CN114557955A - 药物组合物、其制备方法和用途 - Google Patents
药物组合物、其制备方法和用途 Download PDFInfo
- Publication number
- CN114557955A CN114557955A CN202210229677.7A CN202210229677A CN114557955A CN 114557955 A CN114557955 A CN 114557955A CN 202210229677 A CN202210229677 A CN 202210229677A CN 114557955 A CN114557955 A CN 114557955A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- slurry washing
- atropine sulfate
- water
- buffer system
- 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
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 38
- 239000003814 drug Substances 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 27
- 230000007547 defect Effects 0.000 claims abstract description 4
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 claims description 64
- 229960002028 atropine sulfate Drugs 0.000 claims description 64
- 239000002002 slurry Substances 0.000 claims description 59
- 238000005406 washing Methods 0.000 claims description 45
- 239000000243 solution Substances 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 26
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 20
- 239000007853 buffer solution Substances 0.000 claims description 19
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 19
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 19
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 19
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 18
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical group OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 239000000022 bacteriostatic agent Substances 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 15
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical group [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 15
- 230000004379 myopia Effects 0.000 claims description 14
- 208000001491 myopia Diseases 0.000 claims description 14
- 239000012046 mixed solvent Substances 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- 229940124274 edetate disodium Drugs 0.000 claims description 10
- 239000002562 thickening agent Substances 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000004327 boric acid Substances 0.000 claims description 9
- 239000008139 complexing agent Substances 0.000 claims description 9
- 230000003204 osmotic effect Effects 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 238000007670 refining Methods 0.000 claims description 7
- 230000008961 swelling Effects 0.000 claims description 7
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 6
- 229920002678 cellulose Polymers 0.000 claims description 6
- 239000001913 cellulose Substances 0.000 claims description 6
- 239000003889 eye drop Substances 0.000 claims description 6
- 229940012356 eye drops Drugs 0.000 claims description 6
- 239000008363 phosphate buffer Substances 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 6
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- 239000012669 liquid formulation Substances 0.000 claims description 5
- 239000003002 pH adjusting agent Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000007873 sieving Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 claims description 3
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 3
- 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 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 3
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 3
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 3
- 229910021538 borax Inorganic materials 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 229960002798 cetrimide Drugs 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 229960001484 edetic acid Drugs 0.000 claims description 3
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 3
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 3
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 3
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 3
- 230000004438 eyesight Effects 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229960005323 phenoxyethanol Drugs 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 238000011085 pressure filtration Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical group O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 239000004328 sodium tetraborate Substances 0.000 claims description 3
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 3
- SPOMEWBVWWDQBC-UHFFFAOYSA-K tripotassium;dihydrogen phosphate;hydrogen phosphate Chemical compound [K+].[K+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O SPOMEWBVWWDQBC-UHFFFAOYSA-K 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 claims description 3
- 229940113960 edetate calcium Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 229930003347 Atropine Natural products 0.000 abstract description 33
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 abstract description 33
- 229960000396 atropine Drugs 0.000 abstract description 33
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 abstract description 33
- 230000000007 visual effect Effects 0.000 abstract 1
- 239000012535 impurity Substances 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000008215 water for injection Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 239000011259 mixed solution Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229940088679 drug related substance Drugs 0.000 description 5
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
- XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 230000001502 supplementing effect Effects 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 208000006550 Mydriasis Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 206010047513 Vision blurred Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960002645 boric acid Drugs 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000366 juvenile effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 230000004515 progressive myopia Effects 0.000 description 2
- 230000010344 pupil dilation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 201000009487 Amblyopia Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005619 boric acid group Chemical group 0.000 description 1
- UEAVLBXLOZNDHT-UHFFFAOYSA-K calcium;sodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical compound [Na+].[Ca+2].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEAVLBXLOZNDHT-UHFFFAOYSA-K 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000000255 cycloplegia Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000001739 rebound effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/547—Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Abstract
Description
组份 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 |
硫酸阿托品 | 0.005g | 0.010g | 0.050g | 0.010g | 0.020g |
羟丙甲纤维素 | 1.000g | 1.000g | 1.000g | 1.000g | 1.000g |
玻璃酸钠 | - | - | - | 2.0g | 2.0g |
一水磷酸二氢钠 | 0.250g | 0.250g | 0.250g | 0.250g | 0.250g |
磷酸氢二钠 | 0.0025g | 0.0025g | 0.0025g | 0.0025g | 0.0025g |
依地酸二钠 | 0.010g | 0.010g | 0.010g | 0.010g | 0.010g |
苯扎氯铵 | 0.010g | 0.010g | 0.010g | 0.010g | 0.010g |
注射用水 | 余量 | 余量 | 余量 | 余量 | 余量 |
组份 | 实施例7 | 实施例8 | 实施例9 |
硫酸阿托品 | 0.005g | 0.010g | 0.050g |
羟丙甲纤维素 | 1.000g | 1.000g | 1.000g |
丙二醇 | 0.300g | - | 0.300g |
硼酸 | 1.800g | 1.800g | 1.800g |
依地酸二钠 | 0.010g | 0.010g | 0.010g |
苯扎氯铵 | 0.010g | - | 0.010g |
注射用水 | 余量 | 余量 | 余量 |
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210229677.7A CN114557955A (zh) | 2018-09-25 | 2018-09-25 | 药物组合物、其制备方法和用途 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210229677.7A CN114557955A (zh) | 2018-09-25 | 2018-09-25 | 药物组合物、其制备方法和用途 |
CN201811112830.8A CN110934816B (zh) | 2018-09-25 | 2018-09-25 | 一种提高低浓度阿托品眼用制剂稳定性的方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811112830.8A Division CN110934816B (zh) | 2018-09-25 | 2018-09-25 | 一种提高低浓度阿托品眼用制剂稳定性的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114557955A true CN114557955A (zh) | 2022-05-31 |
Family
ID=69905278
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210227935.8A Pending CN114533652A (zh) | 2018-09-25 | 2018-09-25 | 药物组合物、其制备方法和用途 |
CN202210229677.7A Pending CN114557955A (zh) | 2018-09-25 | 2018-09-25 | 药物组合物、其制备方法和用途 |
CN201811112830.8A Active CN110934816B (zh) | 2018-09-25 | 2018-09-25 | 一种提高低浓度阿托品眼用制剂稳定性的方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210227935.8A Pending CN114533652A (zh) | 2018-09-25 | 2018-09-25 | 药物组合物、其制备方法和用途 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811112830.8A Active CN110934816B (zh) | 2018-09-25 | 2018-09-25 | 一种提高低浓度阿托品眼用制剂稳定性的方法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20210393609A1 (zh) |
JP (3) | JP7340139B2 (zh) |
CN (3) | CN114533652A (zh) |
WO (1) | WO2020063320A1 (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111821259A (zh) * | 2020-07-14 | 2020-10-27 | 艾尔健康眼药(辽宁)有限公司 | 一种眼用药物组合物 |
CN112321729A (zh) * | 2020-12-03 | 2021-02-05 | 安徽森淼实业有限公司 | 一种羟丙基甲基纤维素的制备方法 |
CN114668762B (zh) * | 2020-12-24 | 2024-04-16 | 江苏恒瑞医药股份有限公司 | 一种药物组合物 |
CN115721605A (zh) * | 2021-08-31 | 2023-03-03 | 成都倍特药业股份有限公司 | 一种硫酸阿托品液体制剂及其制备方法 |
CN117295491A (zh) * | 2021-09-13 | 2023-12-26 | 安徽欧普视方医药科技有限公司 | 阿托品滴眼液及其制备方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014102829A1 (en) * | 2012-12-31 | 2014-07-03 | Mylan Laboratories Ltd. | Crystalline atropine sulfate |
WO2016016692A1 (en) * | 2014-08-01 | 2016-02-04 | Rouver Investment S.À.R.L | Process for preparation of atropine |
CN106572998A (zh) * | 2014-06-24 | 2017-04-19 | 西德奈克西斯公司 | 眼用组合物 |
CN107456440A (zh) * | 2017-08-07 | 2017-12-12 | 杭州赫尔斯科技有限公司 | 一种低浓度阿托品类药物滴眼液及其制备方法 |
US20210267885A1 (en) * | 2016-05-25 | 2021-09-02 | Singapore Health Services Ptel Ltd | Atropine-containing aqueous composition |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SU417422A1 (zh) * | 1971-07-23 | 1974-02-28 | ||
CN102813651B (zh) * | 2011-06-07 | 2015-02-11 | 成都国为医药科技有限公司 | 一种含埃索美拉唑钠的药物组合物及其制备方法 |
CN103816126B (zh) * | 2014-03-24 | 2015-09-30 | 海南双成药业股份有限公司 | 一种含有丁溴东莨菪碱的药物组合物 |
CN104069064A (zh) * | 2014-06-23 | 2014-10-01 | 天津金耀集团有限公司 | 盐酸消旋山莨菪碱注射液组合物 |
WO2016172712A2 (en) * | 2015-04-23 | 2016-10-27 | Sydnexis, Inc. | Ophthalmic composition |
JP7120018B2 (ja) * | 2016-10-07 | 2022-08-17 | ライオン株式会社 | 眼科用製品及び粘度低下抑制方法 |
CN106855535A (zh) * | 2016-12-29 | 2017-06-16 | 北京中医药大学 | 一种山莨菪碱及其对映体的分离方法 |
CN107982212A (zh) * | 2017-11-28 | 2018-05-04 | 杭州赫尔斯科技有限公司 | 一种阿托品类药物缓释滴眼液及其制备方法 |
-
2018
- 2018-09-25 CN CN202210227935.8A patent/CN114533652A/zh active Pending
- 2018-09-25 CN CN202210229677.7A patent/CN114557955A/zh active Pending
- 2018-09-25 CN CN201811112830.8A patent/CN110934816B/zh active Active
-
2019
- 2019-09-10 WO PCT/CN2019/105010 patent/WO2020063320A1/zh active Application Filing
- 2019-09-10 JP JP2021540354A patent/JP7340139B2/ja active Active
- 2019-09-10 US US17/279,554 patent/US20210393609A1/en active Pending
-
2023
- 2023-04-05 JP JP2023061268A patent/JP2023085454A/ja active Pending
- 2023-04-05 JP JP2023061269A patent/JP2023085455A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014102829A1 (en) * | 2012-12-31 | 2014-07-03 | Mylan Laboratories Ltd. | Crystalline atropine sulfate |
CN106572998A (zh) * | 2014-06-24 | 2017-04-19 | 西德奈克西斯公司 | 眼用组合物 |
WO2016016692A1 (en) * | 2014-08-01 | 2016-02-04 | Rouver Investment S.À.R.L | Process for preparation of atropine |
US20210267885A1 (en) * | 2016-05-25 | 2021-09-02 | Singapore Health Services Ptel Ltd | Atropine-containing aqueous composition |
CN107456440A (zh) * | 2017-08-07 | 2017-12-12 | 杭州赫尔斯科技有限公司 | 一种低浓度阿托品类药物滴眼液及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
US20210393609A1 (en) | 2021-12-23 |
JP7340139B2 (ja) | 2023-09-07 |
CN110934816B (zh) | 2022-04-08 |
WO2020063320A1 (zh) | 2020-04-02 |
CN110934816A (zh) | 2020-03-31 |
JP2022501437A (ja) | 2022-01-06 |
JP2023085455A (ja) | 2023-06-20 |
CN114533652A (zh) | 2022-05-27 |
JP2023085454A (ja) | 2023-06-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110934816B (zh) | 一种提高低浓度阿托品眼用制剂稳定性的方法 | |
CN100522163C (zh) | 长春西汀小容量注射剂及其制备工艺 | |
CN106074568A (zh) | 一种用于预防和治疗白内障的眼用制剂及其制备方法 | |
US20190358152A1 (en) | Aqueous ophthalmic solutions of phentolamine and medical uses thereof | |
CN101991530A (zh) | 含有长春西汀大容量氯化钠注射剂及其制备方法 | |
CN112426405A (zh) | 预防及控制近视发展的药物组合物、滴眼液及其制备方法与应用 | |
CN102113994A (zh) | 一种脑血管扩张药及其制备方法 | |
CN108159026B (zh) | 一种稳定的吸入用盐酸氨溴索溶液及其制备方法 | |
CN105175304A (zh) | 抗胆碱药物格隆溴铵及组合物 | |
CN106539753A (zh) | 一种间苯三酚注射剂及其制备方法 | |
CN102784382A (zh) | 一种阿加曲班药物组合物及其制备方法和应用 | |
CN106474048A (zh) | 一种质量更加稳定的地奈德凝胶制剂 | |
CN102716074B (zh) | 一种贝美前列素滴眼剂及其制备方法 | |
CN103202805B (zh) | 一种含有长春西汀的注射用药物组合物及其制备方法 | |
CN113786380A (zh) | 一种硝酸毛果芸香碱眼用凝胶及其制备方法 | |
CN105030708A (zh) | 一种利鲁唑片及其制备方法 | |
CN114668762A (zh) | 一种药物组合物 | |
CN103520097B (zh) | 一种扎那米韦注射液及其制备方法 | |
CN117205150A (zh) | 硫酸阿托品注射液及其作为m胆碱受体阻滞剂的用途 | |
CN114222565B (zh) | 一种药物组合物 | |
CN103330682B (zh) | 穿琥宁注射液和制法 | |
CN109966256B (zh) | 一种普拉克索缓释药物组合物、其制备方法及用途 | |
AU2022329224A1 (en) | Pharmaceutical composition, preparation method therefor and application thereof | |
WO2023036227A1 (zh) | 阿托品滴眼液及其制备方法 | |
WO2022036794A1 (zh) | 一种单剂量盐酸环喷托酯滴眼液的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40066454 Country of ref document: HK |
|
TA01 | Transfer of patent application right |
Effective date of registration: 20230703 Address after: 110163 Surabaya street, Dongling District, Shenyang, Liaoning Province, No. 68 Applicant after: SHENYANG XINGQI PHARMACEUTICAL Co.,Ltd. Address before: 110000 doors 1 and 2, No. 136, Sanhao Street, Heping District, Shenyang City, Liaoning Province Applicant before: Shenyang Xingqi ophthalmic hospital Co.,Ltd. |
|
TA01 | Transfer of patent application right | ||
CB02 | Change of applicant information |
Address after: No. 25, New Canal Road, Shenyang Area, China (Liaoning) Pilot Free Trade Zone, Hunnan District, Shenyang, Liaoning 110167 Applicant after: SHENYANG XINGQI PHARMACEUTICAL Co.,Ltd. Address before: 110163 Surabaya street, Dongling District, Shenyang, Liaoning Province, No. 68 Applicant before: SHENYANG XINGQI PHARMACEUTICAL Co.,Ltd. |
|
CB02 | Change of applicant information |