AU2002353206B2 - Treatment of faecal incontinence and other conditions with 1R, 2S-Methoxamine - Google Patents
Treatment of faecal incontinence and other conditions with 1R, 2S-Methoxamine Download PDFInfo
- Publication number
- AU2002353206B2 AU2002353206B2 AU2002353206A AU2002353206A AU2002353206B2 AU 2002353206 B2 AU2002353206 B2 AU 2002353206B2 AU 2002353206 A AU2002353206 A AU 2002353206A AU 2002353206 A AU2002353206 A AU 2002353206A AU 2002353206 B2 AU2002353206 B2 AU 2002353206B2
- Authority
- AU
- Australia
- Prior art keywords
- methoxamine
- dose
- composition
- compound
- pharmaceutical composition
- 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.)
- Ceased
Links
- 229960005192 methoxamine Drugs 0.000 title claims description 174
- 208000034347 Faecal incontinence Diseases 0.000 title claims description 36
- WJAJPNHVVFWKKL-UHFFFAOYSA-N Methoxamine Chemical class COC1=CC=C(OC)C(C(O)C(C)N)=C1 WJAJPNHVVFWKKL-UHFFFAOYSA-N 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 61
- 239000000203 mixture Substances 0.000 claims description 59
- 239000000499 gel Substances 0.000 claims description 49
- 210000005070 sphincter Anatomy 0.000 claims description 38
- 230000000694 effects Effects 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 210000005072 internal anal sphincter Anatomy 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 27
- 230000000699 topical effect Effects 0.000 claims description 26
- 230000036772 blood pressure Effects 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 24
- 241000124008 Mammalia Species 0.000 claims description 23
- 230000000284 resting effect Effects 0.000 claims description 20
- 238000011200 topical administration Methods 0.000 claims description 20
- 239000006071 cream Substances 0.000 claims description 16
- 239000002674 ointment Substances 0.000 claims description 16
- 239000000048 adrenergic agonist Substances 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 13
- 210000002255 anal canal Anatomy 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 239000002552 dosage form Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 8
- 210000000436 anus Anatomy 0.000 claims description 8
- OIKHZBFJHONJJB-UHFFFAOYSA-N dimethyl(phenyl)silicon Chemical compound C[Si](C)C1=CC=CC=C1 OIKHZBFJHONJJB-UHFFFAOYSA-N 0.000 claims description 7
- 239000000853 adhesive Substances 0.000 claims description 5
- 230000001070 adhesive effect Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 210000001217 buttock Anatomy 0.000 claims description 4
- 239000006260 foam Substances 0.000 claims description 4
- 239000006072 paste Substances 0.000 claims description 4
- 238000007911 parenteral administration Methods 0.000 claims 2
- 230000000052 comparative effect Effects 0.000 claims 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 42
- 229960001802 phenylephrine Drugs 0.000 description 41
- 229910052739 hydrogen Inorganic materials 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 22
- 210000001035 gastrointestinal tract Anatomy 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 17
- 241000282887 Suidae Species 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 210000003205 muscle Anatomy 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000000902 placebo Substances 0.000 description 13
- 229940068196 placebo Drugs 0.000 description 13
- 231100000673 dose–response relationship Toxicity 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 210000002460 smooth muscle Anatomy 0.000 description 12
- 206010002091 Anaesthesia Diseases 0.000 description 11
- 241000282898 Sus scrofa Species 0.000 description 11
- 238000001949 anaesthesia Methods 0.000 description 11
- 230000037005 anaesthesia Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 230000009885 systemic effect Effects 0.000 description 11
- 230000036470 plasma concentration Effects 0.000 description 10
- 239000005526 vasoconstrictor agent Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000005555 hypertensive agent Substances 0.000 description 9
