JPS62289518A - Composition containing stably blended minocycline - Google Patents
Composition containing stably blended minocyclineInfo
- Publication number
- JPS62289518A JPS62289518A JP12248886A JP12248886A JPS62289518A JP S62289518 A JPS62289518 A JP S62289518A JP 12248886 A JP12248886 A JP 12248886A JP 12248886 A JP12248886 A JP 12248886A JP S62289518 A JPS62289518 A JP S62289518A
- Authority
- JP
- Japan
- Prior art keywords
- minocycline
- composition
- water
- amount
- film
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 229960004023 minocycline Drugs 0.000 title claims abstract description 30
- 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 title claims 3
- 150000002681 magnesium compounds Chemical class 0.000 claims abstract description 13
- 239000000126 substance Substances 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000009472 formulation Methods 0.000 claims description 5
- 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 abstract description 27
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 9
- 229910001629 magnesium chloride Inorganic materials 0.000 abstract description 9
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 abstract description 5
- 239000004098 Tetracycline Substances 0.000 abstract description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 abstract description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 abstract description 5
- 238000002156 mixing Methods 0.000 abstract description 5
- 235000019364 tetracycline Nutrition 0.000 abstract description 5
- 150000003522 tetracyclines Chemical class 0.000 abstract description 5
- 229920000642 polymer Polymers 0.000 abstract description 4
- 229960002180 tetracycline Drugs 0.000 abstract description 4
- 229930101283 tetracycline Natural products 0.000 abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract description 2
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 230000001747 exhibiting effect Effects 0.000 abstract description 2
- 230000003239 periodontal effect Effects 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 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 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 229960002421 minocycline hydrochloride Drugs 0.000 description 9
- 235000011147 magnesium chloride Nutrition 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- -1 minocycline Chemical class 0.000 description 5
- 208000028169 periodontal disease Diseases 0.000 description 5
- 229940072172 tetracycline antibiotic Drugs 0.000 description 5
- 229920003169 water-soluble polymer Polymers 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000004100 Oxytetracycline Substances 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- UYXTWWCETRIEDR-UHFFFAOYSA-N Tributyrin Chemical compound CCCC(=O)OCC(OC(=O)CCC)COC(=O)CCC UYXTWWCETRIEDR-UHFFFAOYSA-N 0.000 description 2
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000001087 glyceryl triacetate Substances 0.000 description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 description 2
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 2
- 239000011654 magnesium acetate Substances 0.000 description 2
- 235000011285 magnesium acetate Nutrition 0.000 description 2
- 229940069446 magnesium acetate Drugs 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 2
- 229960000625 oxytetracycline Drugs 0.000 description 2
- 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 description 2
- 235000019366 oxytetracycline Nutrition 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 235000019423 pullulan Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 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 description 2
- 229960002622 triacetin Drugs 0.000 description 2
- 230000002747 voluntary effect Effects 0.000 description 2
- 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 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- KJDRSWPQXHESDQ-UHFFFAOYSA-N 1,4-dichlorobutane Chemical compound ClCCCCCl KJDRSWPQXHESDQ-UHFFFAOYSA-N 0.000 description 1
- RQDWELNLPMBYMA-UHFFFAOYSA-N 3,4-dihydroxyhexane-2,5-dione Chemical compound CC(=O)C(O)C(O)C(C)=O RQDWELNLPMBYMA-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000004099 Chlortetracycline Substances 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- YUXIBTJKHLUKBD-UHFFFAOYSA-N Dibutyl succinate Chemical compound CCCCOC(=O)CCC(=O)OCCCC YUXIBTJKHLUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008431 aliphatic amides Chemical class 0.000 description 1
- 150000001341 alkaline earth metal compounds Chemical class 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 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 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 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 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- 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 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960002380 dibutyl phthalate Drugs 0.000 description 1
- 229960002097 dibutylsuccinate Drugs 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 229940051250 hexylene glycol Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229960001708 magnesium carbonate Drugs 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 239000001755 magnesium gluconate Substances 0.000 description 1
- 229960003035 magnesium gluconate Drugs 0.000 description 1
- 235000015778 magnesium gluconate Nutrition 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 229960003390 magnesium sulfate Drugs 0.000 description 1
- IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960004989 tetracycline hydrochloride Drugs 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
３、発明の詳細な説明
発明の分野
本発明はテトラサイクリン系抗生物質の一種であるミノ
サイクリンを安定に配合したフィルム状またはシート状
の、特に歯周疾患および粘膜疾患に有用な組成物に関す
る。Detailed Description of the Invention 3. Detailed Description of the Invention Field of the Invention The present invention provides a film or sheet containing a stable combination of minocycline, a type of tetracycline antibiotic, which is particularly useful for periodontal diseases and mucosal diseases. composition.
発明の背景
テトラサイクリン系抗生物質にはテトラサイクリンをは
じめ、ミノサイクリンなど数種の類縁化合物が包含され
るが、これらはいずれも非蕾に不安定な物質であり、従
来からテトラサイクリン系抗生物質を医薬組成物へ安定
に配合するための検討が種々なされている。BACKGROUND OF THE INVENTION Tetracycline antibiotics include tetracycline and several related compounds such as minocycline, but all of these are unstable substances, and it has traditionally been difficult to use tetracycline antibiotics in pharmaceutical compositions. Various studies have been carried out to stably blend it into .
例えば、特開昭５２−９０６１６号は２−ピロリドン水
溶液中でマグネシウム化合物のようなアルカリ土類金属
化合物を用いてオキシテトラサイクリン、ドキシサイク
リン、テトラサイクリン、クロルテトラサイクリンまた
はそれらの塩をキレート化することにより、これらのテ
トラサイクリン系抗生物質の安定化を図った注射用の水
溶液を開示している。また、特開昭５３−９４０２８号
はアルカリ土類金属イオン、ポリビニルピロリドンおよ
び脂肪族アミドを配合し、ｐＨ５，０〜７．５にするこ
とにより、オキシテトラサイクリンの安定化を図った医
薬組成物を開示している。さらに、米国特許第３３３５
０５５号はテトラサイクリンをマグネシウムイオンおよ
びイソニコチン酸アミドなどのピリジン誘導体で安定化
する方法を開示している。For example, JP-A-52-90616 discloses that oxytetracycline, doxycycline, tetracycline, chlortetracycline, or their salts are chelated using an alkaline earth metal compound such as a magnesium compound in an aqueous 2-pyrrolidone solution. Discloses an injectable aqueous solution containing a stabilized tetracycline antibiotic. Furthermore, JP-A No. 53-94028 discloses a pharmaceutical composition in which oxytetracycline is stabilized by blending alkaline earth metal ions, polyvinylpyrrolidone, and an aliphatic amide to adjust the pH to 5.0 to 7.5. Disclosed. Additionally, U.S. Patent No. 3335
No. 055 discloses a method for stabilizing tetracyclines with magnesium ions and pyridine derivatives such as isonicotinamide.
しかしながら、テトラサイクリン系抗生物質の１種であ
るミノサイクリンについては、従来その安定化を検討し
た例は見当らない。However, with respect to minocycline, which is a type of tetracycline antibiotic, there have been no studies on the stabilization of minocycline.
ま１こ、最近にいたり、テトラサイクリンを含む歯周疾
患治療用薬物と水溶性高分子物質とからなるフィルム状
もしくはシート状の歯周疾患治療用製剤が患部に直接投
与でき、その効果も長期間にわたり発揮し得るものであ
ることが報告されている（特開昭５９−２２２４０６号
）。しかし、ミノサイクリンは、その安定化が困難なこ
とから、そのような製剤とすることが困難であった。Recently, a film or sheet-like preparation for the treatment of periodontal disease consisting of a drug containing tetracycline and a water-soluble polymer substance can be administered directly to the affected area, and its effects remain for a long time. It has been reported that this effect can be achieved over a long period of time (Japanese Patent Laid-Open No. 59-222406). However, since minocycline is difficult to stabilize, it has been difficult to formulate such a formulation.
フィルム状またはシート状製剤は、患部へ直接適用でき
、持続的効果を発揮するなど種々の利点を有するもので
あり、ミノサイクリンについても、フィルム状またはシ
ート状に製剤化することが要望されている。Film-like or sheet-like preparations have various advantages, such as being able to be applied directly to the affected area and exhibiting sustained effects, and there is a demand for minocycline to be formulated into film-like or sheet-like forms as well.
本発明者らは先に、マグネシウム化合物を含有する多価
アルコールを基剤とすることにより、ミノサイクリンが
安定化されることを見出し、また、前記組成物に加え、
水溶性高分子物質、ある種のメタアクリル酸系コポリマ
ーおよびその可溶化剤を適宜組み合わせ配合した組成物
が、ミノサイクリンの安定性を損なうことなく、長時間
投与部位に滞留し、効果が持続的なものであることを見
出し、これらの点についてはすてに特許出願をした（特
願昭５９−２５３７８８号および特願昭６０〜２６３３
１８号）。その後、さらにミノサイクリンを安定に配合
したフィルム状またはシート状組成物を得るべく鋭意研
究を重ねた。その結果、マグネシウム化合物を常打する
水溶性高分子物質を基剤とすることにより、ミノサイク
リンが特異的に安定化され、かつ、フィルム状またはシ
ート状の組成物が得られ、なおかつ歯周医徹および粘膜
疾患の治療に有効であることを見出し、本発明を完成す
るにいたつｆこ。The present inventors have previously discovered that minocycline is stabilized by using a polyhydric alcohol containing a magnesium compound as a base, and in addition to the above composition,
A composition containing an appropriate combination of a water-soluble polymer substance, a type of methacrylic acid copolymer, and its solubilizer allows minocycline to remain at the administration site for a long time without impairing its stability, resulting in a sustained effect. He discovered that these points were true and filed patent applications for these points (Japanese Patent Application No. 59-253788 and Japanese Patent Application No. 60-2633).
No. 18). After that, they conducted extensive research in order to obtain a film or sheet composition containing minocycline in a stable manner. As a result, minocycline was specifically stabilized by using a water-soluble polymeric substance containing a magnesium compound as a base, and a composition in the form of a film or sheet was obtained. It was discovered that it was effective in treating diseases, and led to the completion of the present invention.
発明の開示
本発明は、水溶性高分子物質と、ミノサイクリンまたは
その医薬上許容される塩およびマグネシウム化合物を配
合したフィルム状またはシート状の製剤形を有すること
を特徴とするミノサイクリンを安定に配合した組成物、
ことに、歯周疾患および粘膜次像治療用組成物を提供す
るものである。DISCLOSURE OF THE INVENTION The present invention provides a stable blend of minocycline, which is characterized in that it has a film-like or sheet-like formulation, which contains a water-soluble polymeric substance, minocycline or a pharmaceutically acceptable salt thereof, and a magnesium compound. Composition,
In particular, the present invention provides a composition for treating periodontal diseases and mucosal disorders.
本発明のフィルム状またはシート状に調製されたミノサ
イクリンを安定に配合した組成物は、粘膜疾患部位また
は歯周疾患部位に直接適用することらでき、その効果も
長期間にわたり発揮し得ろものである。The film-like or sheet-like composition of the present invention stably containing minocycline can be applied directly to mucosal disease sites or periodontal disease sites, and its effects can be exerted over a long period of time. .
特に、本発明の組成物を疾患部位に直接適用した場合、
これまで経口的にミノサイクリンを投与した時に見られ
た全身的な副作用、例えば、消化器系副作用である食欲
不振、悪心、下痢等の症状の発現、血小板減少、好酸球
増多等の生化学的副作用あるいは菌交代症等の発現が極
力防止されたものとなる。In particular, when the composition of the invention is applied directly to the diseased area,
Systemic side effects that have been observed so far when minocycline is administered orally, such as gastrointestinal side effects such as anorexia, nausea, and diarrhea, and biochemical symptoms such as thrombocytopenia and eosinophilia. The occurrence of side effects or bacterial alteration will be prevented as much as possible.
本発明の組成物中に配合するミノサイクリンは遊離のも
のでも、！二とえば、塩酸塩、硫酸塩、トリクロル酢酸
塩などの医薬上許容される酸付加塩いずれでもよく、組
成物全体に対して０．１−１０．０重量％の範囲で配合
することができる。Even if the minocycline incorporated in the composition of the present invention is free,! For example, any pharmaceutically acceptable acid addition salt such as hydrochloride, sulfate, trichloroacetate, etc. may be used, and it can be blended in an amount of 0.1-10.0% by weight based on the entire composition. .
本発明の組成物において用いるマグネシウム化合物とし
ては、医薬上許容されるものであればいずれでもよく、
例えば、塩化マグネシウム、酢酸マグネシウム、硫酸マ
グネシウム、炭酸マグネシウム、グルコン酸マグネシウ
ムおよびこれらの水和物などが挙げられるが、特に塩化
マグネシウムが好ましい。一般に、マグネシウム化合物
は組成物全１に対して２０重量％までの範囲で配合する
ミノサイクリンの０．１〜１０重量倍を用いろことによ
り、ミノサイクリンの良好な安定化が図れる。The magnesium compound used in the composition of the present invention may be any pharmaceutically acceptable compound,
Examples include magnesium chloride, magnesium acetate, magnesium sulfate, magnesium carbonate, magnesium gluconate, and hydrates thereof, with magnesium chloride being particularly preferred. In general, minocycline can be well stabilized by using a magnesium compound in an amount of 0.1 to 10 times the weight of minocycline, which is blended in an amount of up to 20% by weight based on the total composition.
用いる水溶性高分子物質としては、メチルセルロース、
ヒドロキンエチルセルロース、ヒドロキシプロピルセル
ロース、ヒドロキンプロピルメチルセルロース、カルボ
キシメヂルセ７レロース塩、カルボキシメチルエチルセ
ルロース、ヒドロキシプロピルメチルセルロースフタレ
ート、ヒドロキンプロピルメチルセルロース・アセテー
ト・サクシネートなどの水溶性セルロース誘導体；カラ
ギーナン、キサンタンガム、デキストリン、プルラン、
キヂン、キトサンなどの天七大高分子化合物：メタアク
リル酸誘導体コポリマー、ポリアクリル酸およびその屯
、ポリビニルアルコール、ポリビニルピロリドンなどの
水溶性ビニル重合体などが挙げられ、これらは単独もし
くは２種以上組み合わせて配合することができる。とり
わけ、ミノサイクリンの安定化ならびに徐放効果のため
にはヒドロキシプロピルセルロースが好ましい。The water-soluble polymer substances used include methylcellulose,
Water-soluble cellulose derivatives such as hydroquine ethyl cellulose, hydroxypropyl cellulose, hydroquine propyl methyl cellulose, carboxymedylce 7 reulose salt, carboxymethyl ethyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroquine propyl methyl cellulose acetate succinate; carrageenan, xanthan gum, dextrin , pullulan,
Tenshichi University polymer compounds such as chijin and chitosan: include methacrylic acid derivative copolymers, polyacrylic acid and its salts, water-soluble vinyl polymers such as polyvinyl alcohol and polyvinylpyrrolidone, and these may be used alone or in combination of two or more. It can be blended with In particular, hydroxypropylcellulose is preferred for stabilization and sustained release effects of minocycline.
この水溶性高分子物質は、ミノサイクリンおよびマグネ
シウム化合物から規定されるが組成物全量に対して７０
．０〜９９．５重量％の範囲で配合する。This water-soluble polymeric substance is defined as minocycline and a magnesium compound, and is 70% of the total amount of the composition.
．． It is blended in a range of 0 to 99.5% by weight.
本発明の組成物は、フィルム状またはシート状に調製し
て投与される。フィルムまたはシートの形状は、その大
きさならびに厚さにおいてミノサイクリンの用量、投与
される部位お上び病聾等により変化し、特に限定される
ものではなく、適宜の形状にすることができる。The composition of the present invention is prepared and administered in the form of a film or sheet. The shape of the film or sheet varies in size and thickness depending on the dose of minocycline, the site to be administered, the degree of deafness, etc., and is not particularly limited and can be made into any suitable shape.
しかしなが４、一般的には本発明の組成物は歯周疾患あ
るいは粘膜疾患の治療を目的とするものであるため、長
さ５〜７ ｍｍ、巾０．５〜７０ｍｍ。However, since the composition of the present invention is generally intended for the treatment of periodontal diseases or mucosal diseases, the composition has a length of 5 to 7 mm and a width of 0.5 to 70 mm.
厚さ０．０１〜０ 、５ ｍｍ程度にするのが望ましい
。It is desirable that the thickness be about 0.01 to 0.5 mm.
本発明の組成物には、さらに必要に応じて可塑剤が配合
される。可塑剤としては、グリセリン、エチレングリコ
ール、ジエチレングリコール、プロピレングリコール、
ジプロピレングリコール、ヘキシレングリコール、１．
５−ベンタンジオール、１．３−ブチレングリコールな
どの多価アルコールおよびこれらの２種以上の混合物：
トリアセチン、トリブチリン、ジアセチルエチレングリ
コール、セバシン酸ジエチル、フタル酸ジエチル、フタ
ル酸ジブチル、アジピン酸ジイソプロピル、コハク酸ジ
ブチルなどの低級多価アルコールと低級脂肪酸のエステ
ルおよび低級アルコールとジカルボン酸のエステルおよ
びこれらの２種以上の混合物：および油脂等が挙げられ
る。これらの配合量は、用いる水溶性高分子物質の種類
によって異なるが、通常、組成物全量に対して２０重量
％までにするのが好ましい。可塑剤の添加により、本発
明の組成物は柔軟なものとなり、投与もより容易になる
。The composition of the present invention may further contain a plasticizer, if necessary. Plasticizers include glycerin, ethylene glycol, diethylene glycol, propylene glycol,
Dipropylene glycol, hexylene glycol, 1.
Polyhydric alcohols such as 5-bentanediol and 1,3-butylene glycol, and mixtures of two or more thereof:
Esters of lower polyhydric alcohols and lower fatty acids, such as triacetin, tributyrin, diacetyl ethylene glycol, diethyl sebacate, diethyl phthalate, dibutyl phthalate, diisopropyl adipate, dibutyl succinate, and esters of lower alcohols and dicarboxylic acids, and 2 of these. Mixtures of more than one species: and fats and oils. The amount of these compounds varies depending on the type of water-soluble polymer substance used, but it is usually preferably up to 20% by weight based on the total amount of the composition. The addition of plasticizers makes the compositions of the invention softer and easier to administer.
さらに、本発明の組成物には、着色剤、矯味矯臭剤等を
本発明の効果を損なわない範囲で添加してもよい。Furthermore, coloring agents, flavoring agents, and the like may be added to the composition of the present invention to the extent that they do not impair the effects of the present invention.
本発明の組成物は、通常の製剤化技術に従って調製する
ことができる。Compositions of the invention can be prepared according to conventional formulation techniques.
例えば、マグネシウム化合物および水溶性高分子物質を
有機溶媒に分散、溶解し、これにミノサイクリンまたは
その医薬上許容される塩を加え、均一に混合した後、常
法により、フィルム製造装置を用いるか、またはガラス
板、テフロンシート上等に流延し、風乾し、成形するよ
うな湿潤法により所望の形状および厚さを有するフィル
ム状またはシート状の組成物を得ろことができろ。For example, a magnesium compound and a water-soluble polymeric substance are dispersed and dissolved in an organic solvent, minocycline or a pharmaceutically acceptable salt thereof is added thereto, mixed uniformly, and then a film manufacturing apparatus is used in a conventional manner. Alternatively, a film or sheet composition having a desired shape and thickness can be obtained by a wet method such as casting on a glass plate, Teflon sheet, etc., air drying, and molding.
用いられる溶媒としては、組成物の各成分に対し不活性
なものであるならばいずれでもよく、例えば、水；メタ
ノール、エタノール、イソプロパツールなどのアルコー
ル系溶媒、アセトン、メチルエチルケトンなどのケトン
系溶媒；塩化ブチレン、ジクロロエタン、１．１．１−
トリクロロエタンなどの塩素化炭化水素系溶媒などが挙
げられ、単独でし、２種以上併用して用いてもよい。Any solvent may be used as long as it is inert to each component of the composition, such as water; alcohol solvents such as methanol, ethanol, and isopropanol, and ketone solvents such as acetone and methyl ethyl ketone. ; Butylene chloride, dichloroethane, 1.1.1-
Examples include chlorinated hydrocarbon solvents such as trichloroethane, which may be used alone or in combination of two or more.
さらに、無溶媒下で各成分を粉体混合した後、圧縮成形
する方法によっても所望の組成物を得ることができる。Furthermore, a desired composition can also be obtained by mixing the components in powder form without a solvent and then compression molding the mixture.
実施例 つぎに実施例を挙げて本発明をさらに詳しく説明する。Example Next, the present invention will be explained in more detail with reference to Examples.
実施例１
成分 重量％
ミノサイクリン塩酸塩 ２．０塩化マグ
ネシウム ２．０ヒドロキシプロ
ピルセルロース ９６０成分全量の３０重量倍のエ
タノールに塩化マグネシウムおよびヒドロキシプロピル
セルロースを分散、溶解し、これにミノサイクリン塩酸
塩を添加し、均一に混合した後、常法により厚さ０，１
２ｍｍのフィルム状組成物を得ろ。Example 1 Ingredients Weight % Minocycline hydrochloride 2.0 Magnesium chloride 2.0 Hydroxypropyl cellulose 960 Magnesium chloride and hydroxypropyl cellulose were dispersed and dissolved in 30 times the weight of the total amount of the ingredients, and minocycline hydrochloride was added thereto. , After uniformly mixing, the thickness is 0.1 by the usual method.
Obtain a 2 mm film composition.
実施例２
成分 重量％
ミノサイクリン塩酸塩 ２．０塩化マグ
ネシウム ２０ポリビニルピロリド
ン ９６．０成分全量の１５重里倍のエタ
ノールを用い、実施例１と同様にして厚さ０．２０＋ｎ
ｍのフィルム状組成物を得る。Example 2 Ingredients Weight % Minocycline hydrochloride 2.0 Magnesium chloride 20 Polyvinylpyrrolidone 96.0 Using ethanol in an amount of 15 times the total amount of the ingredients, the thickness was 0.20+n in the same manner as in Example 1.
A film composition of m is obtained.
実施例３
成分 重量％
ミノサイクリン塩酸塩 ２．０塩化マグ
ネシウム ２．０グリセリン
１０．０ポリビニルピロリドン
８６．０成分全量の５重量倍のエタノールを
用い、実施例１と同様にして厚さ０．４０＋ｕｍのフィ
ルム状組成物を得る。Example 3 Ingredients Weight % Minocycline hydrochloride 2.0 Magnesium chloride 2.0 Glycerin
10.0 Polyvinylpyrrolidone
A film composition having a thickness of 0.40+ um is obtained in the same manner as in Example 1 using ethanol in an amount 5 times the weight of the total amount of the 86.0 components.
実施例４
成分 重量％
ミノサイクリン塩酸塩 １．０酢酸マグ
ネシウム １．０ポリビニルピロリ
ドン ９８．０成分全量の１５重量倍の塩
化メチレン−エタノール（１：４）混液を用い、実施例
１と同様にして厚さ０．０２ｍｍのフィルム状組成物を
得る。Example 4 Ingredients Weight % Minocycline hydrochloride 1.0 Magnesium acetate 1.0 Polyvinylpyrrolidone 98.0 A mixture of methylene chloride and ethanol (1:4) in an amount 15 times the total amount of the components by weight was used, and the thickness was increased in the same manner as in Example 1. A film composition with a diameter of 0.02 mm is obtained.
実施例５
成分 重量％
ミノサイクリン塩酸塩 ２．０硫酸マグ
ネシウム ５．０ポリビニルピロ
リドン ９３．０成分全量の２０重量倍
の塩化メチレン−エタノール（１：５）混液を用い、実
施例１と同様にして厚さ０．１５ｍｍのフィルム状組成
物を得る。Example 5 Ingredients Weight % Minocycline hydrochloride 2.0 Magnesium sulfate 5.0 Polyvinylpyrrolidone 93.0 A mixture of methylene chloride and ethanol (1:5) in an amount 20 times the total amount of the components by weight was used, and the thickness was increased in the same manner as in Example 1. A film composition with a diameter of 0.15 mm is obtained.
実施例６
成分 重量％
ミノサイクリン塩酸塩 ０．５塩化マグ
ネシウム ・０．５プルラン
９９．０成分全量の２０重量倍
の３０％エタノール溶液を用い、実施例１と同様にして
厚さ０．３２ｎ＋ｎ＋のフィルム状組成物を得る。Example 6 Ingredients Weight % Minocycline hydrochloride 0.5 Magnesium chloride ・0.5 Pullulan
A film composition having a thickness of 0.32n+n+ is obtained in the same manner as in Example 1 using a 30% ethanol solution that is 20 times the total weight of the 99.0 components.
ミノサイクリンの安定化試験
以下の第１表に示す処方の種々のミノサイクリン塩酸塩
およびテトラサイクリン塩酸塩配合フィルム状組成物を
調製し、調製直後と４０℃で１ケ月保存後のそれら抗生
物質の力価を日本抗生物質基準解説（１９８２年版）に
準じて測定し、配合当初の力価に対する力価残存率（％
）を算出した。結果を第１表に示す。Minocycline stabilization test Various film compositions containing minocycline hydrochloride and tetracycline hydrochloride with the formulations shown in Table 1 below were prepared, and the potency of these antibiotics was measured immediately after preparation and after storage at 40°C for one month. Measured according to the Japanese Antibiotic Standard Explanation (1982 edition), and the residual titer rate (%) of the initial titer was determined.
) was calculated. The results are shown in Table 1.
第１表に示すごとく、マグネシウム化合物と水溶性高分
子物質の組み合わせはミノサイクリンのみを特異的に安
定化する。As shown in Table 1, the combination of a magnesium compound and a water-soluble polymer substance specifically stabilizes only minocycline.
特許出願人 サンスター株式会社 ばか１名代 理 人
弁理士 青白 葆 ほか２名手続補正書（自発）
特許庁長 宮殿 昭和 年 月 日１、事
件の表示
昭和 ６１年特許願第 １２２４８８ 号３、 補正
をする者
事件との関係 特許出願人
住所 大阪府高槻市朝日町３番１号
名称サンスター株式会社
（ばか１名）
４、代理人
５、 補正命令の日付
自 発
６、補正の内容
（１）明細書第６頁下から２行、「メタアクリル酸誘導
体・・・」の前に下記の文言を挿入する。Patent Applicant: Sunstar Co., Ltd., 1 idiot, 1 attorney, Patent Attorneys: Qingbai, 葆, and 2 others Procedural amendment (voluntary) Commissioner of the Japan Patent Office Palace, Showa year, month, day 1, case description Showa 61 Patent Application No. 122488 No. 3, amendment Relationship with the case of a person who makes a patent application Patent applicant Address: 3-1 Asahicho, Takatsuki City, Osaka Name: Sunstar Co., Ltd. (1 idiot) 4. Agent: 5. Date of amendment order: Voluntary statement: 6. Contents of amendment (1) ) The following words should be inserted in the second line from the bottom of page 6 of the specification before "methacrylic acid derivative...".
「アミノアルキルメタアクリレートコポリマーＲ８１ア
ミノアルキルメタアクリレートコポリマーＥ１メタアク
リル酸コポリマーＬなどの」（２）同書第１２頁下から
４行と３行の間に下記の実施例７を挿入する。"Aminoalkyl methacrylate copolymer R81 Aminoalkyl methacrylate copolymer E1 Methacrylic acid copolymer L etc." (2) The following Example 7 is inserted between lines 4 and 3 from the bottom of page 12 of the same book.
「実施例７
成分 重量％
ミノサイクリン塩酸塩 ２．０塩化マグ
ネシウム ２．０トリアセチン
！５．０アミノアルキルメタアク
リレート ８１．０コポリマーＲｓ
成分全量の３０重量倍の塩化メチレン−エタノール（１
：４）混液を用い実施例ｉと同様にして厚さ０．２０ｘ
ｘのフィルム状組成物を得る。」（３）同書第１４頁の
第１表を別紙のとおり差し替えろ。Example 7 Ingredients Weight % Minocycline hydrochloride 2.0 Magnesium chloride 2.0 Triacetin
! 5.0 Aminoalkyl methacrylate 81.0 Copolymer Rs Methylene chloride-ethanol (1
:4) Using the mixed solution, the thickness was 0.20x in the same manner as in Example i.
A film composition of x is obtained. (3) Replace Table 1 on page 14 of the same book as shown in the attached sheet.
以上that's all
Claims (1)
医薬上許容される塩およびマグネシウム化合物を配合し
たフィルム状またはシート状の製剤形を有することを特
徴とするミノサイクリンを安定に配合した組成物。(1) A composition stably containing minocycline, characterized in that it has a film-like or sheet-like formulation, which contains a water-soluble polymeric substance, minocycline or a pharmaceutically acceptable salt thereof, and a magnesium compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61122488A JPH0729930B2 (en) | 1986-05-27 | 1986-05-27 | Composition containing minocycline in a stable manner |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61122488A JPH0729930B2 (en) | 1986-05-27 | 1986-05-27 | Composition containing minocycline in a stable manner |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62289518A true JPS62289518A (en) | 1987-12-16 |
| JPH0729930B2 JPH0729930B2 (en) | 1995-04-05 |
Family
ID=14837085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61122488A Expired - Fee Related JPH0729930B2 (en) | 1986-05-27 | 1986-05-27 | Composition containing minocycline in a stable manner |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0729930B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62298521A (en) * | 1986-06-18 | 1987-12-25 | Advance Co Ltd | Anti-periodontal substance |
| JP2004534030A (en) * | 2001-05-14 | 2004-11-11 | スリーエム イノベイティブ プロパティズ カンパニー | System for delivering cosmetics and pharmaceuticals |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11426351B2 (en) | 2019-12-26 | 2022-08-30 | Sunstar Inc. | Process for producing a pharmaceutical composition containing micro particles |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6412728A (en) * | 1987-07-07 | 1989-01-17 | Fujitsu Ltd | Echo canceller |
-
1986
- 1986-05-27 JP JP61122488A patent/JPH0729930B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6412728A (en) * | 1987-07-07 | 1989-01-17 | Fujitsu Ltd | Echo canceller |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62298521A (en) * | 1986-06-18 | 1987-12-25 | Advance Co Ltd | Anti-periodontal substance |
| JP2004534030A (en) * | 2001-05-14 | 2004-11-11 | スリーエム イノベイティブ プロパティズ カンパニー | System for delivering cosmetics and pharmaceuticals |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0729930B2 (en) | 1995-04-05 |
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