト
ラサイクリン、塩酸オキシテトラサイクリン、セファロ
チン、セファロリジン、セファゾリン、セフォチアム、
セフォペラゾン、アズスレオナム、ヴァンコマイシン、
アルベカシン、リファンピシンから選択された１種また
は２種以上の抗生物質である請求項１または２記載の骨
内部埋め込み用製剤。3. The antibiotic is gentamicin, dibekacin, topramycin, amikacin, canendomycin, lividomycin, sisomicin, fradiomycin,
ampicillin, piperacillin, ticarcillin, tetracycline hydrochloride, oxytetracycline hydrochloride, cephalothin, cephaloridine, cefazolin, cefotiam,
cefoperazone, azureonam, vancomycin,
The preparation for implantation into bone according to claim 1 or 2, which is one or more antibiotics selected from arbekacin and rifampicin.
である請求項１記載の骨内部埋め込み用製剤。4. The preparation for implantation into bone according to claim 1, wherein the polymeric substance is a biodegradable polymeric substance.
ル酸，ポリ−α−シアノアクリル酸エステル，ポリ−β
−ヒドロキシ酪酸，ポリオルソエステル，ポリアミノ酸
，ゼラチン，コラーゲン，コンドロイチン硫酸，ヒアル
ロン酸，アルブミンから選択された１種または２種以上
の混合物あるいは共重合物である請求項１記載の骨内部
埋め込み用製剤。Claim 5: The polymer substance is polylactic acid, polyglycolic acid, poly-α-cyanoacrylate, poly-β
- The preparation for implantation into bone according to claim 1, which is a mixture or copolymer of one or more selected from hydroxybutyric acid, polyorthoester, polyamino acid, gelatin, collagen, chondroitin sulfate, hyaluronic acid, and albumin. .
記載の骨内部埋め込み用製剤。Claim 6: Claim 1 wherein the polymeric substance is polylactic acid.
The preparation for implantation into the bone described above.
，β−トリカルシウムフォスフェートから選択された１
種または２種の人工骨成分である請求項１記載の骨内部
埋め込み用製剤。[Claim 7] The artificial bone component is selected from hydroxyapatite and β-tricalcium phosphate.
The preparation for implantation into bone according to claim 1, which is one or two kinds of artificial bone components.
５０μ以上である請求項１記載の骨内部埋め込み用製剤
。Claim 8: A molded product obtained by compressing a polymer and a drug is 2
The preparation for implantation into bone according to claim 1, which has a diameter of 50μ or more.
が２５０μ以上である請求項１記載の骨内部埋め込み用
製剤。9. The preparation for implantation into bone according to claim 1, wherein the molded product obtained by melting and solidifying the polymer and the drug has a size of 250 μm or more.
を製造する際、薬物と高分子物質を混合し、圧縮若しく
は溶融固化せしめて成型物とした後、これを顆粒状に解
砕し、次いで人工骨成分を混合し、更に圧縮成型するこ
とを特徴とする薬物を含有する骨内部埋め込み用製剤の
製造方法。10. When manufacturing a bone implant containing a drug, the drug and a polymeric substance are mixed and compressed or melted and solidified to form a molded product, which is then crushed into granules, and then A method for producing a drug-containing preparation for implantation into bone, which comprises mixing artificial bone components and compression molding the mixture.
物質である請求項１０記載の骨内部埋め込み用製剤の製
造方法。11. The method for producing a preparation for implantation into bone according to claim 10, wherein the polymeric substance is the polymeric substance according to claim 5.
１０記載の骨内部埋め込み用製剤の製造方法。12. The method for producing a preparation for implantation into bone according to claim 10, wherein the polymeric substance is polylactic acid.
る請求項１０記載の骨内部埋め込み用製剤の製造方法。13. The method for producing a preparation for implantation into bone according to claim 10, wherein the drug is the antibiotic according to claim 3.