- 244000309715 mini pig Species 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- -1 -blockers Chemical compound 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 206010021639 Incontinence Diseases 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000012501 chromatography medium Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000002093 peripheral effect Effects 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 230000008602 contraction Effects 0.000 description 7
- 238000006073 displacement reaction Methods 0.000 description 7
- 238000002565 electrocardiography Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 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 7
- 238000001228 spectrum Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229960003767 alanine Drugs 0.000 description 6
- 230000002526 effect on cardiovascular system Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000001187 pylorus Anatomy 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 206010012735 Diarrhoea Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000006196 drop Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 230000007794 irritation Effects 0.000 description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 238000013375 chromatographic separation Methods 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 230000004217 heart function Effects 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- 238000007689 inspection Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 210000001747 pupil Anatomy 0.000 description 4
- 230000033764 rhythmic process Effects 0.000 description 4
- 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 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 4
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 241000320529 Allobates femoralis Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 208000001953 Hypotension Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000003405 delayed action preparation Substances 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000004882 diastolic arterial blood pressure Effects 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 229940039009 isoproterenol Drugs 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 229960002748 norepinephrine Drugs 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000000718 qrs complex Methods 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000004873 systolic arterial blood pressure Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- WJAJPNHVVFWKKL-CPCISQLKSA-N (1r,2s)-2-amino-1-(2,5-dimethoxyphenyl)propan-1-ol Chemical compound COC1=CC=C(OC)C([C@@H](O)[C@H](C)N)=C1 WJAJPNHVVFWKKL-CPCISQLKSA-N 0.000 description 2
- VSMILISQVUOHED-ZETCQYMHSA-N (2s)-2-amino-1-(2,5-dimethoxyphenyl)propan-1-one Chemical compound COC1=CC=C(OC)C(C(=O)[C@H](C)N)=C1 VSMILISQVUOHED-ZETCQYMHSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DWCGNRKFLRLWCJ-UHFFFAOYSA-N 2-bromo-1,4-dimethoxybenzene Chemical group COC1=CC=C(OC)C(Br)=C1 DWCGNRKFLRLWCJ-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- 241000282412 Homo Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010028735 Nasal congestion Diseases 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940124572 antihypotensive agent Drugs 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000035606 childbirth Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000000916 dilatatory effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- AUATWRLEFASUPL-UFBFGSQYSA-N methyl n-[(1r,2s)-1-(2,5-dimethoxyphenyl)-1-hydroxypropan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)[C@H](O)C1=CC(OC)=CC=C1OC AUATWRLEFASUPL-UFBFGSQYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000002637 mydriatic agent Substances 0.000 description 2
- 239000000133 nasal decongestant Substances 0.000 description 2
- 230000007383 nerve stimulation Effects 0.000 description 2
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 125000004079 stearyl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000829 suppository Substances 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
- 238000007910 systemic administration Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- YGRFXPCHZBRUKP-WJRQTEJMSA-N (1R,2S)-2-amino-1-(2,5-dimethoxyphenyl)propan-1-ol hydrochloride Chemical compound Cl.COC1=CC=C(OC)C([C@@H](O)[C@H](C)N)=C1 YGRFXPCHZBRUKP-WJRQTEJMSA-N 0.000 description 1
- JAFZODJINWJNPZ-VKHMYHEASA-N (2s)-2-(methoxycarbonylamino)propanoic acid Chemical compound COC(=O)N[C@@H](C)C(O)=O JAFZODJINWJNPZ-VKHMYHEASA-N 0.000 description 1
- 229930182836 (R)-noradrenaline Natural products 0.000 description 1
- OHBQPCCCRFSCAX-UHFFFAOYSA-N 1,4-Dimethoxybenzene Chemical class COC1=CC=C(OC)C=C1 OHBQPCCCRFSCAX-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940044613 1-propanol Drugs 0.000 description 1
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- VSMILISQVUOHED-UHFFFAOYSA-N 2-amino-1-(2,5-dimethoxyphenyl)propan-1-one Chemical compound COC1=CC=C(OC)C(C(=O)C(C)N)=C1 VSMILISQVUOHED-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
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100129922 Caenorhabditis elegans pig-1 gene Proteins 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 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
- 101100520057 Drosophila melanogaster Pig1 gene Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 238000006716 Hiyama reaction Methods 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- SNIXRMIHFOIVBB-UHFFFAOYSA-N N-Hydroxyl-tryptamine Chemical compound C1=CC=C2C(CCNO)=CNC2=C1 SNIXRMIHFOIVBB-UHFFFAOYSA-N 0.000 description 1
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
- 229920005439 Perspex® Polymers 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 241000255969 Pieris brassicae Species 0.000 description 1
- 208000006294 Pudendal Neuralgia Diseases 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000009729 Ventricular Premature Complexes Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000009414 anorectal function Effects 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 230000002959 anti-hypotensive effect Effects 0.000 description 1
- 229940124537 antidiarrhoeal agent Drugs 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 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
- 238000004364 calculation method Methods 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 201000000311 contact blepharoconjunctivitis Diseases 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 235000001434 dietary modification Nutrition 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- NUIWRMGOBPOIOY-UHFFFAOYSA-N ethanesulfonic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.CCS(O)(=O)=O NUIWRMGOBPOIOY-UHFFFAOYSA-N 0.000 description 1
- PCGGNOFZZFFFLU-UHFFFAOYSA-N ethyl n,n-dichlorocarbamate Chemical compound CCOC(=O)N(Cl)Cl PCGGNOFZZFFFLU-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000005071 external anal sphincter Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229960005015 local anesthetics Drugs 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
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- VKGYNKWEQAYGSN-QMMMGPOBSA-N methyl n-[(2s)-1-(2,5-dimethoxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)C(=O)C1=CC(OC)=CC=C1OC VKGYNKWEQAYGSN-QMMMGPOBSA-N 0.000 description 1
- VKGYNKWEQAYGSN-UHFFFAOYSA-N methyl n-[1-(2,5-dimethoxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound COC(=O)NC(C)C(=O)C1=CC(OC)=CC=C1OC VKGYNKWEQAYGSN-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002315 pressor effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004514 sphincter of oddi Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- GTCDARUMAMVCRO-UHFFFAOYSA-M tetraethylazanium;acetate Chemical compound CC([O-])=O.CC[N+](CC)(CC)CC GTCDARUMAMVCRO-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 231100000607 toxicokinetics Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000003932 urinary bladder 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
- 230000000007 visual effect Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/08—Mydriatics or cycloplegics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
- C07C217/66—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain
- C07C217/70—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0130763.6 | 2001-12-21 | ||
