JP2013523815A - 過敏性腸症候群の処置方法及びその治療用組成物 - Google Patents
過敏性腸症候群の処置方法及びその治療用組成物 Download PDFInfo
- Publication number
- JP2013523815A JP2013523815A JP2013503808A JP2013503808A JP2013523815A JP 2013523815 A JP2013523815 A JP 2013523815A JP 2013503808 A JP2013503808 A JP 2013503808A JP 2013503808 A JP2013503808 A JP 2013503808A JP 2013523815 A JP2013523815 A JP 2013523815A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- subject
- compound
- administration
- pharmaceutically acceptable
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 72
- 208000002551 irritable bowel syndrome Diseases 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims description 61
- 230000001225 therapeutic effect Effects 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 208000024891 symptom Diseases 0.000 claims abstract description 36
- 239000003814 drug Substances 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 34
- 229940079593 drug Drugs 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 32
- 239000000651 prodrug Substances 0.000 claims description 25
- 229940002612 prodrug Drugs 0.000 claims description 25
- 239000002207 metabolite Substances 0.000 claims description 23
- 230000002411 adverse Effects 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 206010044565 Tremor Diseases 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 14
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
- -1 anti-prostaglandins Substances 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 238000001990 intravenous administration Methods 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- 229960000195 terbutaline Drugs 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 230000036772 blood pressure Effects 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 6
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000935 antidepressant agent Substances 0.000 claims description 5
- 229940005513 antidepressants Drugs 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 239000008141 laxative Substances 0.000 claims description 5
- 229940125722 laxative agent Drugs 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 208000007101 Muscle Cramp Diseases 0.000 claims description 4
- 208000005392 Spasm Diseases 0.000 claims description 4
- 206010047700 Vomiting Diseases 0.000 claims description 4
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 4
- 239000001961 anticonvulsive agent Substances 0.000 claims description 4
- 235000015165 citric acid Nutrition 0.000 claims description 4
- 230000005713 exacerbation Effects 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- 230000008673 vomiting Effects 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 3
- 206010028813 Nausea Diseases 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 206010033557 Palpitations Diseases 0.000 claims description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 229940111134 coxibs Drugs 0.000 claims description 3
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 150000004675 formic acid derivatives Chemical class 0.000 claims description 3
- 239000001530 fumaric acid Substances 0.000 claims description 3
- 235000011087 fumaric acid Nutrition 0.000 claims description 3
- 239000000174 gluconic acid Substances 0.000 claims description 3
- 235000012208 gluconic acid Nutrition 0.000 claims description 3
- 239000003589 local anesthetic agent Substances 0.000 claims description 3
- 229960005015 local anesthetics Drugs 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- 239000011976 maleic acid Substances 0.000 claims description 3
- 229940098895 maleic acid Drugs 0.000 claims description 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 235000011090 malic acid Nutrition 0.000 claims description 3
