ZA200306608B - Pregabalin lactose conjugates. - Google Patents
Pregabalin lactose conjugates. Download PDFInfo
- Publication number
- ZA200306608B ZA200306608B ZA200306608A ZA200306608A ZA200306608B ZA 200306608 B ZA200306608 B ZA 200306608B ZA 200306608 A ZA200306608 A ZA 200306608A ZA 200306608 A ZA200306608 A ZA 200306608A ZA 200306608 B ZA200306608 B ZA 200306608B
- Authority
- ZA
- South Africa
- Prior art keywords
- tetrahydro
- pyran
- pyrrolidin
- isobutyl
- hydroxymethyl
- Prior art date
Links
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 title description 57
- 229960001233 pregabalin Drugs 0.000 title description 57
- 239000008101 lactose Substances 0.000 title description 45
- 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 title description 39
- 150000001875 compounds Chemical class 0.000 claims description 80
- 239000000203 mixture Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 26
- 208000015114 central nervous system disease Diseases 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 14
- BAZBIXRKAXNTCJ-IEPCQTTFSA-N (4s)-4-(2-methylpropyl)-1-[[2,3,4-trihydroxy-5-(hydroxymethyl)oxolan-2-yl]methyl]pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1CC1(O)C(O)C(O)C(CO)O1 BAZBIXRKAXNTCJ-IEPCQTTFSA-N 0.000 claims description 12
- XDWMEMJQXHTKBB-CHXUSJIQSA-N (4s)-4-(2-methylpropyl)-1-[[2,3,5-trihydroxy-4-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl]pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1CC1(O)C(O)C(OC2C(C(O)C(O)C(CO)O2)O)C(O)CO1 XDWMEMJQXHTKBB-CHXUSJIQSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- RCDRJCSOBMHAGQ-CHXUSJIQSA-N (4s)-1-[[2,3-dihydroxy-5-(hydroxymethyl)-4-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl]-4-(2-methylpropyl)pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1CC1(O)C(O)C(OC2C(C(O)C(O)C(CO)O2)O)C(CO)O1 RCDRJCSOBMHAGQ-CHXUSJIQSA-N 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- BQKWHOPNFGYFHX-LONARHHWSA-N (4s)-1-[3,4-dihydroxy-6-(hydroxymethyl)-5-[3,4,5-tris(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]-4-(2-methylpropyl)pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1C1C(O)C(O)C(OC2C(C(CO)C(CO)CO2)CO)C(CO)O1 BQKWHOPNFGYFHX-LONARHHWSA-N 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims 6
- 208000020685 sleep-wake disease Diseases 0.000 claims 3
- 208000012661 Dyskinesia Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 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 39
- AZUXUOROLIYZMA-IEPCQTTFSA-N (4s)-4-(2-methylpropyl)-1-[(2,3,4,5-tetrahydroxyoxan-2-yl)methyl]pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1CC1(O)C(O)C(O)C(O)CO1 AZUXUOROLIYZMA-IEPCQTTFSA-N 0.000 description 34
- 150000003839 salts Chemical class 0.000 description 29
- -1 pyran-2-ylmethyl Chemical group 0.000 description 24
- 238000001228 spectrum Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000002775 capsule Substances 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000002500 ions Chemical class 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- 238000000132 electrospray ionisation Methods 0.000 description 8
- 229930182830 galactose Natural products 0.000 description 8
- 150000003951 lactams Chemical class 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 238000003691 Amadori rearrangement reaction Methods 0.000 description 6
- 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 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- BSKMCHXCKWARJQ-RZAKBIKASA-N (4s)-1-[3,4-dihydroxy-6-(hydroxymethyl)-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]-4-(2-methylpropyl)pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1C1C(O)C(O)C(OC2C(C(O)C(O)C(CO)O2)O)C(CO)O1 BSKMCHXCKWARJQ-RZAKBIKASA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 150000003214 pyranose derivatives Chemical class 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000000089 arabinosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)CO1)* 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229940099112 cornstarch Drugs 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000012154 double-distilled water Substances 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Natural products O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229940039024 pregabalin 25 mg Drugs 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- IVUYGANTXQVDDG-UHFFFAOYSA-N 1-(2-methylpropyl)pyrrolidin-2-one Chemical compound CC(C)CN1CCCC1=O IVUYGANTXQVDDG-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 150000002243 furanoses Chemical group 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 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 2
- 108010005094 Advanced Glycation End Products Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 229930182474 N-glycoside Natural products 0.000 description 2
- 238000012565 NMR experiment Methods 0.000 description 2
- 229920001615 Tragacanth Polymers 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
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000000573 anti-seizure effect Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 150000002341 glycosylamines Chemical class 0.000 description 2
- 229940030980 inova Drugs 0.000 description 2
- 125000003796 lyxosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 238000004262 preparative liquid chromatography Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- QYQBYCXQXJCROQ-QLYLSODFSA-N (4S)-4-(2-methylpropyl)-1-[(2,3,4,5-tetrahydroxyoxan-2-yl)methyl]pyrrolidin-2-one (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.O=C1C[C@H](CC(C)C)CN1CC1(O)C(O)C(O)C(O)CO1 QYQBYCXQXJCROQ-QLYLSODFSA-N 0.000 description 1
- XANWOULVSWKIBE-AFLMEXFJSA-N (4s)-1-[3,4-dihydroxy-6-(hydroxymethyl)-5-[3,4,5,6-tetrakis(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]-4-(2-methylpropyl)pyrrolidin-2-one Chemical compound O=C1C[C@H](CC(C)C)CN1C1C(O)C(O)C(OC2C(C(CO)C(CO)C(CO)O2)CO)C(CO)O1 XANWOULVSWKIBE-AFLMEXFJSA-N 0.000 description 1
- GUGXRXLTTHFKHC-ZETCQYMHSA-N (4s)-4-(2-methylpropyl)pyrrolidin-2-one Chemical compound CC(C)C[C@@H]1CNC(=O)C1 GUGXRXLTTHFKHC-ZETCQYMHSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- GUGXRXLTTHFKHC-UHFFFAOYSA-N 4-(2-methylpropyl)pyrrolidin-2-one Chemical compound CC(C)CC1CNC(=O)C1 GUGXRXLTTHFKHC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 101000878457 Macrocallista nimbosa FMRFamide Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical class O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000012435 analytical chromatography Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000012828 global research and development Methods 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000004340 gradient COSY Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000003929 heteronuclear multiple quantum coherence Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001551 total correlation spectroscopy Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/555—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Genetics & Genomics (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28017601P | 2001-03-30 | 2001-03-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200306608B true ZA200306608B (en) | 2004-11-25 |
Family
ID=23072002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200306608A ZA200306608B (en) | 2001-03-30 | 2003-08-25 | Pregabalin lactose conjugates. |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US7022678B2 (pt) |