| GBGB0130763.6A GB0130763D0 (en) | 2001-12-21 | 2001-12-21 | Treatment methods |
| PCT/GB2002/005864 WO2003055474A1 (en) | 2001-12-21 | 2002-12-20 | Treatment of faecal incontinence and other conditions with 1r, 2s-methoxamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002353206A1 AU2002353206A1 (en) | 2003-07-15 |
| AU2002353206B2 true AU2002353206B2 (en) | 2008-09-04 |
Family
ID=9928258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002353206A Ceased AU2002353206B2 (en) | 2001-12-21 | 2002-12-20 | Treatment of faecal incontinence and other conditions with 1R, 2S-Methoxamine |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20050096397A1 (enExample) |
| EP (2) | EP1458370A1 (enExample) |
| JP (3) | JP5486143B2 (enExample) |
| CN (3) | CN101601665A (enExample) |
| AU (1) | AU2002353206B2 (enExample) |
| CA (1) | CA2471046C (enExample) |
| GB (1) | GB0130763D0 (enExample) |
| MX (1) | MXPA04006142A (enExample) |
| PL (1) | PL217404B1 (enExample) |
| RU (1) | RU2332989C2 (enExample) |
| WO (1) | WO2003055474A1 (enExample) |
| ZA (1) | ZA200404813B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0130763D0 (en) * | 2001-12-21 | 2002-02-06 | Norgine Res Ltd | Treatment methods |
| GB0501580D0 (en) * | 2005-01-25 | 2005-03-02 | Norgine Europe Bv | Compounds for treating urinary incontinence |
| EP2473056A4 (en) | 2009-09-04 | 2013-02-13 | Glaxosmithkline Llc | CHEMICAL COMPOUNDS |
| ES2630102T3 (es) * | 2011-04-26 | 2017-08-18 | Rdd Pharma Ltd. | Oximetazolina para el tratamiento de trastornos ano-rectales |
| CN102976961B (zh) * | 2012-12-24 | 2014-09-24 | 武汉武药制药有限公司 | 盐酸甲氧明的制备方法 |
| US10708086B2 (en) * | 2016-01-19 | 2020-07-07 | National Instruments Corporation | Channel sounding techniques |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998027971A1 (en) * | 1996-12-23 | 1998-07-02 | Michael Albert Kamm | Pharmaceutical composition for treating fecal incontinence and anal itch |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1593261A (en) * | 1976-07-23 | 1981-07-15 | Inveresk Res Int | Controlled release suppository |
| JPS60172953A (ja) * | 1984-02-17 | 1985-09-06 | Sagami Chem Res Center | 光学活性β−アミノアルコ−ルの製造方法 |
| FR2647014B1 (fr) * | 1989-05-16 | 1991-08-30 | Paris V Universite | Composition medicamenteuse pour le traitement et la prevention des symptomes de l'insuffisance cardiaque, renfermant un agent alpha-stimulant vasoconstricteur comme principe actif |
| DK339289D0 (da) | 1989-07-07 | 1989-07-07 | Dak Lab As | Farmaceutisk praeparat |
| DK469989D0 (da) * | 1989-09-22 | 1989-09-22 | Bukh Meditec | Farmaceutisk praeparat |
| NL9102142A (nl) * | 1991-12-20 | 1993-07-16 | Dagra Pharma Bv | Zetpillen met vertraagde afgifte en werkwijze voor de bereiding daarvan. |
| WO1998038587A1 (en) * | 1997-02-26 | 1998-09-03 | Siebel Systems, Inc. | Method of using a cache to determine the visibility to a remote database client of a plurality of database transactions |
| US6539381B1 (en) * | 1999-04-21 | 2003-03-25 | Novell, Inc. | System and method for synchronizing database information |
| GB0028575D0 (en) * | 2000-11-23 | 2001-01-10 | Elan Corp Plc | Oral pharmaceutical compositions containing cyclodextrins |
| US6544927B2 (en) * | 2001-04-28 | 2003-04-08 | University Of Florida | Use of α2-adrenergic receptor agonists and adrenergic inhibitors in reducing defoliation |
| GB0130763D0 (en) | 2001-12-21 | 2002-02-06 | Norgine Res Ltd | Treatment methods |
| US7089228B2 (en) * | 2002-04-18 | 2006-08-08 | International Business Machines Corporation | Computer apparatus and method for caching results of a database query |
-
2001
- 2001-12-21 GB GBGB0130763.6A patent/GB0130763D0/en not_active Ceased
-
2002
- 2002-12-20 AU AU2002353206A patent/AU2002353206B2/en not_active Ceased
- 2002-12-20 MX MXPA04006142A patent/MXPA04006142A/es active IP Right Grant
- 2002-12-20 CN CNA2009101594203A patent/CN101601665A/zh active Pending
- 2002-12-20 CN CNA028253248A patent/CN1604773A/zh active Pending
- 2002-12-20 WO PCT/GB2002/005864 patent/WO2003055474A1/en not_active Ceased
- 2002-12-20 EP EP02788224A patent/EP1458370A1/en not_active Withdrawn
- 2002-12-20 CA CA2471046A patent/CA2471046C/en not_active Expired - Fee Related
- 2002-12-20 RU RU2004122639/15A patent/RU2332989C2/ru not_active IP Right Cessation
- 2002-12-20 JP JP2003556052A patent/JP5486143B2/ja not_active Expired - Fee Related
- 2002-12-20 CN CN2011104050612A patent/CN102516101A/zh active Pending
- 2002-12-20 EP EP10177730A patent/EP2275099A1/en not_active Withdrawn
- 2002-12-20 US US10/499,873 patent/US20050096397A1/en not_active Abandoned
- 2002-12-20 PL PL369828A patent/PL217404B1/pl unknown
-
2004
- 2004-06-17 ZA ZA2004/04813A patent/ZA200404813B/en unknown
-
2009
- 2009-09-30 US US12/586,973 patent/US8491931B2/en not_active Expired - Fee Related
-
2011
- 2011-02-28 JP JP2011041076A patent/JP2011105770A/ja active Pending
- 2011-11-04 JP JP2011241937A patent/JP5544535B2/ja not_active Expired - Fee Related
-
2012
- 2012-11-15 US US13/678,131 patent/US8613948B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998027971A1 (en) * | 1996-12-23 | 1998-07-02 | Michael Albert Kamm | Pharmaceutical composition for treating fecal incontinence and anal itch |
Non-Patent Citations (1)
| Title |
|---|
| Journal of Organic Chemistry (1998) 53(23) pp5415-21 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003055474A1 (en) | 2003-07-10 |
| US20100022657A1 (en) | 2010-01-28 |
| GB0130763D0 (en) | 2002-02-06 |
| MXPA04006142A (es) | 2005-03-31 |
| PL369828A1 (en) | 2005-05-02 |
| US20050096397A1 (en) | 2005-05-05 |
| PL217404B1 (pl) | 2014-07-31 |
| JP2005519888A (ja) | 2005-07-07 |
| CA2471046A1 (en) | 2003-07-10 |
| US8613948B2 (en) | 2013-12-24 |
| JP5544535B2 (ja) | 2014-07-09 |
| JP2012025782A (ja) | 2012-02-09 |
| CN101601665A (zh) | 2009-12-16 |
| ZA200404813B (en) | 2005-10-26 |
| EP2275099A1 (en) | 2011-01-19 |
| JP2011105770A (ja) | 2011-06-02 |
| RU2332989C2 (ru) | 2008-09-10 |
| CA2471046C (en) | 2012-02-07 |
| RU2004122639A (ru) | 2005-05-10 |
| CN1604773A (zh) | 2005-04-06 |
| AU2002353206A1 (en) | 2003-07-15 |
| CN102516101A (zh) | 2012-06-27 |
| EP1458370A1 (en) | 2004-09-22 |
| US20130072567A1 (en) | 2013-03-21 |
| JP5486143B2 (ja) | 2014-05-07 |
| US8491931B2 (en) | 2013-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| USRE40259E1 (en) | Alpha-aminoamide derivatives useful as analgesic agents | |
| ES2197945T3 (es) | Compuestos activos en nuevos sitios de los canales de calcio activados por receptores utiles para el tratamiento de trastornos neurologicos. | |
| US8613948B2 (en) | Treatment of faecal incontinence and other conditions with 1R, 2S-methoxamine | |
| US20080132578A1 (en) | Dosage forms of O-desmethylvenlafaxine | |
| WO2011034849A1 (en) | Novel compounds advantageous in the treatment of central nervous system diseases and disorders | |
| EP2937083B1 (en) | Formulations, salts and polymorphs of transnorsertraline and uses thereof | |
| US20030229145A1 (en) | Pain treatment methods and compositions | |
| US11590089B2 (en) | Beta-2 selective adrenergic receptor agonists | |
| US20070225351A1 (en) | Methods and compositions for controlling body weight and appetite | |
| KR20150020160A (ko) | 과민성 방광의 치료를 위한 무스카린 수용체 길항제 및 베타―3 아드레날린 수용체 작용제의 조합물 | |
| CN115745890A (zh) | 一种酯键化合物及其制备方法和应用、镇痛药物 | |
| MX2008000680A (es) | Inhibidor de la retoma dual de norepinefrina y serotonina altamente selectivo y su uso. | |
| KR100576131B1 (ko) | 2메틸프로피온산유도체 및 그 유도체를 함유하는의약조성물 | |
| EP3860582B1 (en) | Compounds for use in the treatment or prophylaxis of pain, inflammation and/or autoimmunity | |
| HK1169369A (en) | Use of 1 r, 2s-methoxamine in preparing medicines for treating faecal incontinence and other conditions | |
| WO2009073138A2 (en) | Treatment of metabolic syndrome with novel amides | |
| HK40061961B (en) | Compounds for use in the treatment or prophylaxis of pain, inflammation and/or autoimmunity | |
| HK40061961A (en) | Compounds for use in the treatment or prophylaxis of pain, inflammation and/or autoimmunity | |
| WO2006070934A1 (ja) | 二環性縮合複素環誘導体の結晶、その製造法および用途 | |
| HK1139380A (en) | Derivatives of venlafaxine and methods of preparing and using the same | |
| JPH0376302B2 (enExample) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |