CN115531305A - 一种洛索洛芬钠口服溶液剂及其制备方法 - Google Patents
一种洛索洛芬钠口服溶液剂及其制备方法 Download PDFInfo
- Publication number
- CN115531305A CN115531305A CN202211295103.6A CN202211295103A CN115531305A CN 115531305 A CN115531305 A CN 115531305A CN 202211295103 A CN202211295103 A CN 202211295103A CN 115531305 A CN115531305 A CN 115531305A
- Authority
- CN
- China
- Prior art keywords
- loxoprofen sodium
- oral solution
- sodium
- acid
- loxoprofen
- 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
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 title claims abstract description 81
- 229960002373 loxoprofen Drugs 0.000 title claims abstract description 81
- 229940100688 oral solution Drugs 0.000 title claims abstract description 64
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims abstract description 28
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 28
- 229960002216 methylparaben Drugs 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 238000009472 formulation Methods 0.000 claims abstract description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000004376 Sucralose Substances 0.000 claims description 10
- 235000003599 food sweetener Nutrition 0.000 claims description 10
- 235000019408 sucralose Nutrition 0.000 claims description 10
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 10
- 239000003765 sweetening agent Substances 0.000 claims description 10
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 8
- 229940085605 saccharin sodium Drugs 0.000 claims description 8
- 239000001509 sodium citrate Substances 0.000 claims description 8
- 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 8
- 239000006184 cosolvent Substances 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 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 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 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 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 235000021433 fructose syrup Nutrition 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 238000003756 stirring Methods 0.000 description 25
- 239000007788 liquid Substances 0.000 description 24
- 238000005303 weighing Methods 0.000 description 14
- 241000220223 Fragaria Species 0.000 description 12
- 235000016623 Fragaria vesca Nutrition 0.000 description 12
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- 238000000034 method Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000004695 Polyether sulfone Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 229920006393 polyether sulfone Polymers 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 239000004698 Polyethylene Substances 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 229910052782 aluminium Inorganic materials 0.000 description 6
- 230000003385 bacteriostatic effect Effects 0.000 description 6
- 239000002131 composite material Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
- 229920000573 polyethylene Polymers 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 230000001754 anti-pyretic effect Effects 0.000 description 3
- 239000002221 antipyretic Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000008035 Back Pain Diseases 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010034464 Periarthritis Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010008334 Cervicobrachial syndrome Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- -1 patches Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Images
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及药物制剂领域,具体涉及一种洛索洛芬钠口服溶液剂及其制备方法。本发明提供了一种洛索洛芬钠口服溶液剂,其含有洛索洛芬钠和羟苯甲酯;以所述洛索洛芬钠口服溶液剂的总质量为基准,洛索洛芬钠的含量为0.5~0.7wt%;且所述洛索洛芬钠和羟苯甲酯的质量比为3~5:1。本发明将洛索洛芬钠制成能稳定储存的口服溶液剂,相较于含有洛索洛芬钠的其他剂型,具有吸收快、生物利用度高、起效快等优点,同时方便给药,可以满足不同患者的用药需求。
Description
技术领域
本发明涉及药物制剂领域,具体涉及一种洛索洛芬钠口服溶液剂及其制备方法。
背景技术
解热镇痛消炎药是一类发展迅速的药物,在世界畅销药物销售额领先的前50个品种中,解热镇痛消炎药约占据三分之一。目前临床上常用的非甾体解热镇痛药有洛索洛芬、布洛芬、阿司匹林等药物。洛索洛芬钠是第一个苯丙酸类非甾体解热镇痛药。洛索洛芬钠是由日本第一三共株式会社开发的非甾体解热镇痛消炎药,用于治疗风湿性关节炎、类风湿性关节炎、骨性关节炎、变形性关节炎、腰痛、肩周炎、颈肩腕综合征,以及手术后、外伤后以及拔牙后的肿胀与疼痛等症状。
洛索洛芬钠口服后吸收迅速,并以较高的血药浓度分布于肝、肾、血液中,随后大部分以圆形物的葡萄糖醛酸结合物或羰基化合物的葡萄糖醛酸结合物经尿液排出体外。
目前,国内市场上洛索洛芬钠制剂主要有片剂、胶囊剂、颗粒剂、分散片、贴剂以及凝胶贴膏剂等,以上产品存在吸收慢、生物利用度低、起效满等缺点,且片剂、胶囊剂难以满足老人、儿童以及吞咽困难的患者服用。
发明内容
口服溶液剂具有吸收快、生物利用度高、起效快等优点,同时方便给药,可以满足不同患者的用药需求,但是由于洛索洛芬钠具有羧酸的羰基易于带有羟基化合物发生反应生成酯,导致洛索洛芬钠原料药在水溶液中稳定性较差,制备成口服溶液剂会导致杂质增长较大。对此,本发明意外发现,通过控制洛索洛芬钠的含量为0.5~0.7wt%,并控制所述洛索洛芬钠和羟苯甲酯的质量比为3~5:1后,不仅提高了产品的抑菌能力,还可以抑制洛索洛芬钠与带有羟基化合物发生反正生成酯,从而大幅提升了洛索洛芬钠口服溶液剂的稳定性。
基于上述发现,本发明首先提供了一种洛索洛芬钠口服溶液剂,其含有洛索洛芬钠和羟苯甲酯;
以所述洛索洛芬钠口服溶液剂的总质量为基准,洛索洛芬钠的含量为0.5~0.7wt%;
且所述洛索洛芬钠和羟苯甲酯的质量比为3~5:1。
更优选的,以所述洛索洛芬钠口服溶液总质量为基准,其含有0.15±0.02wt%的羟苯甲酯。
作为优选,所述的洛索洛芬钠口服溶液剂还含有0.1~0.2wt%的甜味剂;
所述甜味剂选自葡萄糖、果糖、麦芽糖、蔗糖、三氯蔗糖、糖精钠、阿斯巴甜、安赛蜜、果葡糖浆、山梨醇、木糖醇、甘露醇等中的一种或几种。
上述的甜味剂均可较好地掩饰洛索洛芬钠本身所具有的苦味。
更优选的,所述甜味剂为质量比为(1.5~2.5):1的糖精钠和三氯蔗糖的混合物。
在采用上述的复配甜味剂时,对洛索洛芬钠的掩味效果明显优于其他甜味剂,且掩味效果在制备及保存期内不会发生明显变化。
作为优选,所述的洛索洛芬钠口服溶液剂还含有0.05~0.15wt%的助溶剂;
所述助溶剂选自乙醇、丙二醇、甘油、聚乙二醇、泊洛沙姆、聚乙烯吡咯烷酮等中的一种或几种。
更优选的,所述的助溶剂为丙二醇。本发明在助溶剂中省略了对乙醇的使用,更有利于避免对患者带来的副作用。
作为优选,所述洛索洛芬钠口服溶液剂的pH值为6.5~7.5。
作为优选方案,所述洛索洛芬钠口服溶液剂还含有pH调节剂,所述pH调节剂选自盐酸、醋酸、醋酸钠、枸橼酸、枸橼酸钠、磷酸、磷酸二氢钠、磷酸二氢钾、碳酸钠、碳酸氢钠、氢氧化钠、氢氧化钾、三乙胺、苹果酸、酒石酸、富马酸、马来酸、山梨酸、琥珀酸、水杨酸、氢溴酸、草酸等中的一种或几种。
作为优选,所述的洛索洛芬钠口服溶液剂还含有0.01~0.03wt%的香精。
作为优选,所述的洛索洛芬钠口服溶液剂的溶剂为水。
本领域人员可对上述方案进行组合,得到本发明中洛索洛芬钠口服溶液剂的较优实施例。
作为本发明的一种优选实施方案,所述的洛索洛芬钠口服溶液剂含有如下重量百分比的组分:
进一步的,本发明还提供所述的洛索洛芬钠口服溶液剂的制备方法,包括:在70~80℃下使羟苯甲酯溶于水,而后与其他组分混合。
本发明发现,通过在70~80℃下使羟苯甲酯溶于水,避免在处方中使用乙醇溶解羟苯甲酯,解决了处方中使用乙醇对患者带来的副作用。
作为优选方案,所述的洛索洛芬钠口服溶液剂的制备方法包括:
(1)在70~80℃下使羟苯甲酯溶于水,而后与洛索洛芬钠、甜味剂、助溶剂混合;
(2)待药液温度降至室温后,使用pH调节剂调节药液pH值为6.5~7.5;
(3)将药液与香精混合,并补全水量。
在具体实施时,本领域人员还可以在上述的步骤(3)之后,对获得的药液进行过滤(如通过0.45μm聚醚砜滤芯过滤),而后进行灌装。
本发明的有益效果如下:
本发明将洛索洛芬钠制成能稳定储存的口服溶液剂,相较于含有洛索洛芬钠的其他剂型,具有吸收快、生物利用度高、起效快等优点,同时方便给药,可以满足不同患者的用药需求。
本发明中的洛索洛芬钠口服溶液剂可以用于治疗因类风湿关节炎,骨关节炎,腰痛,肩周炎,颈肩臂综合征,牙痛等引起的炎症和疼痛,也可用于急性上呼吸道炎(包括急性上呼吸道炎伴急性支气管炎)。
附图说明
图1为本发明实验例中的药代动力学实验结果。
具体实施方式
以下实施例用于说明本发明,但不用来限制本发明的范围。
实施例中未注明具体技术或条件者,按照本领域内的文献所描述的技术或条件,或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者,均为可通过正规渠道商购买得到的常规产品。
实施例1:含有洛索洛芬钠60mg的口服溶液剂
本实施例首先提供一种口服溶液剂,配方如下:
本实施例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至80℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。
实施例2:含有洛索洛芬钠60mg的口服溶液剂
本实施例首先提供一种口服溶液剂,配方如下:
本实施例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至70℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。
实施例3:
本实施例首先提供一种口服溶液剂,配方如下:
本实施例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至70℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。
实施例4:
本实施例首先提供一种口服溶液剂,配方如下:
本实施例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至70℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。对比例1:含有洛索洛芬钠60mg的口服溶液剂
本对比例首先提供一种口服溶液剂,配方如下:
本对比例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至80℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。
对比例2:含有洛索洛芬钠60mg的口服溶液剂
本对比例首先提供一种口服溶液剂,配方如下:
本对比例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
量取处方量90wt%的纯化水,加热至60℃并维持此温度,加入处方量的羟苯甲酯,持续搅拌2小时仍不能完全溶解。
对比例3:含有洛索洛芬钠60mg的口服溶液剂
本对比例首先提供一种口服溶液剂,配方如下:
本对比例进一步提供上述口服溶液剂的制备方法,具体步骤如下:
(1)称量:称取处方量原、辅料,备用;
(2)配液:
①量取处方量90wt%的纯化水,加热至90℃并维持此温度,加入处方量的羟苯甲酯,搅拌15min至完全溶解;
②依次加入处方量的丙二醇、糖精钠、三氯蔗糖、枸橼酸钠和洛索洛芬钠,搅拌10min至所有组分完全溶解;
③药液温度降至室温后,使用10wt%枸橼酸溶液调节药液pH值至6.5~7.5;
④加入处方量草莓香精,搅拌5min至完全溶解;
⑤补水至全量后继续搅拌10min;
(3)过滤:经0.45μm聚醚砜滤芯过滤。
(4)灌装至10ml聚酯/铝/聚乙烯药用复合膜袋中,10ml/袋。
实验例
1、药代动力学实验
以比格犬为试验动物,采用双周期交叉实验设计,对本发明的洛索洛芬钠口服溶液制剂(实施例1)和市场在售洛索洛芬钠片剂、胶囊剂、颗粒剂进行了体内药动学实验研究,建立了洛索洛芬钠的体内分析方法。以单次空腹给药,测量血浆中洛索洛芬钠浓度。通过分散分析法对得到的药代动力学参数(AUC、Cmax)进行统计,并分别计算了以上四种剂型中洛索洛芬钠的药代动力学结果。结果见图1和表1。
表1
/ | AUC<sub>t</sub>(μg·h/ml) | C<sub>max</sub>(μg/ml) | T<sub>max</sub>(h) | T<sub>1/2</sub>(h) |
本发明口服溶液剂 | 9.53±1.17 | 6.21±0.92 | 0.32±0.10 | 2.21±0.21 |
