JP2017193554A - 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 - Google Patents
17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 Download PDFInfo
- Publication number
- JP2017193554A JP2017193554A JP2017098138A JP2017098138A JP2017193554A JP 2017193554 A JP2017193554 A JP 2017193554A JP 2017098138 A JP2017098138 A JP 2017098138A JP 2017098138 A JP2017098138 A JP 2017098138A JP 2017193554 A JP2017193554 A JP 2017193554A
- Authority
- JP
- Japan
- Prior art keywords
- peg
- acid
- glyceryl
- dosage form
- oral dosage
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title claims description 248
- DBPWSSGDRRHUNT-UHFFFAOYSA-N 17alpha-hydroxy progesterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)(O)C1(C)CC2 DBPWSSGDRRHUNT-UHFFFAOYSA-N 0.000 title abstract description 106
- -1 17-hydroxyprogesterone ester Chemical class 0.000 title description 33
- 239000006186 oral dosage form Substances 0.000 claims abstract description 171
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 claims abstract description 167
- 239000000654 additive Substances 0.000 claims abstract description 91
- 230000035935 pregnancy Effects 0.000 claims abstract description 61
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000002775 capsule Substances 0.000 claims abstract description 50
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 32
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims abstract description 31
- 229960002903 benzyl benzoate Drugs 0.000 claims abstract description 29
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims abstract description 21
- 238000004090 dissolution Methods 0.000 claims abstract description 14
- 239000003937 drug carrier Substances 0.000 claims abstract description 14
- 230000000968 intestinal effect Effects 0.000 claims abstract description 14
- 239000002552 dosage form Substances 0.000 claims description 84
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 66
- 230000000996 additive effect Effects 0.000 claims description 64
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims description 62
- 239000004359 castor oil Substances 0.000 claims description 56
- 235000019438 castor oil Nutrition 0.000 claims description 56
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 56
- 239000008194 pharmaceutical composition Substances 0.000 claims description 54
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 54
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 53
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 49
- 229920001223 polyethylene glycol Polymers 0.000 claims description 49
- 239000002202 Polyethylene glycol Substances 0.000 claims description 48
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 47
- 125000005456 glyceride group Chemical group 0.000 claims description 45
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims description 43
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 42
- 229940070765 laurate Drugs 0.000 claims description 42
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 claims description 41
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 40
- 208000005107 Premature Birth Diseases 0.000 claims description 39
- 150000001875 compounds Chemical class 0.000 claims description 37
- 229940049964 oleate Drugs 0.000 claims description 37
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 claims description 34
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 33
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 32
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 31
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 30
- 239000000194 fatty acid Substances 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 27
- 229930195729 fatty acid Natural products 0.000 claims description 27
- 229940074046 glyceryl laurate Drugs 0.000 claims description 26
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 26
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 25
- 229920002678 cellulose Polymers 0.000 claims description 25
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 claims description 24
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical group CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 24
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims description 24
- 235000005687 corn oil Nutrition 0.000 claims description 24
- 239000002285 corn oil Substances 0.000 claims description 24
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 24
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 24
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 23
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 23
- 229960002446 octanoic acid Drugs 0.000 claims description 23
- 235000011076 sorbitan monostearate Nutrition 0.000 claims description 23
- 239000001587 sorbitan monostearate Substances 0.000 claims description 23
- 229940035048 sorbitan monostearate Drugs 0.000 claims description 23
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 22
- DTPCFIHYWYONMD-UHFFFAOYSA-N decaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO DTPCFIHYWYONMD-UHFFFAOYSA-N 0.000 claims description 22
- 239000002245 particle Substances 0.000 claims description 22
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 claims description 21
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 229940035044 sorbitan monolaurate Drugs 0.000 claims description 21
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 claims description 21
- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-N 0.000 claims description 20
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 20
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 20
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 claims description 20
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims description 20
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical group 0.000 claims description 19
- 229940035049 sorbitan monooleate Drugs 0.000 claims description 19
- 235000011069 sorbitan monooleate Nutrition 0.000 claims description 19
- 239000001593 sorbitan monooleate Substances 0.000 claims description 19
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 18
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 18
- 235000013772 propylene glycol Nutrition 0.000 claims description 18
- 235000019483 Peanut oil Nutrition 0.000 claims description 17
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 17
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 17
- 229920002301 cellulose acetate Polymers 0.000 claims description 17
- 235000019441 ethanol Nutrition 0.000 claims description 17
- 229940049918 linoleate Drugs 0.000 claims description 17
- 239000000312 peanut oil Substances 0.000 claims description 17
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 17
- 239000001856 Ethyl cellulose Substances 0.000 claims description 16
- 235000021355 Stearic acid Nutrition 0.000 claims description 16
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 16
- 229920001249 ethyl cellulose Polymers 0.000 claims description 16
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 16
- 239000008117 stearic acid Substances 0.000 claims description 16
- 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 15
- 108010010803 Gelatin Proteins 0.000 claims description 15
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 15
- 238000013270 controlled release Methods 0.000 claims description 15
- 239000012530 fluid Substances 0.000 claims description 15
- 229920000159 gelatin Polymers 0.000 claims description 15
- 239000008273 gelatin Substances 0.000 claims description 15
- 229940014259 gelatin Drugs 0.000 claims description 15
- 235000019322 gelatine Nutrition 0.000 claims description 15
- 235000011852 gelatine desserts Nutrition 0.000 claims description 15
- 235000011187 glycerol Nutrition 0.000 claims description 15
- 235000012424 soybean oil Nutrition 0.000 claims description 15
- 239000003549 soybean oil Substances 0.000 claims description 15
- 239000011732 tocopherol Substances 0.000 claims description 15
- 229930003799 tocopherol Natural products 0.000 claims description 15
- 239000001069 triethyl citrate Substances 0.000 claims description 15
- 235000013769 triethyl citrate Nutrition 0.000 claims description 15
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 15
- ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 2-dodecanoyloxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCC ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 0.000 claims description 14
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 14
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 14
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- 229920002125 Sokalan® Polymers 0.000 claims description 14
- 229920006217 cellulose acetate butyrate Polymers 0.000 claims description 14
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 14
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 14
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 14
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 14
- 235000008390 olive oil Nutrition 0.000 claims description 14
- 239000004006 olive oil Substances 0.000 claims description 14
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 13
- HBOQXIRUPVQLKX-BBWANDEASA-N 1,2,3-trilinoleoylglycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/C\C=C/CCCCC)COC(=O)CCCCCCC\C=C/C\C=C/CCCCC HBOQXIRUPVQLKX-BBWANDEASA-N 0.000 claims description 13
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 13
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 13
- 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 13
- 229930195725 Mannitol Natural products 0.000 claims description 13
- 239000005642 Oleic acid Substances 0.000 claims description 13
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 13
- 235000019485 Safflower oil Nutrition 0.000 claims description 13
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims description 13
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 13
- 239000001087 glyceryl triacetate Substances 0.000 claims description 13
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 13
- HBOQXIRUPVQLKX-UHFFFAOYSA-N linoleic acid triglyceride Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC HBOQXIRUPVQLKX-UHFFFAOYSA-N 0.000 claims description 13
- 239000000594 mannitol Substances 0.000 claims description 13
- 235000010355 mannitol Nutrition 0.000 claims description 13
- 235000005713 safflower oil Nutrition 0.000 claims description 13
- 239000003813 safflower oil Substances 0.000 claims description 13
- 235000011803 sesame oil Nutrition 0.000 claims description 13
- 239000008159 sesame oil Substances 0.000 claims description 13
- 235000010384 tocopherol Nutrition 0.000 claims description 13
- 229960001295 tocopherol Drugs 0.000 claims description 13
- 229960002622 triacetin Drugs 0.000 claims description 13
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 claims description 13
- 229940117972 triolein Drugs 0.000 claims description 13
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 13
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims description 12
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 claims description 12
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 claims description 12
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 12
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 12
- 239000005639 Lauric acid Substances 0.000 claims description 12
- 235000021314 Palmitic acid Nutrition 0.000 claims description 12
- 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 12
- 229930006000 Sucrose Natural products 0.000 claims description 12
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 claims description 12
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims description 12
- 229940090949 docosahexaenoic acid Drugs 0.000 claims description 12
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 12
- 229940093471 ethyl oleate Drugs 0.000 claims description 12
- 239000011976 maleic acid Substances 0.000 claims description 12
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 12
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 12
- 235000021313 oleic acid Nutrition 0.000 claims description 12
- 239000005720 sucrose Substances 0.000 claims description 12
- 229940042585 tocopherol acetate Drugs 0.000 claims description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 12
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 claims description 12
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 claims description 11
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims description 11
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 claims description 11
- 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 11
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 11
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 11
- 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 11
- 229930091371 Fructose Natural products 0.000 claims description 11
- 239000005715 Fructose Substances 0.000 claims description 11
- 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 11
- 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 11
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 11
- 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 11
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 11
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims description 11
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 11
- 235000010323 ascorbic acid Nutrition 0.000 claims description 11
- 239000011668 ascorbic acid Substances 0.000 claims description 11
- 229960005070 ascorbic acid Drugs 0.000 claims description 11
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 11
- 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 11
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 11
- 229960001631 carbomer Drugs 0.000 claims description 11
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims description 11
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims description 11
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims description 11
- 229940087068 glyceryl caprylate Drugs 0.000 claims description 11
- 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 11
- 235000014655 lactic acid Nutrition 0.000 claims description 11
- 239000004310 lactic acid Substances 0.000 claims description 11
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 11
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 11
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 239000000377 silicon dioxide Substances 0.000 claims description 11
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 11
- 235000011071 sorbitan monopalmitate Nutrition 0.000 claims description 11
- 239000001570 sorbitan monopalmitate Substances 0.000 claims description 11
- 229940031953 sorbitan monopalmitate Drugs 0.000 claims description 11
- 235000002906 tartaric acid Nutrition 0.000 claims description 11
- 239000011975 tartaric acid Substances 0.000 claims description 11
- 239000000811 xylitol Substances 0.000 claims description 11
- 235000010447 xylitol Nutrition 0.000 claims description 11
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 11
- 229960002675 xylitol Drugs 0.000 claims description 11
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 10
- PAFJZWHXMSQJKV-UQZRNVAESA-N (3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol;octadecanoic acid Chemical compound OC[C@@H](O)C1OC[C@H](O)[C@H]1O.OC[C@@H](O)C1OC[C@H](O)[C@H]1O.OC[C@@H](O)C1OC[C@H](O)[C@H]1O.CCCCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O PAFJZWHXMSQJKV-UQZRNVAESA-N 0.000 claims description 10
- OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 claims description 10
- 239000005711 Benzoic acid Substances 0.000 claims description 10
- 229920001661 Chitosan Polymers 0.000 claims description 10
- 229920002509 Poloxamer 182 Polymers 0.000 claims description 10
- 235000011054 acetic acid Nutrition 0.000 claims description 10
- 235000010233 benzoic acid Nutrition 0.000 claims description 10
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 10
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 10
- 229940074045 glyceryl distearate Drugs 0.000 claims description 10
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 10
- 229940046813 glyceryl palmitostearate Drugs 0.000 claims description 10
- 229920000609 methyl cellulose Polymers 0.000 claims description 10
- 235000010981 methylcellulose Nutrition 0.000 claims description 10
- 239000001923 methylcellulose Substances 0.000 claims description 10
- 229940093426 poloxamer 182 Drugs 0.000 claims description 10
- 229920001993 poloxamer 188 Polymers 0.000 claims description 10
- 229940104257 polyglyceryl-6-dioleate Drugs 0.000 claims description 10
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 10
- 229940026235 propylene glycol monolaurate Drugs 0.000 claims description 10
- 235000012239 silicon dioxide Nutrition 0.000 claims description 10
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 9
- NFIHXTUNNGIYRF-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate Chemical compound CCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCC NFIHXTUNNGIYRF-UHFFFAOYSA-N 0.000 claims description 9
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 9
- 229940068939 glyceryl monolaurate Drugs 0.000 claims description 9
- 229960003511 macrogol Drugs 0.000 claims description 9
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 9
- 229940044519 poloxamer 188 Drugs 0.000 claims description 9
- 235000011067 sorbitan monolaureate Nutrition 0.000 claims description 9
- 229960005078 sorbitan sesquioleate Drugs 0.000 claims description 9
- 239000004375 Dextrin Substances 0.000 claims description 8
- 229920001353 Dextrin Polymers 0.000 claims description 8
- 239000001534 FEMA 4201 Substances 0.000 claims description 8
- 108010077895 Sarcosine Proteins 0.000 claims description 8
- 235000010216 calcium carbonate Nutrition 0.000 claims description 8
- 235000019425 dextrin Nutrition 0.000 claims description 8
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 8
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 claims description 8
- 229940075529 glyceryl stearate Drugs 0.000 claims description 8
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 8
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 229940079862 sodium lauryl sarcosinate Drugs 0.000 claims description 8
- ADWNFGORSPBALY-UHFFFAOYSA-M sodium;2-[dodecyl(methyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCN(C)CC([O-])=O ADWNFGORSPBALY-UHFFFAOYSA-M 0.000 claims description 8
- 229950006451 sorbitan laurate Drugs 0.000 claims description 8
- CLYAQFSQLQTVNO-UHFFFAOYSA-N 3-cyclohexylpropan-1-ol Chemical compound OCCCC1CCCCC1 CLYAQFSQLQTVNO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003613 bile acid Substances 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 239000001944 prunus armeniaca kernel oil Substances 0.000 claims description 6
- 239000004698 Polyethylene Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 2
- OYHQOLUKZRVURQ-HZJYTTRNSA-M 9-cis,12-cis-Octadecadienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O OYHQOLUKZRVURQ-HZJYTTRNSA-M 0.000 claims 2
- 150000002148 esters Chemical class 0.000 abstract description 127
- DBPWSSGDRRHUNT-CEGNMAFCSA-N 17α-hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-CEGNMAFCSA-N 0.000 abstract description 113
- 235000011389 fruit/vegetable juice Nutrition 0.000 abstract 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 43
- 208000000995 spontaneous abortion Diseases 0.000 description 33
- 239000003826 tablet Substances 0.000 description 32
- 206010000234 Abortion spontaneous Diseases 0.000 description 28
- 239000006185 dispersion Substances 0.000 description 28
- 239000004094 surface-active agent Substances 0.000 description 28
- 210000002966 serum Anatomy 0.000 description 27
- 208000015994 miscarriage Diseases 0.000 description 23
- 229920001983 poloxamer Polymers 0.000 description 22
- 229960000502 poloxamer Drugs 0.000 description 21
- 239000000186 progesterone Substances 0.000 description 21
- 229960003387 progesterone Drugs 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 229920001451 polypropylene glycol Polymers 0.000 description 19
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 229940079593 drug Drugs 0.000 description 16
- 239000007788 liquid Substances 0.000 description 16
- 150000003626 triacylglycerols Chemical class 0.000 description 16
- 239000012736 aqueous medium Substances 0.000 description 15
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 15
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 14
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000003085 diluting agent Substances 0.000 description 13
- 235000012054 meals Nutrition 0.000 description 13
- 239000013543 active substance Substances 0.000 description 12
- 229940063557 methacrylate Drugs 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical class CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 10
- 241000640882 Condea Species 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229960004756 ethanol Drugs 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- 210000003754 fetus Anatomy 0.000 description 10
- 235000013305 food Nutrition 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 229940098695 palmitic acid Drugs 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 235000015165 citric acid Nutrition 0.000 description 9
- 235000019197 fats Nutrition 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 229960001367 tartaric acid Drugs 0.000 description 9
- 230000008901 benefit Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 235000010980 cellulose Nutrition 0.000 description 8
- 239000001913 cellulose Substances 0.000 description 8
- 239000011248 coating agent Substances 0.000 description 8
- 238000000576 coating method Methods 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000008774 maternal effect Effects 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 210000002381 plasma Anatomy 0.000 description 8
- 239000007921 spray Substances 0.000 description 8
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 7
- 210000004381 amniotic fluid Anatomy 0.000 description 7
- 235000021342 arachidonic acid Nutrition 0.000 description 7
- 229940114079 arachidonic acid Drugs 0.000 description 7
- LDVVMCZRFWMZSG-UHFFFAOYSA-N captan Chemical compound C1C=CCC2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C21 LDVVMCZRFWMZSG-UHFFFAOYSA-N 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- 230000000938 luteal effect Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 229940032147 starch Drugs 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 6
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 6
- 208000006399 Premature Obstetric Labor Diseases 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 239000000583 progesterone congener Substances 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 229960004274 stearic acid Drugs 0.000 description 6
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 6
- VTHUYJIXSMGYOQ-KOORYGTMSA-N 17-hydroxyprogesterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 VTHUYJIXSMGYOQ-KOORYGTMSA-N 0.000 description 5
- 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 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 235000012343 cottonseed oil Nutrition 0.000 description 5
- 239000002385 cottonseed oil Substances 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 235000013601 eggs Nutrition 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000001605 fetal effect Effects 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 238000005469 granulation Methods 0.000 description 5
- 230000003179 granulation Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229940033355 lauric acid Drugs 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000011859 microparticle Substances 0.000 description 5
- 229960002969 oleic acid Drugs 0.000 description 5
- 210000002826 placenta Anatomy 0.000 description 5
- 239000008389 polyethoxylated castor oil Substances 0.000 description 5
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000007909 solid dosage form Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000004291 uterus Anatomy 0.000 description 5
- MQFYRUGXOJAUQK-UHFFFAOYSA-N 2-[2-[2-(2-octadecanoyloxyethoxy)ethoxy]ethoxy]ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCOC(=O)CCCCCCCCCCCCCCCCC MQFYRUGXOJAUQK-UHFFFAOYSA-N 0.000 description 4
- 102100021752 Corticoliberin Human genes 0.000 description 4
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 4
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 4
- 206010055690 Foetal death Diseases 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 4
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 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 4
- 241001465754 Metazoa Species 0.000 description 4
- 208000034702 Multiple pregnancies Diseases 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 235000019482 Palm oil Nutrition 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 4
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 4
- 206010036590 Premature baby Diseases 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 206010000210 abortion Diseases 0.000 description 4
- 231100000176 abortion Toxicity 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000010477 apricot oil Substances 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 229940041967 corticotropin-releasing hormone Drugs 0.000 description 4
- KLVRDXBAMSPYKH-RKYZNNDCSA-N corticotropin-releasing hormone (human) Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)C)C(C)C)C1=CNC=N1 KLVRDXBAMSPYKH-RKYZNNDCSA-N 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 4
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 208000000509 infertility Diseases 0.000 description 4
- 231100000535 infertility Toxicity 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229940015467 makena Drugs 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000002611 ovarian Effects 0.000 description 4
- 239000003346 palm kernel oil Substances 0.000 description 4
- 235000019865 palm kernel oil Nutrition 0.000 description 4
- 239000002540 palm oil Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000003169 placental effect Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000007711 solidification Methods 0.000 description 4
- 230000008023 solidification Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 230000036266 weeks of gestation Effects 0.000 description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 3
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 3
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 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 description 3
- 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 description 3
- 208000001951 Fetal Death Diseases 0.000 description 3
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 208000008899 Habitual abortion Diseases 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- NKSOSPOXQKNIKJ-CLFAGFIQSA-N Polyoxyethylene dioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCOC(=O)CCCCCCC\C=C/CCCCCCCC NKSOSPOXQKNIKJ-CLFAGFIQSA-N 0.000 description 3
- 206010036600 Premature labour Diseases 0.000 description 3
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 3
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 3
- 229930182558 Sterol Natural products 0.000 description 3
- WPMWEFXCIYCJSA-UHFFFAOYSA-N Tetraethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCO WPMWEFXCIYCJSA-UHFFFAOYSA-N 0.000 description 3
- 241000202921 Ureaplasma urealyticum Species 0.000 description 3
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 3
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229920001400 block copolymer Polymers 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 206010008129 cerebral palsy Diseases 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 230000035606 childbirth Effects 0.000 description 3
- 229920001688 coating polymer Polymers 0.000 description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 210000004696 endometrium Anatomy 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 150000002191 fatty alcohols Chemical class 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 150000002400 hexanoic acid esters Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229960002899 hydroxyprogesterone Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 208000037805 labour Diseases 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 208000026440 premature labor Diseases 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 description 3
- 208000034213 recurrent susceptibility to 1 pregnancy loss Diseases 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 235000011078 sorbitan tristearate Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 150000003432 sterols Chemical class 0.000 description 3
- 235000003702 sterols Nutrition 0.000 description 3
- 208000002254 stillbirth Diseases 0.000 description 3
- 231100000537 stillbirth Toxicity 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 2
- DRAWQKGUORNASA-UHFFFAOYSA-N (2-hydroxy-3-octadec-9-enoyloxypropyl) octadec-9-enoate Chemical compound CCCCCCCCC=CCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCC=CCCCCCCCC DRAWQKGUORNASA-UHFFFAOYSA-N 0.000 description 2
- ZQBULZYTDGUSSK-UHFFFAOYSA-N (3-hydroxy-2-octanoyloxypropyl) octanoate Chemical compound CCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCC ZQBULZYTDGUSSK-UHFFFAOYSA-N 0.000 description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 2
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 2
- KVYUBFKSKZWZSV-FPLPWBNLSA-N 1-[(9Z)-hexadecenoyl]glycerol Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO KVYUBFKSKZWZSV-FPLPWBNLSA-N 0.000 description 2
- QIZPVNNYFKFJAD-UHFFFAOYSA-N 1-chloro-2-prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1Cl QIZPVNNYFKFJAD-UHFFFAOYSA-N 0.000 description 2
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 2
- QHZLMUACJMDIAE-UHFFFAOYSA-N 1-monopalmitoylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 description 2
- NMSBTWLFBGNKON-UHFFFAOYSA-N 2-(2-hexadecoxyethoxy)ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCO NMSBTWLFBGNKON-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- ILCOCZBHMDEIAI-UHFFFAOYSA-N 2-(2-octadecoxyethoxy)ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCO ILCOCZBHMDEIAI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 2
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 2
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 description 2
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229930192844 Albanol Natural products 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 235000019489 Almond oil Nutrition 0.000 description 2
- 201000000736 Amenorrhea Diseases 0.000 description 2
- 206010001928 Amenorrhoea Diseases 0.000 description 2
- 244000144725 Amygdalus communis Species 0.000 description 2
- 235000011437 Amygdalus communis Nutrition 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QYOVMAREBTZLBT-KTKRTIGZSA-N CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO QYOVMAREBTZLBT-KTKRTIGZSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 description 2
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 2
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 2
- 241000723377 Coffea Species 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 2
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 229920000896 Ethulose Polymers 0.000 description 2
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 description 2
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- 102000008857 Ferritin Human genes 0.000 description 2
- 108050000784 Ferritin Proteins 0.000 description 2
- 238000008416 Ferritin Methods 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010051459 Imminent abortion Diseases 0.000 description 2
- 201000006347 Intellectual Disability Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 206010027514 Metrorrhagia Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
- 102100033073 Polypyrimidine tract-binding protein 1 Human genes 0.000 description 2
- 229920003079 Povidone K 17 Polymers 0.000 description 2
- 206010036595 Premature delivery Diseases 0.000 description 2
- 108090000103 Relaxin Proteins 0.000 description 2
- 102000003743 Relaxin Human genes 0.000 description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
- 229920001800 Shellac Polymers 0.000 description 2
- 239000004147 Sorbitan trioleate Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- UYXTWWCETRIEDR-UHFFFAOYSA-N Tributyrin Chemical compound CCCC(=O)OCC(OC(=O)CCC)COC(=O)CCC UYXTWWCETRIEDR-UHFFFAOYSA-N 0.000 description 2
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 2
- NCHJGQKLPRTMAO-XWVZOOPGSA-N [(2R)-2-[(2R,3R,4S)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NCHJGQKLPRTMAO-XWVZOOPGSA-N 0.000 description 2
- KGUHOFWIXKIURA-VQXBOQCVSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl dodecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCC)O[C@@H]1O[C@@]1(CO)[C@@H](O)[C@H](O)[C@@H](CO)O1 KGUHOFWIXKIURA-VQXBOQCVSA-N 0.000 description 2
- FOLJTMYCYXSPFQ-CJKAUBRRSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-(octadecanoyloxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl octadecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCCCCCCCC)O[C@@H]1O[C@@]1(COC(=O)CCCCCCCCCCCCCCCCC)[C@@H](O)[C@H](O)[C@@H](CO)O1 FOLJTMYCYXSPFQ-CJKAUBRRSA-N 0.000 description 2
- LPGFSDGXTDNTCB-UHFFFAOYSA-N [3-(16-methylheptadecanoyloxy)-2,2-bis(16-methylheptadecanoyloxymethyl)propyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)(COC(=O)CCCCCCCCCCCCCCC(C)C)COC(=O)CCCCCCCCCCCCCCC(C)C LPGFSDGXTDNTCB-UHFFFAOYSA-N 0.000 description 2
- QTIMEBJTEBWHOB-PMDAXIHYSA-N [3-[(z)-octadec-9-enoyl]oxy-2,2-bis[[(z)-octadec-9-enoyl]oxymethyl]propyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COC(=O)CCCCCCC\C=C/CCCCCCCC)(COC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC QTIMEBJTEBWHOB-PMDAXIHYSA-N 0.000 description 2
- OCKWAZCWKSMKNC-UHFFFAOYSA-N [3-octadecanoyloxy-2,2-bis(octadecanoyloxymethyl)propyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COC(=O)CCCCCCCCCCCCCCCCC)(COC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC OCKWAZCWKSMKNC-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 235000020224 almond Nutrition 0.000 description 2
- 239000008168 almond oil Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 231100000540 amenorrhea Toxicity 0.000 description 2
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 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 description 2
- 239000003181 biological factor Substances 0.000 description 2
- 235000021324 borage oil Nutrition 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960002681 calcium alginate Drugs 0.000 description 2
- 235000010410 calcium alginate Nutrition 0.000 description 2
- 239000000648 calcium alginate Substances 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229920001727 cellulose butyrate Polymers 0.000 description 2
- 229920006218 cellulose propionate Polymers 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 229940107161 cholesterol Drugs 0.000 description 2
- 108700043024 cholylsarcosine Proteins 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000008139 complexing agent Substances 0.000 description 2
- 210000004246 corpus luteum Anatomy 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
- 229960003964 deoxycholic acid Drugs 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 2
- 229960001348 estriol Drugs 0.000 description 2
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 2
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 231100000479 fetal death Toxicity 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000016354 hearing loss disease Diseases 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 2
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 2
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 108010067471 inhibin A Proteins 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000002563 ionic surfactant Substances 0.000 description 2
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 2
- 235000021388 linseed oil Nutrition 0.000 description 2
- 239000000944 linseed oil Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 238000005399 mechanical ventilation Methods 0.000 description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920003087 methylethyl cellulose Polymers 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- YZUUTMGDONTGTN-UHFFFAOYSA-N nonaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCOCCO YZUUTMGDONTGTN-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 2
- 239000003605 opacifier Substances 0.000 description 2
- 229940077414 peg-12 stearate Drugs 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229940067631 phospholipid Drugs 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229920001713 poly(ethylene-co-vinyl alcohol) Polymers 0.000 description 2
- 229920000223 polyglycerol Polymers 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 201000011461 pre-eclampsia Diseases 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 102000003998 progesterone receptors Human genes 0.000 description 2
- 108090000468 progesterone receptors Proteins 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
- 229940113147 shellac Drugs 0.000 description 2
- 239000004208 shellac Substances 0.000 description 2
- 235000013874 shellac Nutrition 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 2
- 229940045845 sodium myristate Drugs 0.000 description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- WDFRNBJHDMUMBL-OICFXQLMSA-M sodium;(4r)-4-[(3r,5s,7r,8r,9s,10s,13r,14s,17r)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)CC1 WDFRNBJHDMUMBL-OICFXQLMSA-M 0.000 description 2
- JUQGWKYSEXPRGL-UHFFFAOYSA-M sodium;tetradecanoate Chemical compound [Na+].CCCCCCCCCCCCCC([O-])=O JUQGWKYSEXPRGL-UHFFFAOYSA-M 0.000 description 2
- 239000008279 sol Substances 0.000 description 2
- 235000019337 sorbitan trioleate Nutrition 0.000 description 2
- 229960000391 sorbitan trioleate Drugs 0.000 description 2
- 239000001589 sorbitan tristearate Substances 0.000 description 2
- 229960004129 sorbitan tristearate Drugs 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 235000000891 standard diet Nutrition 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229940032085 sucrose monolaurate Drugs 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000009492 tablet coating Methods 0.000 description 2
- 239000002700 tablet coating Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000003390 teratogenic effect Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 2
- 239000002383 tung oil Substances 0.000 description 2
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000004034 viscosity adjusting agent Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 1
- OTKXWJHPGBRXCR-UHFFFAOYSA-N (2-chloro-4-nitrophenoxy)-dimethoxy-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1Cl OTKXWJHPGBRXCR-UHFFFAOYSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- WJTCHBVEUFDSIK-NWDGAFQWSA-N (2r,5s)-1-benzyl-2,5-dimethylpiperazine Chemical compound C[C@@H]1CN[C@@H](C)CN1CC1=CC=CC=C1 WJTCHBVEUFDSIK-NWDGAFQWSA-N 0.000 description 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 1
- RUHCWQAFCGVQJX-RVWHZBQESA-N (3s,8s,9s,10r,13r,14s,17r)-3-hydroxy-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-1-one Chemical compound C1C=C2C[C@H](O)CC(=O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 RUHCWQAFCGVQJX-RVWHZBQESA-N 0.000 description 1
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 1
- NFGXHKASABOEEW-GYMWBFJFSA-N (S)-methoprene Chemical compound COC(C)(C)CCC[C@H](C)C\C=C\C(\C)=C\C(=O)OC(C)C NFGXHKASABOEEW-GYMWBFJFSA-N 0.000 description 1
- SKGWNZXOCSYJQL-BUTYCLJRSA-N 1,2,3-tripalmitoleoylglycerol Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCC)COC(=O)CCCCCCC\C=C/CCCCCC SKGWNZXOCSYJQL-BUTYCLJRSA-N 0.000 description 1
- MQGBAQLIFKSMEM-MAZCIEHSSA-N 1,2-dilinoleoylglycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC MQGBAQLIFKSMEM-MAZCIEHSSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- DRAWQKGUORNASA-CLFAGFIQSA-N 1,3-dioleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)COC(=O)CCCCCCC\C=C/CCCCCCCC DRAWQKGUORNASA-CLFAGFIQSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- ONBWNNUYXGJKKD-UHFFFAOYSA-N 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonic acid;sodium Chemical compound [Na].CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC ONBWNNUYXGJKKD-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-MDZDMXLPSA-N 1-[(9E)-octadecenoyl]glycerol Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-MDZDMXLPSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OURWLMNRUGYRSC-UHFFFAOYSA-N 12-(1-hydroxypropan-2-yloxy)octadecanoic acid Chemical compound CCCCCCC(OC(C)CO)CCCCCCCCCCC(O)=O OURWLMNRUGYRSC-UHFFFAOYSA-N 0.000 description 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 1
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- WCOXQTXVACYMLM-UHFFFAOYSA-N 2,3-bis(12-hydroxyoctadecanoyloxy)propyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC(O)CCCCCC)COC(=O)CCCCCCCCCCC(O)CCCCCC WCOXQTXVACYMLM-UHFFFAOYSA-N 0.000 description 1
- OEZPKXDBWNXBRE-UHFFFAOYSA-N 2,3-bis(2-hydroxyethoxy)propyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(OCCO)COCCO OEZPKXDBWNXBRE-UHFFFAOYSA-N 0.000 description 1
- KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 description 1
- MLQSJCKTTGXTJK-UHFFFAOYSA-N 2-(2,3-dihydroxypropyl)hexadecanoic acid Chemical compound CCCCCCCCCCCCCCC(C(O)=O)CC(O)CO MLQSJCKTTGXTJK-UHFFFAOYSA-N 0.000 description 1
- PHDVPEOLXYBNJY-KTKRTIGZSA-N 2-(2-hydroxyethoxy)ethyl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCOCCO PHDVPEOLXYBNJY-KTKRTIGZSA-N 0.000 description 1
- PWVUXRBUUYZMKM-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCO PWVUXRBUUYZMKM-UHFFFAOYSA-N 0.000 description 1
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- MGYUQZIGNZFZJS-KTKRTIGZSA-N 2-[2-[(z)-octadec-9-enoxy]ethoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCO MGYUQZIGNZFZJS-KTKRTIGZSA-N 0.000 description 1
- SBKDIDITONHJHI-UHFFFAOYSA-N 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCO SBKDIDITONHJHI-UHFFFAOYSA-N 0.000 description 1
- KGULFLCOPRYBEV-KTKRTIGZSA-N 2-[2-[2-[(z)-octadec-9-enoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCO KGULFLCOPRYBEV-KTKRTIGZSA-N 0.000 description 1
- IDTQVQPVUYLMJJ-UHFFFAOYSA-N 2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCO IDTQVQPVUYLMJJ-UHFFFAOYSA-N 0.000 description 1
- HNUQMTZUNUBOLQ-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO HNUQMTZUNUBOLQ-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- OIALAIQRYISUEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]e Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO OIALAIQRYISUEV-UHFFFAOYSA-N 0.000 description 1
- VJYAJQFKKLYARJ-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical class CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 VJYAJQFKKLYARJ-UHFFFAOYSA-N 0.000 description 1
- WITKSCOBOCOGSC-UHFFFAOYSA-N 2-dodecanoyloxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCCCC WITKSCOBOCOGSC-UHFFFAOYSA-N 0.000 description 1
- NYEZZYQZRQDLEH-UHFFFAOYSA-N 2-ethyl-4,5-dihydro-1,3-oxazole Chemical compound CCC1=NCCO1 NYEZZYQZRQDLEH-UHFFFAOYSA-N 0.000 description 1
- JADYBWICRJWGBW-UHFFFAOYSA-N 2-hydroxy-3-(tetradecanoyloxy)propyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCC JADYBWICRJWGBW-UHFFFAOYSA-N 0.000 description 1
- ZVTDEEBSWIQAFJ-KHPPLWFESA-N 2-hydroxypropyl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C)O ZVTDEEBSWIQAFJ-KHPPLWFESA-N 0.000 description 1
- JZSMZIOJUHECHW-GTJZZHROSA-N 2-hydroxypropyl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCC(C)O JZSMZIOJUHECHW-GTJZZHROSA-N 0.000 description 1
- BJRXGOFKVBOFCO-UHFFFAOYSA-N 2-hydroxypropyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(C)O BJRXGOFKVBOFCO-UHFFFAOYSA-N 0.000 description 1
- PPPFYBPQAPISCT-UHFFFAOYSA-N 2-hydroxypropyl acetate Chemical compound CC(O)COC(C)=O PPPFYBPQAPISCT-UHFFFAOYSA-N 0.000 description 1
- VCNPGCHIKPSUSP-UHFFFAOYSA-N 2-hydroxypropyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(C)O VCNPGCHIKPSUSP-UHFFFAOYSA-N 0.000 description 1
- JEMDXOYRWHZUCG-UHFFFAOYSA-N 2-octadecanoyloxypropyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCCCCCCCCCC JEMDXOYRWHZUCG-UHFFFAOYSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000037853 Abnormal uterine bleeding Diseases 0.000 description 1
- 206010061614 Abortion complete Diseases 0.000 description 1
- 206010000217 Abortion incomplete Diseases 0.000 description 1
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 206010049589 Afterbirth pain Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 235000019737 Animal fat Nutrition 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 235000010082 Averrhoa carambola Nutrition 0.000 description 1
- 240000006063 Averrhoa carambola Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- DBMJZOMNXBSRED-UHFFFAOYSA-N Bergamottin Natural products O1C(=O)C=CC2=C1C=C1OC=CC1=C2OCC=C(C)CCC=C(C)C DBMJZOMNXBSRED-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100459320 Caenorhabditis elegans myo-2 gene Proteins 0.000 description 1
- 241000589874 Campylobacter fetus Species 0.000 description 1
- 241001214176 Capros Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010061452 Complication of pregnancy Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241001440269 Cutina Species 0.000 description 1
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 1
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-isoascorbic acid Chemical compound OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010011891 Deafness neurosensory Diseases 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 240000002989 Euphorbia neriifolia Species 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000036646 First trimester pregnancy Diseases 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- 241000207201 Gardnerella vaginalis Species 0.000 description 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- MBXVIRZWSHICAV-UHFFFAOYSA-N Glycerol triundecanoate Chemical compound CCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCC)COC(=O)CCCCCCCCCC MBXVIRZWSHICAV-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- HDIFHQMREAYYJW-XGXNLDPDSA-N Glyceryl Ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCC(O)CO HDIFHQMREAYYJW-XGXNLDPDSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108010015031 Glycochenodeoxycholic Acid Proteins 0.000 description 1
- 108010007979 Glycocholic Acid Proteins 0.000 description 1
- 108010035713 Glycodeoxycholic Acid Proteins 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000945534 Hamana Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- 208000006630 Incomplete Abortion Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 206010022840 Intraventricular haemorrhage Diseases 0.000 description 1
- AXISYYRBXTVTFY-UHFFFAOYSA-N Isopropyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC(C)C AXISYYRBXTVTFY-UHFFFAOYSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 208000035752 Live birth Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- VQENOYXMFIFHCY-UHFFFAOYSA-N Monoglyceride citrate Chemical compound OCC(O)COC(=O)CC(O)(C(O)=O)CC(O)=O VQENOYXMFIFHCY-UHFFFAOYSA-N 0.000 description 1
- 208000009233 Morning Sickness Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 206010050819 Musculoskeletal chest pain Diseases 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- 208000006816 Neonatal Sepsis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- IGFHQQFPSIBGKE-UHFFFAOYSA-N Nonylphenol Natural products CCCCCCCCCC1=CC=C(O)C=C1 IGFHQQFPSIBGKE-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 208000001300 Perinatal Death Diseases 0.000 description 1
- 229920002507 Poloxamer 124 Polymers 0.000 description 1
- 229920002511 Poloxamer 237 Polymers 0.000 description 1
- 229920002516 Poloxamer 331 Polymers 0.000 description 1
- 229920002517 Poloxamer 338 Polymers 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- SFPNSCZLRJDTGT-SDNWHVSQSA-N Polyoxyethylene (600) monoricinoleate Chemical compound CCCCCCC(O)C\C=C\CCCCCCCC(=O)OCCC SFPNSCZLRJDTGT-SDNWHVSQSA-N 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920002700 Polyoxyl 60 hydrogenated castor oil Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 201000009916 Postpartum depression Diseases 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 208000035002 Pregnancy of unknown location Diseases 0.000 description 1
- 235000016311 Primula vulgaris Nutrition 0.000 description 1
- 244000028344 Primula vulgaris Species 0.000 description 1
- 101710145576 Prostaglandin-H2 D-isomerase Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 101000611641 Rattus norvegicus Protein phosphatase 1 regulatory subunit 15A Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 235000019774 Rice Bran oil Nutrition 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- 241001125046 Sardina pilchardus Species 0.000 description 1
- 206010039792 Seborrhoea Diseases 0.000 description 1
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 description 1
- 101150018337 Serpinh1 gene Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000001833 Succinylated monoglyceride Substances 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- XZAGBDSOKNXTDT-UHFFFAOYSA-N Sucrose monopalmitate Chemical compound CCCCCCCCCCCCCCCC(O)=O.OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(CO)O1 XZAGBDSOKNXTDT-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010043220 Temporomandibular joint syndrome Diseases 0.000 description 1
- 229920002807 Thiomer Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 0.000 description 1
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 1
- 208000031271 Unwanted pregnancy Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 108010059705 Urocortins Proteins 0.000 description 1
- 102000005630 Urocortins Human genes 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046788 Uterine haemorrhage Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 206010046910 Vaginal haemorrhage Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 206010047486 Virilism Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 208000034850 Vomiting in pregnancy Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 108010055615 Zein Proteins 0.000 description 1
- NWGKJDSIEKMTRX-BFWOXRRGSA-N [(2r)-2-[(3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)C1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-BFWOXRRGSA-N 0.000 description 1
- RKZXQQPEDGMHBJ-LIGJGSPWSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentakis[[(z)-octadec-9-enoyl]oxy]hexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC RKZXQQPEDGMHBJ-LIGJGSPWSA-N 0.000 description 1
- FSEJJKIPRNUIFL-UHFFFAOYSA-N [2,2-bis(hydroxymethyl)-3-octadecanoyloxypropyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)(CO)COC(=O)CCCCCCCCCCCCCCCCC FSEJJKIPRNUIFL-UHFFFAOYSA-N 0.000 description 1
- DRRMRHKHTQRWMB-UHFFFAOYSA-N [3-(2-ethylhexanoyloxy)-2,2-bis(2-ethylhexanoyloxymethyl)propyl] 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCC(COC(=O)C(CC)CCCC)(COC(=O)C(CC)CCCC)COC(=O)C(CC)CCCC DRRMRHKHTQRWMB-UHFFFAOYSA-N 0.000 description 1
- CONXGOYCVNRCCT-UHFFFAOYSA-F [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O CONXGOYCVNRCCT-UHFFFAOYSA-F 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940009868 aluminum magnesium silicate Drugs 0.000 description 1
- RJZNFXWQRHAVBP-UHFFFAOYSA-I aluminum;magnesium;pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3] RJZNFXWQRHAVBP-UHFFFAOYSA-I 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- LDPIQRWHBLWKPR-UHFFFAOYSA-N aminoboronic acid Chemical class NB(O)O LDPIQRWHBLWKPR-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- DBMJZOMNXBSRED-OQLLNIDSSA-N bergomottin Chemical compound O1C(=O)C=CC2=C1C=C1OC=CC1=C2OC/C=C(C)/CCC=C(C)C DBMJZOMNXBSRED-OQLLNIDSSA-N 0.000 description 1
- GSCLMSFRWBPUSK-UHFFFAOYSA-N beta-Butyrolactone Chemical compound CC1CC(=O)O1 GSCLMSFRWBPUSK-UHFFFAOYSA-N 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 239000010473 blackcurrant seed oil Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- SECPBURWFOCMIZ-UHFFFAOYSA-N butanedioic acid;2,3-dihydroxyhenicosan-4-one Chemical compound OC(=O)CCC(O)=O.CCCCCCCCCCCCCCCCCC(=O)C(O)C(C)O SECPBURWFOCMIZ-UHFFFAOYSA-N 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229960000411 camphor oil Drugs 0.000 description 1
- 239000010624 camphor oil Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000019519 canola oil Nutrition 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- WZNRVWBKYDHTKI-UHFFFAOYSA-N cellulose, acetate 1,2,4-benzenetricarboxylate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.OC(=O)C1=CC(C(=O)O)=CC=C1C(=O)OCC1C(OC2C(C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(COC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)O2)OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)O1 WZNRVWBKYDHTKI-UHFFFAOYSA-N 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940009025 chenodeoxycholate Drugs 0.000 description 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- NGPTYCZGBCGWBE-UHFFFAOYSA-N decanoic acid hexadecanoic acid octadecanoic acid octanoic acid propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O NGPTYCZGBCGWBE-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- XLIDPNGFCHXNGX-UHFFFAOYSA-N dialuminum;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Al+3].[Al+3].[Si+4] XLIDPNGFCHXNGX-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 1
- UYAAVKFHBMJOJZ-UHFFFAOYSA-N diimidazo[1,3-b:1',3'-e]pyrazine-5,10-dione Chemical compound O=C1C2=CN=CN2C(=O)C2=CN=CN12 UYAAVKFHBMJOJZ-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 229960001826 dimethylphthalate Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 201000003511 ectopic pregnancy Diseases 0.000 description 1
- 239000008344 egg yolk phospholipid Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 201000006828 endometrial hyperplasia Diseases 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 235000010350 erythorbic acid Nutrition 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 1
- 229940031016 ethyl linoleate Drugs 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 210000002458 fetal heart Anatomy 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 210000001733 follicular fluid Anatomy 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 229940080812 glyceryl caprate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940116338 glyceryl ricinoleate Drugs 0.000 description 1
- GHCZAUBVMUEKKP-GYPHWSFCSA-N glycochenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 GHCZAUBVMUEKKP-GYPHWSFCSA-N 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- WVULKSPCQVQLCU-BUXLTGKBSA-N glycodeoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 WVULKSPCQVQLCU-BUXLTGKBSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- GHCZAUBVMUEKKP-XROMFQGDSA-N glycoursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 GHCZAUBVMUEKKP-XROMFQGDSA-N 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 235000015201 grapefruit juice Nutrition 0.000 description 1
- 239000008169 grapeseed oil Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000012052 hydrophilic carrier Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- XSEOYPMPHHCUBN-FGYWBSQSSA-N hydroxylated lecithin Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCC[C@@H](O)[C@H](O)CCCCCCCC XSEOYPMPHHCUBN-FGYWBSQSSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 231100001046 intrauterine death Toxicity 0.000 description 1
- 229940026239 isoascorbic acid Drugs 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 229940100556 laureth-23 Drugs 0.000 description 1
- 229940061515 laureth-4 Drugs 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- 208000018773 low birth weight Diseases 0.000 description 1
- 231100000533 low birth weight Toxicity 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 231100000794 masculinization Toxicity 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960004438 mibefradil Drugs 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940037959 monooctanoin Drugs 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000024121 nodulation Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- SNQQPOLDUKLAAF-UHFFFAOYSA-N nonylphenol Chemical compound CCCCCCCCCC1=CC=CC=C1O SNQQPOLDUKLAAF-UHFFFAOYSA-N 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- YYZUSRORWSJGET-UHFFFAOYSA-N octanoic acid ethyl ester Natural products CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229940075643 oleth-3 Drugs 0.000 description 1
- 229940093446 oleth-5 Drugs 0.000 description 1
- 235000021315 omega 9 monounsaturated fatty acids Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229940094916 peg-10 soy sterol Drugs 0.000 description 1
- 229940100460 peg-100 stearate Drugs 0.000 description 1
- 229940077412 peg-12 laurate Drugs 0.000 description 1
- 229940094329 peg-20 soy sterol Drugs 0.000 description 1
- 229940032067 peg-20 stearate Drugs 0.000 description 1
- 229940008456 peg-32 oleate Drugs 0.000 description 1
- 229940119519 peg-32 stearate Drugs 0.000 description 1
- 229940032066 peg-4 dilaurate Drugs 0.000 description 1
- 229940089510 peg-4 stearate Drugs 0.000 description 1
- 229940014773 peg-5 soy sterol Drugs 0.000 description 1
- 229940119517 peg-6 stearate Drugs 0.000 description 1
- 229940032052 peg-8 dioleate Drugs 0.000 description 1
- 229940032051 peg-8 distearate Drugs 0.000 description 1
- 229940094341 pentaerythrityl tetraoleate Drugs 0.000 description 1
- 229940086560 pentaerythrityl tetrastearate Drugs 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 201000005936 periventricular leukomalacia Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- ONJQDTZCDSESIW-UHFFFAOYSA-N polidocanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO ONJQDTZCDSESIW-UHFFFAOYSA-N 0.000 description 1
- 229940093448 poloxamer 124 Drugs 0.000 description 1
- 229940116406 poloxamer 184 Drugs 0.000 description 1
- 229940106032 poloxamer 335 Drugs 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229940097941 polyglyceryl-10 laurate Drugs 0.000 description 1
- 229940056099 polyglyceryl-4 oleate Drugs 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920001444 polymaleic acid Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000010491 poppyseed oil Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 150000003109 potassium Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 230000000757 progestagenic effect Effects 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- XEIOPEQGDSYOIH-MURFETPASA-N propan-2-yl (9z,12z)-octadeca-9,12-dienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC(C)C XEIOPEQGDSYOIH-MURFETPASA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229940116423 propylene glycol diacetate Drugs 0.000 description 1
- 229940116422 propylene glycol dicaprate Drugs 0.000 description 1
- 229940093625 propylene glycol monostearate Drugs 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 239000008165 rice bran oil Substances 0.000 description 1
- WBHHMMIMDMUBKC-QJWNTBNXSA-M ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC([O-])=O WBHHMMIMDMUBKC-QJWNTBNXSA-M 0.000 description 1
- 229940066675 ricinoleate Drugs 0.000 description 1
- 201000004700 rosacea Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 231100000879 sensorineural hearing loss Toxicity 0.000 description 1
- 208000023573 sensorineural hearing loss disease Diseases 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 125000002072 seryl group Chemical group 0.000 description 1
- 239000010686 shark liver oil Substances 0.000 description 1
- 229940069764 shark liver oil Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 230000005808 skin problem Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
- VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 description 1
- UDWXLZLRRVQONG-UHFFFAOYSA-M sodium hexanoate Chemical compound [Na+].CCCCCC([O-])=O UDWXLZLRRVQONG-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 235000010956 sodium stearoyl-2-lactylate Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- 229940045946 sodium taurodeoxycholate Drugs 0.000 description 1
- 229960000776 sodium tetradecyl sulfate Drugs 0.000 description 1
- WYPBVHPKMJYUEO-NBTZWHCOSA-M sodium;(9z,12z)-octadeca-9,12-dienoate Chemical compound [Na+].CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O WYPBVHPKMJYUEO-NBTZWHCOSA-M 0.000 description 1
- YXHRQQJFKOHLAP-FVCKGWAHSA-M sodium;2-[[(4r)-4-[(3r,5r,8r,9s,10s,12s,13r,14s,17r)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 YXHRQQJFKOHLAP-FVCKGWAHSA-M 0.000 description 1
- KNYAZNABVSEZDS-UHFFFAOYSA-M sodium;2-octadecanoyloxypropanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C([O-])=O KNYAZNABVSEZDS-UHFFFAOYSA-M 0.000 description 1
- FIWQZURFGYXCEO-UHFFFAOYSA-M sodium;decanoate Chemical compound [Na+].CCCCCCCCCC([O-])=O FIWQZURFGYXCEO-UHFFFAOYSA-M 0.000 description 1
- UPUIQOIQVMNQAP-UHFFFAOYSA-M sodium;tetradecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCOS([O-])(=O)=O UPUIQOIQVMNQAP-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229950004959 sorbitan oleate Drugs 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000003351 stiffener Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 235000019327 succinylated monoglyceride Nutrition 0.000 description 1
- 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 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 229940035023 sucrose monostearate Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- BHTRKEVKTKCXOH-BJLOMENOSA-N taurochenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-BJLOMENOSA-N 0.000 description 1
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 1
- AWDRATDZQPNJFN-VAYUFCLWSA-N taurodeoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 AWDRATDZQPNJFN-VAYUFCLWSA-N 0.000 description 1
- BHTRKEVKTKCXOH-LBSADWJPSA-N tauroursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-LBSADWJPSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- MAYCICSNZYXLHB-UHFFFAOYSA-N tricaproin Chemical compound CCCCCC(=O)OCC(OC(=O)CCCCC)COC(=O)CCCCC MAYCICSNZYXLHB-UHFFFAOYSA-N 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 239000000777 urocortin Substances 0.000 description 1
- 229940014499 ursodeoxycholate Drugs 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 208000013464 vaginal disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000010698 whale oil Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—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
- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- 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
- 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
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Inorganic Chemistry (AREA)
- Biochemistry (AREA)
- Birds (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
Abstract
【解決手段】治療的有効量の17−ヒドロキシプロゲステロンカプロエート及び製薬上許容可能な担体(ベンジルベンゾエート、ベンジルアルコール、親水性添加物、親油性添加物等)を含み、0.5%w/wラウリル硫酸ナトリウムを有する人工腸液900mL中で、50RPMで37℃で、USP II型溶解装置を用いて測定した場合に、60分後に17−ヒドロキシプロゲステロンカプロエートの用量の少なくとも20重量%を放出する経口剤形(カプセル又は錠剤等)。6時間毎、8時間毎、12時間毎、又は24時間毎に1回、ヒト被験体への投与される方法。
【選択図】図1
Description
例示的実施形態の詳細な説明
定義
発明
主要評価項目測定基準(母体):
1. 周産期死亡率
2. 早産(32週未満の妊娠)
3. 早産(34週未満の妊娠)
4. 早産(37週未満の妊娠)
5. 小児期追跡調査での主要神経発生的身体障害
副次評価項目測定基準(母体):
1. 切迫早期分娩
2. 前分娩自然破水
3. 薬物有害反応
4. 妊娠延長(無作為化と出産との間の間隔)
5. 出産方法
6. 出産前入院数
7. 治療に対する満足感
8. 子宮収縮抑制の使用
副次評価項目測定基準(乳児):
1. 37週完了前に出生
2. 34週完了前に出生
3. 32週完了前に出生
4. 28週完了前に出生
5. 妊娠期間に関する第3百分位数未満の出生時体重
6. 2500グラム未満の出生時体重
7. 5分で7未満のアプガースコア
8. 呼吸窮迫症候群
9. 機械換気の使用
10. 機械換気の継続期間
11. 脳室内出血−等級IIIまたはIV
12. 脳室周囲白質軟化症
13. 未熟児網膜症
14. 未熟児網膜症−等級IIIまたはIV
15. 慢性肺疾患
16. 壊死性全腸炎
17. 新生児敗血症
18. 胎児死亡
19. 新生児死亡
20. 新生児集中治療室に入院
21. 新生児在院時間
22. 催奇作用(女性乳児における男性化現象を含む)
副次評価項目測定基準(小児):
1. 主要感音能力障害(法的盲、補聴器を要する感音難聴、中等度または重度の脳性麻痺、あるいは発達遅延または知的障害のいずれかとして定義される)
2. 発達遅延
3. 知的障害
4. 運動障害
5. 視覚障害
6. 失明
7. 聴覚消失
8. 聴覚障害
9. 脳性麻痺
10. 小児行動
11. 小児気質
12. 学習障害
13. 小児期追跡調査での成長評価(体重、頭周囲長、身長、皮下脂肪厚)
In vitro受精
1.1. 妊娠率
1.2. 生産
1.3. 継続妊娠率
1.4. 妊娠6〜8週での胎児心臓活動の超音波証拠として定義される臨床的妊娠
1.5. 心拍により測定される胎児活力度
1.6. 早期妊娠不全のための医学的処置を受けた24〜48時間後の完全流産率
2.2. 周期取消率
2.3. 生成卵細胞数
2.4. 生成胚数
2.5. 血清ホルモン評価
2.6. 濾胞液評価
2.7. ピークエストラジオールレベル
2.8. 卵巣刺激中に必要とされるゴナドトロピンのアンプル
2.9. 卵巣刺激の日数
2.10. 回収卵細胞数
2.11. 移入胚数
2.12. 凍結胚数
2.13. 胚等級
2.14. 着床率
2.15. 流産率
2.16. 妊娠結果
2.17. 1週間での完全流産率、受胎生成物の娩出までの時間、流産率と血清17−ヒドロキシプロゲステロンレベルとの相関、ならびに妊娠不全の型、出血日数および患者の満足感
2.18. 卵巣応答[制御卵巣刺激および卵採取手順の完了時に査定]。
流産
1.1. 流産
1.2. 12週までの早期流産
1.3. 12週より後および23週未満の流産
1.4. サイトカイン比 IFN/IL−10
1.5. 妊娠8週および12週での臨床的妊娠率
2.1. 母親
a. 疼痛軽減(切迫流産)
b. 「つわり」の重症度−頭痛増強
c. 悪心、胸部圧痛
d. 血栓塞栓性事象の報告
e. 血栓溶解事象
f. 抑うつ
g. 特別治療室への入院
h. その後の受胎
i. PIBFレベル
j. 子宮収縮頻度。
2.2. 小児
a. 早産;
b. 死産;
c. 新生児死亡;
d. 2500g未満の低出生時体重
e. 胎児性器異常;
f. 催奇作用(正常胎児発生を損なう);
g. 特別治療室への入院。
2.3. 全般的
a. 子宮内胎児死亡
b. 死産
c. 胎児
d. 生化学的および臨床的妊娠パラメーターのモニタリング、血清プロゲステロンの毎週評価による妊娠結果の診査分析
e. 生産率、周期取消率、自然流産率、生化学的妊娠率、子宮外妊娠率。
実施例
実施例1〜6 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例7〜10 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例11 − 17−ヒドロキシプロゲステロンカプロエート被覆錠剤
実施例12〜17 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例18〜23 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例24〜28 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例29〜35 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例36 − 17−ヒドロキシプロゲステロンカプロエート錠剤
実施例37〜42 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例43および44 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例46〜50 − 17−ヒドロキシプロゲステロンカプロエート組成物
実施例52 − 17−ヒドロキシプロゲステロンカプロエート負荷ペレット
実施例54 − 17−ヒドロキシプロゲステロンカプロエート組成物in vivo評価
(1)
以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート、および
製薬上許容可能な担体
を含む経口薬学的組成物。
(2)
妊娠支援のために処方される(1)記載の薬学的組成物。
(3)
前記17−ヒドロキシプロゲステロンカプロエートが、約50μm以下の平均粒子直径を有する微粒子形態で組成物中に存在する(1)記載の薬学的組成物。
(4)
前記担体がベンジルベンゾエート、ベンジルアルコールまたはその混合物を包含する(1)記載の薬学的組成物。
(5)
経口剤形中の前記17−ヒドロキシプロゲステロンカプロエートの量対ベンジルベンゾエートおよびベンジルアルコールの合計量が約1:0.01(w/w)〜約1:5(w/w)である(4)記載の薬学的組成物。
(6)
前記17−ヒドロキシプロゲステロンカプロエートの量が総組成物の約5%〜約80%w/wである(1)記載の薬学的組成物。
(7)
カプセルまたは錠剤の形態である(1)記載の薬学的組成物。
(8)
前記組成物がカプセルの形態であり、前記カプセルが約30mg〜約300mgの17−ヒドロキシプロゲステロンカプロエートを含む(7)記載の薬学的組成物。
(9)
前記組成物が錠剤の形態であり、前記錠剤が約20mg〜約800mgの17−ヒドロキシプロゲステロンカプロエートを含む(7)記載の薬学的組成物。
(10)
前記カプセルまたは錠剤が制御放出経口剤形である(7)記載の薬学的組成物。
(11)
前記組成物中の17−ヒドロキシプロゲステロンカプロエートの量対前記カプセルの充填容積の比は約0.02g/mL〜約0.8g/mLである(7)記載の薬学的組成物。
(12)
前記担体が親水性添加物を含む(1)記載の薬学的組成物。
(13)
前記担体が親油性添加物を含む(1)記載の薬学的組成物。
(14)
前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、脂肪酸グリセリド、胆汁酸の塩、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、PEG−8カプリル酸/カプリン酸グリセリド、ラウロイルマクロゴール−32グリセリド、ステアロイルマクロゴールグリセリド、PEG−40硬化ヒマシ油、PEG−35ヒマシ油、オレイン酸ナトリウム、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、PEG−10ラウレート、PEG−20オレエート、PEG−30ステアレート、PEG−40ラウレート、PEG−20グリセリルラウレート、PEG−20グリセリルステアレート、PEG−40グリセリルラウレート、PEG−20グリセリルオレエート、PEG−10ソルビタンラウレート、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノオレエート、ポリグリセリル−10オレエート、ポリグリセリル−10モノ、ジオレエート、ポロキサマー188、ポロキサマー108、マルトース、スクロース、フルクトース、マンニトール、キシリトールおよびその組合せからなる群から選択される化合物を含む(12)記載の薬学的組成物。
(15)
前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、ピロリドン、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、セルロースエステル、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、マルトース、スクロース、フルクトース、マンニトール、キシリトールおよびその組合せからなる群から選択される化合物を含む(12)記載の薬学的組成物。
(16)
前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、ベンジルベンゾエート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、飽和ポリグリコール化グリセリド、リノール酸グリセリド、カプリル酸/カプリン酸グリセリド、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、グリセリルモノオレエート、グリセリルモノリノリエート、グリセリルモノラウレート、グリセロールモノステアレート、グリセリルジステアレート、グリセリルパルミトステアレート、グリセリルラウレート、グリセリルカプリレート、ジステアリン、モノパルミトレイン、モノラウリン、エチルオレエート、PEG−6トウモロコシ油、PEG−6杏仁油、PEG−4カプリル酸/カプリン酸トリグリセリド、PEG−20ソルビタンモノステアレート、PEG−4ラウレート、PEG−6ジラウレート、ポリグリセリル−3オレエート、ポリグリセリル−6ジオレエート、ポロキサマー182、プロピレングリコールモノカプリレート、プロピレングリコールモノラウレート、プロピレングリコールジカプリレート/ジカプレート、プロピレングリコールカプリレート/カプレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノオレエート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタンセスキステアレートおよびその組合せからなる群から選択される化合物を含む(13)記載の薬学的組成物。
(17)
前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、エチルオレエートおよびその組合せからなる群から選択される化合物を含む(13)記載の薬学的組成物。
(18)
前記担体が少なくとも50重量%の親油性添加物を含む(13)記載の薬学的組成物。
(19)
前記担体が、約90:10〜約1:99の親油性添加物対親水性添加物比で、少なくとも1つの親水性添加物および少なくとも1つの親油性添加物を含む(1)記載の薬学的組成物。
(20)
早産の危険がある妊娠女性被験体の処置方法であって、(1)記載の薬学的組成物を女性被験体に投与することを包含する方法。
(21)
以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート、および
製薬上許容可能な担体
を含む経口薬学的組成物であって、0.5%w/wラウリル硫酸ナトリウムを有する人工腸液900mL中で、50RPMで37℃で、USP II型溶解装置を用いて測定した場合に、担体を含有しない等価用量投与される経口剤形より60分後に17−ヒドロキシプロゲステロンカプロエートの少なくとも20重量%より多くを当該経口剤形が放出する組成物。
(22)
前記経口剤形が妊娠支援のために処方される(21)記載の製薬上許容可能な経口剤形。
(23)
前記17−ヒドロキシプロゲステロンカプロエートが、約50μm以下の平均粒子直径を有する微粒子形態で経口剤形中に存在する(21)記載の製薬上許容可能な経口剤形。
(24)
前記担体がベンジルベンゾエート、ベンジルアルコールまたはその混合物を包含する(21)記載の製薬上許容可能な経口剤形。
(25)
経口剤形中の前記17−ヒドロキシプロゲステロンカプロエートの量対ベンジルベンゾエートおよびベンジルアルコールの合計量が約1:0.01(w/w)〜約1:5(w/w)である(24)記載の製薬上許容可能な経口剤形。
(26)
前記17−ヒドロキシプロゲステロンカプロエートの量が総経口剤形の約5%〜約80%w/wである(21)記載の製薬上許容可能な経口剤形。
(27)
前記薬学的経口剤形がカプセルまたは錠剤の形態である(21)記載の製薬上許容可能な経口剤形。
(28)
前記経口剤形がカプセルの形態であり、前記カプセルが約10mg〜約300mgの17−ヒドロキシプロゲステロンカプロエートを含む(27)記載の製薬上許容可能な経口剤形。
(29)
前記経口剤形が錠剤の形態であり、前記錠剤が約20mg〜約800mgの17−ヒドロキシプロゲステロンカプロエートを含む(27)記載の製薬上許容可能な経口剤形。
(30)
前記経口剤形がカプセルであり、前記カプセル中の17−ヒドロキシプロゲステロンカプロエートの量対前記カプセルの充填容積の比が約0.02g/mL〜約0.8g/mLである(27)記載の製薬上許容可能な経口剤形。
(31)
前記担体が親水性添加物を含む(21)記載の製薬上許容可能な経口剤形。
(32)
前記担体が親油性添加物を含む(21)記載の製薬上許容可能な経口剤形。
(33)
前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、脂肪酸グリセリド、胆汁酸の塩、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、PEG−8カプリル酸/カプリン酸グリセリド、ラウロイルマクロゴール−32グリセリド、ステアロイルマクロゴールグリセリド、PEG−40硬化ヒマシ油、PEG−35ヒマシ油、オレイン酸ナトリウム、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、PEG−10ラウレート、PEG−20オレエート、PEG−30ステアレート、PEG−40ラウレート、PEG−20グリセリルラウレート、PEG−20グリセリルステアレート、PEG−40グリセリルラウレート、PEG−20グリセリルオレエート、PEG−10ソルビタンラウレート、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノオレエート、ポリグリセリル−10オレエート、ポリグリセリル−10モノ、ジオレエート、ポロキサマー188、ポロキサマー108、マルトース、スクロース、フルクトース、マンニトール、キシリトールおよびその組合せからなる群から選択される化合物を含む(31)記載の製薬上許容可能な経口剤形。
(34)
前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、ピロリドン、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、セルロースエステル、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、マルトース、スクロース、フルクトース、マンニトール、キシリトールおよびその組合せからなる群から選択される化合物を含む(31)記載の製薬上許容可能な経口剤形。
(35)
前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、ベンジルベンゾエート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、飽和ポリグリコール化グリセリド、リノール酸グリセリド、カプリル酸/カプリン酸グリセリド、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、グリセリルモノオレエート、グリセリルモノリノリエート、グリセリルモノラウレート、グリセロールモノステアレート、グリセリルジステアレート、グリセリルパルミトステアレート、グリセリルラウレート、グリセリルカプリレート、ジステアリン、モノパルミトレイン、モノラウリン、エチルオレエート、PEG−6トウモロコシ油、PEG−6杏仁油、PEG−4カプリル酸/カプリン酸トリグリセリド、PEG−20ソルビタンモノステアレート、PEG−4ラウレート、PEG−6ジラウレート、ポリグリセリル−3オレエート、ポリグリセリル−6ジオレエート、ポロキサマー182、プロピレングリコールモノカプリレート、プロピレングリコールモノラウレート、プロピレングリコールジカプリレート/ジカプレート、プロピレングリコールカプリレート/カプレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノオレエート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタンセスキステアレートおよびその組合せからなる群から選択される化合物を含む(32)記載の製薬上許容可能な経口剤形。
(36)
前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、エチルオレエートおよびその組合せからなる群から選択される化合物を含む(32)記載の製薬上許容可能な経口剤形。
(37)
前記担体が少なくとも50重量%の親油性添加物を含む(32)記載の製薬上許容可能な経口剤形。
(38)
前記担体が、約90:10〜約1:99の親油性添加物対親水性添加物比で、少なくとも1つの親水性添加物および少なくとも1つの親油性添加物を含む(21)記載の製薬上許容可能な経口剤形。
(39)
8時間毎に1回、ヒト被験体への投与のために処方される(21)記載の製薬上許容可能な経口剤形。
(40)
6時間毎に1回、ヒト被験体への投与のために処方される(21)記載の製薬上許容可能な経口剤形。
(41)
12時間毎に1回、ヒト被験体への投与のために処方される(21)記載の製薬上許容可能な経口剤形。
(42)
24時間毎に1回、ヒト被験体への投与のために処方される(21)記載の製薬上許容可能な経口剤形。
(43)
早産の危険がある妊娠女性被験体の処置方法であって、(21)記載の経口剤形を女性被験体に投与することを包含する方法。
(44)
以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート、および
製薬上許容可能な担体
を含む製薬上許容可能な経口剤形であって、0.5%w/wラウリル硫酸ナトリウムを有する人工腸液900mL中で、50RPMで37℃で、USP II型溶解装置を用いて測定した場合に、60分後に17−ヒドロキシプロゲステロンカプロエートの用量の少なくとも20重量%を放出する経口剤形。
(45)
早産の危険がある妊娠女性被験体の処置方法であって、(44)記載の製薬上許容可能な経口剤形を女性被験体に投与することを包含する方法。
(46)
以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート
を含む製薬上許容可能な経口剤形であって、ヒト被験体への単一回経口投与時に、当該剤形が、約0.2対約10ng*hmL−1mg−1の17−ヒドロキシプロゲステロンカプロエートAUC(0−24h)対17−ヒドロキシプロゲステロンカプロエートの用量比を提供し、前記用量が投与される17−ヒドロキシプロゲステロンカプロエートのmgでの量である経口剤形。
(47)
親水性添加物、親油性添加物またはその組合せから選択される担体を含む(46)記載の製薬上許容可能な経口剤形。
(48)
前記17−ヒドロキシプロゲステロンカプロエートが、約50μm以下の平均粒子直径を有する微粒子形態で経口剤形中に存在する(46)記載の製薬上許容可能な経口剤形。
(49)
前記担体がベンジルベンゾエート、ベンジルアルコールまたはその混合物を包含する(46)記載の製薬上許容可能な経口剤形。
(50)
錠剤またはカプセルである(46)記載の製薬上許容可能な経口剤形。
(51)
制御放出型経口剤形である(46)記載の製薬上許容可能な経口剤形。
(52)
即時放出型経口剤形である(46)記載の製薬上許容可能な経口剤形。
(53)
前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、脂肪酸グリセリド、胆汁酸の塩、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、PEG−8カプリル酸/カプリン酸グリセリド、ラウロイルマクロゴール−32グリセリド、ステアロイルマクロゴールグリセリド、PEG−40硬化ヒマシ油、PEG−35ヒマシ油、オレイン酸ナトリウム、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、PEG−10ラウレート、PEG−20オレエート、PEG−30ステアレート、PEG−40ラウレート、PEG−20グリセリルラウレート、PEG−20グリセリルステアレート、PEG−40グリセリルラウレート、PEG−20グリセリルオレエート、PEG−10ソルビタンラウレート、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノオレエート、ポリグリセリル−10オレエート、ポリグリセリル−10モノ、ジオレエート、ポロキサマー188、ポロキサマー108、マルトース、スクロース、フルクトース、マンニトール、キシリトール、ゴムおよびその組合せからなる群から選択される添加物のうちの1つ以上を含む(46)記載の薬学的組成物。
(54)
前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、ベンジルベンゾエート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、飽和ポリグリコール化グリセリド、リノール酸グリセリド、カプリル酸/カプリン酸グリセリド、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、グリセリルモノオレエート、グリセリルモノリノリエート、グリセリルモノラウレート、グリセロールモノステアレート、グリセリルジステアレート、グリセリルパルミトステアレート、グリセリルラウレート、グリセリルカプリレート、ジステアリン、モノパルミトレイン、モノラウリン、エチルオレエート、PEG−6トウモロコシ油、PEG−6杏仁油、PEG−4カプリル酸/カプリン酸トリグリセリド、PEG−20ソルビタンモノステアレート、PEG−4ラウレート、PEG−6ジラウレート、ポリグリセリル−3オレエート、ポリグリセリル−6ジオレエート、ポロキサマー182、プロピレングリコールモノカプリレート、プロピレングリコールモノラウレート、プロピレングリコールジカプリレート/ジカプレート、プロピレングリコールカプリレート/カプレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノオレエート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタンセスキステアレートおよびその組合せからなる群から選択される親油性添加物のうちの1つ以上を含む(46)記載の薬学的組成物。
(55)
早産の危険がある妊娠女性被験体への投与のための医薬品の調製における17−ヒドロキシプロゲステロンカプロエートの使用であって、前記医薬品が(1)、(21)、(44)または(46)のいずれかに記載の組成物を含む使用。
Claims (32)
- 以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート、および
製薬上許容可能な担体
を含む経口薬学的組成物。 - 0.5%w/wラウリル硫酸ナトリウムを有する人工腸液900mL中で、50RPMで37℃で、USP II型溶解装置を用いて測定した場合に、担体を含有しない等価用量投与される経口剤形より60分後に17−ヒドロキシプロゲステロンカプロエートの少なくとも20重量%より多くを当該経口剤形が放出する、請求項1に記載の組成物。
- 妊娠支援のために処方される請求項1または2記載の薬学的組成物。
- 前記17−ヒドロキシプロゲステロンカプロエートが、約50μm以下の平均粒子直径を有する微粒子形態で組成物中に存在する請求項1または2記載の薬学的組成物。
- 前記担体がベンジルベンゾエート、ベンジルアルコールまたはその混合物を包含する請求項1または2記載の薬学的組成物。
- 経口剤形中の前記17−ヒドロキシプロゲステロンカプロエートの量対ベンジルベンゾエートおよびベンジルアルコールの合計量が約1:0.01(w/w)〜約1:5(w/w)である請求項5記載の薬学的組成物。
- 前記17−ヒドロキシプロゲステロンカプロエートの量が総組成物の約5%〜約80%w/wである請求項1または2記載の薬学的組成物。
- カプセルまたは錠剤の形態である請求項1または2記載の薬学的組成物。
- 前記組成物がカプセルの形態であり、前記カプセルが約30mg〜約300mgの17−ヒドロキシプロゲステロンカプロエートを含む請求項8記載の薬学的組成物。
- 前記組成物が錠剤の形態であり、前記錠剤が約20mg〜約800mgの17−ヒドロキシプロゲステロンカプロエートを含む請求項8記載の薬学的組成物。
- 前記組成物がカプセルまたは錠剤の形態であって、前記カプセルまたは錠剤が制御放出経口剤形である請求項1記載の薬学的組成物。
- 前記組成物中の17−ヒドロキシプロゲステロンカプロエートの量対前記カプセルの充填容積の比は約0.02g/mL〜約0.8g/mLである請求項8記載の薬学的組成物。
- 前記担体が親水性添加物を含む請求項1または2記載の薬学的組成物。
- 前記担体が親油性添加物を含む請求項1または2記載の薬学的組成物。
- 前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、脂肪酸グリセリド、胆汁酸の塩、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、PEG−8カプリル酸/カプリン酸グリセリド、ラウロイルマクロゴール−32グリセリド、ステアロイルマクロゴールグリセリド、PEG−40硬化ヒマシ油、PEG−35ヒマシ油、オレイン酸ナトリウム、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、PEG−10ラウレート、PEG−20オレエート、PEG−30ステアレート、PEG−40ラウレート、PEG−20グリセリルラウレート、PEG−20グリセリルステアレート、PEG−40グリセリルラウレート、PEG−20グリセリルオレエート、PEG−10ソルビタンラウレート、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノオレエート、ポリグリセリル−10オレエート、ポリグリセリル−10モノ、ジオレエート、ポロキサマー188、ポロキサマー108、マルトース、スクロース、フルクトース、マンニトール、キシリトールおよびその組合せからなる群から選択される化合物を含む請求項13記載の薬学的組成物。
- 前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、ベンジルベンゾエート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、飽和ポリグリコール化グリセリド、リノール酸グリセリド、カプリル酸/カプリン酸グリセリド、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、グリセリルモノオレエート、グリセリルモノリノリエート、グリセリルモノラウレート、グリセロールモノステアレート、グリセリルジステアレート、グリセリルパルミトステアレート、グリセリルラウレート、グリセリルカプリレート、ジステアリン、モノパルミトレイン、モノラウリン、エチルオレエート、PEG−6トウモロコシ油、PEG−6杏仁油、PEG−4カプリル酸/カプリン酸トリグリセリド、PEG−20ソルビタンモノステアレート、PEG−4ラウレート、PEG−6ジラウレート、ポリグリセリル−3オレエート、ポリグリセリル−6ジオレエート、ポロキサマー182、プロピレングリコールモノカプリレート、プロピレングリコールモノラウレート、プロピレングリコールジカプリレート/ジカプレート、プロピレングリコールカプリレート/カプレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノオレエート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタンセスキステアレートおよびその組合せからなる群から選択される化合物を含む請求項14記載の薬学的組成物。
- 前記担体が少なくとも50重量%の親油性添加物を含む請求項14記載の薬学的組成物。
- 前記担体が、約90:10〜約1:99の親油性添加物対親水性添加物比で、少なくとも1つの親水性添加物および少なくとも1つの親油性添加物を含む請求項1または2記載の薬学的組成物。
- 早産の危険がある妊娠女性被験体の処置方法であって、請求項1または2記載の薬学的組成物を女性被験体に投与することを包含する方法。
- 6時間毎、8時間毎、12時間毎、または24時間毎に1回、ヒト被験体への投与のために処方される請求項1または2記載の薬学的組成物。
- 以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート、および
製薬上許容可能な担体
を含む製薬上許容可能な経口剤形であって、0.5%w/wラウリル硫酸ナトリウムを有する人工腸液900mL中で、50RPMで37℃で、USP II型溶解装置を用いて測定した場合に、60分後に17−ヒドロキシプロゲステロンカプロエートの用量の少なくとも20重量%を放出する経口剤形。 - 早産の危険がある妊娠女性被験体の処置方法であって、請求項21記載の製薬上許容可能な経口剤形を女性被験体に投与することを包含する方法。
- 以下の:
治療的有効量の17−ヒドロキシプロゲステロンカプロエート
を含む製薬上許容可能な経口剤形であって、ヒト被験体への単一回経口投与時に、当該剤形が、約0.2〜約10ng*hmL−1mg−1の17−ヒドロキシプロゲステロンカプロエートAUC(0−24h)対17−ヒドロキシプロゲステロンカプロエートの用量比を提供し、前記用量が投与される17−ヒドロキシプロゲステロンカプロエートのmgでの量である経口剤形。 - 親水性添加物、親油性添加物またはその組合せから選択される担体を含む請求項23記載の製薬上許容可能な経口剤形。
- 前記17−ヒドロキシプロゲステロンカプロエートが、約50μm以下の平均粒子直径を有する微粒子形態で経口剤形中に存在する請求項23記載の製薬上許容可能な経口剤形。
- 前記担体がベンジルベンゾエート、ベンジルアルコールまたはその混合物を包含する請求項23記載の製薬上許容可能な経口剤形。
- 錠剤またはカプセルである請求項23記載の製薬上許容可能な経口剤形。
- 制御放出型経口剤形である請求項23記載の製薬上許容可能な経口剤形。
- 即時放出型経口剤形である請求項23記載の製薬上許容可能な経口剤形。
- 前記担体が、クエン酸、マレイン酸、酒石酸、酢酸、アスコルビン酸、安息香酸および乳酸の塩、水酸化カリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸カルシウム、二酸化ケイ素、ケイ酸アルミニウムマグネシウム、ヒドロキシプロピルシクロデキストリン、脂肪酸グリセリド、胆汁酸の塩、ポリビニルピロリドン、エチルアルコール、ベンジルアルコール、グリセロール、プロピレングリコール、ポリエチレングリコール、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボマー、キトサン、メタクリレート、ポリビニルアルコール、ゼラチン、PEG−8カプリル酸/カプリン酸グリセリド、ラウロイルマクロゴール−32グリセリド、ステアロイルマクロゴールグリセリド、PEG−40硬化ヒマシ油、PEG−35ヒマシ油、オレイン酸ナトリウム、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、PEG−10ラウレート、PEG−20オレエート、PEG−30ステアレート、PEG−40ラウレート、PEG−20グリセリルラウレート、PEG−20グリセリルステアレート、PEG−40グリセリルラウレート、PEG−20グリセリルオレエート、PEG−10ソルビタンラウレート、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノオレエート、ポリグリセリル−10オレエート、ポリグリセリル−10モノ、ジオレエート、ポロキサマー188、ポロキサマー108、マルトース、スクロース、フルクトース、マンニトール、キシリトール、ゴムおよびその組合せからなる群から選択される添加物のうちの1つ以上を含む請求項23記載の製薬上許容可能な経口剤形。
- 前記担体が、トリブチルシトレート、トリエチルシトレート、トリアセチン、エチルセルロース、セルロースエステル、セルロースアセテート、セルロースアセテートブチレート、セルロースアセテートフタレート、ヒドロキシプロピルメチルセルロースフタレート、トコフェロール、トコフェロールアセテート、トコフェロールスクシネート、ベンジルベンゾエート、トウモロコシ油、オリーブ油、落花生油、ベニバナ油、ゴマ油、ダイズ油、硬化ヒマシ油、グリセリルトリカプレート、グリセリルトリラウレート、グリセリルトリオレエート、グリセリルトリリノリエート、グリセリルトリカプリレート/カプレート、グリセリルトリカプリレート/カプレート/ラウレート、グリセリルトリカプリレート/カプレート/リノリエート、グリセリルトリカプリレート/カプレート/ステアレート、飽和ポリグリコール化グリセリド、リノール酸グリセリド、カプリル酸/カプリン酸グリセリド、カプリン酸、カプリル酸、パルミチン酸、ラウリン酸、ステアリン酸、リノール酸、オレイン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸、グリセリルモノオレエート、グリセリルモノリノリエート、グリセリルモノラウレート、グリセロールモノステアレート、グリセリルジステアレート、グリセリルパルミトステアレート、グリセリルラウレート、グリセリルカプリレート、ジステアリン、モノパルミトレイン、モノラウリン、エチルオレエート、PEG−6トウモロコシ油、PEG−6杏仁油、PEG−4カプリル酸/カプリン酸トリグリセリド、PEG−20ソルビタンモノステアレート、PEG−4ラウレート、PEG−6ジラウレート、ポリグリセリル−3オレエート、ポリグリセリル−6ジオレエート、ポロキサマー182、プロピレングリコールモノカプリレート、プロピレングリコールモノラウレート、プロピレングリコールジカプリレート/ジカプレート、プロピレングリコールカプリレート/カプレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノオレエート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタンセスキステアレートおよびその組合せからなる群から選択される親油性添加物のうちの1つ以上を含む請求項23記載の製薬上許容可能な経口剤形。
- 早産の危険がある妊娠女性被験体への投与のための医薬品の調製における17−ヒドロキシプロゲステロンカプロエートの使用であって、前記医薬品が請求項1、2、21または23のいずれかに記載の組成物または経口剤形を含む使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/193,571 | 2011-07-28 | ||
US13/193,571 US8951996B2 (en) | 2011-07-28 | 2011-07-28 | 17-hydroxyprogesterone ester-containing oral compositions and related methods |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014523096A Division JP6479470B2 (ja) | 2011-07-28 | 2012-07-27 | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2017193554A true JP2017193554A (ja) | 2017-10-26 |
Family
ID=47597718
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014523096A Active JP6479470B2 (ja) | 2011-07-28 | 2012-07-27 | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
JP2017098138A Pending JP2017193554A (ja) | 2011-07-28 | 2017-05-17 | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014523096A Active JP6479470B2 (ja) | 2011-07-28 | 2012-07-27 | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
Country Status (13)
Country | Link |
---|---|
US (10) | US8951996B2 (ja) |
EP (2) | EP2736515B1 (ja) |
JP (2) | JP6479470B2 (ja) |
KR (1) | KR101957264B1 (ja) |
CN (2) | CN108514545A (ja) |
AU (1) | AU2012286620B2 (ja) |
BR (1) | BR112014001942B1 (ja) |
CA (1) | CA2879401C (ja) |
IL (1) | IL230665B (ja) |
MX (1) | MX385798B (ja) |
RU (1) | RU2640912C2 (ja) |
WO (1) | WO2013016697A2 (ja) |
ZA (1) | ZA201401464B (ja) |
Families Citing this family (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10993879B2 (en) | 2010-02-08 | 2021-05-04 | Shenzhen Evergreen Therapeutics Co., Ltd. | Pulmonary delivery of progestogen |
US10987361B2 (en) | 2010-02-08 | 2021-04-27 | Shenzhen Evergreen Therapeutics Co., Ltd. | Treating auto-immune and auto-inflammatory diseases |
US9375437B2 (en) | 2010-06-18 | 2016-06-28 | Lipocine Inc. | Progesterone containing oral dosage forms and kits |
US8951996B2 (en) | 2011-07-28 | 2015-02-10 | Lipocine Inc. | 17-hydroxyprogesterone ester-containing oral compositions and related methods |
BR112014012444B1 (pt) | 2011-11-23 | 2021-12-14 | Therapeuticsmd, Inc | Composição farmacêutica compreendendo estradiol solubilizado, progesterona e um agente de solubilização, bem como usos desta para tratar um sintoma relacionado à menopausa em uma mulher |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
EP3382391A1 (en) | 2012-10-24 | 2018-10-03 | NYU Winthrop Hospital | Non-invasive biomarker to identify subjects at risk of preterm delivery |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
JP2017516768A (ja) | 2014-05-22 | 2017-06-22 | セラピューティックスエムディー インコーポレーテッドTherapeuticsmd, Inc. | 天然の併用ホルモン補充療法剤及び療法 |
BR112016029338A2 (pt) | 2014-07-29 | 2017-08-22 | Therapeuticsmd Inc | creme transdérmico |
KR101561406B1 (ko) * | 2015-02-02 | 2015-10-16 | 환인제약 주식회사 | 두타스테라이드 함유 고체 분산체 및 이를 포함하는 조성물 |
US9844558B1 (en) | 2015-04-30 | 2017-12-19 | Amag Pharmaceuticals, Inc. | Methods of reducing risk of preterm birth |
ES3005883T3 (en) | 2015-06-22 | 2025-03-17 | Lipocine Inc | 17-hydroxyprogesterone ester-containing oral compositions and related methods |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
EP3344338A4 (en) * | 2015-09-21 | 2019-05-08 | Prairie Pharmaceuticals, LLC | PULMONARY RELEASE OF PROGESTOGEN |
JP2018529767A (ja) * | 2015-09-21 | 2018-10-11 | プレーリー ファーマシューティカルズ エルエルシー | 自己免疫疾患及び自己炎症疾患の治療方法 |
WO2017059070A1 (en) * | 2015-09-29 | 2017-04-06 | Amag Pharmaceuticals, Inc. | Crystalline and amorphous form of 17-a- hydroxyprogesterone caproate |
WO2017081725A1 (ja) * | 2015-11-09 | 2017-05-18 | 花王株式会社 | 口腔用組成物 |
WO2017105512A1 (en) | 2015-12-18 | 2017-06-22 | Proinvet Innovations S.A. | Formulations and methods for controlling the reproductive cycle and ovulation |
RU2018133932A (ru) | 2016-04-01 | 2020-05-12 | Терапьютиксмд, Инк. | Фармацевтическая композиция стероидного гормона |
WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
CN109219442A (zh) | 2016-04-04 | 2019-01-15 | Omeza有限公司 | 鱼油局部组合物 |
EP4183431A1 (en) | 2016-05-06 | 2023-05-24 | Gambro Lundia AB | Systems and methods for peritoneal dialysis having point of use dialysis fluid preparation using water accumulator and disposable set |
CA3022693A1 (en) * | 2016-05-16 | 2017-11-23 | Amag Pharmaceuticals, Inc. | Polymeric extended release compositions of hydroxyprogesterone caproate and methods of using same |
WO2018027013A1 (en) * | 2016-08-03 | 2018-02-08 | Indiana University Research & Technology Corporation | Monohydroxylated 17alpha-hydroxyprogesterone caproate for reducing contractility |
TW202247855A (zh) | 2016-09-13 | 2022-12-16 | 美商愛力根公司 | 非蛋白梭菌毒素組成物 |
WO2018060866A1 (en) * | 2016-09-28 | 2018-04-05 | Dr. Reddy’S Laboratories Limited | Oral retinoid compositions |
BR112019021396A2 (pt) | 2017-04-14 | 2020-04-28 | Capsugel Belgium Nv | processo para fabricação de pululano |
BR112019021391A2 (pt) | 2017-04-14 | 2020-05-05 | Capsugel Belgium Nv | cápsulas de pululano |
CA3075688A1 (en) | 2017-09-13 | 2019-03-21 | Progenity, Inc. | Preeclampsia biomarkers and related systems and methods |
WO2019094688A1 (en) * | 2017-11-10 | 2019-05-16 | Dispersol Technologies, Llc | Improved drug formulations |
MX391097B (es) * | 2017-11-27 | 2025-03-21 | Umecrine Cognition Ab | FORMULACIÓN FARMACÉUTICA DE 3A-ETINIL-3ß-HIDROXIANDROSTAN-17-ONA OXIMA. |
US20210033619A1 (en) * | 2018-02-09 | 2021-02-04 | Metabolomic Diagnostics Limited | Methods of predicting pre term birth from preeclampsia using metabolic and protein biomarkers |
WO2021026285A1 (en) * | 2019-08-06 | 2021-02-11 | Kirkland Justin | Formulations including dihydrohonokiol |
EP4070113A4 (en) | 2019-12-04 | 2023-12-20 | Biora Therapeutics, Inc. | ASSESSMENT OF PREECAMPSIA USING FREE AND DISSOCIATE PLACENTAL GROWTH FACTOR ASSAYS |
CN113616660A (zh) * | 2020-05-07 | 2021-11-09 | 深圳埃格林医药有限公司 | 孕激素制剂及其用途 |
CN111975205B (zh) * | 2020-09-04 | 2022-04-22 | 内蒙古工业大学 | 重度磨损截齿修补方法 |
US11969434B1 (en) | 2022-08-29 | 2024-04-30 | Lipocine Inc. | Oral allopregnanolone compositions and methods of use |
CN116077416B (zh) * | 2021-11-05 | 2024-12-06 | 深圳埃格林医药有限公司 | 一种包含孕激素的口服制剂及制备方法和应用 |
WO2023107796A1 (en) * | 2021-12-11 | 2023-06-15 | The Regents Of The University Of California | Ophthalmic formulations for macular degeneration |
US12186327B2 (en) | 2022-08-29 | 2025-01-07 | Lipocine Inc. | Oral allopregnanolone compositions and methods of use |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3164520A (en) * | 1962-10-29 | 1965-01-05 | Olin Mathieson | Injectable steroid compositions containing at least 75% benzyl benzoate |
US5620705A (en) * | 1994-08-04 | 1997-04-15 | Alza Corporation | Progestin tablet |
JP2000514051A (ja) * | 1996-06-28 | 2000-10-24 | クリンゲ ファーマ ジーエムビーエイチ | ベンズイミダゾール誘導体を活性成分とする経口投与用の安定な薬剤形およびその製造方法 |
US20040266025A1 (en) * | 2003-02-06 | 2004-12-30 | Durlin Hickok | Screening and treatment methods for prevention of preterm delivery |
CN1623550A (zh) * | 2003-12-04 | 2005-06-08 | 张伟 | 己酸羟孕酮口服制剂和用途 |
JP2006524238A (ja) * | 2003-03-17 | 2006-10-26 | バクスター・インターナショナル・インコーポレイテッド | 小粒子を調製するための方法 |
JP2007119479A (ja) * | 1998-12-17 | 2007-05-17 | Euro-Celtique Sa | 制御/調整放出型メチルフェニデート経口製剤 |
JP2009501785A (ja) * | 2005-07-20 | 2009-01-22 | パナセア バイオテック リミテッド | 新規な調節放出性医薬製剤シクロオキシゲナーゼ酵素阻害剤 |
US20110152840A1 (en) * | 2009-12-23 | 2011-06-23 | Drugtech Corporation | Methods for reducing the occurrence of preterm delivery and other pregnancy-related conditions |
JP2014521660A (ja) * | 2011-07-28 | 2014-08-28 | リポカイン インコーポレーテッド | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
Family Cites Families (70)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL151903B (nl) | 1965-03-24 | 1977-01-17 | Schering Ag | Werkwijze ter bereiding van een injectievloeistof door een steroid op te lossen in een mengsel van ricinusolie en benzylbenzoaat. |
US4147783A (en) | 1974-02-28 | 1979-04-03 | Akzona Incorporated | Oral pharmaceutical preparation |
US4181721A (en) * | 1975-10-27 | 1980-01-01 | Schering Aktiengesellschaft | Depot preparations in an oily, unsaturated solution for intramuscular injection |
FR2408345A1 (fr) | 1976-11-30 | 1979-06-08 | Besins Jean Louis | Nouvelle composition a action anti-conceptionnelle |
US4230702A (en) | 1978-01-09 | 1980-10-28 | Kali-Chemie Pharma Gmbh | Readily enterally absorbable pharmaceutical compositions of per se poorly enterally absorbable pharmacologically active agents |
WO1981002671A1 (en) * | 1980-03-20 | 1981-10-01 | Ferring Farma Lab | Pharmaceutical composition and method for the treatment of colitis ulcerosa and crohn's disease by oral administration |
US4439432A (en) | 1982-03-22 | 1984-03-27 | Peat Raymond F | Treatment of progesterone deficiency and related conditions with a stable composition of progesterone and tocopherols |
US5314882A (en) * | 1984-01-03 | 1994-05-24 | International Foundation For Biochemical Endocrinology | Method for promoting growth and improved meat quality in meat producing animals with female steroidal hormones |
US5140021A (en) | 1986-04-16 | 1992-08-18 | Genesis Systems Corporation | Method and dosage form for treatment of premenstrual syndrome |
GB8730011D0 (en) | 1987-12-23 | 1988-02-03 | Smithkline Dauelsberg | Pharmaceutical compositions |
GB8802671D0 (en) | 1988-02-05 | 1988-03-02 | Goodfellow J W | Orthopaedic joint components tools & methods |
WO1990008537A1 (en) | 1989-02-06 | 1990-08-09 | Abbott Laboratories | Pharmaceutical compositions for oral administration |
IT1252867B (it) | 1991-12-31 | 1995-06-28 | Gentili Ist Spa | Composizioni farmaceutiche contenenti progesterone ad elevata biodisponibilita' |
DK95093D0 (da) | 1993-08-20 | 1993-08-20 | Novo Nordisk As | Farmaceutisk formulering indeholdende et hormon |
US5543150A (en) | 1993-09-15 | 1996-08-06 | Columbia Laboratories, Inc. | Method of progesterone delivery and affect thereof |
GB9405304D0 (en) | 1994-03-16 | 1994-04-27 | Scherer Ltd R P | Delivery systems for hydrophobic drugs |
WO1996005851A1 (de) | 1994-08-23 | 1996-02-29 | Dgf Stoess Ag | Verwendung von geschmacksneutralem, hydrolysiertem kollagen und mittel enthaltend dasselbe |
SK284421B6 (sk) | 1997-04-28 | 2005-04-01 | Melania Kaszas-Savos | Spôsob spätného získavania surovín z odpadov a zvyškových látok a zariadenie na vykonávanie tohto spôsobu |
DE19718012C1 (de) | 1997-04-29 | 1998-10-08 | Jenapharm Gmbh | Verfahren zur Herstellung peroral anwendbarer fester Arzneiformen mit gesteuerter Wirkstoffabgabe |
DE19739916C2 (de) | 1997-09-11 | 2001-09-13 | Hesch Rolf Dieter | Verwendung einer Kombination aus einem Gestagen und einem Estrogen zur kontinuierlichen Ovulationshemmung und ggf. gleichzeitigen Behandlung und/oder Prophylaxe von Tumoren der Brustdrüsen |
FR2772617B1 (fr) | 1997-12-19 | 2001-03-09 | Besins Iscovesco Lab | Comprime de progesterone et son procede de preparation |
FR2775599B1 (fr) | 1998-03-09 | 2001-08-17 | Besins Iscovesco Lab | Composition pharmaceutique a base de progesterone naturelle de synthese et d'oestradiol et son procede de preparation |
US6602521B1 (en) | 1998-09-29 | 2003-08-05 | Impax Pharmaceuticals, Inc. | Multiplex drug delivery system suitable for oral administration |
US6214815B1 (en) | 1998-12-23 | 2001-04-10 | Ortho-Mcneil Pharmaceuticals, Inc. | Triphasic oral contraceptive |
US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US7374779B2 (en) | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
GB9907715D0 (en) | 1999-04-01 | 1999-05-26 | Scherer Corp R P | Pharmaceutical compositions |
US20030236236A1 (en) | 1999-06-30 | 2003-12-25 | Feng-Jing Chen | Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs |
US20020131988A1 (en) | 1999-12-16 | 2002-09-19 | Foster Todd P. | Pharmaceutical implant containing immediate-release and sustained-release components and method of administration |
US6544553B1 (en) | 1999-12-28 | 2003-04-08 | Watson Pharmaceuticals, Inc. | Dosage forms and methods for oral delivery of progesterone |
US8067032B2 (en) * | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
FR2818905A1 (fr) | 2000-12-28 | 2002-07-05 | Cll Pharma | Compositions pharmaceutiques colloidales micellaires renfermant un principe actif lipophile |
FR2821555B1 (fr) | 2001-03-01 | 2003-05-16 | Besins Int Lab | Progestatif co-micronise avec un tensioactif, composition pharmaceutique le comprenant, leurs procedes de fabrication et leurs utilisations |
US20030022875A1 (en) | 2001-07-27 | 2003-01-30 | Wilson Leland F. | As-needed administration of orally active androgenic agents to enhance female sexual desire and responsiveness |
FR2832065B1 (fr) | 2001-11-13 | 2004-11-05 | Besins Int Belgique | Composition pharmaceutique a base de progesterone micronisee son procede de preparation et ses utilisations |
PL368744A1 (en) * | 2001-11-30 | 2005-04-04 | Solvay Pharmaceuticals Gmbh | Prevention of miscarriage with immunomodulating non-endogenous gestagen compounds |
CA2476744A1 (en) * | 2002-03-07 | 2003-09-12 | Novartis Ag | Solid pharmaceutical compositions comprising lumiracoxib |
JP2005526083A (ja) | 2002-03-14 | 2005-09-02 | ワトソン ファーマシューティカルズ, インコーポレイテッド | プロゲステロンの経口薬物送達システム |
JP2005532387A (ja) * | 2002-07-05 | 2005-10-27 | テムレル・インコーポレイテッド | 制御放出組成物 |
US8216609B2 (en) | 2002-08-05 | 2012-07-10 | Torrent Pharmaceuticals Limited | Modified release composition of highly soluble drugs |
CN1231210C (zh) | 2002-08-20 | 2005-12-14 | 杭州容立医药科技有限公司 | 黄体酮胶囊组合物及其制备方法 |
NZ538342A (en) | 2002-08-28 | 2007-08-31 | Robert Casper | Estrogen replacement regimen |
DE60330695D1 (de) | 2002-09-05 | 2010-02-04 | Pantarhei Bioscience Bv | Orale pharmazeutische zusammensetzung enthaltend 15-hydroxytestosteron und seine derivate |
JP2004155780A (ja) | 2002-10-16 | 2004-06-03 | Taisho Pharmaceut Co Ltd | 生活習慣病改善剤組成物 |
AU2003295409B2 (en) * | 2002-11-06 | 2010-02-11 | Durect Corporation | Controlled release depot formulations |
ES2350689T3 (es) | 2002-12-13 | 2011-01-26 | Durect Corporation | Sistema de suministro de fármacos oral que comprende materiales vehículo líquidos de alta viscosidad. |
CN1282459C (zh) | 2002-12-24 | 2006-11-01 | 上海医药工业研究院 | 黄体酮胶丸及制备方法 |
GB0305941D0 (en) | 2003-03-14 | 2003-04-23 | Camurus Ab | Composition |
CN1299686C (zh) | 2003-04-03 | 2007-02-14 | 上海医药工业研究院 | 黄体酮半固体骨架制剂的组合物 |
DK1663216T3 (da) | 2003-08-29 | 2012-02-20 | Veloxis Pharmaceuticals As | Tacrolimus-holdige sammensætninger med modificeret frigivelse |
WO2005055983A2 (en) | 2003-12-09 | 2005-06-23 | Medcrystalforms, Llc | Method of preparation of mixed phase co-crystals with active agents |
WO2005092441A2 (en) | 2004-03-19 | 2005-10-06 | Warner Chilcott Company, Inc. | Extended cycle multiphasic oral contraceptive method |
GT200500186A (es) | 2004-07-07 | 2006-03-02 | Regimenes anticonceptivos con antagonistas del receptor de progesterona y kits | |
CA2599758A1 (en) | 2005-03-08 | 2006-09-14 | Lifecycle Pharma A/S | Pharmaceutical compositions comprising sirolimus and/or an analogue thereof |
US7473687B2 (en) | 2005-03-24 | 2009-01-06 | Emory University | Methods for the treatment of a traumatic central nervous system injury |
EP2985026B1 (en) | 2005-04-15 | 2022-08-03 | Clarus Therapeutics, Inc. | Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same |
ES2381495T3 (es) | 2005-05-26 | 2012-05-28 | Teva Women's Health, Inc. | Formas de dosificación oral que comprenden progesterona y métodos para fabricar y usar las mismas |
JP2008546781A (ja) * | 2005-06-20 | 2008-12-25 | エラン・ファルマ・インターナショナル・リミテッド | アリール−複素環式化合物を含んでなるナノ粒状及び制御放出の組成物 |
US8828981B2 (en) | 2007-02-06 | 2014-09-09 | George Creasy | Progesterone for the treatment or prevention of spontaneous preterm birth |
SI2200588T1 (sl) | 2007-09-25 | 2019-08-30 | Solubest Ltd. | Sestavki, ki obsegajo lipofilne aktivne spojine, in postopek za njihovo pripravo |
CA2744906A1 (en) | 2007-11-29 | 2009-06-04 | Gregg A. Jackson | Progesterone-containing compositions and devices |
MX2011008647A (es) * | 2009-02-20 | 2011-10-28 | Micro Labs Ltd | Producto de prostaglandina de almacenamiento estable. |
US9011908B2 (en) | 2009-04-06 | 2015-04-21 | Banner Life Sciences Llc | Progesterone solutions for increased bioavailability |
EP2494363A1 (en) | 2009-10-29 | 2012-09-05 | The Trustees Of The University Of Pennsylvania | Method of predicting risk of preterm birth |
WO2011112747A1 (en) | 2010-03-09 | 2011-09-15 | Catholic Healthcare West | Methods for inhibiting preterm labor and uterine contractility disorders and preventing cervical ripening |
US20110312928A1 (en) | 2010-06-18 | 2011-12-22 | Lipocine Inc. | Progesterone Containing Oral Dosage Forms and Related Methods |
US20110312927A1 (en) | 2010-06-18 | 2011-12-22 | Satish Kumar Nachaegari | Progesterone Containing Oral Dosage Forms and Related Methods |
US9375437B2 (en) | 2010-06-18 | 2016-06-28 | Lipocine Inc. | Progesterone containing oral dosage forms and kits |
US20120148675A1 (en) | 2010-12-10 | 2012-06-14 | Basawaraj Chickmath | Testosterone undecanoate compositions |
-
2011
- 2011-07-28 US US13/193,571 patent/US8951996B2/en active Active
-
2012
- 2012-07-27 RU RU2014102285A patent/RU2640912C2/ru active
- 2012-07-27 BR BR112014001942A patent/BR112014001942B1/pt active IP Right Grant
- 2012-07-27 CN CN201810536203.0A patent/CN108514545A/zh active Pending
- 2012-07-27 AU AU2012286620A patent/AU2012286620B2/en active Active
- 2012-07-27 JP JP2014523096A patent/JP6479470B2/ja active Active
- 2012-07-27 CN CN201280047331.XA patent/CN103826640A/zh active Pending
- 2012-07-27 EP EP12818254.0A patent/EP2736515B1/en active Active
- 2012-07-27 WO PCT/US2012/048708 patent/WO2013016697A2/en active Application Filing
- 2012-07-27 EP EP20175435.5A patent/EP3763360A1/en not_active Withdrawn
- 2012-07-27 MX MX2014001101A patent/MX385798B/es unknown
- 2012-07-27 KR KR1020147005538A patent/KR101957264B1/ko active Active
- 2012-07-27 CA CA2879401A patent/CA2879401C/en active Active
-
2014
- 2014-01-27 IL IL230665A patent/IL230665B/en active IP Right Grant
- 2014-02-26 ZA ZA2014/01464A patent/ZA201401464B/en unknown
- 2014-04-24 US US14/261,057 patent/US9364547B2/en active Active
- 2014-09-04 US US14/477,771 patent/US9358298B2/en active Active
-
2015
- 2015-02-27 US US14/633,545 patent/US9399069B2/en active Active
- 2015-07-16 US US14/801,737 patent/US9358299B2/en active Active
-
2016
- 2016-04-05 US US15/090,800 patent/US10022384B2/en active Active
- 2016-09-15 US US15/266,206 patent/US20170007623A1/en not_active Abandoned
-
2017
- 2017-05-17 JP JP2017098138A patent/JP2017193554A/ja active Pending
-
2018
- 2018-06-15 US US16/010,188 patent/US20180289724A1/en not_active Abandoned
-
2019
- 2019-03-28 US US16/368,431 patent/US10709716B2/en not_active Expired - Fee Related
-
2020
- 2020-07-10 US US16/926,506 patent/US11471470B2/en active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3164520A (en) * | 1962-10-29 | 1965-01-05 | Olin Mathieson | Injectable steroid compositions containing at least 75% benzyl benzoate |
US5620705A (en) * | 1994-08-04 | 1997-04-15 | Alza Corporation | Progestin tablet |
JP2000514051A (ja) * | 1996-06-28 | 2000-10-24 | クリンゲ ファーマ ジーエムビーエイチ | ベンズイミダゾール誘導体を活性成分とする経口投与用の安定な薬剤形およびその製造方法 |
JP2007119479A (ja) * | 1998-12-17 | 2007-05-17 | Euro-Celtique Sa | 制御/調整放出型メチルフェニデート経口製剤 |
US20040266025A1 (en) * | 2003-02-06 | 2004-12-30 | Durlin Hickok | Screening and treatment methods for prevention of preterm delivery |
JP2006524238A (ja) * | 2003-03-17 | 2006-10-26 | バクスター・インターナショナル・インコーポレイテッド | 小粒子を調製するための方法 |
CN1623550A (zh) * | 2003-12-04 | 2005-06-08 | 张伟 | 己酸羟孕酮口服制剂和用途 |
JP2009501785A (ja) * | 2005-07-20 | 2009-01-22 | パナセア バイオテック リミテッド | 新規な調節放出性医薬製剤シクロオキシゲナーゼ酵素阻害剤 |
US20110152840A1 (en) * | 2009-12-23 | 2011-06-23 | Drugtech Corporation | Methods for reducing the occurrence of preterm delivery and other pregnancy-related conditions |
JP2014521660A (ja) * | 2011-07-28 | 2014-08-28 | リポカイン インコーポレーテッド | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6479470B2 (ja) | 17−ヒドロキシプロゲステロンエステル含有経口組成物および関連方法 | |
US11590147B2 (en) | 17-hydroxyprogesterone ester-containing oral compositions and related methods | |
JP2014521721A (ja) | プロゲステロン含有の経口剤形及び関連する方法 | |
NZ620698B2 (en) | 17-hydroxyprogesterone ester-containing oral compositions and related methods |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180306 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180605 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180801 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180906 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20181204 |