KR20220004640A - 운동이상증 치료 약물 - Google Patents
운동이상증 치료 약물 Download PDFInfo
- Publication number
- KR20220004640A KR20220004640A KR1020217034115A KR20217034115A KR20220004640A KR 20220004640 A KR20220004640 A KR 20220004640A KR 1020217034115 A KR1020217034115 A KR 1020217034115A KR 20217034115 A KR20217034115 A KR 20217034115A KR 20220004640 A KR20220004640 A KR 20220004640A
- Authority
- KR
- South Korea
- Prior art keywords
- levodopa
- tandospiron
- prodrug
- pharmaceutically acceptable
- acceptable salt
- 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.)
- Withdrawn
Links
- 208000012661 Dyskinesia Diseases 0.000 title claims abstract description 313
- 238000011282 treatment Methods 0.000 title claims abstract description 37
- 239000003814 drug Substances 0.000 title claims description 112
- 229940079593 drug Drugs 0.000 title claims description 82
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims abstract description 276
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims abstract description 275
- 229960004502 levodopa Drugs 0.000 claims abstract description 267
- 239000000203 mixture Substances 0.000 claims abstract description 182
- 150000003839 salts Chemical class 0.000 claims abstract description 160
- 239000000651 prodrug Substances 0.000 claims abstract description 142
- 229940002612 prodrug Drugs 0.000 claims abstract description 142
- 238000000034 method Methods 0.000 claims abstract description 88
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 83
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 51
- 230000005764 inhibitory process Effects 0.000 claims abstract description 14
- 238000011321 prophylaxis Methods 0.000 claims abstract description 4
- 208000024891 symptom Diseases 0.000 claims description 124
- 238000009472 formulation Methods 0.000 claims description 89
- 239000003795 chemical substances by application Substances 0.000 claims description 51
- 230000006872 improvement Effects 0.000 claims description 39
- 238000007911 parenteral administration Methods 0.000 claims description 33
- 239000008280 blood Substances 0.000 claims description 31
- 210000004369 blood Anatomy 0.000 claims description 31
- 238000007920 subcutaneous administration Methods 0.000 claims description 24
- 230000002265 prevention Effects 0.000 claims description 23
- 230000002503 metabolic effect Effects 0.000 claims description 15
- 239000000853 adhesive Substances 0.000 claims description 13
- 230000001070 adhesive effect Effects 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 12
- 230000001976 improved effect Effects 0.000 claims description 12
- 230000035515 penetration Effects 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 238000004904 shortening Methods 0.000 claims description 11
- 238000007918 intramuscular administration Methods 0.000 claims description 10
- 230000007012 clinical effect Effects 0.000 claims description 9
- 229940000425 combination drug Drugs 0.000 claims description 8
- 230000004044 response Effects 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 230000006866 deterioration Effects 0.000 claims description 7
- 239000002532 enzyme inhibitor Substances 0.000 claims description 7
- 230000002051 biphasic effect Effects 0.000 claims description 6
- 229940125532 enzyme inhibitor Drugs 0.000 claims description 6
- 230000001629 suppression Effects 0.000 claims description 3
- 229940126585 therapeutic drug Drugs 0.000 abstract description 8
- 239000007924 injection Substances 0.000 description 42
- 238000002347 injection Methods 0.000 description 42
- 238000011156 evaluation Methods 0.000 description 40
- 241000700159 Rattus Species 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- 230000006399 behavior Effects 0.000 description 33
- 230000000694 effects Effects 0.000 description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- 239000004480 active ingredient Substances 0.000 description 24
- 238000004519 manufacturing process Methods 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000001802 infusion Methods 0.000 description 21
- 238000011552 rat model Methods 0.000 description 21
- -1 dihydroxyphenyl Chemical group 0.000 description 20
- 238000012360 testing method Methods 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 16
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 239000000902 placebo Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000002674 ointment Substances 0.000 description 11
- 239000003960 organic solvent Substances 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 210000003491 skin Anatomy 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000002513 implantation Methods 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 9
- 239000012790 adhesive layer Substances 0.000 description 8
- 238000003745 diagnosis Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 8
- 230000002459 sustained effect Effects 0.000 description 8
- 238000010998 test method Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 239000000654 additive Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 229960004205 carbidopa Drugs 0.000 description 7
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 7
- 238000011049 filling Methods 0.000 description 7
- 229930195733 hydrocarbon Natural products 0.000 description 7
- 150000002430 hydrocarbons Chemical class 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 7
- 230000003204 osmotic effect Effects 0.000 description 7
- 238000013519 translation Methods 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229960003638 dopamine Drugs 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 230000005713 exacerbation Effects 0.000 description 6
- 210000003414 extremity Anatomy 0.000 description 6
- 229940057995 liquid paraffin Drugs 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 238000010254 subcutaneous injection Methods 0.000 description 6
- 239000007929 subcutaneous injection Substances 0.000 description 6
- 238000000585 Mann–Whitney U test Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- NULMGOSOSZBEQL-QMMMGPOBSA-N etilevodopa Chemical compound CCOC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 NULMGOSOSZBEQL-QMMMGPOBSA-N 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 210000000434 stratum corneum Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000015592 Involuntary movements Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 206010044565 Tremor Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000024453 abnormal involuntary movement Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229960004046 apomorphine Drugs 0.000 description 3
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229960001820 etilevodopa Drugs 0.000 description 3
- 238000004299 exfoliation Methods 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 229940001089 sinemet Drugs 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 229920002725 thermoplastic elastomer Polymers 0.000 description 3
- GBLRQXKSCRCLBZ-YVQAASCFSA-N (1R,2S,1'R,2'S)-doxacurium Chemical compound COC1=C(OC)C(OC)=CC(C[C@H]2[N@+](CCC3=C2C(=C(OC)C(OC)=C3)OC)(C)CCCOC(=O)CCC(=O)OCCC[N@@+]2(C)[C@@H](C3=C(OC)C(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=C(OC)C=2)=C1 GBLRQXKSCRCLBZ-YVQAASCFSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 2
- ACVFJYKNBOHIMH-DPFKZJTMSA-N 99095-10-0 Chemical compound Cl.O=C([C@H]1[C@@H](C2=O)[C@]3([H])CC[C@]1(C3)[H])N2CCCCN(CC1)CCN1C1=NC=CC=N1 ACVFJYKNBOHIMH-DPFKZJTMSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 2
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000017911 HTR1A Human genes 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 206010029333 Neurosis Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 239000003522 acrylic cement Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940035678 anti-parkinson drug Drugs 0.000 description 2
- 229940125713 antianxiety drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- HUXSAESWQBPYHL-UHFFFAOYSA-N azecane-2,10-dione Chemical compound O=C1CCCCCCCC(=O)N1 HUXSAESWQBPYHL-UHFFFAOYSA-N 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
- 229960000516 bezafibrate Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical group OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 239000003954 decarboxylase inhibitor Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000000534 dopa decarboxylase inhibitor Substances 0.000 description 2
- 230000007977 dopaminergic denervation Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 239000000806 elastomer Substances 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 2
- 229960003337 entacapone Drugs 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940043274 prophylactic drug Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 229960003946 selegiline Drugs 0.000 description 2