- 230000008693 nausea Effects 0.000 claims description 3
- 210000005036 nerve Anatomy 0.000 claims description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000006041 probiotic Substances 0.000 claims description 3
- 235000018291 probiotics Nutrition 0.000 claims description 3
- 229960001634 ritodrine Drugs 0.000 claims description 3
- 229960004889 salicylic acid Drugs 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000008454 Hyperhidrosis Diseases 0.000 claims description 2
- 208000013016 Hypoglycemia Diseases 0.000 claims description 2
- 206010023379 Ketoacidosis Diseases 0.000 claims description 2
- 208000007976 Ketosis Diseases 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 2
- 208000032140 Sleepiness Diseases 0.000 claims description 2
- 206010041349 Somnolence Diseases 0.000 claims description 2
- 230000001142 anti-diarrhea Effects 0.000 claims description 2
- 230000003431 anti-prostaglandin Effects 0.000 claims description 2
- 229940125714 antidiarrheal agent Drugs 0.000 claims description 2
- 239000003793 antidiarrheal agent Substances 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 208000002173 dizziness Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 208000005333 pulmonary edema Diseases 0.000 claims description 2
- 230000037321 sleepiness Effects 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 230000035900 sweating Effects 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 230000009610 hypersensitivity Effects 0.000 claims 1
- 238000001361 intraarterial administration Methods 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 235000011044 succinic acid Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- VPCOODFYDJWLHD-YMZXMBPUSA-N 2-[[(7s)-7-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)phenyl]ethyl]amino]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]-n,n-dimethylacetamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1([C@@H](O)CN[C@H]2CCC3=CC=C(C=C3C2)OCC(=O)N(C)C)=CC=C(O)C(CCO)=C1.C1([C@@H](O)CN[C@H]2CCC3=CC=C(C=C3C2)OCC(=O)N(C)C)=CC=C(O)C(CCO)=C1 VPCOODFYDJWLHD-YMZXMBPUSA-N 0.000 description 39
- 238000001802 infusion Methods 0.000 description 18
- 108010058846 Ovalbumin Proteins 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 230000004899 motility Effects 0.000 description 16
- 229940092253 ovalbumin Drugs 0.000 description 16
- 229920000642 polymer Polymers 0.000 description 15
- 210000003932 urinary bladder Anatomy 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 230000009467 reduction Effects 0.000 description 13
- 206010012735 Diarrhoea Diseases 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 210000003238 esophagus Anatomy 0.000 description 11
- 239000006210 lotion Substances 0.000 description 11
- 206010010774 Constipation Diseases 0.000 description 10
- 239000006071 cream Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 239000000227 bioadhesive Substances 0.000 description 9
- 239000000969 carrier Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 208000004998 Abdominal Pain Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 208000002193 Pain Diseases 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 230000002572 peristaltic effect Effects 0.000 description 8
- 210000001599 sigmoid colon Anatomy 0.000 description 8
- 238000002604 ultrasonography Methods 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 239000000808 adrenergic beta-agonist Substances 0.000 description 7
- 230000008602 contraction Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000036407 pain Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 206010000060 Abdominal distension Diseases 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000033001 locomotion Effects 0.000 description 6
- 210000000111 lower esophageal sphincter Anatomy 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- 238000009530 blood pressure measurement Methods 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000012669 liquid formulation Substances 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 229940068196 placebo Drugs 0.000 description 5
- 239000000902 placebo Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000001953 sensory effect Effects 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- KUQWZSZYIQGTHT-UHFFFAOYSA-N hexa-1,5-diene-3,4-diol Chemical compound C=CC(O)C(O)C=C KUQWZSZYIQGTHT-UHFFFAOYSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000012931 lyophilized formulation Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- IOVGROKTTNBUGK-SJKOYZFVSA-N (1S,2R)-ritodrine Chemical compound N([C@H](C)[C@@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJKOYZFVSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 0 **Oc1cc(CC(CC2)NCC(c(cc3*)ccc3O)O)c2cc1 Chemical compound **Oc1cc(CC(CC2)NCC(c(cc3*)ccc3O)O)c2cc1 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 3
- 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 3
- 229920000148 Polycarbophil calcium Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229920002678 cellulose Chemical class 0.000 description 3
- 239000001913 cellulose Chemical class 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 230000002920 convulsive effect Effects 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 230000013872 defecation Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 230000035487 diastolic blood pressure Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 239000012052 hydrophilic carrier Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000036724 intravesical pressure Effects 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 230000003232 mucoadhesive effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 239000003961 penetration enhancing agent Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229950005134 polycarbophil Drugs 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 241000167880 Hirundinidae Species 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- VVIVBRYHTLRZGY-MBANBULQSA-N Meluadrine tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CC(C)(C)NC[C@H](O)C1=CC=C(O)C=C1Cl VVIVBRYHTLRZGY-MBANBULQSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010061296 Motor dysfunction Diseases 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 229910052788 barium Inorganic materials 0.000 description 2
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000035587 bioadhesion Effects 0.000 description 2
- 238000010170 biological method Methods 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 235000017471 coenzyme Q10 Nutrition 0.000 description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 238000002052 colonoscopy Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000037020 contractile activity Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 239000008387 emulsifying waxe Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 229940095399 enema Drugs 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229960002598 fumaric acid Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 229950006191 gluconic acid Drugs 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 229960005150 glycerol Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003979 granulating agent Substances 0.000 description 2
- 208000024798 heartburn Diseases 0.000 description 2
- 235000012907 honey Nutrition 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940099690 malic acid Drugs 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 229940042472 mineral oil Drugs 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 230000037023 motor activity Effects 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008855 peristalsis Effects 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229940023488 pill Drugs 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 238000002579 sigmoidoscopy Methods 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000036318 urination frequency Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 description 1
- RKUNBYITZUJHSG-FXUDXRNXSA-N (S)-atropine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1 RKUNBYITZUJHSG-FXUDXRNXSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- DSAYAFZWRDYBQY-UHFFFAOYSA-N 2,5-dimethylhexa-1,5-diene Chemical compound CC(=C)CCC(C)=C DSAYAFZWRDYBQY-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 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 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 240000009087 Crescentia cujete Species 0.000 description 1
- 235000005983 Crescentia cujete Nutrition 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 241000509579 Draco Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- VTUSIVBDOCDNHS-UHFFFAOYSA-N Etidocaine Chemical compound CCCN(CC)C(CC)C(=O)NC1=C(C)C=CC=C1C VTUSIVBDOCDNHS-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical class C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-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
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 201000010538 Lactose Intolerance Diseases 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
- PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 1
- 241000327799 Thallomys paedulcus Species 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000009557 abdominal ultrasonography Methods 0.000 description 1
- 230000007488 abnormal function Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 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 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229960003655 bromfenac Drugs 0.000 description 1
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960003150 bupivacaine Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- SZKQYDBPUCZLRX-UHFFFAOYSA-N chloroprocaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl SZKQYDBPUCZLRX-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Natural products C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940000593 crinone Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- CURUTKGFNZGFSE-UHFFFAOYSA-N dicyclomine Chemical compound C1CCCCC1C1(C(=O)OCCN(CC)CC)CCCCC1 CURUTKGFNZGFSE-UHFFFAOYSA-N 0.000 description 1
- 229960002777 dicycloverine Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 235000021045 dietary change Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
- 229960004192 diphenoxylate Drugs 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229960003976 etidocaine Drugs 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 235000020900 high-residue-diet Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229960003210 hyoscyamine Drugs 0.000 description 1
- 229930005342 hyoscyamine Natural products 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 description 1
- 229960000511 lactulose Drugs 0.000 description 1
- PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 description 1
- 229960004194 lidocaine 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
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960002409 mepivacaine Drugs 0.000 description 1
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- BLYOHBPLFYXHQA-UHFFFAOYSA-N n,n-bis(prop-2-enyl)prop-2-enamide Chemical compound C=CCN(CC=C)C(=O)C=C BLYOHBPLFYXHQA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229940087419 nonoxynol-9 Drugs 0.000 description 1
- 229920004918 nonoxynol-9 Polymers 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229920001277 pectin Chemical class 0.000 description 1
- 239000001814 pectin Chemical class 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 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
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 1
- 229960003040 rifaximin Drugs 0.000 description 1
- 229960000720 ritodrine hydrochloride Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000004071 soot Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- SDVOJIRXJLEGCY-ZFRLFKIJSA-N spc3 Chemical compound N([C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCCCC[C@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)C(=O)NCCCC[C@H](NC(=O)[C@H](CCCCNC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)C(=O)NCCCC[C@H](NC(=O)[C@H](CCCCNC(=O)[C@H](CCCCNC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)NC(=O)[C@H](CCCCNC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CN)C(=O)NCCC(O)=O)C(=O)CNC(=O)[C@@H]1CCCN1C(=O)CN SDVOJIRXJLEGCY-ZFRLFKIJSA-N 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- KFVSLSTULZVNPG-UHFFFAOYSA-N terbutaline sulfate Chemical group [O-]S([O-])(=O)=O.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1 KFVSLSTULZVNPG-UHFFFAOYSA-N 0.000 description 1
- 229960005105 terbutaline sulfate Drugs 0.000 description 1
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 229960002494 tetracaine hydrochloride Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QNTNKSLOFHEFPK-UPTCCGCDSA-N ubiquinol-10 Chemical compound COC1=C(O)C(C)=C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)C(O)=C1OC QNTNKSLOFHEFPK-UPTCCGCDSA-N 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
【化1】
Description
、その代謝産物、そのプロドラッグ又はこれらのうちいずれかの薬学的に許容可能な塩を投与する工程を含む方法を提供する。
本明細書で使用するとき及び添付の特許請求の範囲において、単数形(「a」、「an」及び「the」)は、文脈上明確に記載されていない限り、複数の意味を含むことに留意すべきである。
一態様では、本明細書に提示するように、対象の過敏性腸症候群を予防する及び/若しくは処置する又はその症状を和らげるための方法であって、有効量の化合物を対象に投与する工程を含む方法を提供する。
、その代謝産物、そのプロドラッグ又はこれらのうちいずれかの薬学的に許容可能な塩を投与する工程を含む方法を提供する。
、その代謝産物、そのプロドラッグ又はこれらのうちいずれかの薬学的に許容可能な塩を投与する工程を含む方法を提供する。
又はその薬学的に許容可能な塩を投与する工程を含む方法を提供する。
本発明の方法、組成物及び装置で使用される化合物は次の通りである。
、その代謝産物、そのプロドラッグ又はこれらのうちいずれかの薬学的に許容可能な塩である。
、その代謝産物、そのプロドラッグ又はこれらのうちいずれかの薬学的に許容可能な塩である。
又はその薬学的に許容可能な塩である。
一態様では、本発明で使用される化合物は、化合物と薬学的に許容堪能な担体とを含む組成物として投与される。本発明で使用される化合物は、薬学的に許容可能な液体の有機若しくは無機担体、半液体の有機若しくは無機担体又は固体の有機若しくは無機担体等の従来の賦形剤と混合して投与されてよく、前記賦形剤は混合したときに活性な化合物と有害に反応しないものである。好適な薬学的に許容可能な担体とは、水、塩溶液、アルコール、植物油、ポリエチレングリコール、ゼラチン、ラクトース、アミロース、ステアリン酸マグネシウム、タルク、ケイ酸、粘性パラフィン、香油、脂肪酸モノグリセリド及び脂肪酸ジグリセリド、ペンタエリスリトール脂肪酸エステル、ヒドロキシメチルセルロース、ポリビニルピロリドン等が挙げられるが、これらに限定されない。
(−)−ビス(2−[[(2S)−2−({(2R)−2−ヒドロキシ−2−[4−ヒドロキシ−3−(2−ヒドロキシエチル)フェニル]エチル}アミノ)−1,2,3,4−テトラヒドロナフタレン−7−イル]オキシ]−N,N−ジメチル−アセトアミド)一硫酸塩
直腸S状結腸の運動性に対するMN−221の効果
本調査では、過敏性腸症候群(irritable bowel syndrome、IBS)に罹患した被験者の、直腸S状結腸の運動性に対するMN−221の効果について調べる。
被験者
24歳〜52歳の男女が本調査に参加している。IBSの診断は次の基準に基づいて行われる。1)症状が数カ月以上続いている、2)食事の有無にかかわらず腹痛がある、3)便秘である、又は下痢と便秘を併発している、4)正常大腸バリウム注腸及びS状結腸鏡検査、5)乳糖不耐症に関する検査が陰性である、及び6)便培養での所見が陰性である。
12時間絶食後、患者全員に、空気を注入させずにS状結腸鏡検査を行う。1本〜3本のポリエチレン製カテーテルの付いたプローブをS状結腸鏡から挿入して、近位カテーテルが肛門周縁部から約18〜20cmにあり、第2カテーテルの先端部がそれよりも約5cm下にあり、そして第3カテーテルが内括約筋の丁度内側に位置するようにする。2本の遠位カテーテルはそれぞれ約5cm長のバルーンで囲まれている。遠位バルーンを約20ミリリットル(mL)の空気で膨らませて、装置が遠位方向において移動しないようにする。上部直腸内の、中央のカテーテルと接触しているバルーンは、記録セッション中、被験者のうち10人では約80mLの空気で膨らませたままにし、そして残りの2人の被験者では約60mLの空気で膨らませたままにする。3回の試験の間、被験者毎のバルーン容量は同じである。
結果は、平均±標準偏差(SEM)で表す。対照期間と試験期間との差は、対データに関するウィルコクスン符号順位検定(Wilcoxon signed rank test)で検定する。
MN−221の血漿濃度は、液体クロマトグラフィー及び質量分析法で求める。
S状結腸の運動性
基本条件及びプラセボ効果。S状結腸の運動指数は被験者間で大幅に異なり、また、同一被験者でも日によってかなり変化する。運動活性は、主に3種の異なる運動波で構成される。最も一般的な形状は、周波数が2〜3周期/分の圧力波である。振幅は一般に1〜4kPaであり、そして各波の持続時間は10〜25秒である。これら重要な波の合間に、低振幅でしかも周波数が6〜8周期/分の別の波形が現れる場合もある。運動活性の高い期間では、多くの場合、3周期/分の波と7周期/分の小さな重畳波とが群発して基準圧が増大する可能性がある。プラセボ注入後、収縮活動が波の周波数と持続期間と振幅を増大させる傾向がある。その結果、被験者のS状結腸の運動性が高まることが分かる。
近位直腸バルーンで検知された直腸の運動性からは、記録日ごとに運動性にかなり個人差があることが分かった。全対照期間のうち3分の1では、運動性がほぼ0であった。このパターンは、MN−221の注入後も変化しない。
プラセボ注入後は、それ以前の対照期間に比べて心拍数の変化又は血圧の変化がほとんど生じない。MN−221を合計0.50mg静脈内注入した後に、最大血圧の増加、最低血圧の低下及び/又は心拍数の増加はほとんど認められない。MN−221を合計1.0mgまで静脈内注入しても、最大血圧の増加、最低血圧の低下及び/又は心拍数の増加はほとんど生じない。MN−221の注入後、患者は主訴又は不快感のどちらも示さない。その結果、MN−221の使用は、最低血圧の増加及び心拍数の増加を含む望ましくない著しく有害な副作用の発生を伴うテルブタリンの使用に比べて、有害な副作用をほとんど又は全く伴わないことが分かる。
薬剤の注入後、薬剤の血漿濃度が用量依存的に増加する。
本調査からは、MN−221を投与することで、IBSを罹患した被験者のS状結腸の運動性がかなり低下することが分かる。プラセボ注入後、運動性が試験期間中に高まる傾向があり、このことがMN−221の抑制効果を更に際立たせる。MN−221の血漿濃度は、臨床現場で用いられる治療濃度の範囲内であると認められる。
ヒト食道の蠕動運動に対するMN−221の効果
過敏性腸症候群を罹患している被験者は、胸やけ及び嚥下障害を含む上部消化管症状を訴える可能性がある。NM−221は、IBSを罹患している被験者の食道の蠕動運動を抑制し、しかも下部食道括約筋の緊張を阻害する。
圧力計での調査は、3重管を用い、溝それぞれに水0.5mL/分を低コンプライアンス毛管系からかん流させながら行う。溝を圧力トランスデューサにつなげて、グラス(Grass)ポリグラフで記録する。圧力を記録する部位の間隔は約8cmである。一晩絶食させた後、被験者を、経鼻挿入した圧力計プローブで標準化された位置に座らせて検査する。プローブは、下部食道括約筋(lower esophageal sphincter、LES)から約2cm離れた、遠位記録点に配置する。これにより、LESから約18cm離れた位置(食道上部)、LESから約10cm離れた位置(食道中央部)及びLESから約2cm離れた位置(食道下部)の圧力を記録する。
各セッションで休息時の被験者の心拍数を記録して、2分間平均を計算する。手指振戦は光学的方法(例えば、ドラコ(Draco)製オプト・トレモア・グラフ(Opt-Tremor Graph))で評価し、右手中指を選んで測定する。振戦評価をデジタルデータで表示して、動いた距離の合計を毎分ミリメーターで示す。
各セッションでは、静脈血試料を最後の嚥下試験直後に採取する。試料は、遠心分離にかけてから、分析するまで−20℃で保存する。MN−221の血漿濃度は、液体クロマトグラフィーと質量分析法とで求める。
頻脈及び振戦は、次の4段階に分類する:なし、軽度(気にならない)、中程度(気にはなるが、日常生活に支障をきたすほどではない)及び重度(日常生活に支障をきたす)。
食道の蠕動運動
MN−221を経口投与すると、食道の蠕動運動圧が大幅に低下する。この低下は、食道上部、食道中央部及び/又は食道下部ではっきりと認められる。投与から1週間後でもまだ蠕動運動圧が低下する傾向がある。
腸外の変数である心拍数及び手指振戦は、MN−221の投薬中は変化しない。すなわち、心拍数及び振戦はいずれも、投薬前とほぼ同じ状態のままである。投薬期間終了時(例えば、投薬10日目)にも、心拍数又は手指振戦には変化がほとんど認められない。被験者のMN−221耐性は実質上認められない。
MN−221を用いた過敏性腸症候群の処置
35歳男性患者はIBSに付随する症状を訴えており、粘液の流出及び出血を伴う下痢、腹部けいれん痛、並びに/又は潰瘍パッチによる粘膜の炎症及び浮腫が挙げられる。MN−221を5mg含む錠剤で1日3回、少なくとも2ヶ月間患者を処置する。当該期間の後に、患者からは、症状の軽減を含む好ましい効果が報告される。同様の好ましい効果は、IBSに起因する1つ以上の同様の症状を訴えている他の男性又は女性患者にも観られる。
MN−221を用いた過敏性腸症候群の処置
既報では、感作モルモットにオボアルブミンを膀胱内注入することで膀胱収縮が増大することが証明されている。アフルワリア(Ahluwalia)ら著の「感作ラットの膀胱におけるオボアルブミン誘発神経性炎症(Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats)」、Br. J. Pharmacol. (1998年)第124巻、190〜6頁を参照のこと。本調査では、MN−221が、炎症誘発性の膀胱過活動ラットモデルにおいてオボアルブミン誘発膀胱収縮を抑えるのに役立つことが分かる。このラットモデルは、過敏性腸症候群の動物モデルにもなる。
A.ラットの感作
本調査ではスプラーグドーリー系ラット(n=50、200±250g)を用いる。動物は5つの群(n=10)に分ける。第1群は対照の役割を果たし、第2群はオボアルブミン(OA)で感作する。第3群、第4群及び第5群も前述と同様にして感作されるが、急激なオボアルブミン投与の前にMN−221の経口強制飼養を受ける。
全ての動物に膀胱過活動評価を行う。簡単に言えば、腹面下腹部の中心線に沿って1cm切開する。膀胱を体外に取り出し、そして膀胱穹窿部に挿入したポリエチレンチューブ(例えば、クレイ・アダムス(Clay Adams)製PE50)を利用してカテーテルを挿入して2−0ブレードシルク縫合糸(2-0 braided silk suture)を用いて所定の位置に縫合する。膀胱を腹に戻すとともに、カテーテルラインを切開部から抜き取る。次に、カテーテルを圧力トランスデューサ(例えば、カリフォルニア州モローベイ(Morro Bay)のUFI製)に接続し、そこから輸液ポンプ(例えば、マサチューセッツ州ハーバード・アパレイタス(Harvard Apparatus)製)に接続する。連続充填式膀胱内圧測定中に、圧力を、プログラムLabVIEW(テキサス州ナショナル・インスツルメンツ(National Instruments)製)を利用して圧力トランスデューサで記録する。
処置群の出力である膀胱内圧測定図(CMG)を比較する。無傷ラット膀胱に0.9%生理食塩水を注入すると、正常な比較可能な排尿回数及びNVC数が生じる。OA感作ラットでは、膀胱内OA(10mg/mL)注入は、非感作の食塩水注入値と比べてNVCの増加をもたらす。MN−221で前処理すると、OAが誘発するNVCの変化及びICIの変化が用量依存的に阻害される。対照群(第1群)と種々の処置群(第2〜5群)とでは、排尿頻度にほとんど差が認められない。
は本発明の範囲を例示するものであって、それを限定するものではないと理解されるべきである。本発明の範囲内の他の態様、利点及び変更は、本発明が属する技術分野の当業者には自明であろう。
Claims (23)
- 前記対象がメス又はオスの哺乳動物である、請求項1又は5に記載の方法。
- 非ステロイド系抗炎症薬、抗生物質、プロバイオティクス、抗プロスタグランジン薬、COX−2阻害薬、局所麻酔薬、緩下剤、下痢止め薬、抗けいれん薬及び抗鬱剤から成る群から選択される1種以上の薬物を前記対象に投与する工程を更に含む、請求項1又は5に記載の方法。
- 前記薬物が、前記組成物に同時に又は逐次的に投与される、請求項7に記載の方法。
- 前記投与が経口投与である、請求項1又は5に記載の方法。
- 前記化合物が錠剤、カプセル、ゲル又は溶液の形態である、請求項9に記載の方法。
- 前記投与が、静脈内投与、筋肉内投与、動脈内投与、経皮投与(percutaneous)又は皮下投与から選択される非経口投与である、請求項1又は5に記載の方法。
- 前記投与が経皮投与(transdermal)である、請求項1又は5に記載の方法。
- 前記プロドラッグが、対象に投与されたときに開裂して遊離ヒドロキシル基又はアミン基をそれぞれ形成する基にヒドロキシル基又はアミン基が結合した化合物類から選択される、請求項1又は5に記載の方法。
- 前記プロドラッグが、ヒドロキシル官能基の酢酸エステル誘導体、ギ酸エステル誘導体、安息香酸エステル誘導体及びリン酸エステル誘導体、並びにアミン官能基のアセチル誘導体及びベンゾイル誘導体からなる群から選択される、請求項1又は5に記載の方法。
- 前記薬学的に許容可能な塩が酸付加塩であって、前記酸が塩酸、硫酸、リン酸、酢酸、クエン酸、シュウ酸、マロン酸、サリチル酸、リンゴ酸、グルコン酸、フマル酸、コハク酸、アスコルビン酸、マレイン酸及びメタンスルホン酸から選択される、請求項1又は5に記載の方法。
- 前記化合物が、薬学的に許容可能な担体を含む組成物に含まれている、請求項1又は5に記載の方法。
- 前記化合物が、1日当たり体重1キログラムにつき約0.0001〜500mgの投与量で投与される、請求項1又は5に記載の方法。
- 前記化合物の投与によって、前記対象における1つ以上の有害な副作用の発生を軽減する、請求項1又は5に記載の方法。
- 前記対象における1つ以上の有害な副作用の発生数が、テルブタリン、リトドリン又はメルアドリンを投与した対象に認められるこのような発生数に比べて低い、請求項18に記載の方法。
- 前記1つ以上の有害な副作用が、動悸、末梢部位の振戦、心拍数の増加、血圧低下、肺水腫、低血糖症、既往の糖尿病の悪化、既往のケトアシドーシスの悪化、振戦、神経過敏、めまい、頭痛、眠気、嘔吐、悪心、発汗、筋けいれん並びに心電図(electrocardiogram、ECG)の変化から選択される、請求項18に記載の方法。
- 対象における心拍数の増加、振戦の増強、平均血圧の低下又はこれら全ての発症数が、テルブタリンを投与した対象に認められるこのような発症数に比べて低い、請求項18に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32220110P | 2010-04-08 | 2010-04-08 | |
US61/322,201 | 2010-04-08 | ||
PCT/US2011/031066 WO2011126967A1 (en) | 2010-04-08 | 2011-04-04 | Methods and compositions for the treatment of irritable bowel syndrome |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013523815A true JP2013523815A (ja) | 2013-06-17 |
JP5841994B2 JP5841994B2 (ja) | 2016-01-13 |
Family
ID=44763232
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013503808A Active JP5841994B2 (ja) | 2010-04-08 | 2011-04-04 | 過敏性腸症候群の処置方法及びその治療用組成物 |
Country Status (8)
Country | Link |
---|---|
US (2) | US8518995B2 (ja) |
EP (1) | EP2556049A1 (ja) |
JP (1) | JP5841994B2 (ja) |
KR (1) | KR20130040862A (ja) |
CN (1) | CN102869645A (ja) |
BR (1) | BR112012025703A2 (ja) |
CA (1) | CA2794849A1 (ja) |
WO (1) | WO2011126967A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8518995B2 (en) * | 2010-04-08 | 2013-08-27 | Medicinova, Inc. | Methods and compositions for the treatment of irritable bowel syndrome |
US11224590B2 (en) * | 2018-03-16 | 2022-01-18 | Anji Pharmaceuticals Inc. | Compositions and methods for treating severe constipation |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06506676A (ja) * | 1991-04-12 | 1994-07-28 | 藤沢薬品工業株式会社 | 抗頻尿作用を有するエタノールアミン誘導体 |
JPH06506955A (ja) * | 1992-02-03 | 1994-08-04 | 藤沢薬品工業株式会社 | 交感神経様作用および抗頻尿作用を有するエタノールアミン誘導体 |
WO1997030023A1 (fr) * | 1996-02-19 | 1997-08-21 | Kissei Pharmaceutical Co., Ltd. | Derives de phenylethanolaminotetralinecarboxamide 3,4-disubstitue |
JPH09255637A (ja) * | 1996-03-27 | 1997-09-30 | Kissei Pharmaceut Co Ltd | 3,4−ジ置換フェニルエタノールアミノテトラリンカルボン酸誘導体 |
JP2009529042A (ja) * | 2006-03-08 | 2009-08-13 | アストラゼネカ・アクチエボラーグ | β2アドレナリン受容体アゴニストとしてのフェネタノールアミン誘導体 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6696486B1 (en) * | 1992-01-22 | 2004-02-24 | Glaxo Group Limited | Medical use for atypical β-adrenoceptor agonists |
US5859044A (en) | 1996-07-31 | 1999-01-12 | Pfizer Inc. | β-adrenergic agonists |
US8518995B2 (en) * | 2010-04-08 | 2013-08-27 | Medicinova, Inc. | Methods and compositions for the treatment of irritable bowel syndrome |
-
2011
- 2011-04-04 US US13/079,566 patent/US8518995B2/en active Active
- 2011-04-04 EP EP11766544A patent/EP2556049A1/en not_active Withdrawn
- 2011-04-04 JP JP2013503808A patent/JP5841994B2/ja active Active
- 2011-04-04 KR KR1020127028876A patent/KR20130040862A/ko not_active Application Discontinuation
- 2011-04-04 CN CN2011800176910A patent/CN102869645A/zh active Pending
- 2011-04-04 BR BR112012025703A patent/BR112012025703A2/pt not_active IP Right Cessation
- 2011-04-04 WO PCT/US2011/031066 patent/WO2011126967A1/en active Application Filing
- 2011-04-04 CA CA2794849A patent/CA2794849A1/en not_active Abandoned
-
2013
- 2013-08-26 US US14/010,308 patent/US20140066513A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06506676A (ja) * | 1991-04-12 | 1994-07-28 | 藤沢薬品工業株式会社 | 抗頻尿作用を有するエタノールアミン誘導体 |
JPH06506955A (ja) * | 1992-02-03 | 1994-08-04 | 藤沢薬品工業株式会社 | 交感神経様作用および抗頻尿作用を有するエタノールアミン誘導体 |
WO1997030023A1 (fr) * | 1996-02-19 | 1997-08-21 | Kissei Pharmaceutical Co., Ltd. | Derives de phenylethanolaminotetralinecarboxamide 3,4-disubstitue |
JPH09255637A (ja) * | 1996-03-27 | 1997-09-30 | Kissei Pharmaceut Co Ltd | 3,4−ジ置換フェニルエタノールアミノテトラリンカルボン酸誘導体 |
JP2009529042A (ja) * | 2006-03-08 | 2009-08-13 | アストラゼネカ・アクチエボラーグ | β2アドレナリン受容体アゴニストとしてのフェネタノールアミン誘導体 |
Also Published As
Publication number | Publication date |
---|---|
BR112012025703A2 (pt) | 2016-07-05 |
CA2794849A1 (en) | 2011-10-13 |
US8518995B2 (en) | 2013-08-27 |
US20140066513A1 (en) | 2014-03-06 |
CN102869645A (zh) | 2013-01-09 |
US20110319490A1 (en) | 2011-12-29 |
EP2556049A1 (en) | 2013-02-13 |
WO2011126967A1 (en) | 2011-10-13 |
JP5841994B2 (ja) | 2016-01-13 |
KR20130040862A (ko) | 2013-04-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2388466C2 (ru) | Производные феноксиалкилкарбоновых кислот при лечении воспалительных заболеваний | |
AU2008233088B2 (en) | Calcimimetic compounds for use in the treatment of bowel disorders | |
JP2010509298A (ja) | N−アリール−ヒドロキシアルキリデン−カルボキサミド化合物およびそれらの使用 | |
CN1298309A (zh) | 治疗肛门区疼痛的方法及其组合物 | |
EA030145B1 (ru) | Комбинации агонистов бета-3-адренергических рецепторов и антагонистов мускариновых рецепторов для лечения гиперактивности мочевого пузыря | |
TWI331920B (en) | Unit dosage form for relieving or treating constipation in human patients | |
US20070110805A1 (en) | Modified-release pharmaceutical compositions | |
JP2006511624A (ja) | α2δサブユニット・カルシウム・チャンネル調節因子を使用する無痛性膀胱障害を処置するための方法 | |
JP5841994B2 (ja) | 過敏性腸症候群の処置方法及びその治療用組成物 | |
CN107921011A (zh) | 逼尿肌过度活动伴收缩功能受损的改善剂 | |
JP2017031200A (ja) | 肛門直腸疾患の処置のためのオキシメタゾリン | |
US9867850B2 (en) | Mixture of processed salt and sugar in the manufacture of a medicament employed for treating lax vagina syndrome or colpoxerosis disease in a mammal | |
CN113242735A (zh) | 使用氨基甲酸酯化合物预防、缓解或治疗并发的癫痫发作 | |
JP2021502952A (ja) | 間質性膀胱炎の処置方法 | |
US20120035265A1 (en) | Compositions, methods, and devices for the treatment of dysmenorrhea | |
CA2356829A1 (en) | Method for treating asthma using pregabalin | |
EP4098254A1 (en) | Cannabidiol for use in the treatment of pain resulting from an indoleamine 2,3-dioxygenase-1 (ido1) related disease | |
RU2783733C1 (ru) | Применение соединения карбамата для предотвращения, облегчения или лечения диабетической периферической нейропатии или индуцированной химиотерапией периферической нейропатии | |
US20210059963A1 (en) | Beta-blockers for treating and/or preventing pathological scars | |
EP3854391A1 (en) | Carbamate compound and use of formulation comprising same in preventing, alleviating, or treating acute stress disorder or post-traumatic stress disorder | |
CN115715191A (zh) | 排尿症状治疗剂 | |
JP4632644B2 (ja) | リポポリサッカライドを有効成分とする肛門圧低下外用剤 | |
JP2001233770A (ja) | 勃起機能不全治療用の経口薬の組合わせ | |
JP2022546914A (ja) | 排便を誘導するための組成物および方法 | |
US20060189698A1 (en) | Treatment of interstitial cystitis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140214 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150203 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150422 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150602 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150625 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150731 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20151027 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20151116 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5841994 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |