WO2013158837A1 - Méthodes et compositions de traitement du trouble d'hyperactivité avec déficit de l'attention - Google Patents
Méthodes et compositions de traitement du trouble d'hyperactivité avec déficit de l'attention Download PDFInfo
- Publication number
- WO2013158837A1 WO2013158837A1 PCT/US2013/037105 US2013037105W WO2013158837A1 WO 2013158837 A1 WO2013158837 A1 WO 2013158837A1 US 2013037105 W US2013037105 W US 2013037105W WO 2013158837 A1 WO2013158837 A1 WO 2013158837A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- curcumin
- lipoic acid
- gallate
- epigallocatechin
- pharmaceutical composition
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 46
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 title claims abstract description 36
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 title claims abstract description 35
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title abstract description 39
- 238000011282 treatment Methods 0.000 title description 15
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims abstract description 142
- 229940109262 curcumin Drugs 0.000 claims abstract description 71
- 235000012754 curcumin Nutrition 0.000 claims abstract description 71
- 239000004148 curcumin Substances 0.000 claims abstract description 71
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims abstract description 71
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims abstract description 55
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229930014124 (-)-epigallocatechin gallate Natural products 0.000 claims abstract description 53
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 51
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 51
- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 claims abstract description 50
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 claims abstract description 49
- 229940075559 piperine Drugs 0.000 claims abstract description 48
- 235000019100 piperine Nutrition 0.000 claims abstract description 48
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims abstract description 47
- 229960004308 acetylcysteine Drugs 0.000 claims abstract description 46
- BTNNPSLJPBRMLZ-LGMDPLHJSA-N benfotiamine Chemical compound C=1C=CC=CC=1C(=O)SC(/CCOP(O)(O)=O)=C(/C)N(C=O)CC1=CN=C(C)N=C1N BTNNPSLJPBRMLZ-LGMDPLHJSA-N 0.000 claims abstract description 42
- 229960002873 benfotiamine Drugs 0.000 claims abstract description 41
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 57
- 239000008194 pharmaceutical composition Substances 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 229940124597 therapeutic agent Drugs 0.000 claims description 20
- 239000002775 capsule Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 4
- 244000269722 Thea sinensis Species 0.000 claims description 4
- 235000009569 green tea Nutrition 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 230000003340 mental effect Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 abstract description 45
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 61
- 241000282472 Canis lupus familiaris Species 0.000 description 51
- 150000001875 compounds Chemical class 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 19
- 235000013305 food Nutrition 0.000 description 19
- -1 oxalic Chemical class 0.000 description 16
- 230000008901 benefit Effects 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 239000004033 plastic Substances 0.000 description 8
- 229920003023 plastic Polymers 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 235000003392 Curcuma domestica Nutrition 0.000 description 4
- 244000008991 Curcuma longa Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 235000003373 curcuma longa Nutrition 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- WTIZXHYCCKUVHY-UHFFFAOYSA-N hept-1-ene-3,5-dione Chemical compound CCC(=O)CC(=O)C=C WTIZXHYCCKUVHY-UHFFFAOYSA-N 0.000 description 4
- 239000000314 lubricant Substances 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
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 235000013976 turmeric Nutrition 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 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 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 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
- 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 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000206672 Gelidium Species 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 208000013403 hyperactivity Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000037023 motor activity Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 230000006886 spatial memory Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 235000003276 Apios tuberosa Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 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
- 241000282465 Canis Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 206010017367 Frequent bowel movements Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- 206010038743 Restlessness Diseases 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 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
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 235000013614 black pepper Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 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
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 229940099242 dexedrine Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229940030275 epigallocatechin gallate Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 235000020744 piper nigrum extract Nutrition 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000011120 plywood Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 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
- 229920001592 potato starch Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940099204 ritalin Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000007596 spatial working memory Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/82—Theaceae (Tea family), e.g. camellia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
Definitions
- the invention provides methods, compositions, and medical kits for treating attention deficit hyperactivity disorder.
- the invention provides a collection of active ingredients, such as curcumin, piperine, and epigallocatechin-3-gallate, and methods of using such active ingredients to treat attention deficit hyperactivity disorder.
- ADHD Attention deficit hyperactivity disorder
- Common features of patients suffering from ADHD include inattention, excessive motor activity, and impulsivity. Inattentive behavior can involve difficulty focusing on one task, failure to pay attention to details, and making careless mistakes. Excessive motor activity can include unusually frequent motion, suffering feelings of restlessness, and difficulty engaging in sedentary activities.
- Impulsivity can involve behavior where the patient frequently interrupts conversations or others' activities, is very impatient, has difficulty waiting for things they want, blurts out inappropriate comments, shows their emotions without restraint, and acts without regard for consequences. These behavioral conditions can place the patient at risk for poor educational achievement, underemployment, and difficulty maintaining normal social relationships.
- ADHD has been reported to be highly heritable and genetics are believed to contribute to about three-quarters of patients suffering form ADHD. Most patients suffering from ADHD had their first symptoms of the disorder during childhood. A small number of ADHD cases have been reported where the disorder was acquired after conception due to brain injury caused by toxins or physical trauma.
- Current medical treatments for ADHD include the use of mild central nervous system stimulant drugs, such as Ritalin, Cylert, and Dexedrine. However, these medications can have multiple adverse side effects, including insomnia, loss of appetite, headaches, stomachaches, hyperactivity, drowsiness, and cardiac arrhythmia. As a result, there is a need for new therapies to treat ADHD.
- the present invention addresses the need for new therapies to treat ADHD and provides other related advantages.
- the invention provides methods, compositions, and medical kits for treating attention deficit hyperactivity disorder.
- the methods involve administering, preferably for convenience as a mixture, a therapeutically effective amount of curcumin, piperine, epigallocatechin-3-gallate, and one or more of N-acetylcysteine, benfotiamine, and lipoic acid to a patient suffering from attention deficit hyperactivity disorder.
- a combination of the active ingredients curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid may be taken together to form a pharmaceutical composition, and each of these ingredients optionally may be in the form of a pharmaceutically acceptable salt.
- Medical kits for treating attention deficit hyperactivity disorder using a collection of the active ingredients are provided.
- one aspect of the invention provides a method of treating attention deficit hyperactivity disorder in a patient.
- the method comprises administering to a patent in need thereof a therapeutically effective amount of a collection of active ingredients described herein (which collectively constitute a therapeutic agent), such as two or more of curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid.
- the curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt.
- the particular collection of active ingredients administered to the patient may be selected in order to achieve a desired clinical benefit.
- the method comprises administering to a patent in need thereof a therapeutically effective amount of curcumin, piperine,
- the curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt.
- the curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid may be administered in the form of an extract of a naturally occurring composition, such as where the curcumin is provided in the form of an extract of turmeric.
- Another aspect of the invention provides a pharmaceutical composition
- a pharmaceutical composition comprising a collection of active ingredients described herein and optionally a pharmaceutically acceptable carrier.
- the active ingredients may be taken together to form a therapeutic agent, such as a therapeutic agent comprising two or more of curcumin, piperine, epigallocatechin-3-gallate, N- acetylcysteine, benfotiamine, and lipoic acid.
- the curcumin, piperine, epigallocatechin-3- gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt.
- the particular collection of active ingredients taken together to form the therapeutic agent may be selected in order to achieve a desired clinical benefit.
- the invention provides a pharmaceutical composition
- a pharmaceutical composition comprising (a) a therapeutic agent present in an amount for treating attention deficit hyperactivity disorder in a patient and consisting essentially of curcumin, piperine, epigallocatechin-3-gallate, and one or more of N-acetylcysteine, benfotiamine, and lipoic acid, wherein the curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt; and (b) optionally a pharmaceutically acceptable carrier.
- kits for treating attention deficit hyperactivity disorder comprises a pharmaceutical composition described herein and instructions for treating attention deficit hyperactivity disorder.
- Figure 1 shows bar graphs of baseline cognitive test scores as a function of group prior to treatment, as explained in Example 1. Bars represent group means and error bars are standard errors of the mean.
- Figure 2 shows bar graphs of the results of the Landmark Discrimination Learning Test described in Example 1. Dogs in both groups (i.e., the control group and the group that received the cocktail) underwent a systematic training protocol of learning to select one of two identical objects on the basis of the location of a landmark. Bars indicate group means and error bars standard errors of the mean. Individual data points are also shown by circles in graphs A-E DE TAILED DESCRIPTION OF THE INVENTION
- the invention provides methods, compositions, and medical kits for treating attention deficit hyperactivity disorder.
- the methods involve administering a therapeutically effective amount of curcumin, piperine, epigallocatechin-3-gallate, and one or more of N- acetylcysteine, benfotiamine, and lipoic acid to a patient suffering from attention deficit hyperactivity disorder.
- the active ingredients curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid may be taken together to form a pharmaceutical composition, and each these active ingredients may optionally be in the form of a
- kits for treating attention deficit hyperactivity disorder using a collection of the active ingredients described herein are also provided.
- the term "patient” refers to organisms to be treated by the methods of the present invention.
- Such organisms preferably include, but are not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans.
- treating includes any effect, e.g., lessening, reducing, modulating, ameliorating or eliminating, that results in the improvement of the condition, disease, disorder, and the like, or ameliorating a symptom thereof.
- the term "effective amount” refers to the amount of a compound sufficient to effect beneficial or desired results.
- An effective amount can be administered in one or more administrations, applications or dosages and is not intended to be limited to a particular formulation or administration route.
- the phrase "therapeutically-effective amount” as used herein means that amount of a compound, material, or composition comprising a compound of the present invention which is effective for producing some desired therapeutic effect in at least a sub-population of cells in an animal at a reasonable benefit/risk ratio applicable to any medical treatment.
- phrases "pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
- the term "pharmaceutically acceptable salt” refers to any pharmaceutically acceptable salt (e.g., acid or base) of a compound of the present invention which, upon administration to a subject, is capable of providing a compound of this invention or an active metabolite or residue thereof.
- salts of the compounds of the present invention may be derived from inorganic or organic acids and bases.
- acids include, but are not limited to, hydrochloric, hydrobromic, sulfuric, nitric, perchloric, fumaric, maleic, phosphoric, glycolic, lactic, salicylic, succinic, toluene-p-sulfonic, tartaric, acetic, citric, methanesulfonic, ethanesulfonic, formic, benzoic, malonic, naphthalene- 2-sulfonic, benzenesulfonic acid, and the like.
- Other acids such as oxalic, while not in themselves pharmaceutically acceptable, may be employed in the preparation of salts useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts.
- bases include, but are not limited to, alkali metal hydroxides, alkaline earth metals hydroxides, ammonia, and compounds of formula NW , wherein W is C 1-4 alkyl, and the like.
- Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like.
- Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like.
- salts include, but are not limited to: acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate,
- salts include anions of the compounds of the present invention compounded with a suitable cation such as Na + , NH 4 + , and NW 4 + (wherein W is a C 1-4 alkyl group), and the like.
- alkyl refers to a saturated straight or branched hydrocarbon, such as a straight or branched group of 1-12, 1-10, or 1-6 carbon atoms, referred to herein as Ci-Cioalkyl, and Ci-C 6 alkyl, respectively.
- exemplary alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, 2-methyl-l -propyl, 2-methyl-2- propyl, butyl, etc.
- Certain compounds may exist in particular geometric or stereoisomeric forms.
- the structure of certain compounds include asymmetric carbon atoms.
- the isomers arising from such asymmetry e.g., all enantiomers and diastereomers
- mixtures of such isomers e.g., a mixture of enantiomers
- These compounds may be designated by the symbols "R” or "S,” depending on the configuration of substituents around the stereogenic carbon atom.
- Such isomers can be obtained in substantially pure form by classical separation techniques and by stereochemically controlled synthesis.
- Alkenes can include either the E- or Z-geometry, where appropriate.
- the structures and other compounds and moieties discussed in this application also include all tautomers thereof.
- compositions and kits are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions and kits of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.
- compositions specifying a percentage are by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, then the previous definition of the variable controls.
- One aspect of the invention provides methods of treating attention deficit hyperactivity disorder in a patient.
- the method comprises administering to a patent in need thereof a therapeutically effective amount a collection of active ingredients described herein, such as two or more of curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid, each of which are optionally in the form of a pharmaceutically acceptable salt.
- the method comprises administering to a patent in need thereof a therapeutically effective amount of curcumin, piperine, epigallocatechin-3-gallate, and one or more of N-acetylcysteine, benfotiamine, and lipoic acid, wherein the curcumin, piperine, epigallocatechin-3-gallate, N- acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a
- a therapeutically effective amount of each of curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, and lipoic acid are administered to the patient.
- a therapeutically effective amount of each of curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid are administered to the patient.
- curcumin, piperine, epigallocatechin-3-gallate, N-acetylcysteine, benfotiamine, and lipoic acid may be administered in the form of an extract of a naturally occurring composition, such as where the curcumin is provided in the form of an extract of turmeric.
- the methods are contemplated to provide various benefits to patients suffering from attention deficit hyperactivity disorder.
- exemplary benefits include improving the patient's ability to maintain mental focus on a task and reducing the frequency with which the patient becomes distracted relative to the patient's rate of distraction without therapy.
- the patient is desirably a human, and often a male less than 19 years of age.
- Curcumin refers to the chemical compound (lis,6is)-l,7-bis (4-hydroxy-3- methoxyphenyl)-l,6-heptadiene-3,5-dione and includes (i) tautomers thereof and (ii) mixtures of (lis,6is)-l,7-bis (4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione and a tautomer thereof.
- the compound (lis,6is)-l,7-bis (4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5- dione has the chemical formula shown below.
- Curcumin may be administered at a daily dosage of, for example, at least about 4 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, or 60 mg/kg. In certain embodiments, the curcumin is administered at a daily dosage of at least 4 mg/kg.
- the curcumin is administered at a daily dosage in the range of from about 4 mg/kg to about 60 mg/kg, from about 4 mg/kg to about 30 mg/kg, from about 4 mg/kg to about 15 mg/kg, from about 25 mg/kg to about 60 mg/kg, from about 25 mg/kg to about 40 mg/kg, from about 30 mg/kg to about 60 mg/kg, or from about 45 mg/kg to about 60 mg/kg.
- the daily dosage of curcumin may be achieved by administering the patient a single pharmaceutical composition containing curcumin once per day. Alternatively, the daily dosage of curcumin may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing curcumin.
- Curcumin may be administered in the form of an extract of a naturally occurring composition, such as where the curcumin is provided in the form of an extract of turmeric.
- Piperine is l-[(2£ ' ,4£)-5-(l,3-benzodioxol-5-yl)-l-oxo-2,4-pentadienyl]piperidine and has the chemical formula shown below.
- Piperine may be administered at a daily dosage of, for example, at least about 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, or 5 mg/kg. In certain embodiments, piperine is administered at a daily dosage of at least 0.5 mg/kg. In certain other embodiments, piperine is administered at a daily dosage in the range of from about 0.5 mg/kg to about 5 mg/kg, from about 0.5 mg/kg to about 3 mg/kg, from about 0.5 mg/kg to about 1 mg/kg, from about 2 mg/kg to about 5 mg/kg, from about 2 mg/kg to about 4 mg/kg, from about 3 mg/kg to about 5 mg/kg, or from about 4 mg/kg to about 5 mg/kg.
- the daily dosage of piperine may be achieved by administering the patient a single pharmaceutical composition containing piperine once per day. Alternatively, the daily dosage of piperine may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing piperine.
- Piperine may be administered in the form of an extract of a naturally occurring composition, such as where the piperine is provided in the form of an extract of black pepper.
- Epigallocatechin-3-gallate is [(2R,3R)-5,7-dihydroxy-2-(3,4,5- trihydroxyphenyl)chroman-3-yl] 3,4,5-trihydroxybenzoate and has the chemical formula shown below.
- Epigallocatechin-3-gallate may be administered at a daily dosage of, for example, at least about 4 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, or 60 mg/kg. In certain embodiments, the epigallocatechin-3-gallate is administered at a daily dosage of at least 4 mg/kg.
- the epigallocatechin-3-gallate is administered at a daily dosage in the range of from about 4 mg/kg to about 60 mg/kg, from about 4 mg/kg to about 30 mg/kg, from about 4 mg/kg to about 15 mg/kg, from about 25 mg/kg to about 60 mg/kg, from about 25 mg kg to about 40 mg/kg, from about 30 mg/kg to about 60 mg/kg, or from about 45 mg/kg to about 60 mg/kg.
- the daily dosage of epigallocatechin-3 -gallate may be achieved by administering the patient a single pharmaceutical composition containing epigallocatechin-3 -gallate once per day.
- the daily dosage of epigallocatechin-3 - gallate may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing epigallocatechin-3 -gallate.
- Epigallocatechin-3 -gallate may be administered in the form of an extract of a naturally occurring composition, such as where the epigallocatechin-3 -gallate is provided in the form of an extract of green tea.
- N- Acetylcysteine is (R)-2-acetamido-3-sulfanylpropanoic acid, which has the structure shown below.
- N-Acetylcysteine may be administered at a daily dosage of, for example, at least about 2 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, or 25 mg/kg. In certain embodiments, the N-acetylcysteine is administered at a daily dosage of at least 2 mg/kg.
- the N-acetylcysteine is administered at a daily dosage in the range of from about 2 mg/kg to about 25 mg/kg, from about 2 mg/kg to about 15 mg/kg, from about 2 mg/kg to about 10 mg/kg, from about 10 mg/kg to about 25 mg/kg, from about 10 mg/kg to about 15 mg/kg, from about 15 mg/kg to about 25 mg/kg, or from about 20 mg/kg to about 25 mg/kg.
- the daily dosage of N-acetylcysteine may be achieved by administering the patient a single pharmaceutical composition containing N-acetylcysteine once per day. Alternatively, the daily dosage of N-acetylcysteine may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing N-acetylcysteine.
- Benfotiamine refers to S-[(2Z)-2- ⁇ [(4-amino-2-methylpyrimidin-5-yl)methyl] (formyl)amino ⁇ -5-(phosphonooxy)pent-2-en-3-yl] benzenecarbothioate, which has the chemical structure provided below.
- Benfotiamine may be provided in the form of a pharmaceutically acceptable salt, such as an alkali metal salt (e.g., a sodium or potassium salt), alkaline earth metal salt (e.g., a calcium salt), or ammonium salt.
- a pharmaceutically acceptable salt such as an alkali metal salt (e.g., a sodium or potassium salt), alkaline earth metal salt (e.g., a calcium salt), or ammonium salt.
- Benfotiamine may be administered at a daily dosage of, for example, at least about 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, or 5 mg/kg. In certain embodiments, the benfotiamine is administered at a daily dosage of at least 0.5 mg/kg.
- the benfotiamine is administered at a daily dosage in the range of from about 0.5 mg/kg to about 5 mg/kg, from about 0.5 mg/kg to about 3 mg/kg, from about 0.5 mg/kg to about 1 mg/kg, from about 2 mg/kg to about 5 mg/kg, from about 2 mg/kg to about 4 mg/kg, from about 3 mg/kg to about 5 mg/kg, or from about 4 mg/kg to about 5 mg/kg.
- the daily dosage of benfotiamine may be achieved by administering the patient a single pharmaceutical composition containing benfotiamine once per day. Alternatively, the daily dosage of benfotiamine may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing benfotiamine.
- Lipoic acid is 5-(l,2-dithiolan-3-yl)pentanoic acid and includes all stereoisomeric forms and mixtures of stereoisomeric forms. The structure of lipoic acid is shown below.
- the lipoic acid is (R)-lipoic acid, which has the formula:
- Lipoic acid may be administered at a daily dosage of, for example, at least about 1 mg/kg, 5 mg/kg, 10 mg/kg, or 15 mg/kg. In certain embodiments, the lipoic acid is administered at a daily dosage of at least 1 mg/kg. In certain other embodiments, the lipoic acid is administered at a daily dosage in the range of from about 1 mg/kg to about 15 mg/kg, from about 1 mg/kg to about 10 mg/kg, from about 1 mg/kg to about 5 mg/kg, from about 5 mg/kg to about 15 mg/kg, or from about 10 mg/kg to about 15 mg/kg.
- the daily dosage of lipoic acid may be achieved by administering the patient a single pharmaceutical composition containing lipoic acid once per day. Alternatively, the daily dosage of lipoic acid may be achieved by administering to the patient multiple times per day a pharmaceutical composition containing lipoic acid.
- the active ingredients may be administered to the patient by any medically accepted route of administration.
- the active ingredients are administered orally.
- the active ingredients may be administered to the patient at the same time, such as when the active ingredients are formulated into a pharmaceutical composition that is administered to the patient.
- at least a portion of the active ingredients may be administered sequentially to the patient.
- the amount of each active ingredient that is administered to the patient can be selected to achieve particular clinical benefits.
- the weight percent ratio of curcumin, epigallocatechin-3-gallate, and piperine administered to a patient on a daily basis is in the range about 10-15 : 10-15 : 1.
- the weight percent ratio of curcumin, epigallocatechin-3-gallate, and N-acetylcysteine administered to a patient on a daily basis is in the range about 2-4 : 2-4 : 1.
- the weight percent ratio of curcumin, epigallocatechin-3-gallate, and lipoic acid administered to a patient on a daily basis is in the range about 3-6 : 3-6 : 1.
- Another aspect of the invention provides a pharmaceutical composition
- a pharmaceutical composition comprising a collection of active ingredients described herein and optionally a pharmaceutically acceptable carrier.
- the active ingredients may be taken together to form a therapeutic agent, such as a therapeutic agent comprising two or more of curcumin, piperine, epigallocatechin-3-gallate, N- acetylcysteine, benfotiamine, and lipoic acid.
- a therapeutic agent comprising two or more of curcumin, piperine, epigallocatechin-3-gallate, N- acetylcysteine, benfotiamine, and lipoic acid.
- the curcumin, piperine, epigallocatechin-3- gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt.
- the invention provides a pharmaceutical composition
- a pharmaceutical composition comprising (a) a therapeutic agent present in an amount for treating attention deficit hyperactivity disorder in a patient and consisting essentially of curcumin, piperine, epigallocatechin-3 -gallate, and one or more of N-acetylcysteine, benfotiamine, and lipoic acid, wherein the curcumin, piperine, epigallocatechin-3 -gallate, N-acetylcysteine, benfotiamine, and lipoic acid are each optionally in the form of a pharmaceutically acceptable salt; and (b) optionally a pharmaceutically acceptable carrier.
- the therapeutic agent specified above is the only agent in the pharmaceutical composition that provides a therapeutic effect in treating attention deficit hyperactivity disorder.
- the aforementioned therapeutic agent contains N-acetylcysteine.
- the aforementioned therapeutic agent contains benfotiamine.
- the aforementioned therapeutic agent therapeutic agent contains lipoic acid.
- therapeutic agent consists essentially of curcumin, piperine, epigallocatechin-3 -gallate, N-acetylcysteine, and lipoic acid, each of which are optionally in the form of a pharmaceutically acceptable salt.
- curcumin, piperine, epigallocatechin-3 -gallate, N-acetylcysteine, benfotiamine, and lipoic acid may be administered in the form of an extract of a naturally occurring composition, such as where the curcumin is provided in the form of an extract of turmeric.
- the pharmaceutical composition may contain an active ingredient in one of the forms (e.g., a salt form, stereoisomeric form, or extract) described in Section I above.
- forms e.g., a salt form, stereoisomeric form, or extract
- the curcumin is provided in the form of an extract of tumeric.
- the epigallocatechin-3 -gallate is provided in the form of an extract of green tea.
- the lipoic acid is (R)-lipoic acid.
- the pharmaceutical composition may contain the active ingredients in ratios that provide particular advantages for treating attention deficit hyperactivity disorder.
- the weight percent ratio of curcumin, epigallocatechin-3 -gallate, and piperine in the pharmaceutical composition is in the range about 10-15 : 10-15 : 1.
- the weight percent ratio of curcumin, epigallocatechin-3-gallate, and N- acetylcysteine in the pharmaceutical composition is in the range about 2-4 : 2-4 : 1.
- the weight percent ratio of curcumin, epigallocatechin-3-gallate, and lipoic acid in the pharmaceutical composition is in the range about 3-6 : 3-6 : 1.
- the pharmaceutical composition may be characterized according to whether it contains an active ingredient at a concentration sufficient to provide one of the daily dosage amounts described in Section I.
- the pharmaceutical composition contains curcumin at a concentration sufficient so that administration of a single unit dose provides the patient with at least about 4 mg/kg of curcumin.
- Exemplary pharmaceutical compositions are provided in Tables 1 and 2 below, which list the relative amounts of the active ingredients.
- Another aspect of the invention provides a unit dosage pharmaceutical composition, such as a tablet or capsule.
- Tablets and capsules can be prepared based on procedures known in the art and as described below.
- the pharmaceutical compositions desirably comprise a therapeutically-effective amount of one or more of the compounds described above, formulated together with one or more pharmaceutically acceptable carriers (additives) and/or diluents.
- the pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for the following: (1) oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; (2) parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained- release formulation; (3) topical application, for example, as a cream, ointment, or a controlled- release patch or spray applied to the skin; (4) intravaginally or intrarectally, for example, as a pes
- pharmaceutically-acceptable carrier means a pharmaceutically- acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid), or solvent encapsulating material, involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body.
- manufacturing aid e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid
- solvent encapsulating material involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body.
- Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.
- pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) algin
- wetting agents such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.
- antioxidants examples include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.
- water soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like
- oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), le
- Formulations of the present invention include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration.
- the formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy.
- the amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration.
- the amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect.
- Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present invention as an active ingredient.
- lozenges using a flavored basis, usually sucrose and acacia or tragacanth
- a compound of the present invention may also be administered as a bolus, electuary or paste.
- the active ingredient is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin;
- compositions may also comprise buffering agents.
- Solid compositions of a similar type may also be employed as fillers in soft and hard-shelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.
- a tablet may be made by compression or molding, optionally with one or more accessory ingredients.
- Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface- active or dispersing agent.
- Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.
- the tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be formulated for rapid release, e.g., freeze-dried.
- compositions may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.
- These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner.
- embedding compositions which can be used include polymeric substances and waxes.
- the active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients.
- Liquid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs.
- the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
- inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and
- the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.
- adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.
- Suspensions in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.
- suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.
- parenteral administration and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal,
- systemic administration means the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.
- Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.
- the selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, or the salt thereof, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the rate and extent of absorption, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
- a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required.
- the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.
- a suitable daily dose of a compound of the invention will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Generally, oral, intravenous, intracerebroventricular and subcutaneous doses of the compounds of this invention for a patient, when used for the indicated analgesic effects, will range from about 0.0001 to about 100 mg per kilogram of body weight per day.
- the effective daily dose of the active ingredient may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. Preferred dosing is one administration per day. III. Medical Kits
- kits for treating attention deficit hyperactivity disorder comprises a pharmaceutical composition described herein (such as one of pharmaceutical compositions in Section II) and instructions for treating attention deficit hyperactivity disorder.
- the instructions may provide dosing procedures, including route of administration, dosing frequency, and other information desirable for safe and effective use of the medical kit.
- the Curcumin Test Cocktail was formulated to include green tea extract (203 mg epigallocatechingallate or 36.3% by weight), piper nigrum extract (17 mg Bioperine, 95% piperine, 3.0% by weight), N-acetyl-Z-cysteine (85 mg, 15.3% by weight), curcumin (203 mg, 36.3% by weight) and (R)-lipoic acid (51 mg, 9.1% by weight). Control capsules were formulated without any of these active ingredients.
- Test procedures are described below, along with a description of the apparatus used in the tests.
- the test apparatus was a 25" x 3 ' x 4' wooden box constructed from plywood coated with melamine.
- the box was equipped with a sliding black laminate tray containing three food wells which are covered by objects.
- One teaspoon (approximately 4 mL) of wet dog food was formed into a ball and placed in one food well to serve as the food reward.
- Vertical stainless steel bars (adjusted to provide openings appropriate for individual dog sizes) served as the front of the box.
- the tester sat behind a hinged door that allowed a sliding tray to be either pushed toward the dog or obscured from the dog's view.
- a 60W light was placed above the presentation tray to light the objects.
- the first test session was used to establish object preferences. On each trial, the hinged door separating the tester and the dog was raised and the presentation tray was pushed forward. The left and right food wells were covered by the two objects. The food reward was placed in both the left and right food wells beneath each object. Dogs were required to displace an object to expose the food reward.
- Ten trials were given with two objects presented simultaneously (a yellow plastic Megablock and a blue plastic ball mounted on a blue plastic coaster), and with food reward beneath both objects. The objects appeared randomly five times each on the left or right side. The preferred object was whichever object was chosen more frequently (i.e., six or more times). Subsequently, the preferred object was used as the positive stimulus.
- each dog was given ten daily trials with the food reward beneath the designated positive object. To prevent the dogs from using olfactory cues, the food odors were smeared over both wells. Further, a piece of food was pressed inside the negative stimulus such that the dog could smell it but not see it or eat it. A correct response was recorded when dogs approached and displaced the positive stimulus. An error was committed if dogs displaced the negative object. One correction per test session was allowed, with subsequent errors resulting in immediate withdrawal of the tray and no food reward. Dogs were trained until one of two criterion levels was met: 9/10 correct on one day or 8/10 correct on two consecutive days. A maximum of 400 trials were given if a dog could not reach criterion.
- Dogs were given 50 days of testing consisting of 12 trials/day, with the location of the reward appearing four times each in the 3 food wells. During the 50 days of testing, if an animal reached criterion at the five-second delay, the delay was increased to 10 seconds, followed by gradually increasing delay intervals. Two scores were calculated from this test - total number of errors made to reach criterion (or after 50 days of testing if criterion was not met) at the five- second delay, and maximal memory score, which represented the maximum delay interval animals could reach criterion at in the 50 days of testing. Following incremental delay interval increases over a 50 day period, dogs were given a variable delay procedure for 20 days.
- Dogs were given either a 20, 70 or 1 10 second delay in a single day of testing, with four trials at each delay interval. Accuracy scores for each delay interval were calculated as a measure of spatial working memory. Animals were tested on the spatial non-matching to position task at both baseline and after eight months of treatment.
- One group of dogs was given the Curcumin Test Cocktail.
- the other group of dogs i.e., the control group
- Two different colored pills were formulated to allow testing technicians to be blind with respect to treatment condition and yet also be able to administer the treatment. Dogs were given two capsules per day, one in the morning prior to cognitive testing and one in the afternoon, after cognitive testing was completed.
- the landmark was moved at successively greater distances (5, 18, or 24 cm) away from the reward object, with animals required to meet criterion before progressing to testing with a longer landmark distance. Animals that could not reach criterion at any of the longer distances within 400 trials stopped testing on this stepwise protocol. Once all animals had been tested out to a 24 cm distance on the landmark
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne des méthodes, des compositions, et des kits médicaux de traitement du trouble d'hyperactivité avec déficit de l'attention. Plus particulièrement, l'invention concerne un ensemble de principes actifs, tels que la curcumine, la pipérine, l'épigallocatéchin-3-gallate, et un ou plusieurs des éléments suivants : N-acétylcysteine, benfotiamine, et acide lipoïque, ainsi que des méthodes d'utilisation de tels principes actifs dans le traitement du trouble d'hyperactivité avec déficit de l'attention. L'invention concerne également des kits médicaux de traitement du trouble d'hyperactivité avec déficit de l'attention faisant intervenir un ensemble desdits principes actifs.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261625781P | 2012-04-18 | 2012-04-18 | |
US61/625,781 | 2012-04-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013158837A1 true WO2013158837A1 (fr) | 2013-10-24 |
Family
ID=49384057
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2013/037105 WO2013158837A1 (fr) | 2012-04-18 | 2013-04-18 | Méthodes et compositions de traitement du trouble d'hyperactivité avec déficit de l'attention |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2013158837A1 (fr) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2258359A2 (fr) * | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenèse par modulation des récepteurs muscariniques avec sabcomeline |
US20110275591A1 (en) * | 2004-12-01 | 2011-11-10 | Concourse Health Sciences Llc | Cocktail for modulation of alzheimer's disease |
-
2013
- 2013-04-18 WO PCT/US2013/037105 patent/WO2013158837A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110275591A1 (en) * | 2004-12-01 | 2011-11-10 | Concourse Health Sciences Llc | Cocktail for modulation of alzheimer's disease |
EP2258359A2 (fr) * | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenèse par modulation des récepteurs muscariniques avec sabcomeline |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7514534B2 (ja) | 認知障害を処置するためのベンゾジアゼピン誘導体、組成物および方法 | |
US20060211686A1 (en) | Alpha7 Neuronal nicotinic receptor ligand and antipsychotic compositions | |
TW200829244A (en) | Therapeutic combinations 482 | |
US20200323823A1 (en) | Methods for the treatment of depression | |
KR20100105841A (ko) | 니코틴 작용제를 포함하는 조성물 및 이를 이용한 방법 | |
EP2043649A2 (fr) | Combinaisons de flibansérine avec de la caféine, procédé pour leur préparation et utilisation de celles-ci en tant que médicaments | |
JP6137833B2 (ja) | 脱髄性および他の神経系疾患を患っている患者における神経認知的および/または神経精神医学的障害を改善するための4−アミノピリジンの使用 | |
US20200022981A9 (en) | Novel compositions and methods | |
JP2007517049A (ja) | 再発性病状を治療するための組成物および方法 | |
Naidoo | THE EFFECTS OF RESERPINE (SERPASIL®) ON THE CHRONIC DISTURBED SCHIZOPHRENIC: A COMPARATIVE STUDY OF RAUWOLFIA ALKALOIDS AND ELECTROCONVULSIVE THERAPY | |
AU2516201A (en) | Drug combination for the treatment of depression and related disorders comprising mirtazapine and gepirone | |
AU2018264030A1 (en) | Treatment regimens | |
BARSA et al. | Amitriptyline (Elavil), a new antidepressant | |
US20220125803A1 (en) | Methods for the treatment of perimenopause and menopause | |
TWI583679B (zh) | 使用環醯胺衍生物治療精神分裂症之方法 | |
JP7265526B2 (ja) | てんかん治療剤 | |
JP6242746B2 (ja) | 記憶学習機能を向上する医薬、食品、組成物 | |
EP1642576A2 (fr) | Méthodes, kits et compositions pour utiliser dérivés à structure pyrrolique contre l'anxiété | |
WO2013158837A1 (fr) | Méthodes et compositions de traitement du trouble d'hyperactivité avec déficit de l'attention | |
WO2012154710A1 (fr) | Traitement de troubles cognitifs par certains agonistes du récepteur nicotinique alpha-7 en combinaison avec la nicotine | |
Gruen et al. | Drugs affecting animal behavior | |
EP3423049B1 (fr) | Méthodes de traitement ou de soulagement de troubles mentaux et des symptômes associés | |
CN104884060A (zh) | 治疗方案 | |
WO2021063387A1 (fr) | Utilisation d'une composition d'imatinib et d'un dérivé de celui-ci dans la préparation d'un médicament pour la prévention, le traitement et le contrôle d'une rechute d'addiction | |
WO2022261263A1 (fr) | Méthodes de traitement de troubles neuropsychiatriques |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13778545 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 13778545 Country of ref document: EP Kind code of ref document: A1 |