TWI260983B - Compositions for treating resistance to antihypertensives and related conditions - Google Patents
Compositions for treating resistance to antihypertensives and related conditions Download PDFInfo
- Publication number
- TWI260983B TWI260983B TW090116904A TW90116904A TWI260983B TW I260983 B TWI260983 B TW I260983B TW 090116904 A TW090116904 A TW 090116904A TW 90116904 A TW90116904 A TW 90116904A TW I260983 B TWI260983 B TW I260983B
- Authority
- TW
- Taiwan
- Prior art keywords
- melatonin
- blood pressure
- pharmaceutical composition
- page
- patient
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 17
- 239000002220 antihypertensive agent Substances 0.000 title claims abstract description 14
- 229940030600 antihypertensive agent Drugs 0.000 title claims abstract description 5
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims abstract description 82
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims abstract description 81
- 229960003987 melatonin Drugs 0.000 claims abstract description 81
- 230000036772 blood pressure Effects 0.000 claims abstract description 51
- 230000000694 effects Effects 0.000 claims abstract description 19
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 208000028867 ischemia Diseases 0.000 claims abstract description 8
- 229960000890 hydrocortisone Drugs 0.000 claims abstract description 6
- 230000006872 improvement Effects 0.000 claims abstract description 3
- 238000013270 controlled release Methods 0.000 claims description 26
- 239000002552 dosage form Substances 0.000 claims description 25
- 206010020772 Hypertension Diseases 0.000 claims description 18
- 229940088597 hormone Drugs 0.000 claims description 14
- 239000005556 hormone Substances 0.000 claims description 14
- 230000035488 systolic blood pressure Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 230000008859 change Effects 0.000 claims description 8
- 230000002079 cooperative effect Effects 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 229940127088 antihypertensive drug Drugs 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 229960000830 captopril Drugs 0.000 claims description 4
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 4
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 4
- 229960004166 diltiazem Drugs 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims description 3
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 3
- 108010061435 Enalapril Proteins 0.000 claims description 3
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 3
- 229960002274 atenolol Drugs 0.000 claims description 3
- 229960002896 clonidine Drugs 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 230000001771 impaired effect Effects 0.000 claims description 3
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims description 3
- 229960003632 minoxidil Drugs 0.000 claims description 3
- 239000003607 modifier Substances 0.000 claims description 3
- 229960001289 prazosin Drugs 0.000 claims description 3
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 claims description 3
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 claims description 3
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims description 3
- 229960004699 valsartan Drugs 0.000 claims description 3
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 230000002996 emotional effect Effects 0.000 claims description 2
- 229960000873 enalapril Drugs 0.000 claims description 2
- 229960002237 metoprolol Drugs 0.000 claims description 2
- 210000000664 rectum Anatomy 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims 10
- 238000000576 coating method Methods 0.000 claims 10
- 239000000463 material Substances 0.000 claims 10
- 238000004090 dissolution Methods 0.000 claims 4
- 239000008187 granular material Substances 0.000 claims 4
- 239000002245 particle Substances 0.000 claims 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- 206010036790 Productive cough Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims 1
- 229960003022 amoxicillin Drugs 0.000 claims 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims 1
- 229960002386 prazosin hydrochloride Drugs 0.000 claims 1
- WFXFYZULCQKPIP-UHFFFAOYSA-N prazosin hydrochloride Chemical compound [H+].[Cl-].N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 WFXFYZULCQKPIP-UHFFFAOYSA-N 0.000 claims 1
- 208000024794 sputum Diseases 0.000 claims 1
- 210000003802 sputum Anatomy 0.000 claims 1
- 229960001367 tartaric acid Drugs 0.000 claims 1
- 229960001909 terazosin hydrochloride Drugs 0.000 claims 1
- 239000002023 wood Substances 0.000 claims 1
- 230000033764 rhythmic process Effects 0.000 abstract description 13
- 230000036651 mood Effects 0.000 abstract description 6
- 230000002159 abnormal effect Effects 0.000 abstract description 2
- 230000001627 detrimental effect Effects 0.000 abstract 1
- 230000000422 nocturnal effect Effects 0.000 abstract 1
- 230000000069 prophylactic effect Effects 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000007423 decrease Effects 0.000 description 9
- 241000602850 Cinclidae Species 0.000 description 8
- 230000003276 anti-hypertensive effect Effects 0.000 description 8
- 230000035487 diastolic blood pressure Effects 0.000 description 8
- 239000003246 corticosteroid Substances 0.000 description 7
- -1 hydroxyl cortisol Chemical compound 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 6
- 229960001334 corticosteroids Drugs 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000001631 hypertensive effect Effects 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000002354 daily effect Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 206010022437 insomnia Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000005555 hypertensive agent Substances 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 210000004560 pineal gland Anatomy 0.000 description 2
- 229960003401 ramipril Drugs 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229960001693 terazosin Drugs 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000001419 Melatonin receptor Human genes 0.000 description 1
- 108050009605 Melatonin receptor Proteins 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 244000236658 Paeonia lactiflora Species 0.000 description 1
- 235000008598 Paeonia lactiflora Nutrition 0.000 description 1
- 241001674048 Phthiraptera Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010037714 Quadriplegia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- VPSRQEHTHIMDQM-FKLPMGAJSA-N benazepril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 VPSRQEHTHIMDQM-FKLPMGAJSA-N 0.000 description 1
- 229960003619 benazepril hydrochloride Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 238000009223 counseling Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000000517 effect on sleep Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229960000309 enalapril maleate Drugs 0.000 description 1
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000001020 rhythmical effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 230000004620 sleep latency Effects 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000002438 stress hormone Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 229940035722 triiodothyronine Drugs 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Treatments Of Macromolecular Shaped Articles (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IL2000/000009 WO2001049286A1 (en) | 2000-01-05 | 2000-01-05 | Method and formulation for treating resistance to antihypertensives and related conditions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI260983B true TWI260983B (en) | 2006-09-01 |
Family
ID=11042938
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW090116904A TWI260983B (en) | 2000-01-05 | 2001-07-10 | Compositions for treating resistance to antihypertensives and related conditions |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US7332177B1 (https=) |
| EP (1) | EP1272177B1 (https=) |
| JP (1) | JP4996803B2 (https=) |
| CN (1) | CN1414851A (https=) |
| AT (1) | ATE359072T1 (https=) |
| AU (1) | AU782266B2 (https=) |
| BG (1) | BG65637B1 (https=) |
| BR (1) | BR0016918A (https=) |
| CA (1) | CA2396129C (https=) |
| CY (2) | CY1108018T1 (https=) |
| CZ (1) | CZ299931B6 (https=) |
| DE (1) | DE60034373T2 (https=) |
| DK (1) | DK1272177T3 (https=) |
| EA (1) | EA004679B1 (https=) |
| EE (1) | EE200200379A (https=) |
| ES (1) | ES2284471T3 (https=) |
| HK (1) | HK1052655A1 (https=) |
| HU (1) | HU227002B1 (https=) |
| IL (1) | IL150190A0 (https=) |
| IS (1) | IS6439A (https=) |
| MX (1) | MXPA02005783A (https=) |
| NO (1) | NO322567B1 (https=) |
| NZ (1) | NZ520078A (https=) |
| PL (1) | PL201219B1 (https=) |
| PT (1) | PT1272177E (https=) |
| SI (1) | SI1272177T1 (https=) |
| SK (1) | SK287508B6 (https=) |
| TR (1) | TR200201724T2 (https=) |
| TW (1) | TWI260983B (https=) |
| UA (1) | UA77394C2 (https=) |
| WO (1) | WO2001049286A1 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL144900A (en) * | 2001-08-14 | 2013-12-31 | Neurim Pharma 1991 | Melatonin and drugs containing it for use in the treatment of primary insomnia, and the manufacture of those drugs |
| IL155666A (en) | 2003-04-29 | 2013-12-31 | Neurim Pharma 1991 | Insomnia treatment |
| US9119846B2 (en) | 2003-04-29 | 2015-09-01 | Neurim Pharmaceuticals (1991) Ltd. | Method and composition for enhancing cognition in alzheimer's patients |
| US20050020666A1 (en) * | 2003-07-25 | 2005-01-27 | Dabur Research Foundation | Cardioprotective agents |
| US20050137247A1 (en) * | 2003-12-22 | 2005-06-23 | The Brigham And Women's Hospital, Inc. | Methods and compositions for treatment of hypertension |
| JP3964417B2 (ja) | 2004-09-27 | 2007-08-22 | 国立大学法人金沢大学 | インドール誘導体を有効成分とするα２受容体遮断剤及び血管拡張剤 |
| KR101053780B1 (ko) * | 2008-02-29 | 2011-08-02 | 동아제약주식회사 | 도세탁셀을 함유하는 단일액상의 안정한 약제학적 조성물 |
| US20130325151A1 (en) * | 2010-10-25 | 2013-12-05 | Uico, Llc | Control system with solid state touch sensor for complex surface geometry |
| US9532952B2 (en) | 2011-01-28 | 2017-01-03 | Physician's Seal, LLC | Controlled-release compositions of melatonin combined with sedative and/or analgesic ingredients |
| US8691275B2 (en) | 2011-01-28 | 2014-04-08 | Zx Pharma, Llc | Controlled-release melatonin compositions and related methods |
| WO2018033546A1 (en) * | 2016-08-18 | 2018-02-22 | Koninklijke Philips N.V. | Blood-pressure management |
| US10849856B2 (en) | 2016-10-31 | 2020-12-01 | Neurim Pharmaceuticals Ltd. | Melatonin mini-tablets and method of manufacturing the same |
| JP6830156B2 (ja) | 2016-10-31 | 2021-02-17 | ニューリム・ファーマシューティカルズ・リミテッドＮｅｕｒｉｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ． | メラトニンミニタブレットおよびその製造方法 |
| WO2019038586A1 (en) | 2017-08-19 | 2019-02-28 | Ftf Pharma Private Limited | PHARMACEUTICAL COMPOSITION OF MELATONIN |
| ES2724933A1 (es) * | 2018-03-13 | 2019-09-17 | Ocupharm Diagnostics Sl | Terapia combinada con melatonina para la reducción de la presión intraocular |
| GB2617102A (en) * | 2022-03-29 | 2023-10-04 | John Hemming Trading Ltd | Sleep therapy |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2134789T3 (es) * | 1991-05-09 | 1999-10-16 | Neurim Pharma 1991 | Composiciones que contienen melatonina. |
| CA2116036A1 (en) * | 1991-10-18 | 1993-04-29 | F. Eugene Yates | Device for the transdermal administration of melatonin |
| US5646049A (en) * | 1992-03-27 | 1997-07-08 | Abbott Laboratories | Scheduling operation of an automated analytical system |
| DE69303919T2 (de) * | 1992-04-07 | 1997-01-30 | Neurim Pharma 1991 | Verwendung von Melatonin zur Herstellung eines Arzneimittels zur Behandlung der gutartigen Prostatahyperplasie |
| EP0664339A4 (en) * | 1993-07-09 | 1999-04-28 | Wakunaga Seiyaku Kk | METHOD FOR DISCRIMINATION OF NUCLEIC ACIDS AND TEST KIT FOR THIS PURPOSE. |
| MD1716C2 (ro) | 1995-02-01 | 2002-02-28 | Neurim Pharmaceuticals (1991) Ltd. | Utilizare a melatoninei pentru tratamentul pacienţilor dependenţi de benzodiazepine |
| US5648727A (en) * | 1995-10-24 | 1997-07-15 | Dpc Cirrus Inc. | Capacitive level sensing pipette probe |
| US5700828A (en) | 1995-12-07 | 1997-12-23 | Life Resuscitation Technologies, Inc. | Treatment or prevention of anoxic or ischemic brain injury with melatonin-containing compositions |
| AU2583397A (en) * | 1996-04-10 | 1997-10-29 | Chronorx, Llc | Unit dosage forms, containing magnesium, vitamin c, vitamin e, folate and selenium, for treatment of vasoconstriction and related conditions |
| RU2134108C1 (ru) | 1998-10-06 | 1999-08-10 | Заславская Рина Михайловна | Средство для лечения артериальной гипертонии, способ лечения артериальной гипертонии |
-
2000
- 2000-01-05 MX MXPA02005783A patent/MXPA02005783A/es active IP Right Grant
- 2000-01-05 JP JP2001549654A patent/JP4996803B2/ja not_active Expired - Lifetime
- 2000-01-05 SI SI200030958T patent/SI1272177T1/sl unknown
- 2000-01-05 AU AU18882/00A patent/AU782266B2/en not_active Expired
- 2000-01-05 CZ CZ20022346A patent/CZ299931B6/cs not_active IP Right Cessation
- 2000-01-05 TR TR2002/01724T patent/TR200201724T2/xx unknown
- 2000-01-05 BR BR0016918-8A patent/BR0016918A/pt not_active IP Right Cessation
- 2000-01-05 EP EP00900110A patent/EP1272177B1/en not_active Expired - Lifetime
- 2000-01-05 IL IL15019000A patent/IL150190A0/xx unknown
- 2000-01-05 SK SK973-2002A patent/SK287508B6/sk not_active IP Right Cessation
- 2000-01-05 HK HK03105037.1A patent/HK1052655A1/zh unknown
- 2000-01-05 PT PT00900110T patent/PT1272177E/pt unknown
- 2000-01-05 NZ NZ520078A patent/NZ520078A/en not_active IP Right Cessation
- 2000-01-05 US US10/169,467 patent/US7332177B1/en not_active Expired - Lifetime
- 2000-01-05 WO PCT/IL2000/000009 patent/WO2001049286A1/en not_active Ceased
- 2000-01-05 DE DE60034373T patent/DE60034373T2/de not_active Expired - Lifetime
- 2000-01-05 HU HU0204089A patent/HU227002B1/hu unknown
- 2000-01-05 EA EA200200738A patent/EA004679B1/ru not_active IP Right Cessation
- 2000-01-05 EE EEP200200379A patent/EE200200379A/xx unknown
- 2000-01-05 AT AT00900110T patent/ATE359072T1/de active
- 2000-01-05 CA CA2396129A patent/CA2396129C/en not_active Expired - Lifetime
- 2000-01-05 DK DK00900110T patent/DK1272177T3/da active
- 2000-01-05 CN CN00818153A patent/CN1414851A/zh active Pending
- 2000-01-05 ES ES00900110T patent/ES2284471T3/es not_active Expired - Lifetime
- 2000-01-05 PL PL356325A patent/PL201219B1/pl unknown
- 2000-05-01 UA UA2002076326A patent/UA77394C2/uk unknown
-
2001
- 2001-07-10 TW TW090116904A patent/TWI260983B/zh not_active IP Right Cessation
-
2002
- 2002-06-24 IS IS6439A patent/IS6439A/is unknown
- 2002-06-27 NO NO20023102A patent/NO322567B1/no not_active IP Right Cessation
- 2002-08-05 BG BG106978A patent/BG65637B1/bg unknown
-
2007
- 2007-07-10 CY CY20071100916T patent/CY1108018T1/el unknown
- 2007-12-04 US US11/950,039 patent/US8075914B2/en not_active Expired - Fee Related
- 2007-12-18 CY CY200700033C patent/CY2007033I1/el unknown
-
2011
- 2011-10-25 US US13/281,212 patent/US8728511B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI260983B (en) | Compositions for treating resistance to antihypertensives and related conditions | |
| Luque et al. | The discovery and status of sibutramine as an anti-obesity drug | |
| TW389696B (en) | Accelerated release composition containing bromocriptine | |
| US20080171085A1 (en) | Novel biphasic delivery system for a pharmaceutical or nutraceutical composition and method of administration | |
| WO1997029739A2 (en) | Use of 5ht4 receptor antagonists for overcoming gastrointestinal effects of serotonin reuptake inhibitors | |
| MX2012013014A (es) | Regimenes terapeuticos. | |
| TW483757B (en) | A pharmceutical formulation containing melatonin for use in treating preventing symptoms of dependence on, tolerance of, or addiction to benzodiazepine drugs | |
| TW383222B (en) | Pharmaceutical composition of bicycloheptane derivatives | |
| Karagianis et al. | Orally disintegrating olanzapine and potential differences in treatment‐emergent weight gain | |
| Belza et al. | The β-adrenergic antagonist propranolol partly abolishes thermogenic response to bioactive food ingredients | |
| Prabhakar | Combination therapy: a new tool for the management of obesity | |
| IL150190A (en) | Use of melatonin in the manufacture of controlled release medicaments for inprovement in mood and daytime vigilance, modifying the 24-hour cortisol profile, protection against carodic ischemia, and prevention or treatment of hypertension in a patient resistant to other antihypertensive drugs | |
| Tomlinson et al. | Sustained-release isradipine compared with spirapril in the treatment of elderly patients with isolated systolic hypertension | |
| HK1164136A1 (en) | Method and formulation for treating resistance to antihypertensives and related conditions | |
| CN1905882A (zh) | 血管内膜增厚抑制剂 | |
| ZA200206228B (en) | Method and formulation for treating resistance to antihypertensives and related conditions. | |
| Lai et al. | Pharmacologic treatment for detrusor overactivity | |
| RU2424803C2 (ru) | Фармацевтическая композиция с противомигреневым действием (варианты) | |
| Heßelmann et al. | P. 1.053 Mirtazapine in seasonal affective disorder (SAD)—A preliminary report | |
| Rahman | In Vitro Kinetic Studies of Combined Amlodipine (5mg) and Atenolol (50mg) Tablet Dosage Form: A Comparative Study with Similar Market Products Available in Bangladesh | |
| Lewis, SA, Oswald, I., Dunleavy, DLF & Brezinova | Fenfluramine: cerebral effects and dependence in chronic use | |
| TW200838535A (en) | Therapeutic agent for multiple sclerosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Expiration of patent term of an invention patent |