EA029400B1 - Фармацевтическая композиция для лечения ожирения и сопутствующих метаболических расстройств и способ лечения - Google Patents
Фармацевтическая композиция для лечения ожирения и сопутствующих метаболических расстройств и способ лечения Download PDFInfo
- Publication number
- EA029400B1 EA029400B1 EA201300133A EA201300133A EA029400B1 EA 029400 B1 EA029400 B1 EA 029400B1 EA 201300133 A EA201300133 A EA 201300133A EA 201300133 A EA201300133 A EA 201300133A EA 029400 B1 EA029400 B1 EA 029400B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- pharmaceutical composition
- antibody
- bei
- composition according
- activated
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 95
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 66
- 208000008589 Obesity Diseases 0.000 title claims abstract description 43
- 235000020824 obesity Nutrition 0.000 title claims abstract description 43
- 208000030159 metabolic disease Diseases 0.000 title claims abstract description 14
- 238000011282 treatment Methods 0.000 title abstract description 60
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 82
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 82
- 102000018208 Cannabinoid Receptor Human genes 0.000 claims abstract description 60
- 108050007331 Cannabinoid receptor Proteins 0.000 claims abstract description 60
- 238000010790 dilution Methods 0.000 claims description 73
- 239000012895 dilution Substances 0.000 claims description 73
- 230000001632 homeopathic effect Effects 0.000 claims description 50
- 230000037396 body weight Effects 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 39
- 230000009467 reduction Effects 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 15
- 210000004556 brain Anatomy 0.000 claims description 13
- 229960004425 sibutramine Drugs 0.000 claims description 13
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims description 13
- 235000012631 food intake Nutrition 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 9
- 239000012634 fragment Substances 0.000 claims description 9
- 230000037406 food intake Effects 0.000 claims description 8
- 239000002552 dosage form Substances 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 5
- 238000013207 serial dilution Methods 0.000 claims description 4
- 235000019786 weight gain Nutrition 0.000 claims description 3
- 230000004584 weight gain Effects 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 23
- 235000018102 proteins Nutrition 0.000 description 76
- 239000000243 solution Substances 0.000 description 56
- 208000033255 Progressive myoclonic epilepsy type 1 Diseases 0.000 description 49
- 238000012360 testing method Methods 0.000 description 48
- 208000025569 Tobacco Use disease Diseases 0.000 description 41
- 206010057852 Nicotine dependence Diseases 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 28
- 229940079593 drug Drugs 0.000 description 27
- 230000000391 smoking effect Effects 0.000 description 27
- 239000003826 tablet Substances 0.000 description 26
- 230000000694 effects Effects 0.000 description 25
- 208000019901 Anxiety disease Diseases 0.000 description 24
- 239000000902 placebo Substances 0.000 description 24
- 229940068196 placebo Drugs 0.000 description 24
- 101100460719 Mus musculus Noto gene Proteins 0.000 description 23
- 101100187345 Xenopus laevis noto gene Proteins 0.000 description 23
- 230000036506 anxiety Effects 0.000 description 23
- 239000000556 agonist Substances 0.000 description 20
- 230000008569 process Effects 0.000 description 20
- 241000283973 Oryctolagus cuniculus Species 0.000 description 19
- 239000011159 matrix material Substances 0.000 description 19
- 239000000427 antigen Substances 0.000 description 17
- 102000036639 antigens Human genes 0.000 description 17
- 108091007433 antigens Proteins 0.000 description 17
- 229960002715 nicotine Drugs 0.000 description 17