市售片剂 | 8.26±1.21 | 5.43±0.87 | 0.58±0.18 | 2.24±0.28 |
市售胶囊剂 | 8.09±0.87 | 5.62±1.25 | 0.53±0.14 | 2.18±0.19 |
市售颗粒剂 | 8.17±0.95 | 5.86±1.40 | 0.48±0.15 | 2.16±0.35 |
药代动力学实验结果表明:与片剂、胶囊剂、颗粒剂相比,本发明洛索洛芬钠口服溶液具有生物利用度更高、吸收快、起效快的优点。
2、稳定性实验
分别将实施例1、实施例3、实施例4与对比例1进行抑菌效力试验检测,并在产品储存12月后分别检测微生物限度和有关物质变化,结果见表2及表3。
表2微生物限度检测结果
抑菌效力实验结果表明:当羟苯甲酯处方量为12~20mg时,产品抑菌效力符合规定,且储存12个月后微生物增长较少,微生物限度符合规定;当羟苯甲酯处方量为10mg时,产品抑菌效力不符合规定,且储存12个月后微生物增长较多,需氧菌、霉菌和酵母菌均超出限度要求。市售口服溶液剂抑菌效力不符合规定,储存12个月后微生物增长速度明显高于实施例1、实施例3、实施例4,说明本发明制备的洛索洛芬钠口服溶液可以明显增强产品的抑菌效力,降低产品在储存过程中受微生物污染的风险。
表3有关物质对比结果
抑菌效力实验结果表明:当羟苯甲酯处方量为12~20mg时,储存12个月后有关物质增长较少;当羟苯甲酯处方量为10mg时,储存12个月后杂质增长较大,说明羟苯甲酯处方量为12~20mg时可有效抑制洛索洛芬钠降解,提高产品稳定性。
3、羟苯甲酯含量检测
对实施例1、实施例2、对比例3产品中羟苯甲酯量进行检测,结果见表4。
表4羟苯甲酯含量检测结果
羟苯甲酯含量检测结果表明,羟苯甲酯在高温下易降解,当溶解羟苯甲酯的温度达到90℃以上时,羟苯甲酯降解较多,已超过限度要求,不符合规定;由对比例2可知,当溶解羟苯甲酯的温度为60℃时,搅拌2小时羟苯甲酯仍不能完全溶解。所以在70~80℃溶解羟苯甲酯较为合适,既可以保证羟苯甲酯迅速溶解,又能避免其降解。
虽然,上文中已经用一般性说明及具体实施方案对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (10)
1.一种洛索洛芬钠口服溶液剂,其特征在于,其含有洛索洛芬钠和羟苯甲酯;
以所述洛索洛芬钠口服溶液剂的总质量为基准,洛索洛芬钠的含量为0.5~0.7wt%;
且所述洛索洛芬钠和羟苯甲酯的质量比为(3~5):1。
2.根据权利要求1所述的洛索洛芬钠口服溶液剂,其特征在于,以所述洛索洛芬钠口服溶液总质量为基准,其含有0.15±0.02wt%的羟苯甲酯。
3.根据权利要求1或2所述的洛索洛芬钠口服溶液剂,其特征在于,其还含有0.1~0.2wt%的甜味剂;
所述甜味剂选自葡萄糖、果糖、麦芽糖、蔗糖、三氯蔗糖、糖精钠、阿斯巴甜、安赛蜜、果葡糖浆、山梨醇、木糖醇、甘露醇等中的一种或几种。
4.根据权利要求3所述的洛索洛芬钠口服溶液剂,其特征在于,所述甜味剂为质量比为(1.5~2.5):1的糖精钠和三氯蔗糖的混合物。
5.根据权利要求1~4中任一项所述的洛索洛芬钠口服溶液剂,其特征在于,其还含有0.05~0.15wt%的助溶剂;
所述助溶剂选自乙醇、丙二醇、甘油、聚乙二醇、泊洛沙姆、聚乙烯吡咯烷酮等中的一种或几种。
6.根据权利要求1~5中任一项所述的洛索洛芬钠口服溶液剂,其特征在于,其pH值为6.5~7.5。
7.根据权利要求1~6中任一项所述的洛索洛芬钠口服溶液剂,其特征在于,其还含有pH调节剂,所述pH调节剂选自盐酸、醋酸、醋酸钠、枸橼酸、枸橼酸钠、磷酸、磷酸二氢钠、磷酸二氢钾、碳酸钠、碳酸氢钠、氢氧化钠、氢氧化钾、三乙胺、苹果酸、酒石酸、富马酸、马来酸、山梨酸、琥珀酸、水杨酸、氢溴酸、草酸等中的一种或几种。
8.根据权利要求1~7中任一项所述的洛索洛芬钠口服溶液剂,其特征在于,其还含有0.01~0.03wt%的香精。
9.根据权利要求1~8中任一项所述的洛索洛芬钠口服溶液剂,其特征在于,其溶剂为水。
10.权利要求1~9中任一项所述的洛索洛芬钠口服溶液剂的制备方法,其特征在于,包括:在70~80℃下使羟苯甲酯溶于水,而后与其他组分混合。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211295103.6A CN115531305B (zh) | 2022-10-21 | 2022-10-21 | 一种洛索洛芬钠口服溶液剂及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211295103.6A CN115531305B (zh) | 2022-10-21 | 2022-10-21 | 一种洛索洛芬钠口服溶液剂及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115531305A true CN115531305A (zh) | 2022-12-30 |
CN115531305B CN115531305B (zh) | 2023-11-07 |
Family
ID=84736026
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211295103.6A Active CN115531305B (zh) | 2022-10-21 | 2022-10-21 | 一种洛索洛芬钠口服溶液剂及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115531305B (zh) |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001031562A (ja) * | 1999-07-16 | 2001-02-06 | Taisho Pharmaceut Co Ltd | 内服液剤 |
CN1297264C (zh) * | 2001-12-18 | 2007-01-31 | 复旦大学 | 一种注射用洛索洛芬钠药物组合物 |
JP2011068636A (ja) * | 2009-07-30 | 2011-04-07 | Kowa Co | 液体充填カプセル剤 |
JP5853430B2 (ja) * | 2010-06-21 | 2016-02-09 | 大正製薬株式会社 | 内服液剤 |
JP5915013B2 (ja) * | 2010-07-30 | 2016-05-11 | 大正製薬株式会社 | 内服液剤 |
JP6410408B2 (ja) * | 2013-05-23 | 2018-10-24 | 東洋カプセル株式会社 | ロキソプロフェンナトリウム含有経口カプセル剤 |
EP2926810A1 (en) * | 2014-03-31 | 2015-10-07 | Sanovel Ilac Sanayi ve Ticaret A.S. | Oral liquid pharmaceutical formulations of loxoprofen |
CN110893190A (zh) * | 2019-12-03 | 2020-03-20 | 广州奥博医药科技有限公司 | 一种复方洛索洛芬滴眼剂及其制备方法 |
CN114436824A (zh) * | 2022-03-04 | 2022-05-06 | 浙江普洛家园药业有限公司 | 一种洛索洛芬钠降解杂质的制备方法 |
-
2022
- 2022-10-21 CN CN202211295103.6A patent/CN115531305B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN115531305B (zh) | 2023-11-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10201519B2 (en) | Stabilized pediatric suspension of carisbamate | |
EP2465497A1 (en) | Pharmaceutical suspension composition | |
CA2749245C (en) | A formulation for oral transmucosal administration of analgesic and/or antispasmodic molecules | |
KR100841893B1 (ko) | 프레가발린 조성물 | |
WO2012127497A1 (en) | Stable pharmaceutical compositions of ketorolac or salts thereof | |
JP4959335B2 (ja) | メチルフェニデート溶液および関連する投与および製造方法 | |
CN115531305A (zh) | 一种洛索洛芬钠口服溶液剂及其制备方法 | |
US20040116528A1 (en) | Ketoprofen compositons and methods of making them | |
WO2018069805A2 (en) | Method for preparation of liquid oral composition of l-thyroxin | |
WO2022021769A1 (zh) | 一种盐酸氨溴索口腔喷雾溶液及其制备方法 | |
EP3582765B1 (en) | Midodrine hydrochloride oral solution and uses thereof | |
CN113784711A (zh) | 包含格隆溴铵的口崩片剂和提高生物利用度的方法 | |
EP4081187B1 (en) | Liquid composition comprising ibuprofen and phenylephrine | |
CN115715758B (zh) | 一种间苯三酚口服液及其生产方法 | |
AU2773892A (en) | Trimethoprim oral liquid | |
WO2022247609A1 (zh) | 一种替扎尼定液体制剂及其用途 | |
EP1894557A1 (en) | Liquid composition for prevention and/or treatment of different bone metabolic diseases, uses thereof, and preparation process therefore | |
CN118304258A (zh) | 一种艾司西酞普兰口服液体制剂 | |
CN115645357A (zh) | 一种拉考沙胺口服溶液处方及其制备工艺 | |
US20230301945A1 (en) | Stable pharmaceutical compositions of hydroxyurea | |
CN114288246A (zh) | 一种含有加巴喷丁复合物的聚合物胶束口服液及其制备方法 | |
CN115518035A (zh) | 一种酮咯酸液体组合物、其制备方法及应用 | |
TW200302721A (en) | Zoniporide mesylate pharmaceutical compositions and process for improving solubility of zoniporide |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |