HRP20040893A2 - Low dose liquid entecavir formulations and use - Google Patents
Low dose liquid entecavir formulations and use Download PDFInfo
- Publication number
- HRP20040893A2 HRP20040893A2 HR20040893A HRP20040893A HRP20040893A2 HR P20040893 A2 HRP20040893 A2 HR P20040893A2 HR 20040893 A HR20040893 A HR 20040893A HR P20040893 A HRP20040893 A HR P20040893A HR P20040893 A2 HRP20040893 A2 HR P20040893A2
- Authority
- HR
- Croatia
- Prior art keywords
- entecavir
- amount
- present
- formulation
- constitutive
- Prior art date
Links
- 229960000980 entecavir Drugs 0.000 title claims description 103
- 239000000203 mixture Substances 0.000 title claims description 59
- 238000009472 formulation Methods 0.000 title claims description 56
- 239000007788 liquid Substances 0.000 title claims description 33
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 title claims 32
- 239000000843 powder Substances 0.000 claims description 68
- 239000012669 liquid formulation Substances 0.000 claims description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims description 32
- 235000003599 food sweetener Nutrition 0.000 claims description 27
- 239000003765 sweetening agent Substances 0.000 claims description 27
- 239000003755 preservative agent Substances 0.000 claims description 25
- 239000006172 buffering agent Substances 0.000 claims description 24
- 235000019264 food flavour enhancer Nutrition 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 15
- 208000002672 hepatitis B Diseases 0.000 claims description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000004097 EU approved flavor enhancer Substances 0.000 claims description 9
- 230000002335 preservative effect Effects 0.000 claims description 9
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 8
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 8
- 235000019640 taste Nutrition 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- GBBJCSTXCAQSSJ-JVZYCSMKSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 GBBJCSTXCAQSSJ-JVZYCSMKSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 108010021119 Trichosanthin Proteins 0.000 claims description 6
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 6
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 claims description 6
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims description 6
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 4
- RLAHNGKRJJEIJL-RFZPGFLSSA-N [(2r,4r)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1CO[C@@H](CO)O1 RLAHNGKRJJEIJL-RFZPGFLSSA-N 0.000 claims description 4
- 239000008351 acetate buffer Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000000470 constituent Substances 0.000 claims description 4
- 235000010449 maltitol Nutrition 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 4
- 229960002216 methylparaben Drugs 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 235000010241 potassium sorbate Nutrition 0.000 claims description 4
- 239000004302 potassium sorbate Substances 0.000 claims description 4
- 229940069338 potassium sorbate Drugs 0.000 claims description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 4
- 229960003415 propylparaben Drugs 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 229960003885 sodium benzoate Drugs 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 239000000811 xylitol Substances 0.000 claims description 4
- 235000010447 xylitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 4
- 229960002675 xylitol Drugs 0.000 claims description 4
- CKTSBUTUHBMZGZ-CHKWXVPMSA-N 4-amino-1-[(2s,4r,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 CKTSBUTUHBMZGZ-CHKWXVPMSA-N 0.000 claims description 3
- HSBKFSPNDWWPSL-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1C=C[C@H](CO)O1 HSBKFSPNDWWPSL-VDTYLAMSSA-N 0.000 claims description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims description 3
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 claims description 3
- 229960004748 abacavir Drugs 0.000 claims description 3
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 3
- 229960001997 adefovir Drugs 0.000 claims description 3
- 229960003205 adefovir dipivoxil Drugs 0.000 claims description 3
- 229960002656 didanosine Drugs 0.000 claims description 3
- 229960000366 emtricitabine Drugs 0.000 claims description 3
- 229960004396 famciclovir Drugs 0.000 claims description 3
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 230000002519 immonomodulatory effect Effects 0.000 claims description 3
- 239000002955 immunomodulating agent Substances 0.000 claims description 3
- 229940121354 immunomodulator Drugs 0.000 claims description 3
- 229960001627 lamivudine Drugs 0.000 claims description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 3
- 239000000845 maltitol Substances 0.000 claims description 3
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical group OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 3
- 229940035436 maltitol Drugs 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000002777 nucleoside Substances 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 229960005311 telbivudine Drugs 0.000 claims description 3
- 229960004556 tenofovir Drugs 0.000 claims description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 230000009385 viral infection Effects 0.000 claims 2
- 229960001855 mannitol Drugs 0.000 claims 1
- 229960002920 sorbitol Drugs 0.000 claims 1
- 229960004793 sucrose Drugs 0.000 claims 1
- -1 surcose Substances 0.000 claims 1
- QDGZDCVAUDNJFG-FXQIFTODSA-N entecavir (anhydrous) Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)C1=C QDGZDCVAUDNJFG-FXQIFTODSA-N 0.000 description 71
- 241000700721 Hepatitis B virus Species 0.000 description 5
- 230000000840 anti-viral effect Effects 0.000 description 5
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 4
- 235000019658 bitter taste Nutrition 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 238000012959 renal replacement therapy Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 239000007857 degradation product Substances 0.000 description 3
- 241000167854 Bourreria succulenta Species 0.000 description 2
- 235000016623 Fragaria vesca Nutrition 0.000 description 2
- 240000009088 Fragaria x ananassa Species 0.000 description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 240000008790 Musa x paradisiaca Species 0.000 description 2
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 2
- 235000000556 Paullinia cupana Nutrition 0.000 description 2
- 240000003444 Paullinia cupana Species 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 229940067596 butylparaben Drugs 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000007501 Thymosin Human genes 0.000 description 1
- 108010046075 Thymosin Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 1
- 229960005164 acesulfame Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
- 229960005486 vaccine Drugs 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/12—Antivirals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37067402P | 2002-04-08 | 2002-04-08 | |
| PCT/US2003/010371 WO2003086367A1 (en) | 2002-04-08 | 2003-04-03 | Low dose liquid entecavir formulations and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20040893A2 true HRP20040893A2 (en) | 2005-02-28 |
Family
ID=29250568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20040893A HRP20040893A2 (en) | 2002-04-08 | 2004-09-29 | Low dose liquid entecavir formulations and use |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US20030190334A1 (es) |
| EP (1) | EP1492510A4 (es) |
| JP (1) | JP2005528389A (es) |
| KR (1) | KR20040099403A (es) |
| CN (1) | CN1319517C (es) |
| AR (1) | AR039388A1 (es) |
| AU (1) | AU2003226259A1 (es) |
| BR (1) | BR0309057A (es) |
| CA (1) | CA2481092A1 (es) |
| EA (1) | EA008102B1 (es) |
| EC (1) | ECSP045349A (es) |
| HR (1) | HRP20040893A2 (es) |
| MX (1) | MXPA04009735A (es) |
| MY (1) | MY131488A (es) |
| NO (1) | NO20044451L (es) |
| NZ (1) | NZ535535A (es) |
| PE (1) | PE20040324A1 (es) |
| PL (1) | PL372322A1 (es) |
| RS (1) | RS88404A (es) |
| TW (1) | TWI275392B (es) |
| WO (1) | WO2003086367A1 (es) |
| ZA (1) | ZA200407672B (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7511139B2 (en) | 2004-06-04 | 2009-03-31 | Bristol-Myers Squibb Company | Process for the preparation of entecavir and novel intermediates thereof via carbon-silicon oxidation |
| CN1732944B (zh) * | 2005-09-02 | 2013-05-08 | 海南中和药业有限公司 | 恩替卡韦分散片及其制备方法 |
| US20070060599A1 (en) * | 2005-09-09 | 2007-03-15 | Dimarco John D | Crystalline forms of [1S-(1alpha, 3alpha, 4beta)]-2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one |
| RU2381807C1 (ru) * | 2008-07-18 | 2010-02-20 | Алексей Глебович Одинец | Противовирусное средство |
| CN101869569A (zh) * | 2009-04-21 | 2010-10-27 | 李迪 | 即用型恩替卡韦组合物 |
| EP2508172A1 (en) | 2011-04-06 | 2012-10-10 | Zentiva, a.s. | Stable and uniform formulations of entecavir and preparation method thereof |
| UY34262A (es) | 2011-08-16 | 2013-04-05 | Gilead Sciences Inc | Hemifumarato de tenofovir alafenamida, sus composiciones, método de preparación, métodos para tratar infecciones virales y su uso para preparar medi camentos |
| CN102908312B (zh) * | 2011-11-10 | 2014-06-04 | 陈小花 | 抗乙肝病毒液体组合物 |
| US8517850B1 (en) * | 2012-12-11 | 2013-08-27 | Cobra Golf Incorporated | Golf club grip with device housing |
| KR101462018B1 (ko) * | 2013-04-01 | 2014-11-19 | 썬시스템즈(주) | 엔테카비르 함유 구강 붕해형 필름제제 |
| CN103301071A (zh) * | 2013-06-03 | 2013-09-18 | 北京阜康仁生物制药科技有限公司 | 一种稳定的恩替卡韦无糖型颗粒剂及其制备方法 |
| JP2016527308A (ja) * | 2013-08-06 | 2016-09-08 | ドン クック ファーマシューティカル カンパニー リミテッド | エンテカビル微小球及びこれを含む非経口投与用医薬組成物 |
| EP3158998A4 (en) * | 2014-06-20 | 2018-02-14 | CTC Bio, Inc. | Pharmaceutical preparation containing entecavir as active ingredient, and preparation method therefor |
| CN104083374A (zh) * | 2014-07-18 | 2014-10-08 | 石家庄创建医药科技有限公司 | 一种恩替卡韦口服液组合物 |
| CN109984996B (zh) * | 2018-01-02 | 2022-01-18 | 扬子江药业集团有限公司 | 恩替卡韦口服溶液及其制备方法 |
| CN108434096A (zh) * | 2018-06-20 | 2018-08-24 | 广州大光制药有限公司 | 一种恩替卡韦口服溶液及其制备方法 |
| EP3815704A4 (en) * | 2018-06-29 | 2022-04-20 | The Doshisha | FORMULATION CONTAINING EMRICASAN |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4489026A (en) * | 1982-09-07 | 1984-12-18 | The Upjohn Company | Process for preparing solid unit dosage forms of ultra-low dose drugs |
| US5206244A (en) * | 1990-10-18 | 1993-04-27 | E. R. Squibb & Sons, Inc. | Hydroxymethyl (methylenecyclopentyl) purines and pyrimidines |
| TW536403B (en) * | 1997-03-24 | 2003-06-11 | Glaxo Group Ltd | An ethanol and ethylenediaminetetraacetic acid free pharmaceutical composition comprising lamivudine and exhibiting antimicrobial preservative efficacy |
| US5997905A (en) * | 1998-09-04 | 1999-12-07 | Mcneil-Ppc | Preparation of pharmaceutically active particles |
| BR9916893A (pt) * | 1999-01-12 | 2001-11-20 | Smithkline Beecham Biolog | Tratamento |
| RS51561B (sr) * | 2000-02-29 | 2011-08-31 | Bristol-Myers Squibb Co. | Formulacija male doze entekavira i upotreba |
| CA2311734C (en) * | 2000-04-12 | 2011-03-08 | Bristol-Myers Squibb Company | Flash-melt oral dosage formulation |
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2003
- 2003-04-02 TW TW092107553A patent/TWI275392B/zh not_active IP Right Cessation
- 2003-04-02 MY MYPI20031228A patent/MY131488A/en unknown
- 2003-04-03 AU AU2003226259A patent/AU2003226259A1/en not_active Abandoned
- 2003-04-03 WO PCT/US2003/010371 patent/WO2003086367A1/en active Application Filing
- 2003-04-03 NZ NZ535535A patent/NZ535535A/en unknown
- 2003-04-03 BR BR0309057-4A patent/BR0309057A/pt not_active IP Right Cessation
- 2003-04-03 PL PL03372322A patent/PL372322A1/xx unknown
- 2003-04-03 MX MXPA04009735A patent/MXPA04009735A/es not_active Application Discontinuation
- 2003-04-03 JP JP2003583388A patent/JP2005528389A/ja active Pending
- 2003-04-03 RS YU88404A patent/RS88404A/sr unknown
- 2003-04-03 CN CNB038132877A patent/CN1319517C/zh not_active Expired - Fee Related
- 2003-04-03 KR KR10-2004-7015936A patent/KR20040099403A/ko not_active Application Discontinuation
- 2003-04-03 EA EA200401298A patent/EA008102B1/ru not_active IP Right Cessation
- 2003-04-03 CA CA002481092A patent/CA2481092A1/en not_active Abandoned
- 2003-04-03 EP EP03746598A patent/EP1492510A4/en not_active Withdrawn
- 2003-04-04 US US10/407,287 patent/US20030190334A1/en not_active Abandoned
- 2003-04-07 AR ARP030101211A patent/AR039388A1/es not_active Application Discontinuation
- 2003-04-08 PE PE2003000351A patent/PE20040324A1/es not_active Application Discontinuation
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2004
- 2004-09-22 ZA ZA200407672A patent/ZA200407672B/en unknown
- 2004-09-29 HR HR20040893A patent/HRP20040893A2/hr not_active Application Discontinuation
- 2004-10-08 EC EC2004005349A patent/ECSP045349A/es unknown
- 2004-10-19 NO NO20044451A patent/NO20044451L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EA200401298A1 (ru) | 2005-02-24 |
| KR20040099403A (ko) | 2004-11-26 |
| AU2003226259A1 (en) | 2003-10-27 |
| PE20040324A1 (es) | 2004-05-29 |
| CN1658844A (zh) | 2005-08-24 |
| WO2003086367A1 (en) | 2003-10-23 |
| MXPA04009735A (es) | 2005-01-11 |
| RS88404A (en) | 2006-12-15 |
| TWI275392B (en) | 2007-03-11 |
| EP1492510A1 (en) | 2005-01-05 |
| PL372322A1 (en) | 2005-07-11 |
| TW200306840A (en) | 2003-12-01 |
| JP2005528389A (ja) | 2005-09-22 |
| US20030190334A1 (en) | 2003-10-09 |
| NZ535535A (en) | 2006-09-29 |
| AR039388A1 (es) | 2005-02-16 |
| EP1492510A4 (en) | 2006-01-11 |
| ZA200407672B (en) | 2005-10-12 |
| EA008102B1 (ru) | 2007-04-27 |
| ECSP045349A (es) | 2005-01-03 |
| BR0309057A (pt) | 2005-02-01 |
| NO20044451L (no) | 2004-11-04 |
| MY131488A (en) | 2007-08-30 |
| CN1319517C (zh) | 2007-06-06 |
| CA2481092A1 (en) | 2003-10-23 |
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