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 208000024891 symptom Diseases 0.000 description 16
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 13
- 230000003247 decreasing effect Effects 0.000 description 13
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 12
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 102000012234 Cannabinoid receptor type 1 Human genes 0.000 description 10
- 108050002726 Cannabinoid receptor type 1 Proteins 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 239000000779 smoke Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 235000013305 food Nutrition 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 206010012335 Dependence Diseases 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 7
- 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 7
- 239000007853 buffer solution Substances 0.000 description 7
- 235000019504 cigarettes Nutrition 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 235000003642 hunger Nutrition 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 230000003053 immunization Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 101000710899 Homo sapiens Cannabinoid receptor 1 Proteins 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 150000001200 N-acyl ethanolamides Chemical class 0.000 description 4
- 241000208125 Nicotiana Species 0.000 description 4
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- -1 benzphytamine Chemical compound 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229930003827 cannabinoid Natural products 0.000 description 4
- 239000003557 cannabinoid Substances 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000002621 endocannabinoid Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 102000056964 human CNR1 Human genes 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 238000009533 lab test Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 3
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 3
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 3
- 208000020401 Depressive disease Diseases 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000003925 brain function Effects 0.000 description 3
- 229940065144 cannabinoids Drugs 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000005714 functional activity Effects 0.000 description 3
- 239000000905 isomalt Substances 0.000 description 3
- 235000010439 isomalt Nutrition 0.000 description 3
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 2
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010033307 Overweight Diseases 0.000 description 2
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 229940126513 cyclase activator Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- GWQVMPWSEVRGPY-UHFFFAOYSA-N europium cryptate Chemical compound [Eu+3].N=1C2=CC=CC=1CN(CC=1N=C(C=CC=1)C=1N=C(C3)C=CC=1)CC(N=1)=CC(C(=O)NCCN)=CC=1C(N=1)=CC(C(=O)NCCN)=CC=1CN3CC1=CC=CC2=N1 GWQVMPWSEVRGPY-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000005470 impregnation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000037023 motor activity Effects 0.000 description 2
- 231100000989 no adverse effect Toxicity 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 238000012346 open field test Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 238000003672 processing method Methods 0.000 description 2
- 108010077112 prolyl-proline Proteins 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 201000006152 substance dependence Diseases 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229940098465 tincture Drugs 0.000 description 2
- 238000002562 urinalysis Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- 101800000263 Acidic protein Proteins 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 241001514645 Agonis Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000218236 Cannabis Species 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102100023882 Endoribonuclease ZC3H12A Human genes 0.000 description 1