| EP (1) | EP1377318A2 (pt) |
| JP (1) | JP2004524357A (pt) |
| KR (1) | KR20040008146A (pt) |
| CN (1) | CN1511043A (pt) |
| AP (1) | AP2003002873A0 (pt) |
| AR (1) | AR033024A1 (pt) |
| BG (1) | BG108193A (pt) |
| BR (1) | BR0208439A (pt) |
| CA (1) | CA2440468C (pt) |
| CZ (1) | CZ20032547A3 (pt) |
| DO (1) | DOP2002000356A (pt) |
| EA (1) | EA200300954A1 (pt) |
| EC (1) | ECSP034740A (pt) |
| EE (1) | EE200300480A (pt) |
| GT (1) | GT200200051A (pt) |
| HU (1) | HUP0303956A2 (pt) |
| IL (1) | IL157879A0 (pt) |
| IS (1) | IS6912A (pt) |
| MA (1) | MA27004A1 (pt) |
| MX (1) | MXPA03007437A (pt) |
| NO (1) | NO20034348L (pt) |
| OA (1) | OA12456A (pt) |
| PA (1) | PA8542101A1 (pt) |
| PE (1) | PE20021016A1 (pt) |
| PL (1) | PL369179A1 (pt) |
| SK (1) | SK11832003A3 (pt) |
| SV (1) | SV2003000928A (pt) |
| TN (1) | TNSN02038A1 (pt) |
| UY (1) | UY27233A1 (pt) |
| WO (1) | WO2002078747A2 (pt) |
| ZA (1) | ZA200306608B (pt) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9710536A (pt) | 1996-07-24 | 1999-08-17 | Warner Lambert Co | Isobutilgaba e seus derivados para o tratamento da dor |
| WO2007035890A1 (en) | 2005-09-19 | 2007-03-29 | Teva Pharmaceutical Industries Ltd. | An asymmetric synthesis of ( s ) - ( + ) -3- (aminomethyl) -5-methylhexanoic acid |
| DE102007019071A1 (de) | 2007-04-23 | 2008-10-30 | Ratiopharm Gmbh | Stabilisierte pharmazeutische Zusammensetzung enthaltend Pregabalin |
| SG176464A1 (en) | 2008-05-09 | 2011-12-29 | Agency Science Tech & Res | Diagnosis and treatment of kawasaki disease |
| KR20100107500A (ko) * | 2008-06-23 | 2010-10-05 | 테바 파마슈티컬 인더스트리즈 리미티드 | (ｓ) 또는 (ｒ)-이소-부틸-글루타릭 에스테르의 입체선택적 효소 합성방법 |
| WO2010115612A2 (en) | 2009-04-10 | 2010-10-14 | Synthon B.V. | Pregabalin compositions |
| WO2010150221A1 (en) | 2009-06-25 | 2010-12-29 | Wockhardt Research Centre | Taste masked pharmaceutical compositions of pregabalin |
| HU230031B1 (hu) | 2010-03-01 | 2015-05-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Pregabalint és izomaltot tartalmazó stabilizált gyógyszerkészítmény |
| CN103494796B (zh) * | 2013-09-30 | 2016-01-20 | 浙江华义医药有限公司 | 普瑞巴林稳定的药物组合物及其制备方法 |
| CN104311608B (zh) * | 2014-10-28 | 2016-10-05 | 河南中烟工业有限责任公司 | 亲水型烟草增香保润剂Mal-Hyp、制备方法及其应用 |
| CN104370986B (zh) * | 2014-10-28 | 2017-07-04 | 河南中烟工业有限责任公司 | 糖衍生物烟用增香保润剂Mal‑Pro、制备方法及其应用 |
| CN105520918B (zh) * | 2015-12-31 | 2018-12-11 | 常州市阳光药业有限公司 | 普瑞巴林胶囊 |
| CN105434395B (zh) * | 2015-12-31 | 2018-12-11 | 常州市阳光药业有限公司 | 普瑞巴林胶囊及其制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6197819B1 (en) | 1990-11-27 | 2001-03-06 | Northwestern University | Gamma amino butyric acid analogs and optical isomers |
| FR2781793B1 (fr) * | 1998-08-03 | 2001-07-20 | Prographarm Lab | Procede de fabrication de granules de gabapentine enrobes |
| WO2000023067A1 (en) * | 1998-10-16 | 2000-04-27 | Warner-Lambert Company | Method for the treatment of mania and bipolar disorder |
| EP1337271B1 (en) * | 2000-11-30 | 2004-11-03 | Pfizer Products Inc. | Combination of gaba agonists and sorbitol dehydrogenase inhibitors |
-
2002
- 2002-01-28 US US10/058,903 patent/US7022678B2/en not_active Expired - Fee Related
- 2002-02-25 CN CNA028067509A patent/CN1511043A/zh active Pending
- 2002-02-25 BR BR0208439-2A patent/BR0208439A/pt not_active IP Right Cessation
- 2002-02-25 KR KR10-2003-7012714A patent/KR20040008146A/ko not_active Application Discontinuation
- 2002-02-25 SK SK1183-2003A patent/SK11832003A3/sk not_active Application Discontinuation
- 2002-02-25 EA EA200300954A patent/EA200300954A1/ru unknown
- 2002-02-25 MX MXPA03007437A patent/MXPA03007437A/es active IP Right Grant
- 2002-02-25 EE EEP200300480A patent/EE200300480A/xx unknown
- 2002-02-25 OA OA1200300232A patent/OA12456A/en unknown
- 2002-02-25 WO PCT/IB2002/000647 patent/WO2002078747A2/en active Application Filing
- 2002-02-25 PL PL02369179A patent/PL369179A1/xx not_active Application Discontinuation
- 2002-02-25 CZ CZ20032547A patent/CZ20032547A3/cs unknown
- 2002-02-25 CA CA002440468A patent/CA2440468C/en not_active Expired - Fee Related
- 2002-02-25 HU HU0303956A patent/HUP0303956A2/hu unknown
- 2002-02-25 EP EP02702614A patent/EP1377318A2/en not_active Withdrawn
- 2002-02-25 IL IL15787902A patent/IL157879A0/xx unknown
- 2002-02-25 JP JP2002577011A patent/JP2004524357A/ja active Pending
- 2002-02-25 AP APAP/P/2003/002873A patent/AP2003002873A0/en unknown
- 2002-03-07 DO DO2002000356A patent/DOP2002000356A/es unknown
- 2002-03-19 GT GT200200051A patent/GT200200051A/es unknown
- 2002-03-22 SV SV2002000928A patent/SV2003000928A/es not_active Application Discontinuation
- 2002-03-27 PE PE2002000252A patent/PE20021016A1/es not_active Application Discontinuation
- 2002-03-27 PA PA20028542101A patent/PA8542101A1/es unknown
- 2002-03-27 AR ARP020101140A patent/AR033024A1/es unknown
- 2002-03-27 UY UY27233A patent/UY27233A1/es not_active Application Discontinuation
- 2002-03-29 TN TNTNSN02038A patent/TNSN02038A1/fr unknown
-
2003
- 2003-08-14 IS IS6912A patent/IS6912A/is unknown
- 2003-08-21 EC EC2003004740A patent/ECSP034740A/es unknown
- 2003-08-25 ZA ZA200306608A patent/ZA200306608B/en unknown
- 2003-09-17 MA MA27315A patent/MA27004A1/fr unknown
- 2003-09-24 BG BG108193A patent/BG108193A/xx unknown
- 2003-09-29 NO NO20034348A patent/NO20034348L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2440468C (en) | Pregabalin lactose conjugates | |
| DE60005017T2 (de) | Prodrugs von impdh-inhibierenden carbamaten | |
| DE68906942T3 (de) | Pharmazeutische Zusammensetzungen für die parenterale Anwendung. | |
| JPH01294663A (ja) | 脳を標的とする薬剤供給用のレドックス系 | |
| EP2968381A1 (en) | Sugar-linker-drug conjugates | |
| DE102009051799A1 (de) | Bifunktionale Prodrugs und Drugs | |
| HUE034562T2 (en) | Polymixins, preparations, methods of preparation and methods of application | |
| CN103781472A (zh) | 丙泊酚苷衍生物的合成和使用 | |
| EP1945182B1 (en) | Formulations of tipifarnib for intravenous application | |
| WO2014152718A1 (en) | Saccharide conjugates | |
| EP2269980A1 (de) | Creatinamide, verfahren zu ihrer herstellung und wirkstoff zur ausführung einer neuroprotektiven aktion | |
| CN112004799A (zh) | Akr1c3抑制剂及医药用途 | |
| JPH0414643B2 (pt) | ||
| WO1986004332A1 (en) | Open chain-morpholino adriamycins | |
| JP2022510480A (ja) | ドーパミン応答性障害の治療のための糖にコンジュゲートされたｌ－ｄｏｐａ及び／またはｄｏｐａデカルボキシラーゼ阻害剤 | |
| Lovdahl et al. | Synthesis and characterization of pregabalin lactose conjugate degradation products | |
| AU2002236134A1 (en) | Pregabalin lactose conjugates | |
| JPH09510469A (ja) | 興奮性毒性に関連した中枢神経系の急性ならびに慢性障害に有用な、神経保護、神経栄養、ならびに抗炎症作用を有するｎ−アシルアルキルアミンのグルコシド誘導体 | |
| RU2768451C1 (ru) | Селективный антагонист рецепторов типа A2A | |
| EP0351784B1 (en) | Therapeutic use of the isopropyl ester derivative of monosialoganglioside in nervous pathologies with an inflammatory component | |
| KR100456088B1 (ko) | 5-이미노-13-데옥시 안트라시클린 유도체와 그 이용 및 그제조방법 | |
| CN112174865A (zh) | Akr1c3抑制剂及医药用途 | |
| KR20210013081A (ko) | 나프록센 및 프레가발린의 1-(아실옥시)-알킬 카르바메이트 약물 복합체의 결정형 | |
| EP3988559A1 (en) | 2-benzylidene hydrazinoadenosine compounds having a2a adenosine receptor agnostic activity | |
| EP4410831A1 (en) | Regioselective conjugate of functional substance and antibody or salt of said conjugate, and antibody derivative and compound for use in production of said conjugate, or salt of said antibody derivative and compound |