成分である請求項１０記載の骨内部埋め込み用製剤の製
造方法。14. The method for producing a preparation for implantation into a bone according to claim 10, wherein the artificial bone component is the artificial bone component according to claim 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3153805A JPH04279520A (en) | 1990-05-31 | 1991-05-30 | Pharmaceutical preparation for embedding in bone |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2-139885 | 1990-05-31 | ||
| JP13988590 | 1990-05-31 | ||
| JP3153805A JPH04279520A (en) | 1990-05-31 | 1991-05-30 | Pharmaceutical preparation for embedding in bone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04279520A true JPH04279520A (en) | 1992-10-05 |
Family
ID=26472566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3153805A Pending JPH04279520A (en) | 1990-05-31 | 1991-05-30 | Pharmaceutical preparation for embedding in bone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04279520A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2285924A (en) * | 1994-01-29 | 1995-08-02 | Cho Se Hyun | Polymer beads containing antibiotics for use in orthopaedic surgery |
| JPH10229A (en) * | 1996-04-19 | 1998-01-06 | Dainippon Ink & Chem Inc | Slow-releasable bioactive and bioabsorbable organic-inorganic compounded material having bone inducing or bone conducting function |
| GB2281709B (en) * | 1993-09-14 | 1998-04-08 | Fujitsu Ltd | Biodegradable resin moulded article |
| WO1999012554A1 (en) * | 1997-09-09 | 1999-03-18 | The University Of Western Australia | Chemical supplementation of bone |
| EP0911355A3 (en) * | 1997-10-21 | 2000-03-01 | Aesculap AG & Co. KG | Resorbable polyester |
| JP2001517613A (en) * | 1997-09-22 | 2001-10-09 | バフォード バイオメディカル， インコーポレイテッド | Inorganic-polymer conjugates for controlled release of drug-containing compounds |
| AU755049B2 (en) * | 1997-09-09 | 2002-12-05 | Robert Edward Day | Chemical supplementation of bone |
| US6894027B2 (en) | 2000-07-19 | 2005-05-17 | The Board Of Regents, The University Of Texas System | Stimulation of bone growth with thrombin peptide derivatives |
| JP2005161062A (en) * | 1995-02-10 | 2005-06-23 | Purdue Res Found | Bone transplantation composition |
-
1991
- 1991-05-30 JP JP3153805A patent/JPH04279520A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2281709B (en) * | 1993-09-14 | 1998-04-08 | Fujitsu Ltd | Biodegradable resin moulded article |
| GB2285924A (en) * | 1994-01-29 | 1995-08-02 | Cho Se Hyun | Polymer beads containing antibiotics for use in orthopaedic surgery |
| GB2285924B (en) * | 1994-01-29 | 1998-01-28 | Cho Se Hyun | Polymer beads containing antibiotics for use in orthopaedic surgery |
| JP2005161062A (en) * | 1995-02-10 | 2005-06-23 | Purdue Res Found | Bone transplantation composition |
| JPH10229A (en) * | 1996-04-19 | 1998-01-06 | Dainippon Ink & Chem Inc | Slow-releasable bioactive and bioabsorbable organic-inorganic compounded material having bone inducing or bone conducting function |
| JP2001515761A (en) * | 1997-09-09 | 2001-09-25 | ザ・ユニヴァーシティ・オヴ・ウェスタン・オーストラリア | Chemical replenishment of bone |
| AU755049B2 (en) * | 1997-09-09 | 2002-12-05 | Robert Edward Day | Chemical supplementation of bone |
| WO1999012554A1 (en) * | 1997-09-09 | 1999-03-18 | The University Of Western Australia | Chemical supplementation of bone |
| JP2001517613A (en) * | 1997-09-22 | 2001-10-09 | バフォード バイオメディカル， インコーポレイテッド | Inorganic-polymer conjugates for controlled release of drug-containing compounds |
| EP0911355A3 (en) * | 1997-10-21 | 2000-03-01 | Aesculap AG & Co. KG | Resorbable polyester |
| US6894027B2 (en) | 2000-07-19 | 2005-05-17 | The Board Of Regents, The University Of Texas System | Stimulation of bone growth with thrombin peptide derivatives |
| US6914050B2 (en) | 2000-07-19 | 2005-07-05 | The Board Of Regents, The University Of Texas System | Stimulation of bone growth with thrombin peptide derivatives |
| US7304035B2 (en) | 2000-07-19 | 2007-12-04 | Orthologic Corp. | Stimulation of bone growth with thrombin peptide derivatives |
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