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000006211 transdermal dosage form Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- XZVHHLNLLVICFA-SNVBAGLBSA-N α-difluoromethyl-dopa Chemical compound FC(F)[C@](C(O)=O)(N)CC1=CC=C(O)C(O)=C1 XZVHHLNLLVICFA-SNVBAGLBSA-N 0.000 description 2
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 description 1
- QXWYKJLNLSIPIN-YUMQZZPRSA-N (2s,3s)-2-azaniumyl-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])[C@@H](O)C1=CC=C(O)C(O)=C1 QXWYKJLNLSIPIN-YUMQZZPRSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- NWLPAIVRIWBEIT-SEPHDYHBSA-N (e)-but-2-enedioic acid;dihydrate Chemical compound O.O.OC(=O)\C=C\C(O)=O NWLPAIVRIWBEIT-SEPHDYHBSA-N 0.000 description 1
- KPAPHODVWOVUJL-UHFFFAOYSA-N 1-benzofuran;1h-indene Chemical compound C1=CC=C2CC=CC2=C1.C1=CC=C2OC=CC2=C1 KPAPHODVWOVUJL-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- DHSSDEDRBUKTQY-UHFFFAOYSA-N 6-prop-2-enyl-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-2-amine Chemical compound C1CN(CC=C)CCC2=C1N=C(N)S2 DHSSDEDRBUKTQY-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 229940081615 DOPA decarboxylase inhibitor Drugs 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 229940123736 Decarboxylase inhibitor Drugs 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101150015707 HTR1A gene Proteins 0.000 description 1
- 239000013032 Hydrocarbon resin Substances 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 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 1
- 239000004166 Lanolin Substances 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000037490 Medically Unexplained Symptoms Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 208000035755 Psychosomatic disease Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 1
- AMHPTVWBZSYFSS-BZUAXINKSA-N [(1r,3r,5r)-6,6,9-trimethyl-9-azabicyclo[3.3.1]nonan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound O([C@H]1C[C@@H]2C(C)(C)CC[C@H](C1)N2C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 AMHPTVWBZSYFSS-BZUAXINKSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 102000003802 alpha-Synuclein Human genes 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 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
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-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
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000911 benserazide Drugs 0.000 description 1
- 229960001335 benserazide hydrochloride Drugs 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 1
- 229960003003 biperiden Drugs 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- AZDOLIXTFBPILY-UHFFFAOYSA-N butanedioic acid;dihydrate Chemical compound O.O.OC(=O)CCC(O)=O AZDOLIXTFBPILY-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960004596 cabergoline Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003829 desipramine hydrochloride Drugs 0.000 description 1
- XAEWZDYWZHIUCT-UHFFFAOYSA-N desipramine hydrochloride Chemical compound [H+].[Cl-].C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 XAEWZDYWZHIUCT-UHFFFAOYSA-N 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- OJLOUXPPKZRTHK-UHFFFAOYSA-N dodecan-1-ol;sodium Chemical compound [Na].CCCCCCCCCCCCO OJLOUXPPKZRTHK-UHFFFAOYSA-N 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 229960001104 droxidopa Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 238000001227 electron beam curing Methods 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000007757 hot melt coating Methods 0.000 description 1
- 229920006270 hydrocarbon resin Polymers 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003983 inhalation anesthetic agent Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000005001 laminate film Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229960000219 mazaticol Drugs 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- XBBDACCLCFWBSI-ZETCQYMHSA-N melevodopa Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 XBBDACCLCFWBSI-ZETCQYMHSA-N 0.000 description 1
- 229960001794 melevodopa Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- WFGNJLMSYIJWII-FJXQXJEOSA-N methyl (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WFGNJLMSYIJWII-FJXQXJEOSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000002552 multiple reaction monitoring Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 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
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 229920006285 olefinic elastomer Polymers 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960004851 pergolide Drugs 0.000 description 1
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000005011 phenolic resin Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 150000003097 polyterpenes Chemical class 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- AMLFJZRZIOZGPW-UHFFFAOYSA-N prop-1-en-1-amine Chemical compound CC=CN AMLFJZRZIOZGPW-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- YXKPMPXNTYMMKQ-VIFPVBQESA-N propyl (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoate Chemical compound CCCOC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 YXKPMPXNTYMMKQ-VIFPVBQESA-N 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229960000245 rasagiline Drugs 0.000 description 1
- RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960003179 rotigotine Drugs 0.000 description 1
- KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 description 1
- NEMGRZFTLSKBAP-LBPRGKRZSA-N safinamide Chemical compound C1=CC(CN[C@@H](C)C(N)=O)=CC=C1OCC1=CC=CC(F)=C1 NEMGRZFTLSKBAP-LBPRGKRZSA-N 0.000 description 1
- 229950002652 safinamide Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229950008418 talipexole Drugs 0.000 description 1
- 229950000505 tandospirone Drugs 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 229960001032 trihexyphenidyl Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
- 229960002911 zonisamide Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/4015—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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16/395,531 | 2019-04-26 | ||
| US16/395,531 US10758535B1 (en) | 2019-04-26 | 2019-04-26 | Therapeutic drug for dyskinesia |
| PCT/JP2020/017652 WO2020218487A1 (en) | 2019-04-26 | 2020-04-24 | Therapeutic drug for dyskinesia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20220004640A true KR20220004640A (ko) | 2022-01-11 |
Family
ID=72241591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020217034115A Withdrawn KR20220004640A (ko) | 2019-04-26 | 2020-04-24 | 운동이상증 치료 약물 |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US10758535B1 (enExample) |
| EP (1) | EP3958972A4 (enExample) |
| JP (2) | JP7695891B2 (enExample) |
| KR (1) | KR20220004640A (enExample) |
| CN (1) | CN113646045A (enExample) |
| AU (1) | AU2020260895A1 (enExample) |
| BR (1) | BR112021021184A8 (enExample) |
| CA (1) | CA3137400A1 (enExample) |
| EA (1) | EA202192928A1 (enExample) |
| MX (1) | MX2021013070A (enExample) |
| PH (1) | PH12021552681A1 (enExample) |
| SG (1) | SG11202111852TA (enExample) |
| WO (1) | WO2020218487A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11559525B2 (en) * | 2019-04-26 | 2023-01-24 | Sumitomo Pharma Co., Ltd. | Therapeutic drug for dyskinesia |
| MX2023002422A (es) | 2020-08-31 | 2023-03-22 | Sumitomo Pharma Co Ltd | Farmaco terapeutico para complicaciones motoras en enfermedad de parkinson. |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11228414A (ja) | 1998-02-06 | 1999-08-24 | Sumitomo Pharmaceut Co Ltd | タンドスピロン経皮剤 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4507303A (en) | 1981-12-22 | 1985-03-26 | Sumitomo Chemical Company, Limited | Succinimide derivatives, compositions and method of use |
| BR0306919A (pt) * | 2002-01-28 | 2004-11-09 | Kyowa Hakko Kogyo Kk | Métodos para reduzir ou suprimir a efetividade adversa da terapia de l-dopa e/ou do agonista da dopamina, e para tratamento moderado de l-dopa, composição para tratamento moderado de l-dopa, método para tratar doença de parkinson e/ou complicações motoras de l-dopa, composição para o tratamento da doença de parkinson, e, métodos para prolongar o tratamento eficaz da doença de parkinson, e para tratar os distúrbios de movimento |
| JPWO2005117886A1 (ja) * | 2004-06-01 | 2008-04-03 | 久光製薬株式会社 | 貼付剤 |
| ATE413166T1 (de) | 2004-11-22 | 2008-11-15 | Hisamitsu Pharmaceutical Co | Transdermales pflaster enthaltend einen schmelzpunktsenkenden hilfsstoff |
| JP4873871B2 (ja) | 2005-02-28 | 2012-02-08 | 久光製薬株式会社 | 粘着剤及び貼付剤 |
| WO2008044336A1 (en) | 2006-10-11 | 2008-04-17 | Hisamitsu Pharmaceutical Co., Inc. | Crystal-containing adhesive preparation |
| EP2729176A1 (en) | 2011-07-05 | 2014-05-14 | Contera Pharma APS | The use of serotonin receptor agonists for treatment of movement disorders |
| SG11201406690SA (en) | 2012-04-18 | 2014-11-27 | Contera Pharma Aps | Orally available pharmaceutical formulation suitable for improved management of movement disorders |
| ES2966929T3 (es) * | 2018-12-20 | 2024-04-25 | Contera Pharma As | Tratamiento de trastornos del movimiento |
-
2019
- 2019-04-26 US US16/395,531 patent/US10758535B1/en active Active
-
2020
- 2020-04-22 US US16/855,213 patent/US20210060015A1/en not_active Abandoned
- 2020-04-24 EP EP20794266.5A patent/EP3958972A4/en active Pending
- 2020-04-24 PH PH1/2021/552681A patent/PH12021552681A1/en unknown
- 2020-04-24 JP JP2021561833A patent/JP7695891B2/ja active Active
- 2020-04-24 WO PCT/JP2020/017652 patent/WO2020218487A1/en not_active Ceased
- 2020-04-24 MX MX2021013070A patent/MX2021013070A/es unknown
- 2020-04-24 AU AU2020260895A patent/AU2020260895A1/en not_active Abandoned
- 2020-04-24 US US17/606,394 patent/US20220193075A1/en not_active Abandoned
- 2020-04-24 KR KR1020217034115A patent/KR20220004640A/ko not_active Withdrawn
- 2020-04-24 CA CA3137400A patent/CA3137400A1/en active Pending
- 2020-04-24 BR BR112021021184A patent/BR112021021184A8/pt not_active Application Discontinuation
- 2020-04-24 EA EA202192928A patent/EA202192928A1/ru unknown
- 2020-04-24 SG SG11202111852TA patent/SG11202111852TA/en unknown
- 2020-04-24 CN CN202080029464.9A patent/CN113646045A/zh active Pending
-
2025
- 2025-02-04 JP JP2025017181A patent/JP2025072496A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11228414A (ja) | 1998-02-06 | 1999-08-24 | Sumitomo Pharmaceut Co Ltd | タンドスピロン経皮剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP7695891B2 (ja) | 2025-06-19 |
| PH12021552681A1 (en) | 2022-09-19 |
| BR112021021184A2 (enExample) | 2021-12-14 |
| JP2025072496A (ja) | 2025-05-09 |
| JP2022529661A (ja) | 2022-06-23 |
| WO2020218487A1 (en) | 2020-10-29 |
| CA3137400A1 (en) | 2020-10-29 |
| AU2020260895A1 (en) | 2021-12-23 |
| US20210060015A1 (en) | 2021-03-04 |
| EA202192928A1 (ru) | 2022-02-07 |
| BR112021021184A8 (pt) | 2023-02-28 |
| US20220193075A1 (en) | 2022-06-23 |
| EP3958972A4 (en) | 2023-01-04 |
| US10758535B1 (en) | 2020-09-01 |
| CN113646045A (zh) | 2021-11-12 |
| MX2021013070A (es) | 2021-11-17 |
| EP3958972A1 (en) | 2022-03-02 |
| SG11202111852TA (en) | 2021-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102014883B1 (ko) | 근위축성 측삭 경화증 치료용 신규 조성물 | |
| JP2025072496A (ja) | ジスキネジア治療薬 | |
| TW201707704A (zh) | 激酶調節及其適應症 | |
| KR20210055052A (ko) | 아미노산 영양소, 및 아미노산 영양소를 포함하는 약제학적 조성물의 적용 | |
| CN107405347A (zh) | 用于治疗处理或美容处理过量体脂肪的nk‑3受体拮抗剂 | |
| KR20160070077A (ko) | 안구내 투여를 위한 에피네프린-기반 안과용 조성물 및 이의 제조 방법 | |
| AU2017315757A1 (en) | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof | |
| HU219482B (hu) | (+)Doxazoszin alkalmazása vizeletfolyást fokozó gyógyászati készítmények előállítására | |
| MX2007001172A (es) | Gotas acuosas para ojos que promueven la penetracion intraocular. | |
| US20230241062A1 (en) | Therapeutic drug for motor complications in parkinson's disease | |
| CA2962655C (en) | A combination of kynurenine and antigen presenting cells (apc) as therapeutics and methods for their use in immune modulation | |
| CN110402142A (zh) | 含局麻药的酸性乳液组合物 | |
| US11559525B2 (en) | Therapeutic drug for dyskinesia | |
| EA046505B1 (ru) | Терапевтическое лекарственное средство для лечения дискинезии | |
| US20210346318A1 (en) | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof | |
| US20240058320A1 (en) | Mydriatic compositions and methods for fabricating thereof | |
| JPH09500375A (ja) | パーキンソン病の治療を目的とする医薬品の製造のためのエファロキサンおよびその誘導体の使用 | |
| WO2016001682A1 (en) | Treatment of hypertransaminasemia | |
| US20230270755A1 (en) | Combination of medications in a parenteral dosage form for long-term anaesthesia | |
| HK40119997A (zh) | 软性抗胆碱能药类似物的制剂 | |
| EP2351565A1 (en) | Medicine for preventing or treating pain related to herpes zoster | |
| HK40119619A (zh) | 软性抗胆碱能药类似物的制剂 | |
| HK40119620A (zh) | 软性抗胆碱能药类似物的制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20211021 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1202 | Submission of document of withdrawal before decision of registration |
Comment text: [Withdrawal of Procedure relating to Patent, etc.] Withdrawal (Abandonment) Patent event code: PC12021R01D Patent event date: 20240429 |
|
| WITB | Written withdrawal of application |