ZA200103527B - Dispersible compositions containing L-DOPA ethyl ester. - Google Patents
Dispersible compositions containing L-DOPA ethyl ester. Download PDFInfo
- Publication number
- ZA200103527B ZA200103527B ZA200103527A ZA200103527A ZA200103527B ZA 200103527 B ZA200103527 B ZA 200103527B ZA 200103527 A ZA200103527 A ZA 200103527A ZA 200103527 A ZA200103527 A ZA 200103527A ZA 200103527 B ZA200103527 B ZA 200103527B
- Authority
- ZA
- South Africa
- Prior art keywords
- amount
- moisture content
- starch
- weight
- microcrystalline cellulose
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 214
- NULMGOSOSZBEQL-QMMMGPOBSA-N etilevodopa Chemical compound CCOC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 NULMGOSOSZBEQL-QMMMGPOBSA-N 0.000 title claims description 126
- 229920002472 Starch Polymers 0.000 claims description 109
- 235000019698 starch Nutrition 0.000 claims description 109
- 239000008107 starch Substances 0.000 claims description 108
- 229940032147 starch Drugs 0.000 claims description 108
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 101
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 101
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 101
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 101
- 229960004205 carbidopa Drugs 0.000 claims description 99
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 71
- 239000008194 pharmaceutical composition Substances 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 48
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 42
- 239000003826 tablet Substances 0.000 claims description 42
- 239000007919 dispersible tablet Substances 0.000 claims description 39
- 239000000945 filler Substances 0.000 claims description 36
- 235000019359 magnesium stearate Nutrition 0.000 claims description 35
- 229940123736 Decarboxylase inhibitor Drugs 0.000 claims description 33
- 239000003954 decarboxylase inhibitor Substances 0.000 claims description 33
- 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 claims description 32
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 32
- 229930195725 Mannitol Natural products 0.000 claims description 32
- 239000007884 disintegrant Substances 0.000 claims description 32
- 239000000594 mannitol Substances 0.000 claims description 32
- 235000010355 mannitol Nutrition 0.000 claims description 32
- 229960004502 levodopa Drugs 0.000 claims description 28
- 239000000314 lubricant Substances 0.000 claims description 28
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 23
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 23
- 239000001913 cellulose Substances 0.000 claims description 20
- 239000003963 antioxidant agent Substances 0.000 claims description 18
- 230000003078 antioxidant effect Effects 0.000 claims description 18
- 235000006708 antioxidants Nutrition 0.000 claims description 18
- 239000011230 binding agent Substances 0.000 claims description 16
- 235000010980 cellulose Nutrition 0.000 claims description 16
- 229920002678 cellulose Polymers 0.000 claims description 16
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 16
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 12
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 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 claims description 10
- 239000008103 glucose Substances 0.000 claims description 10
- 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 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 235000015424 sodium Nutrition 0.000 claims description 9
- 229940083542 sodium Drugs 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000005995 Aluminium silicate Substances 0.000 claims description 8
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 8
- 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 claims description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 8
- 229920000881 Modified starch Polymers 0.000 claims description 8
- 235000012211 aluminium silicate Nutrition 0.000 claims description 8
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 8
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 8
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 8
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 8
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 7
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 7
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 7
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 7
- 239000004296 sodium metabisulphite Substances 0.000 claims description 7
- 239000000811 xylitol Substances 0.000 claims description 7
- 235000010447 xylitol Nutrition 0.000 claims description 7
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 7
- 229960002675 xylitol Drugs 0.000 claims description 7
- 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 claims description 6
- 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 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 235000010323 ascorbic acid Nutrition 0.000 claims description 6
- 239000011668 ascorbic acid Substances 0.000 claims description 6
- 229960005070 ascorbic acid Drugs 0.000 claims description 6
- 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 claims description 6
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 6
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 6
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 6
- 229960005055 sodium ascorbate Drugs 0.000 claims description 6
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 6
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 claims description 5
- 235000001727 glucose Nutrition 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 4
- 229920002261 Corn starch Polymers 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 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 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 4
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 4
- 235000013539 calcium stearate Nutrition 0.000 claims description 4
- 239000008116 calcium stearate Substances 0.000 claims description 4
- 239000008120 corn starch Substances 0.000 claims description 4
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 229920001206 natural gum Polymers 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 235000019814 powdered cellulose Nutrition 0.000 claims description 4
- 229920003124 powdered cellulose Polymers 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 4
- 239000008109 sodium starch glycolate Substances 0.000 claims description 4
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 claims description 3
- 229960000911 benserazide Drugs 0.000 claims description 3
- 235000010216 calcium carbonate Nutrition 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 235000011010 calcium phosphates Nutrition 0.000 claims description 3
- 235000011132 calcium sulphate Nutrition 0.000 claims description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 3
- 230000007423 decrease Effects 0.000 claims description 3
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000008173 hydrogenated soybean oil Substances 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- 102000004031 Carboxy-Lyases Human genes 0.000 claims description 2
- 108090000489 Carboxy-Lyases Proteins 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical group NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 claims 17
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 239000004698 Polyethylene Substances 0.000 claims 1
- 235000004443 Ricinus communis Nutrition 0.000 claims 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 235000001465 calcium Nutrition 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- QTAOMKOIBXZKND-PPHPATTJSA-N carbidopa Chemical compound O.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 QTAOMKOIBXZKND-PPHPATTJSA-N 0.000 description 80
- 238000009472 formulation Methods 0.000 description 63
- 239000007916 tablet composition Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 10
- 238000004090 dissolution Methods 0.000 description 10
- 239000008187 granular material Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 150000004682 monohydrates Chemical class 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000005469 granulation Methods 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 238000005057 refrigeration Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- -1 L-DOPA ETHYL Chemical class 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229920003084 Avicel® PH-102 Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010030312 On and off phenomenon Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 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
- 238000005259 measurement Methods 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229940100688 oral solution Drugs 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- PGDQAPYNCJPYNY-QQJKHFBISA-N (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound O=C(O)[C@@H](N)CC1=CC=C(O)C(O)=C1.O=C(O)[C@@H](N)CC1=CC=C(O)C(O)=C1.O=C(O)[C@@H](N)CC1=CC=C(O)C(O)=C1.O=C(O)[C@@H](N)CC1=CC=C(O)C(O)=C1 PGDQAPYNCJPYNY-QQJKHFBISA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 101150003530 Tsnax gene Proteins 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
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- 230000036765 blood level Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
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- 230000002183 duodenal effect Effects 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
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- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
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- 230000000977 initiatory effect Effects 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10789398P | 1998-11-10 | 1998-11-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200103527B true ZA200103527B (en) | 2002-05-09 |
Family
ID=22319025
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200103527A ZA200103527B (en) | 1998-11-10 | 2001-05-02 | Dispersible compositions containing L-DOPA ethyl ester. |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6376545B1 (no) |
| EP (1) | EP1135118A1 (no) |
| JP (1) | JP2002529407A (no) |
| CN (1) | CN1329487A (no) |
| AU (1) | AU764742B2 (no) |
| CA (1) | CA2350304A1 (no) |
| HK (1) | HK1041441A1 (no) |
| HU (1) | HUP0104586A3 (no) |
| IL (1) | IL143071A0 (no) |
| NO (1) | NO20012265L (no) |
| NZ (1) | NZ512027A (no) |
| WO (1) | WO2000027385A1 (no) |
| ZA (1) | ZA200103527B (no) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6376545B1 (en) | 1998-11-10 | 2002-04-23 | Teva Pharmaceutical Industries, Ltd. | Dispersible compositions containing L-DOPA ethyl ester |
| IL159813A0 (en) * | 2001-07-12 | 2004-06-20 | Teva Pharma | Dual release formulation comprising levodopa ethyl ester and a decarboxylase inhibitor in immediate release layer with levodopa ethyl ester and a decarboxylase inhibitor in a controlled release core |
| WO2003041646A2 (en) | 2001-11-13 | 2003-05-22 | Teva Pharmaceutical Industries, Ltd. | L-dopa ethyl ester salts and uses thereof |
| US20050147670A1 (en) * | 2002-05-29 | 2005-07-07 | Impax Laboratories Inc. | Oral disintegrating dosage forms |
| US8158149B2 (en) * | 2004-05-12 | 2012-04-17 | Chelsea Therapeutics, Inc. | Threo-DOPS controlled release formulation |
| WO2004100929A1 (en) | 2003-05-12 | 2004-11-25 | Synergia Pharma, Inc. | Threo-dops controlled release formulation |
| US8815950B2 (en) | 2003-08-29 | 2014-08-26 | Janssen Biotech, Inc. | Pharmaceutical compositions and method of using levodopa and carbidopa |
| AU2004270174B2 (en) * | 2003-08-29 | 2010-05-20 | Transform Pharmaceuticals, Inc. | Pharmaceutical compositions and method of using levodopa and carbidopa |
| US20070010584A1 (en) * | 2003-09-04 | 2007-01-11 | Peroutka Stephen J | Compositions and methods for orthostatic intolerance |
| WO2005105035A2 (en) * | 2004-04-29 | 2005-11-10 | The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth | Targeted nanoparticles for drug delivery |
| WO2006035414A2 (en) * | 2004-09-30 | 2006-04-06 | Ranbaxy Laboratories Limited | Carbidopa and levodopa dispersible tablets |
| US20070003621A1 (en) * | 2005-06-23 | 2007-01-04 | Spherics, Inc. | Dosage forms for movement disorder treatment |
| US20080131492A1 (en) * | 2006-06-23 | 2008-06-05 | Spherics, Inc. | Dosage forms for movement disorder treatment |
| ES2383768T3 (es) * | 2006-06-28 | 2012-06-26 | Chelsea Therapeutics Inc. | Composiciones farmacéuticas que comprenden droxidopa |
| CA2673511A1 (en) * | 2006-12-22 | 2008-07-03 | Combinatorx, Incorporated | Pharmaceutical compositions for treatment of parkinson's disease and related disorders |
| JP2010520885A (ja) * | 2007-03-09 | 2010-06-17 | チェルシー・セラピューティクス，インコーポレイテッド | 線維筋痛症の治療のためのドロキシドパ及びその医薬組成物 |
| WO2008137923A2 (en) * | 2007-05-07 | 2008-11-13 | Chelsea Therapeutics, Inc. | Droxidopa and pharmaceutical composition thereof for the treatment of mood disorders, sleep disorders, or attention deficit disorders |
| ES2615511T3 (es) | 2009-05-19 | 2017-06-07 | Celgene Corporation | Formulaciones de 4-amino-2-(2,6-dioxopiperidina-3-il)isoindolin-1,3-diona |
| US20130017274A1 (en) * | 2011-03-16 | 2013-01-17 | Buck Institute For Research On Aging | Low dose lithium in the treatment or prophylaxis of parkinson's disease |
| JP5880913B2 (ja) | 2011-05-17 | 2016-03-09 | 三郎 佐古田 | パーキンソン病の体幹症状（姿勢反射異常）の治療剤 |
| US10987313B2 (en) | 2013-10-07 | 2021-04-27 | Impax Laboratories, Llc | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof |
| US10098845B2 (en) | 2013-10-07 | 2018-10-16 | Impax Laboratories, Llc | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof |
| JP6622310B2 (ja) * | 2014-09-04 | 2019-12-18 | ロブソル・ファーマシューティカルズ・アクチボラグＬｏｂｓｏｒ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ａｋｔｉｅｂｏｌａｇ | レボドパ、ドーパミン脱炭酸酵素阻害薬およびｃｏｍｔ阻害薬を含む医薬組成物ならびにその投与方法 |
| WO2016179540A1 (en) | 2015-05-06 | 2016-11-10 | Synagile Corporation | Pharmaceutical suspensions containing drug particles, devices for their administration, and methods of their use |
| RU2697411C2 (ru) * | 2017-10-11 | 2019-08-14 | федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет) | Композиция для лечения болезни Паркинсона |
| US11986449B2 (en) | 2020-12-22 | 2024-05-21 | Amneal Pharmaceuticals Llc | Levodopa dosing regimen |
| US11291701B1 (en) * | 2021-02-04 | 2022-04-05 | Seed Edibles | Orally disintegrating, sublingual and buccal formulations |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA716958B (en) | 1970-10-30 | 1973-01-31 | Hoffmann La Roche | Phenylalanine amides |
| US3803120A (en) | 1971-09-28 | 1974-04-09 | Hoffmann La Roche | Di-and tripeptides of 3-(3,4-dihydroxyphenyl)-alanine |
| DE2246013A1 (de) | 1972-09-20 | 1974-03-28 | Boehringer Mannheim Gmbh | Verfahren zur herstellung von poroesen tabletten |
| US3939253A (en) | 1973-11-02 | 1976-02-17 | Interx Research Corporation | Novel, transient pro-drug forms of l-dopa useful in the treatment of parkinson's disease |
| JPS5157813A (en) | 1974-11-14 | 1976-05-20 | Sankyo Co | Ll dooba mataha sonojudotaiseizaino seiho |
| US4035507A (en) | 1975-04-17 | 1977-07-12 | Interx Research Corporation | Novel, transient pro-drug forms of L-DOPA to treat Parkinson's disease |
| US4916151A (en) | 1985-12-05 | 1990-04-10 | Merrell Dow Pharmaceuticals Inc. | Method of treating parkinson's syndrome |
| US4771073A (en) | 1985-12-30 | 1988-09-13 | Merck & Co., Inc. | Rectally absorbable form of L-dopa |
| US4663349A (en) | 1985-12-30 | 1987-05-05 | Merck & Co., Inc. | Rectally absorbable form of L-dopa |
| ES2042520T3 (es) | 1986-06-10 | 1993-12-16 | Chiesi Farma Spa | Composiciones farmaceuticas que contienen el ester metilico de levodopa, preparacion y aplicaciones terapeuticas del mismo. |
| IL92952A (en) | 1990-01-03 | 1994-06-24 | Teva Pharma | R-enantiomers of n-propargyl-1-aminoindan compounds, their preparation and pharmaceutical compositions containing them |
| EP0522128B1 (en) | 1991-01-30 | 1996-01-17 | The Wellcome Foundation Limited | Water-dispersible tablets |
| US5354885A (en) * | 1992-12-24 | 1994-10-11 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Process for preparing ethyl ester of L-DOPA |
| US5607969A (en) * | 1992-12-24 | 1997-03-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | L-DOPA ethyl ester to treat Parkinson's disease |
| US5840756A (en) * | 1995-07-21 | 1998-11-24 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition of L-DOPA ester |
| US6376545B1 (en) | 1998-11-10 | 2002-04-23 | Teva Pharmaceutical Industries, Ltd. | Dispersible compositions containing L-DOPA ethyl ester |
-
1999
- 1999-11-10 US US09/437,699 patent/US6376545B1/en not_active Expired - Fee Related
- 1999-11-10 AU AU17168/00A patent/AU764742B2/en not_active Ceased
- 1999-11-10 JP JP2000580614A patent/JP2002529407A/ja active Pending
- 1999-11-10 EP EP99960257A patent/EP1135118A1/en not_active Withdrawn
- 1999-11-10 WO PCT/US1999/026546 patent/WO2000027385A1/en not_active Application Discontinuation
- 1999-11-10 CN CN99814098A patent/CN1329487A/zh active Pending
- 1999-11-10 CA CA002350304A patent/CA2350304A1/en not_active Abandoned
- 1999-11-10 HU HU0104586A patent/HUP0104586A3/hu unknown
- 1999-11-10 NZ NZ512027A patent/NZ512027A/en not_active Application Discontinuation
- 1999-11-10 IL IL14307199A patent/IL143071A0/xx unknown
-
2001
- 2001-05-02 ZA ZA200103527A patent/ZA200103527B/en unknown
- 2001-05-08 NO NO20012265A patent/NO20012265L/no unknown
-
2002
- 2002-02-25 US US10/083,959 patent/US6703424B2/en not_active Expired - Fee Related
- 2002-03-22 HK HK02102206.4A patent/HK1041441A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0104586A2 (en) | 2002-06-29 |
| AU1716800A (en) | 2000-05-29 |
| NZ512027A (en) | 2004-04-30 |
| EP1135118A1 (en) | 2001-09-26 |
| US20020151589A1 (en) | 2002-10-17 |
| US6703424B2 (en) | 2004-03-09 |
| JP2002529407A (ja) | 2002-09-10 |
| NO20012265L (no) | 2001-07-03 |
| US6376545B1 (en) | 2002-04-23 |
| AU764742B2 (en) | 2003-08-28 |
| CN1329487A (zh) | 2002-01-02 |
| WO2000027385A1 (en) | 2000-05-18 |
| IL143071A0 (en) | 2002-04-21 |
| CA2350304A1 (en) | 2000-05-18 |
| HK1041441A1 (zh) | 2002-07-12 |
| NO20012265D0 (no) | 2001-05-08 |
| HUP0104586A3 (en) | 2002-12-28 |
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