CN1660057A - 格列本脲固体分散体、口服组合物及其制备方法 - Google Patents
格列本脲固体分散体、口服组合物及其制备方法 Download PDFInfo
- Publication number
- CN1660057A CN1660057A CN2004100659937A CN200410065993A CN1660057A CN 1660057 A CN1660057 A CN 1660057A CN 2004100659937 A CN2004100659937 A CN 2004100659937A CN 200410065993 A CN200410065993 A CN 200410065993A CN 1660057 A CN1660057 A CN 1660057A
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- Prior art keywords
- glibenclamide
- solid dispersion
- disperse medium
- medicine
- diabetes
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- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 title claims abstract description 128
- 229960004580 glibenclamide Drugs 0.000 title claims abstract description 127
- 239000007962 solid dispersion Substances 0.000 title claims description 67
- 238000002360 preparation method Methods 0.000 title description 20
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 238000001694 spray drying Methods 0.000 claims abstract description 7
- 238000000227 grinding Methods 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims description 19
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 4
- 229960003105 metformin Drugs 0.000 claims description 4
- 229960005095 pioglitazone Drugs 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
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- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims description 2
- 229940122069 Glycosidase inhibitor Drugs 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 2
- 229960002632 acarbose Drugs 0.000 claims description 2
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000003316 glycosidase inhibitor Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000000413 hydrolysate Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229960002354 repaglinide Drugs 0.000 claims description 2
- 229960004586 rosiglitazone Drugs 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 229940126701 oral medication Drugs 0.000 claims 3
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 21
- 239000007787 solid Substances 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 23
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 239000002245 particle Substances 0.000 description 15
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 14
- 229920002472 Starch Polymers 0.000 description 14
- 229960004329 metformin hydrochloride Drugs 0.000 description 14
- 229940016286 microcrystalline cellulose Drugs 0.000 description 14
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- 239000000843 powder Substances 0.000 description 14
- 239000008107 starch Substances 0.000 description 14
- 235000019698 starch Nutrition 0.000 description 14
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 13
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 13
- 239000002775 capsule Substances 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 239000008187 granular material Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 238000000113 differential scanning calorimetry Methods 0.000 description 5
- 239000006069 physical mixture Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 3
- 239000013557 residual solvent Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- HCEQQASHRRPQFE-UHFFFAOYSA-N 5-chloro-n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 HCEQQASHRRPQFE-UHFFFAOYSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 229940112611 glucovance Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 230000005184 men's health Effects 0.000 description 2
- 229940093462 metformin hydrochloride 250 mg Drugs 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 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 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- HUXIQPLYZRLRFJ-UHFFFAOYSA-N azanium;dihydrogen phosphate;methanol Chemical compound [NH4+].OC.OP(O)([O-])=O HUXIQPLYZRLRFJ-UHFFFAOYSA-N 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- -1 compound metformin hydrochloride Chemical class 0.000 description 1
- 235000013409 condiments Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940103776 metformin hydrochloride 500 mg Drugs 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 229940084921 micronized glyburide Drugs 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 238000011003 system suitability test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- 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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
试验时间(月) | 考察项目 | ||
固体分散体外观 | 45min溶出度(%) | 含量(%) | |
实施例1样品 | |||
0 | 白色颗粒或粉末 | 97.5 | 99.8 |
1 | 白色颗粒或粉末 | 98.6 | 98.8 |
2 | 白色颗粒或粉末 | 97.7 | 99.5 |
3 | 白色颗粒或粉末 | 97.7 | 99.3 |
6 | 白色颗粒或粉末 | 97.5 | 99.5 |
实施例12样品 | |||
0 | 白色颗粒或粉末 | 97.7 | 98.1 |
1 | 白色颗粒或粉末 | 97.8 | 99.3 |
2 | 白色颗粒或粉末 | 98.4 | 100.2 |
3 | 白色颗粒或粉末 | 97.8 | 100.4 |
6 | 白色颗粒或粉末 | 97.6 | 100.1 |
受试者 | 格列本脲 | 盐酸二甲双胍 | ||
F0-24(%) | F0-∞(%) | F0-24(%) | F0-∞(%) | |
A | 124.2 | 123.9 | 81.2 | 81.2 |
B | 122.3 | 124.7 | 108.7 | 108.6 |
C | 120.9 | 125.6 | 99.6 | 98.0 |
D | 106.7 | 104.9 | 86.4 | 87.4 |
E | 72.1 | 71.8 | 90.9 | 91.2 |
F | 90.7 | 90.7 | 72.6 | 72.5 |
G | 78.3 | 78.2 | 95.5 | 96.4 |
H | 122.2 | 121.8 | 92.0 | 92.6 |
I | 102.9 | 105.2 | 73.4 | 73.1 |
J | 110.6 | 108.4 | 104.4 | 107.2 |
K | 123.3 | 124.7 | 123.5 | 122.6 |
L | 116.9 | 116.8 | 116.0 | 116.6 |
M | 83.0 | 80.6 | 123.6 | 122.7 |
N | 100.3 | 98.8 | 111.6 | 111.3 |
O | 130.5 | 133.0 | 72.4 | 73.8 |
P | 89.4 | 89.0 | 79.1 | 80.8 |
Q | 109.0 | 108.5 | 76.7 | 77.8 |
R | 89.4 | 89.2 | 78.8 | 83.5 |
S | 106.5 | 104.2 | 74.6 | 74.4 |
T | 100.7 | 99.3 | 121.8 | 124.5 |
Mean | 105.0 | 105.0 | 94.1 | 94.8 |
±s | 16.9 | 17.8 | 18.3 | 18.1 |
Claims (10)
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CNB2004100659937A CN100341495C (zh) | 2004-12-29 | 2004-12-29 | 格列本脲固体分散体、口服组合物及其制备方法 |
PCT/CN2005/002180 WO2006069519A1 (fr) | 2004-12-29 | 2005-12-14 | Dispersion solide de glibenclamide, sa composition orale et procedes |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102397257A (zh) * | 2010-09-17 | 2012-04-04 | 北京化工大学 | 一种超细格列本脲颗粒的制备方法 |
CN102631332A (zh) * | 2012-04-28 | 2012-08-15 | 邹立兴 | 一种伏格列波糖片剂及其制备方法 |
CN103142521A (zh) * | 2013-03-21 | 2013-06-12 | 西南药业股份有限公司 | 格列本脲片及其制备方法 |
CN106309444A (zh) * | 2016-09-27 | 2017-01-11 | 山东明仁福瑞达制药股份有限公司 | 一种瑞格列奈和盐酸二甲双胍组合物制备方法 |
CN107412239A (zh) * | 2017-04-26 | 2017-12-01 | 中国人民解放军第二军医大学 | 格列本脲在制备防护放射性肺损伤药物中的应用 |
CN113214121A (zh) * | 2020-01-21 | 2021-08-06 | 江苏恒瑞医药股份有限公司 | 一种格列本脲-精氨酸共无定型 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT974356E (pt) * | 1998-07-15 | 2004-02-27 | Merck Sante Sas | Comprimidos compreendendo uma combinacao de metformina e de glibenclamida |
US20010036479A1 (en) * | 2000-01-14 | 2001-11-01 | Gillian Cave | Glyburide composition |
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2004
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102397257A (zh) * | 2010-09-17 | 2012-04-04 | 北京化工大学 | 一种超细格列本脲颗粒的制备方法 |
CN102631332A (zh) * | 2012-04-28 | 2012-08-15 | 邹立兴 | 一种伏格列波糖片剂及其制备方法 |
CN103142521A (zh) * | 2013-03-21 | 2013-06-12 | 西南药业股份有限公司 | 格列本脲片及其制备方法 |
CN106309444A (zh) * | 2016-09-27 | 2017-01-11 | 山东明仁福瑞达制药股份有限公司 | 一种瑞格列奈和盐酸二甲双胍组合物制备方法 |
CN107412239A (zh) * | 2017-04-26 | 2017-12-01 | 中国人民解放军第二军医大学 | 格列本脲在制备防护放射性肺损伤药物中的应用 |
CN107412239B (zh) * | 2017-04-26 | 2019-10-29 | 中国人民解放军第二军医大学 | 格列本脲在制备防护放射性肺损伤药物中的应用 |
CN113214121A (zh) * | 2020-01-21 | 2021-08-06 | 江苏恒瑞医药股份有限公司 | 一种格列本脲-精氨酸共无定型 |
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CN100341495C (zh) | 2007-10-10 |
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