CN116459225B - Alagox sodium tablet and preparation process thereof - Google Patents
Alagox sodium tablet and preparation process thereof Download PDFInfo
- Publication number
- CN116459225B CN116459225B CN202310462234.7A CN202310462234A CN116459225B CN 116459225 B CN116459225 B CN 116459225B CN 202310462234 A CN202310462234 A CN 202310462234A CN 116459225 B CN116459225 B CN 116459225B
- Authority
- CN
- China
- Prior art keywords
- sodium
- alagolide
- tablet
- butyrate
- antigelling agent
- 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.)
- Active
Links
- 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 title claims abstract description 108
- 239000011734 sodium Substances 0.000 title claims abstract description 108
- 229910052708 sodium Inorganic materials 0.000 title claims abstract description 108
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 24
- 239000011248 coating agent Substances 0.000 claims description 15
- 238000000576 coating method Methods 0.000 claims description 15
- 239000000945 filler Substances 0.000 claims description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 9
- -1 sorbitan fatty acid Chemical class 0.000 claims description 9
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 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 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
- 235000010355 mannitol Nutrition 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 229940069328 povidone Drugs 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
- 229920000881 Modified starch Polymers 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- 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 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 229940078456 calcium stearate Drugs 0.000 claims description 3
- 239000007884 disintegrant Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 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-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
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 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 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 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
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 claims description 2
- 229940063655 aluminum stearate Drugs 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 235000001465 calcium Nutrition 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 2
- 229920001531 copovidone Polymers 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 150000002191 fatty alcohols Chemical class 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound 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 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 229940057948 magnesium stearate Drugs 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Chemical class 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 2
- 239000008109 sodium starch glycolate Substances 0.000 claims description 2
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 2
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims 2
- 239000000853 adhesive Substances 0.000 claims 1
- 230000001070 adhesive effect Effects 0.000 claims 1
- 229960004274 stearic acid Drugs 0.000 claims 1
- 150000003951 lactams Chemical class 0.000 abstract description 13
- 239000012535 impurity Substances 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000003860 storage Methods 0.000 abstract description 6
- 239000003349 gelling agent Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 47
- 238000004090 dissolution Methods 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000013011 mating Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 231100000303 OECD 422 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test Toxicity 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010074268 Reproductive toxicity Diseases 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000007696 reproductive toxicity Effects 0.000 description 2
- 231100000372 reproductive toxicity Toxicity 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 150000003385 sodium Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- WRDMYTORSDPYMO-UHFFFAOYSA-N 4-(2-oxopyrrolidin-1-yl)butanoic acid Chemical compound OC(=O)CCCN1CCCC1=O WRDMYTORSDPYMO-UHFFFAOYSA-N 0.000 description 1
- 244000125300 Argania sideroxylon Species 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 231100000476 OECD 421 Reproduction/Developmental Toxicity Screening Test Toxicity 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000010669 acid-base reaction Methods 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007705 chemical test Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 231100000191 repeated dose toxicity Toxicity 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to an Alagox sodium tablet and a preparation process thereof. The sodium esagole tablet comprises sodium esagole and an antigelling agent which is sodium 4- (2-oxo-pyrrolidin-1-yl) butyrate. The inventors have surprisingly found that sodium 4- (2-oxo-pyrrolidin-1-yl) butyrate can act as a gelling agent in the sodium alagolide tablet, not only can effectively reduce the formation of alagolide gel, can enable the drug to be released rapidly, smoothly and uniformly, but also can improve the stability of the sodium alagolide, in particular inhibit the generation of lactam impurities, thereby prolonging the storage time of the sodium alagolide tablet and improving the medication safety.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an Alagox sodium tablet and a preparation process thereof.
Background
Sodium elagogram (elagoix, CAS No. 832720-36-2) is a gonadotropin releasing hormone (GnRH) antagonist developed by Abbvie corporation (Abbvie) and is used clinically to relieve moderate to severe pain symptoms caused by uterine fibroids, endometriosis, etc. in adult females.
In developing oral tablets of elagoke sodium, ibovi corporation found at least two difficulties (CN 111698992A, CN111246850 a): 1. the tendency of sodium alagolide to form gels when applied orally in solid dosage forms, particularly when the solid formulation does not contain suitable antigelling agents, is even greater, the gel formed limiting the dissolution of sodium alagolide, which may ultimately lead to a great variation in bioavailability between and among patients; 2. the sodium elagose may degrade to form compounds with lactam structures. By adopting the pharmaceutical composition of 'Igacross sodium+sodium carbonate', the gelation of Igacross sodium can be reduced and/or the generation of lactam degradation products can be reduced, so that the safety and efficacy of the product can be maintained. However, although the use of sodium carbonate improved the dissolution rate of the alagolic tablet to some extent, the dissolution rate was still slow for the first 30 minutes, indicating that the anti-gelling effect was still limited and that sodium carbonate had a weaker efficacy in inhibiting the production of lactam impurity, the tablet comprising sodium carbonate only reduced the content of lactam impurity by about 50% compared to the tablet without the anti-gelling agent.
Accordingly, there remains an unmet need for developing oral sodium argan tablets with improved dissolution rate and storage stability.
Disclosure of Invention
In order to solve the above problems, the present invention provides an alagolica sodium tablet comprising alagolica sodium and an antigelling agent which is sodium 4- (2-oxopyrrolidin-1-yl) butyrate.
The chemical structural formula of the Alagox sodium is shown as follows:
the chemical structural formula of the sodium 4- (2-oxo-pyrrolidin-1-yl) butyrate is shown as follows:
sodium 4- (2-oxopyrrolidin-1-yl) butyrate is readily available from the acid-base reaction of commercially available 4- (2-oxopyrrolidin-1-yl) butyric acid with a base such as sodium hydroxide.
Further, the weight ratio of the sodium elagose to the antigelling agent is 1:1 to 20:1. For example, the weight ratio of the sodium elagogram to the antigelling agent is 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, or 20:1.
Still further, the weight ratio of the sodium elagose to the antigelling agent is 4:1.
Further, the sodium argatrovix tablet comprises 10-40wt% of sodium argatrovix. For example, the sodium argyi tablet comprises 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt%, 16wt%, 17wt%, 18wt%, 19wt%, 20wt%, 21wt%, 22wt%, 23wt%, 24wt%, 25wt%, 26wt%, 27wt%, 28wt%, 29wt%, 30wt%, 31wt%, 32wt%, 33wt%, 34wt%, 35wt%, 36wt%, 37wt%, 38wt%, 39wt%, or 40wt% sodium argyi. Still further, the sodium argatrovix tablet comprises 50mg, 100mg, 150mg, 200mg, 250mg or 300mg of sodium argatrovix.
Further, the sodium alagolicum tablet also comprises a pharmaceutically acceptable excipient.
Further, the pharmaceutically acceptable excipients include one or more of fillers, binders, lubricants, disintegrants, glidants, and surfactants.
Further, the filler includes one or more of starch, pregelatinized starch, mannitol, sorbitol, lactose, sucrose, microcrystalline cellulose, and calcium phosphate. Still further, the filler comprises mannitol or pregelatinized starch or a combination thereof.
Further, the filler is contained in the sodium argag tablet in an amount of 5 to 65wt%, or 10 to 60wt%, or 15 to 55wt%, or 10 to 50wt%, or 15 to 45wt%, or 20 to 40wt%, or 25 to 40wt%, or 30 to 40wt%.
Further, the sodium alagolicum tablet comprises 20wt% to 50wt% of the first filler and 1wt% to 20wt% of the second filler. Further, the sodium alagolicum tablet comprises 25wt% to 40wt% of the first filler and 5wt% to 15wt% of the second filler. Further, the sodium alagolicum tablet comprises 38wt% of the first filler and 12wt% of the second filler. Further, the first filler is mannitol and the second filler is pregelatinized starch.
Further, the binder includes one or more of povidone, copovidone, polyacrylate, polymethacrylate, polyacrylamide, polyvinyl alcohol, vinyl acetate polymer, hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, oligosaccharides, and polysaccharides. Still further, the binder comprises povidone or hydroxypropyl cellulose.
Further, the binder is present in the sodium alagogram tablet in an amount of 0.1 to 20wt%, or 0.5 to 15wt%, or 1 to 10wt%, or 1.5 to 18wt%, or 2 to 16wt%, or 2.5 to 14wt%, or 3 to 12wt%, or 3.5 to 10wt%, or 4 to 8wt%, or 3 to 7wt%, or 2 to 9wt%, or 2 to 6wt%, or 1 to 5wt%, or 1.5 to 5wt%, or 2 to 5wt%, or 2.5 to 5wt%, or 3 to 5wt%.
Further, the lubricant includes one or more of magnesium stearate, calcium stearate, aluminum stearate, glyceryl monostearate, stearic acid and talc, preferably one or more of magnesium stearate, calcium stearate and talc. Still further, the lubricant comprises magnesium stearate.
Further, the lubricant is contained in the sodium argag tablet in an amount of 0.1 to 10wt%, or 0.5 to 8wt%, or 1 to 5wt%, or 1.5 to 9wt%, or 1.7 to 8wt%, or 1.6 to 7wt%, or 1.7 to 6wt%, or 1.8 to 5wt%, or 1.9 to 4wt%, or 2 to 3wt%, or 1.5 to 6wt%, or 1.5 to 5wt%, or 1.5 to 4wt%, or 1.5 to 3wt%, or 1 to 2wt%.
Further, the disintegrant comprises one or more of crospovidone, croscarmellose sodium, sodium carboxymethylcellulose, calcium carboxymethylcellulose, low substituted hydroxypropyl cellulose and sodium starch glycolate. Further, the content of the disintegrating agent in the sodium argyi-goke tablet is 0-20wt%.
Further, the glidant includes one or more of colloidal silicon dioxide and talc. Further, the content of the disintegrating agent in the sodium argyi-goke tablet is 0-5wt%.
Further, the surfactant comprises one or more of polysorbate, sorbitan fatty acid, glyceride fatty acid, sucrose fatty acid ester, polyoxyethylene fatty alcohol ether, poloxamer, sodium dodecyl sulfate and sodium docusate. Further, the content of the disintegrating agent in the sodium argyi-goke tablet is 0-3wt%.
Further, the sodium alagolicum tablet further comprises a coating.
Further, the coating may be used, for example, to facilitate easy swallowing of the tablet. The coating may also be used to improve taste and provide a beautiful appearance. The coating may comprise one or a mixture or copolymer of at least two of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, polyethylene glycol, polyvinyl alcohol, povidone, etc., such as polyvinyl alcohol-polyethylene glycol graft copolymer, for exampleII or->IR. The coating may also include talc as an anti-adherent. The coating may comprise less than about 5% by weight of the tablet.
The invention also provides a method for preparing the sodium Igurative tablet, which comprises the steps of uniformly mixing sodium Igurative, an antigelling agent and a pharmaceutically acceptable excipient, granulating, mixing, tabletting and coating to obtain the sodium Igurative tablet.
Further, the method comprises pulverizing the antigelling agent and sieving with an 80 mesh sieve; weighing the raw materials and pharmaceutically acceptable excipients according to the prescription, mixing, granulating, weighing the antigelling agent and pharmaceutically acceptable excipients according to the prescription, mixing, tabletting and coating to obtain the Igacross sodium tablets. Further, the granulating includes dry granulating or wet granulating.
Advantageous effects of the invention
The inventors have unexpectedly found that sodium 4- (2-oxopyrrolidin-1-yl) butyrate can act as an antigelling agent in the sodium alagolide tablet, not only can effectively reduce the formation of alagolide gel, can enable the drug to be released rapidly, smoothly and uniformly, but also can improve the stability of the alagolide sodium, in particular, inhibit the generation of lactam impurities, thereby prolonging the storage time of the sodium alagolide tablet and improving the medication safety. In contrast, sodium (2S) -2- (2-oxopyrrolidin-1-yl) butyrate, which is a structural analogue of sodium 4- (2-oxopyrrolidin-1-yl) butyrate, does not possess this feature (its structure is described in the examples). Without being bound by theory, it is believed that this is probably due to the lower pKa of sodium (2S) -2- (2-oxopyrrolidin-1-yl) butyrate compared to sodium 4- (2-oxopyrrolidin-1-yl) butyrate.
On one hand, the sodium esagole tablet has excellent dissolution characteristics, and the problem that esagole sodium is easy to gel is successfully solved by using the sodium esagole 4- (2-oxo-pyrrolidine-1-yl) butyrate, so that quick dissolution in the first 30min is realized, the dissolution performance of the medicine is improved, and the good release and absorption of the medicine in a body are facilitated. The sodium argatrovix tablet of the invention shows excellent dissolution rate in the medium simulating the conditions of pre-meal (pH 1.2) and post-meal (pH 4.5), especially the dissolution rate of the first 30min is obviously improved, which shows the rapidity of the anti-gelling agent effect and the durability of the anti-gelling effect.
On the other hand, the sodium esagole tablet has excellent stability and can remarkably inhibit the generation of lactam impurities. The examples demonstrate that the lactam impurity content is almost unchanged after 10 days of storage and less than about 0.3wt% after 20 days of storage when accelerated stability studies are carried out at 60 ℃ and 40% relative humidity.
Drawings
Fig. 1 shows the dissolution profile of the sodium alagolide tablets of examples 1-4 at pH 1.2.
Fig. 2 shows the dissolution profile of the sodium alagolide tablets of examples 1-4 at pH 4.5.
Detailed Description
The present invention is further illustrated below with reference to specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Examples 1 to 4: preparation of sodium Igacross tablets of different formulations
The sodium alagolide tablets were prepared according to the following formulation of table 1:
table 1: formula (mass percent) of different Alagox sodium tablets
Wherein sodium (2S) -2- (2-oxopyrrolidin-1-yl) butyrate is compared as a structural analogue of sodium 4- (2-oxopyrrolidin-1-yl) butyrate in the examples of the present invention, the chemical structural formula is shown below:
the preparation method of the sodium Igacross tablet by dry granulation comprises the following steps:
step (1) pretreatment: crushing sodium 4- (2-oxo-pyrrolidin-1-yl) butyrate (or sodium (2S) -2- (2-oxo-pyrrolidin-1-yl) butyrate or sodium carbonate), and sieving with a 80-mesh sieve;
and (2) weighing: respectively weighing raw materials and auxiliary materials according to the prescription amount;
and (3) granulating: mixing sodium alagolicum, mannitol, pregelatinized starch, magnesium stearate and povidone in a mixer, and performing dry granulation by using a dry granulator with the following parameters: rotation speed of the press roller: 6rpm, feed rate: 32rpm, nip: 1.0mm, pressure of the press roll: 80-90 bar, finishing speed of 100rpm, finishing screen 14 mesh;
step (4) total mixing: mixing the granules obtained in the step (3) with magnesium stearate, sodium 4- (2-oxo-pyrrolidin-1-yl) butyrate (or sodium (2S) -2- (2-oxo-pyrrolidin-1-yl) butyrate or sodium carbonate) and mannitol;
and (5) tabletting: adding the total mixed materials into a rotary tablet press, and adjusting the loading (the loading is 450 mg) and tabletting (the hardness is 8-10 kg);
coating in the step (6): adopts a high-efficiency coating machineAnd II, coating, wherein the weight of the coating is increased by 3%, and the Alagox sodium tablet is prepared.
Example 5: dissolution characteristics of the sodium Igacross tablets of examples 1-4
Dissolution rate measurement method: according to the general oral solid preparation dissolution test technical guidelines and dissolution and release rate measurement methods (four general regulations of Chinese pharmacopoeia 2020 edition), a hydrochloric acid solution with a pH of 1.2 and a citrate buffer solution with a pH of 4.5 are respectively used as dissolution media, the volume of the dissolution media is 900ml, the rotating speed is 50rpm, the dissolution media are respectively sampled at 5, 10, 15, 20, 25, 30, 45 and 60min, the absorbance (n=6) is measured at the wavelength of ultraviolet 274nm, and the dissolution curves are shown in figures 1 and 2.
As can be seen from the results of fig. 1 and 2, the dissolution profile of the alagolica sodium tablet is slightly better using sodium 4- (2-oxopyrrolidin-1-yl) butyrate as an antigelling agent (example 1) than using sodium carbonate as an antigelling agent. Instead of using an antigelling agent or using sodium (2S) -2- (2-oxopyrrolidin-1-yl) butyrate as an antigelling agent, the dissolution characteristics of the alagolica sodium tablet are significantly deteriorated.
Example 6: stability characteristics of the Alagox sodium tablets of examples 1-4
The chemical structural formula of the lactam impurity of the sodium elagose is shown as follows:
the lactam impurity content was determined using reverse phase High Performance Liquid Chromatography (HPLC) and detection with ultraviolet light (UV) at 275nm as described in CN 111698992. The HPLC system consisted of a C8 column with a flow rate of 1.1mL/min. Throughout the analysis, the column temperature was maintained at 50 ℃. Both mobile phases a and B were used, wherein mobile phase a was a triethylamine/acetic acid buffer solution at ph5.3 and the ratio of water to triethylamine to acetic acid was 100:0.1:0.06 (v/v) and mobile phase B was acetonitrile. The diluent is a 50:50 (v/v) ratio of triethylamine/acetic acid buffer and acetonitrile. The detection limit standard is prepared in a diluent having a known concentration of about 0.06 μg of alagolica sodium per ml.
The sodium esagole tablets of examples 1-4 were subjected to accelerated stability studies at 60 ℃ and 40% relative humidity, sampled over a defined period of time and analyzed using HPLC, and the results are shown in table 2.
Table 2: results of lactam impurity content test of the Alagox sodium tablets of examples 1 to 4
From the results of table 2, it is seen that the use of sodium 4- (2-oxopyrrolidin-1-yl) butyrate as an antigelling agent (example 1) resulted in a slow increase in lactam impurity after storage of the drug for a certain period of time, and that the effect of inhibiting the production of lactam impurity was significantly better than that of sodium carbonate (antigelling agent used in CN111698992, example 3) or sodium (2S) -2- (2-oxopyrrolidin-1-yl) butyrate (example 2).
Example 7: reproductive toxicity characteristics of the sodium Igacross tablet of example 1
Reproduction toxicity was tested in a repeat dose toxicity study in combination with reproduction/developmental toxicity screening test (Guideline for the testing of chemicals, combined Repeated Dose Toxicity Study with the Reproduction/Development Toxicity Screening Test) similar to the OECD422 method "chemical test guidelines. According to this test, the method comprises administering (preferably orally) test substances in graded doses to groups of male and female rats allowed to mate. The males under test will be dosed for a minimum of four weeks up to and including the day prior to the scheduled kill, including: a minimum of two weeks before mating, during the mating period, and about two weeks after mating. A combination of two weeks of pre-mating dosing period, followed by observation of mating and fertility during at least four weeks of total dosing, and then detailed histopathology of the male gonads is considered sufficient to be able to detect major effects on male fertility and spermatogenesis. Female rats were dosed throughout the study.
The sodium alagolide tablets according to the invention show no evidence of any reproductive toxicity when tested in Han Wistar rats according to OECD422 guidelines.
In the description of the specification, reference to the term "one embodiment," "a particular embodiment," "an example," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The foregoing is merely illustrative and explanatory of the invention, as various modifications and additions may be made to the particular embodiments described, or by similar arrangements, by those skilled in the art, without departing from the scope of the invention or beyond the scope of the appended claims.
Claims (10)
1. An elargogue sodium tablet comprising elargogue sodium and an antigelling agent which is sodium 4- (2-oxopyrrolidin-1-yl) butyrate.
2. The sodium alagolide tablet of claim 1, wherein the weight ratio of the sodium alagolide to the antigelling agent is 1:1 to 20:1.
3. The sodium alagolide tablet of claim 1, wherein the weight ratio of the sodium alagolide to the antigelling agent is 4:1.
4. The sodium alagolide tablet of claim 1, wherein the sodium alagolide tablet comprises 10-40wt% of sodium alagolide.
5. The sodium alagolide tablet of claim 1, wherein the sodium alagolide tablet further comprises a pharmaceutically acceptable excipient.
6. The sodium alagolide tablet of claim 5, wherein the pharmaceutically acceptable excipients comprise one or more of fillers, binders, lubricants, disintegrants, glidants and surfactants.
7. The sodium alagolide tablet of claim 6, wherein the filler comprises one or more of starch, pregelatinized starch, mannitol, sorbitol, lactose, sucrose, microcrystalline cellulose, and calcium phosphate;
the adhesive comprises one or more of povidone, copovidone, polyacrylate, polymethacrylate, polyacrylamide, polyvinyl alcohol, vinyl acetate polymer, hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, oligosaccharides and polysaccharides;
the lubricant comprises one or more of magnesium stearate, calcium stearate, aluminum stearate, glyceryl monostearate, stearic acid and talcum powder;
the disintegrating agent comprises one or more of crospovidone, croscarmellose sodium, sodium carboxymethylcellulose, calcium carboxymethylcellulose, low-substituted hydroxypropyl cellulose and sodium starch glycolate;
the glidant comprises one or more of colloidal silicon dioxide and talcum powder;
the surfactant comprises one or more of polysorbate, sorbitan fatty acid, glyceride fatty acid, sucrose fatty acid ester, polyoxyethylene fatty alcohol ether, poloxamer, sodium dodecyl sulfate and sodium docusate.
8. The sodium alagolide tablet of claim 1, wherein the sodium alagolide tablet further comprises a coating.
9. The sodium alagolide tablet of claim 8, wherein the coating comprises one or a mixture of at least two of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, polyethylene glycol, polyvinyl alcohol, and povidone.
10. A process for preparing the sodium alagolide tablet according to any one of claims 8 to 9, comprising the steps of mixing the sodium alagolide and the antigelling agent uniformly, granulating, mixing, tabletting and coating to obtain the sodium alagolide tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310462234.7A CN116459225B (en) | 2023-04-26 | 2023-04-26 | Alagox sodium tablet and preparation process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310462234.7A CN116459225B (en) | 2023-04-26 | 2023-04-26 | Alagox sodium tablet and preparation process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116459225A CN116459225A (en) | 2023-07-21 |
| CN116459225B true CN116459225B (en) | 2023-11-10 |
Family
ID=87182289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310462234.7A Active CN116459225B (en) | 2023-04-26 | 2023-04-26 | Alagox sodium tablet and preparation process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116459225B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013087563A1 (en) * | 2011-12-16 | 2013-06-20 | Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A. | Pharmaceutical composition comprising (s)-2-(2-oxopyrrolidin-1-yl)butanamid |
| CN111246850A (en) * | 2017-08-18 | 2020-06-05 | 艾伯维公司 | Solid pharmaceutical formulation for the treatment of endometriosis, uterine fibroids, polycystic ovary syndrome and adenomyosis |
| CN111698992A (en) * | 2017-08-18 | 2020-09-22 | 艾伯维公司 | Pharmaceutical formulation for the treatment of endometriosis, uterine fibroids, polycystic ovarian syndrome or adenomyosis |
| US11273128B1 (en) * | 2021-04-15 | 2022-03-15 | Sandoz Ag | Elagolix formulation |
| CN114948889A (en) * | 2022-06-17 | 2022-08-30 | 哈药集团技术中心 | Preparation method of oxalagrange tablets and prepared oxalagrange tablets |
| CN115177595A (en) * | 2022-07-06 | 2022-10-14 | 金陵药业股份有限公司 | Oxagolide sodium tablet and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY143249A (en) * | 2005-09-15 | 2011-04-15 | Ucb Pharma Sa | 4-substituted pyrrolidin-2-ones and their use |
| US8354444B2 (en) * | 2008-09-18 | 2013-01-15 | Hoffmann-La Roche Inc. | Substituted pyrrolidine-2-carboxamides |
-
2023
- 2023-04-26 CN CN202310462234.7A patent/CN116459225B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013087563A1 (en) * | 2011-12-16 | 2013-06-20 | Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A. | Pharmaceutical composition comprising (s)-2-(2-oxopyrrolidin-1-yl)butanamid |
| CN111246850A (en) * | 2017-08-18 | 2020-06-05 | 艾伯维公司 | Solid pharmaceutical formulation for the treatment of endometriosis, uterine fibroids, polycystic ovary syndrome and adenomyosis |
| CN111698992A (en) * | 2017-08-18 | 2020-09-22 | 艾伯维公司 | Pharmaceutical formulation for the treatment of endometriosis, uterine fibroids, polycystic ovarian syndrome or adenomyosis |
| US11273128B1 (en) * | 2021-04-15 | 2022-03-15 | Sandoz Ag | Elagolix formulation |
| CN114948889A (en) * | 2022-06-17 | 2022-08-30 | 哈药集团技术中心 | Preparation method of oxalagrange tablets and prepared oxalagrange tablets |
| CN115177595A (en) * | 2022-07-06 | 2022-10-14 | 金陵药业股份有限公司 | Oxagolide sodium tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 噁拉戈利关键中间体的新合成方法;孔锐;中国医药工业杂志;第52卷;1-4 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116459225A (en) | 2023-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101524164B1 (en) | Controlled release pharmaceutical composition | |
| EP2029134B1 (en) | Stabilized pharmaceutical compositions comprising fesoterodine | |
| EP1441713B2 (en) | Modified release tamsulosin tablets | |
| AU2009321728B2 (en) | Solid dosage forms of bendamustine | |
| KR20100015764A (en) | Stabilised pharmaceutical composition containing pregabaline | |
| WO2019219920A1 (en) | Stable pharmaceutical compositions of dpp-iv inhibitors in combination with metformin in the form of immediate release tablets | |
| US8772346B2 (en) | Pharmaceutical composition | |
| CN116459225B (en) | Alagox sodium tablet and preparation process thereof | |
| WO2010098482A1 (en) | Stable capsule preparation and method for producing same | |
| JP6680297B2 (en) | Pharmaceutical composition for oral administration | |
| EP3679927A1 (en) | A method of manufacturing a pharmaceutical composition comprising nefopam and acetaminophen, and the pharmaceutical composition obtained thereby | |
| WO2000071117A1 (en) | Immediate release medicinal compositions for oral use | |
| EP2934494B1 (en) | Pharmaceutical formulation of n- [5- [2-(3,5-dimethoxyphenyl) ethyl]-2h-pyrazol-3-yl]-4-[(3r,5s)-3,5-dimethylpiperazin-1-yl]benzamide | |
| JP7355020B2 (en) | Pharmaceutical composition for oral administration | |
| Kestur et al. | Excipients for conventional oral solid dosage forms | |
| CN108078945B (en) | Canagliflozin pharmaceutical composition | |
| CN115804774B (en) | Pharmaceutical composition of oxarogeli, pharmaceutical preparation containing pharmaceutical composition and application of pharmaceutical composition | |
| WO2005020978A1 (en) | Sustained release oral tablets of gabapentin and process for their preparation | |
| EP2197423B1 (en) | Improved pharmaceutical composition containing a selective estrogen receptor modulator and method for the preparation thereof | |
| WO2022042646A1 (en) | Lurasidone hydrochloride composition and preparation method therefor | |
| EP4212150A1 (en) | A bilayer tablet composition comprising amorphous dapagliflozin and metformin | |
| WO2023149546A1 (en) | Oral solid preparation | |
| EP4079296A1 (en) | A bilayer tablet formulation comprising amorphous dapagliflozin and metformin | |
| EP3928771A1 (en) | Pharmaceutical compositions of 1,2-benzisoxazole-3-methanesulfonamide |
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 |