- 101710112715 Endoribonuclease ZC3H12A Proteins 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 239000004866 Hashish Substances 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- ZYTPOUNUXRBYGW-YUMQZZPRSA-N Met-Met Chemical compound CSCC[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CCSC ZYTPOUNUXRBYGW-YUMQZZPRSA-N 0.000 description 1
- 101100182721 Mus musculus Ly6e gene Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- MFOCDFTXLCYLKU-CMPLNLGQSA-N Phendimetrazine Chemical compound O1CCN(C)[C@@H](C)[C@@H]1C1=CC=CC=C1 MFOCDFTXLCYLKU-CMPLNLGQSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 235000008406 SarachaNachtschatten Nutrition 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 235000004790 Solanum aculeatissimum Nutrition 0.000 description 1
- 235000008424 Solanum demissum Nutrition 0.000 description 1
- 235000018253 Solanum ferox Nutrition 0.000 description 1
- 235000000208 Solanum incanum Nutrition 0.000 description 1
- 240000002915 Solanum macrocarpon Species 0.000 description 1
- 235000013131 Solanum macrocarpon Nutrition 0.000 description 1
- 235000009869 Solanum phureja Nutrition 0.000 description 1
- 235000000341 Solanum ptychanthum Nutrition 0.000 description 1
- 235000017622 Solanum xanthocarpum Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- UWAOJIWUVCMBAZ-UHFFFAOYSA-N [1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl]-dimethylazanium;chloride Chemical compound Cl.C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UWAOJIWUVCMBAZ-UHFFFAOYSA-N 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 230000000141 anti-hypoxic effect Effects 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 230000001152 anti-nicotinic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 1
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 229960004890 diethylpropion Drugs 0.000 description 1
- XXEPPPIWZFICOJ-UHFFFAOYSA-N diethylpropion Chemical compound CCN(CC)C(C)C(=O)C1=CC=CC=C1 XXEPPPIWZFICOJ-UHFFFAOYSA-N 0.000 description 1
- ADYPXRFPBQGGAH-UMYZUSPBSA-N dihydroergotamine mesylate Chemical compound CS(O)(=O)=O.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C)C1=CC=CC=C1 ADYPXRFPBQGGAH-UMYZUSPBSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000005288 electromagnetic effect Effects 0.000 description 1
- 230000005672 electromagnetic field Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 229960001582 fenfluramine Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 235000020845 low-calorie diet Nutrition 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 description 1
- 229960000299 mazindol Drugs 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 229940045623 meridia Drugs 0.000 description 1
- 108010085203 methionylmethionine Proteins 0.000 description 1
- 108010077055 methylated bovine serum albumin Proteins 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000004751 neurological system process Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 238000002670 nicotine replacement therapy Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001777 nootropic effect Effects 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000011422 pharmacological therapy Methods 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 229960000436 phendimetrazine Drugs 0.000 description 1
- 229960003562 phentermine Drugs 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000007094 prostatitis Diseases 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 231100000272 reduced body weight Toxicity 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000003762 serotonin receptor affecting agent Substances 0.000 description 1
- 238000000742 single-metal deposition Methods 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 230000007103 stamina Effects 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/06—Preparations for care of the skin for countering cellulitis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Mycology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Microbiology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2010129289/15A RU2552221C2 (ru) | 2010-07-15 | 2010-07-15 | Способ лечения ожирения и сопутствующих метаболических расстройств и лекарственное средство для лечения ожирения и сопутствующих метаболических расстройств |
| RU2010130350/15A RU2533224C2 (ru) | 2010-07-21 | 2010-07-21 | Способ лечения зависимости от психоактивных веществ, алкоголизма и табакокурения и лекарственное средство для лечения зависимости от психоактивных веществ, алкоголизма и табакокурения |
| RU2011122407A RU2610438C2 (ru) | 2011-06-02 | 2011-06-02 | Способ лечения патологического синдрома и лекарственное средство центрального и периферического действия для лечения патологического синдрома |
| PCT/IB2011/002404 WO2012007847A2 (en) | 2010-07-15 | 2011-07-15 | Pharmaceutical compositions and methods of treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201300133A1 EA201300133A1 (ru) | 2014-03-31 |
| EA029400B1 true EA029400B1 (ru) | 2018-03-30 |
Family
ID=44899164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201300133A EA029400B1 (ru) | 2010-07-15 | 2011-07-15 | Фармацевтическая композиция для лечения ожирения и сопутствующих метаболических расстройств и способ лечения |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US8865163B2 (enExample) |
| EP (1) | EP2593477A2 (enExample) |
| JP (1) | JP2013535436A (enExample) |
| KR (1) | KR20140012009A (enExample) |
| CN (1) | CN103124742A (enExample) |
| AR (1) | AR082246A1 (enExample) |
| AU (1) | AU2011278040B2 (enExample) |
| BR (1) | BR112013000841A2 (enExample) |
| CA (1) | CA2805091A1 (enExample) |
| CL (1) | CL2013000098A1 (enExample) |
| CZ (1) | CZ2013104A3 (enExample) |
| DE (1) | DE112011102349T5 (enExample) |
| DK (1) | DK201370078A (enExample) |
| EA (1) | EA029400B1 (enExample) |
| EE (1) | EE05760B1 (enExample) |
| ES (1) | ES2542042R1 (enExample) |
| FI (1) | FI20135146L (enExample) |
| FR (1) | FR2962653A1 (enExample) |
| GB (1) | GB2496076B (enExample) |
| IT (1) | ITTO20110641A1 (enExample) |
| LT (1) | LT5987B (enExample) |
| MX (1) | MX361778B (enExample) |
| MY (1) | MY158183A (enExample) |
| NO (1) | NO20130219A1 (enExample) |
| NZ (1) | NZ606768A (enExample) |
| PE (1) | PE20131338A1 (enExample) |
| PH (1) | PH12013500109A1 (enExample) |
| SE (1) | SE1350179A1 (enExample) |
| SG (1) | SG187037A1 (enExample) |
| WO (1) | WO2012007847A2 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2181297C2 (ru) | 2000-06-20 | 2002-04-20 | Эпштейн Олег Ильич | Способ лечения патологического синдрома и лекарственное средство |
| RU2309732C1 (ru) * | 2006-03-13 | 2007-11-10 | Олег Ильич Эпштейн | Спрессованная твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата |
| FR2962652A1 (fr) | 2010-07-15 | 2012-01-20 | Oleg Iliich Epshtein | Composition pharmaceutique d'association et son utilisation dans des procedes pour traiter les maladies ou affections associees a des maladies neurodegeneratives |
| MX2013000543A (es) | 2010-07-15 | 2013-10-28 | Oleg Iliich Epshtein | Un metodo para aumentar el efecto de una forma activa potenciada de un anticuerpo. |
| FR2962655A1 (fr) * | 2010-07-15 | 2012-01-20 | Oleg Iliich Epshtein | Composition pharmaceutique d'association et ses utilisations dans les procedes de traitement des troubles du systeme genito-urinaire |
| PH12013500144A1 (en) | 2010-07-21 | 2018-03-21 | Oleg Iliich Epshtein | A method of treating attention deficit hyperactivity disorder |
| CN103118707A (zh) * | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | 复合药物组合物及对糖尿病和代谢紊乱进行治疗的方法 |
| FR2962909A1 (fr) * | 2010-07-21 | 2012-01-27 | Oleg Iliich Epshtein | Composition pharmaceutique d'association et son utilisation dans des procedes pour traiter les maladies ou affections associees avec une maladie ou affection respiratoire |
| US20130058981A1 (en) * | 2010-07-21 | 2013-03-07 | Oleg Iliich Epshtein | Combination pharmaceutical compositions and method of treatment of vertigo, kinetosis and vegetative-vascular dystonia |
| CZ2013159A3 (cs) * | 2010-08-06 | 2013-06-12 | Iliich Epshtein@Oleg | Kombinovaná farmaceutická kompozice a zpusoby lécby a prevence infekcních chorob |
| RU2013111962A (ru) * | 2013-03-18 | 2014-09-27 | Олег Ильич Эпштейн | Способ определения выраженности модифицирующей активности, ассоциированной с носителем |
| RU2013111961A (ru) * | 2013-03-18 | 2014-09-27 | Олег Ильич Эпштейн | Способ определения выраженности модифицирующей активности, ассоциированной с носителем |
| JP6598844B2 (ja) * | 2014-03-27 | 2019-10-30 | バード・ロック・バイオ・インコーポレイテッド | ヒトカンナビノイド1(cb1)受容体に結合する抗体 |
| CN104524568B (zh) * | 2015-01-08 | 2018-04-20 | 中国人民解放军第二军医大学 | 一种治疗肥胖症的药物组合物及其应用 |
| JP2019502651A (ja) * | 2015-09-30 | 2019-01-31 | バード・ロック・バイオ・インコーポレイテッドBird Rock Bio, Inc. | ヒトカンナビノイド1(cb1)受容体に結合する抗体 |
| CN114375200A (zh) * | 2019-08-29 | 2022-04-19 | 奥列格·伊利奇·爱泼斯坦 | 治疗传染病的药物和方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050100513A1 (en) * | 2003-11-10 | 2005-05-12 | Watkins Mary B. | Homeopathic method and system for treating nicotine addiction |
| EP1547612A1 (en) * | 2002-08-02 | 2005-06-29 | Oleg Iliich Epshtein | Medicinal agent and method for curing erectile dysfunction |
| EP1550460A1 (en) * | 2002-08-02 | 2005-07-06 | Oleg Iliich Epshtein | Method for correcting immune responses and medicinal agent |
| WO2008070305A2 (en) * | 2006-10-23 | 2008-06-12 | Eli Lilly And Company | 1, 5-diphenyl-3-pyridinylamino-1, 5-dihydropyrrolidin-2-one as cbl' receptor modulator |
| WO2008122618A1 (en) * | 2007-04-04 | 2008-10-16 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Selective inhibitors of cb2 receptor expression and/or activity for the treatment of obesity and obesity-related disorders |
| EP2036574A1 (en) * | 2006-06-06 | 2009-03-18 | Oleg Iliich Epshtein | Medicinal agent for treating fatness, diabetes, and diseases associated with impaired glucose tolerance |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4311897A (en) | 1979-08-28 | 1982-01-19 | Union Carbide Corporation | Plasma arc torch and nozzle assembly |
| AU723812B2 (en) | 1996-02-12 | 2000-09-07 | Oleg Iliich Epshtein | Medicinal preparation and a method of medicinal action on human organism |
| US5849528A (en) | 1997-08-21 | 1998-12-15 | Incyte Pharmaceuticals, Inc.. | Polynucleotides encoding a human S100 protein |
| RU2156621C1 (ru) | 1999-03-04 | 2000-09-27 | Эпштейн Олег Ильич | Нейротропное лекарственное средство |
| RU2181297C2 (ru) | 2000-06-20 | 2002-04-20 | Эпштейн Олег Ильич | Способ лечения патологического синдрома и лекарственное средство |
| RU2201255C1 (ru) | 2001-12-26 | 2003-03-27 | Эпштейн Олег Ильич | Лекарственное средство и способ регуляции сосудистого тонуса |
| RU2209084C1 (ru) * | 2001-12-26 | 2003-07-27 | Эпштейн Олег Ильич | Лекарственное средство и способ лечения депрессивных расстройств |
| UA76641C2 (uk) | 2002-08-02 | 2006-08-15 | Олєг Ільіч Епштєйн | Гомеопатичний лікарський засіб та спосіб лікування захворювань передміхурової залози |
| UA76638C2 (en) | 2002-08-02 | 2006-08-15 | Oleh Illich Epshtein | Homeopathic medication based on anti-interferon antibodies and method for treating a pathological syndrome associated with interferon |
| GB2414670B (en) | 2003-03-14 | 2008-03-19 | Nutrition Res Inc | Homeopathic formulations useful for treating pain and/or inflammation |
| EP1574211A1 (en) * | 2004-03-09 | 2005-09-14 | Inserm | Use of antagonists of the CB1 receptor for the manufacture of a composition useful for the treatment of hepatic diseases |
| RU2309732C1 (ru) * | 2006-03-13 | 2007-11-10 | Олег Ильич Эпштейн | Спрессованная твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата |
| RU2437678C2 (ru) | 2006-06-06 | 2011-12-27 | Олег Ильич Эпштейн | Лекарственное средство для перорального лечения ожирения и способ получения твердой лекарственной формы для пероральной терапии ожирения |
| RU2438707C2 (ru) * | 2006-06-06 | 2012-01-10 | Олег Ильич Эпштейн | Лекарственное средство для перорального лечения сахарного диабета и других заболеваний, сопровождающихся нарушением толерантности к глюкозе, и способ получения твердой лекарственной формы для пероральной терапии сахарного диабета и других заболеваний, сопровождающихся нарушением толерантности к глюкозе |
| JP2010132631A (ja) * | 2008-11-04 | 2010-06-17 | Bizen Chemical Co Ltd | カンナビノイド受容体のインバースアゴニストおよびアンタゴニスト活性を有する組成物 |
| FR2962652A1 (fr) | 2010-07-15 | 2012-01-20 | Oleg Iliich Epshtein | Composition pharmaceutique d'association et son utilisation dans des procedes pour traiter les maladies ou affections associees a des maladies neurodegeneratives |
| MY157564A (en) | 2010-07-15 | 2016-06-30 | Epshtein Oleg Lliich | Combination pharmaceutical composition and methods of treating functional diseases or conditions of gastrointestinal tract |
| PH12013500144A1 (en) | 2010-07-21 | 2018-03-21 | Oleg Iliich Epshtein | A method of treating attention deficit hyperactivity disorder |
| US20130058981A1 (en) | 2010-07-21 | 2013-03-07 | Oleg Iliich Epshtein | Combination pharmaceutical compositions and method of treatment of vertigo, kinetosis and vegetative-vascular dystonia |
| WO2012010978A2 (en) | 2010-07-21 | 2012-01-26 | Oleg Iliich Epshtein | A method of treating alzheimer's disease |
| WO2012014078A2 (en) | 2010-07-21 | 2012-02-02 | Olge Iliich Epshtein | Method of treatment of organic diseases of nervous system, psychoorganic syndrome and encephalopathy |
| CN103118707A (zh) | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | 复合药物组合物及对糖尿病和代谢紊乱进行治疗的方法 |
-
2011
- 2011-07-15 EA EA201300133A patent/EA029400B1/ru not_active IP Right Cessation
- 2011-07-15 EP EP11788222.5A patent/EP2593477A2/en not_active Ceased
- 2011-07-15 DE DE112011102349T patent/DE112011102349T5/de not_active Ceased
- 2011-07-15 KR KR1020137003750A patent/KR20140012009A/ko not_active Ceased
- 2011-07-15 AU AU2011278040A patent/AU2011278040B2/en not_active Ceased
- 2011-07-15 CA CA2805091A patent/CA2805091A1/en not_active Abandoned
- 2011-07-15 WO PCT/IB2011/002404 patent/WO2012007847A2/en not_active Ceased
- 2011-07-15 MY MYPI2013000110A patent/MY158183A/en unknown
- 2011-07-15 ES ES201390003A patent/ES2542042R1/es active Pending
- 2011-07-15 US US13/135,893 patent/US8865163B2/en not_active Expired - Fee Related
- 2011-07-15 CN CN2011800442270A patent/CN103124742A/zh active Pending
- 2011-07-15 NZ NZ606768A patent/NZ606768A/en not_active IP Right Cessation
- 2011-07-15 SE SE1350179A patent/SE1350179A1/sv unknown
- 2011-07-15 JP JP2013519178A patent/JP2013535436A/ja active Pending
- 2011-07-15 FI FI20135146A patent/FI20135146L/fi not_active IP Right Cessation
- 2011-07-15 GB GB1302653.9A patent/GB2496076B/en not_active Expired - Fee Related
- 2011-07-15 MX MX2013000545A patent/MX361778B/es active IP Right Grant
- 2011-07-15 FR FR1156473A patent/FR2962653A1/fr not_active Withdrawn
- 2011-07-15 IT IT000641A patent/ITTO20110641A1/it unknown
- 2011-07-15 EE EEP201300005A patent/EE05760B1/et not_active IP Right Cessation
- 2011-07-15 BR BR112013000841A patent/BR112013000841A2/pt not_active IP Right Cessation
- 2011-07-15 PH PH1/2013/500109A patent/PH12013500109A1/en unknown
- 2011-07-15 SG SG2013002316A patent/SG187037A1/en unknown
- 2011-07-15 PE PE2013000073A patent/PE20131338A1/es not_active Application Discontinuation
- 2011-07-15 CZ CZ20130104A patent/CZ2013104A3/cs unknown
- 2011-07-18 AR ARP110102576A patent/AR082246A1/es unknown
-
2013
- 2013-01-10 CL CL2013000098A patent/CL2013000098A1/es unknown
- 2013-02-08 NO NO20130219A patent/NO20130219A1/no not_active Application Discontinuation
- 2013-02-14 DK DKPA201370078A patent/DK201370078A/da not_active Application Discontinuation
- 2013-02-14 LT LT2013015A patent/LT5987B/lt not_active IP Right Cessation
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1547612A1 (en) * | 2002-08-02 | 2005-06-29 | Oleg Iliich Epshtein | Medicinal agent and method for curing erectile dysfunction |
| EP1550460A1 (en) * | 2002-08-02 | 2005-07-06 | Oleg Iliich Epshtein | Method for correcting immune responses and medicinal agent |
| US20050100513A1 (en) * | 2003-11-10 | 2005-05-12 | Watkins Mary B. | Homeopathic method and system for treating nicotine addiction |
| EP2036574A1 (en) * | 2006-06-06 | 2009-03-18 | Oleg Iliich Epshtein | Medicinal agent for treating fatness, diabetes, and diseases associated with impaired glucose tolerance |
| WO2008070305A2 (en) * | 2006-10-23 | 2008-06-12 | Eli Lilly And Company | 1, 5-diphenyl-3-pyridinylamino-1, 5-dihydropyrrolidin-2-one as cbl' receptor modulator |
| WO2008122618A1 (en) * | 2007-04-04 | 2008-10-16 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Selective inhibitors of cb2 receptor expression and/or activity for the treatment of obesity and obesity-related disorders |
Non-Patent Citations (3)
| Title |
|---|
| JONAS WAYNE B ET AL: "A critical overview of homeopathy.", ANNALS OF INTERNAL MEDICINE, AMERICAN COLLEGE OF PHYSICIANS, NEW YORK, NY; US, vol. 138, no. 5, 4 March 2003 (2003-03-04), NEW YORK, NY; US, pages 393 - 399, XP002355318, ISSN: 0003-4819 * |
| SHANG, A. ; HUWILER-MUNTENER, K. ; NARTEY, L. ; JUNI, P. ; DORIG, S. ; STERNE, J.A. ; PEWSNER, D. ; EGGER, M.: "Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy", THE LANCET (LETTERS TO THE EDITOR), THE LANCET PUBLISHING GROUP, GB, vol. 366, no. 9487, 27 August 2005 (2005-08-27), GB, pages 726 - 732, XP025277623, ISSN: 0140-6736, DOI: 10.1016/S0140-6736(05)67177-2 * |
| VICKERS A J: "CLINICAL TRIALS OF HOMEOPATHY AND PLACEBO: ANALYSIS OF A SCIENTIFIC DEBATE", JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE, MARY ANN LIEBERT, NEW YORK, NY,, US, vol. 06, no. 01, 1 February 2000 (2000-02-01), US, pages 49 - 56, XP008055722, ISSN: 1075-5535 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA029400B1 (ru) | Фармацевтическая композиция для лечения ожирения и сопутствующих метаболических расстройств и способ лечения | |
| FR2962910A1 (fr) | Compositions pharmaceutiques d'association et leur utilisation dans un procede du traitement du vertige, de la kinetose et de la dystonie vasculaire vegetative | |
| FR2962651A1 (fr) | Composition pharmaceutique d'association et son utilisation dans des procedes pour traiter les maladies ou affections fonctionnelles du tractus gastro-intestinal | |
| ES2425315A2 (es) | Composición farmacéutica y su uso para preparar un medicamento destinado al tratamiento sintomático de una enfermedad o afección respiratoria | |
| ES2445846A2 (es) | Una composición de combinación farmacéutica y su uso para preparar un medicamento destinado al tatamiento de la diabetes de tipo l y los trastornos metabólicos | |
| AU2011278039B2 (en) | A combination pharmaceutical composition and methods of treating diseases or conditions associated with the cardiovascular system | |
| JP2016216483A (ja) | 活性化増強型抗体の効果を増大させる方法 | |
| EA029199B1 (ru) | Комбинированная фармацевтическая композиция для лечения синдрома дефицита внимания и гиперактивности и способы лечения синдрома дефицита внимания и гиперактивности | |
| RU2610438C2 (ru) | Способ лечения патологического синдрома и лекарственное средство центрального и периферического действия для лечения патологического синдрома | |
| Hao et al. | Protective Effect of Propofol on Electroconvulsive Shock Induced Learning and Memory Function Impairment Involves Up-Regulation of NMDA Receptor NR2A/2B Subunit in A Rat Model of Depression | |
| KR20120093647A (ko) | 이온화 알칼리성 미네랄 복합체을 함유하는 인체면역 증강용 기능성 음료 | |
| KR20090052430A (ko) | 유기성 다목적 알칼리 이온수용체의 제조방법 및 이를함유한 기능성음료 | |
| UA112749C2 (uk) | Фармацевтичні композиції та методи лікування | |
| CN103108657A (zh) | 提高活性强化形式的抗体的效果的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |