CA1138776A - Methode de preparation de d-penicillamine et preparation qui en renferme - Google Patents

Methode de preparation de d-penicillamine et preparation qui en renferme

Info

Publication number: CA1138776A
Authority: CA; Canada
Prior art keywords: penicillamine; composition; acid; synthetic; cellulose
Prior art date: 1972-03-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000167082A

Other languages

English (en)

Other versions

CA167082S (en

Inventor

Friedrich Asinger

Heribert Offermanns

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Evonik Operations GmbH

Original Assignee

Deutsche Gold und Silber Scheideanstalt

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1972-03-25

Filing date

1973-03-26

Publication date

1983-01-04

1973-03-26 Application filed by Deutsche Gold und Silber Scheideanstalt filed Critical Deutsche Gold und Silber Scheideanstalt

1983-01-04 Application granted granted Critical

1983-01-04 Publication of CA1138776A publication Critical patent/CA1138776A/fr

Status Expired legal-status Critical Current

Links

229960001639 penicillamine Drugs 0.000 title claims abstract description 97
238000002360 preparation method Methods 0.000 title claims abstract description 11
VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 title claims abstract 29
238000000034 method Methods 0.000 title claims description 32
VVNCNSJFMMFHPL-UHFFFAOYSA-N penicillamine Chemical class CC(C)(S)C(N)C(O)=O VVNCNSJFMMFHPL-UHFFFAOYSA-N 0.000 claims abstract description 19
RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims abstract description 6
RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims abstract description 6
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims abstract description 6
KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims abstract description 6
229960002179 ephedrine Drugs 0.000 claims abstract 5
239000000203 mixture Substances 0.000 claims description 69
239000000243 solution Substances 0.000 claims description 40
-1 aliphatic alcohols Chemical class 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 18
239000003826 tablet Substances 0.000 claims description 18
239000002674 ointment Substances 0.000 claims description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 16
235000010980 cellulose Nutrition 0.000 claims description 15
229920002678 cellulose Polymers 0.000 claims description 15
239000000126 substance Substances 0.000 claims description 14
239000001913 cellulose Substances 0.000 claims description 13
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 12
229920001223 polyethylene glycol Polymers 0.000 claims description 12
235000011187 glycerol Nutrition 0.000 claims description 11
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
239000002775 capsule Substances 0.000 claims description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
239000000829 suppository Substances 0.000 claims description 10
239000000725 suspension Substances 0.000 claims description 10
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
229940068917 polyethylene glycols Drugs 0.000 claims description 9
239000000377 silicon dioxide Substances 0.000 claims description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 8
239000003708 ampul Substances 0.000 claims description 8
239000008187 granular material Substances 0.000 claims description 8
229910001385 heavy metal Inorganic materials 0.000 claims description 8
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 8
239000000454 talc Substances 0.000 claims description 8
229910052623 talc Inorganic materials 0.000 claims description 8
235000012222 talc Nutrition 0.000 claims description 8
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 7
SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims description 7
229920002472 Starch Polymers 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
150000001298 alcohols Chemical class 0.000 claims description 7
239000000839 emulsion Substances 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
229960000581 salicylamide Drugs 0.000 claims description 7
239000007787 solid Substances 0.000 claims description 7
239000008107 starch Substances 0.000 claims description 7
235000019698 starch Nutrition 0.000 claims description 7
150000005846 sugar alcohols Polymers 0.000 claims description 7
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
239000011248 coating agent Substances 0.000 claims description 6
238000000576 coating method Methods 0.000 claims description 6
239000003925 fat Substances 0.000 claims description 6
239000004615 ingredient Substances 0.000 claims description 6
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
239000004408 titanium dioxide Substances 0.000 claims description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 5
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 5
229930195725 Mannitol Natural products 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 5
239000000443 aerosol Substances 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 claims description 5
239000000945 filler Substances 0.000 claims description 5
210000004051 gastric juice Anatomy 0.000 claims description 5
239000007788 liquid Substances 0.000 claims description 5
235000019359 magnesium stearate Nutrition 0.000 claims description 5
239000000594 mannitol Substances 0.000 claims description 5
235000010355 mannitol Nutrition 0.000 claims description 5
229920000151 polyglycol Polymers 0.000 claims description 5
239000010695 polyglycol Substances 0.000 claims description 5
239000000843 powder Substances 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
108010010803 Gelatin Proteins 0.000 claims description 4
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
235000021314 Palmitic acid Nutrition 0.000 claims description 4
235000021355 Stearic acid Nutrition 0.000 claims description 4
239000001506 calcium phosphate Substances 0.000 claims description 4
229960000541 cetyl alcohol Drugs 0.000 claims description 4
230000000536 complexating effect Effects 0.000 claims description 4
239000008139 complexing agent Substances 0.000 claims description 4
229920001577 copolymer Polymers 0.000 claims description 4
229940113088 dimethylacetamide Drugs 0.000 claims description 4
239000008298 dragée Substances 0.000 claims description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
239000008273 gelatin Substances 0.000 claims description 4
229920000159 gelatin Polymers 0.000 claims description 4
229940014259 gelatin Drugs 0.000 claims description 4
235000019322 gelatine Nutrition 0.000 claims description 4
235000011852 gelatine desserts Nutrition 0.000 claims description 4
229940116364 hard fat Drugs 0.000 claims description 4
UFIYKNIUNRVRSI-UHFFFAOYSA-N hexadecyl octadecyl sulfate;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCCCOS(=O)(=O)OCCCCCCCCCCCCCCCC UFIYKNIUNRVRSI-UHFFFAOYSA-N 0.000 claims description 4
229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
235000015110 jellies Nutrition 0.000 claims description 4
239000000787 lecithin Substances 0.000 claims description 4
239000011707 mineral Substances 0.000 claims description 4
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
239000003921 oil Substances 0.000 claims description 4
235000019198 oils Nutrition 0.000 claims description 4
229920000642 polymer Polymers 0.000 claims description 4
239000003755 preservative agent Substances 0.000 claims description 4
239000003381 stabilizer Substances 0.000 claims description 4
210000002784 stomach Anatomy 0.000 claims description 4
239000011732 tocopherol Substances 0.000 claims description 4
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 4
229940078499 tricalcium phosphate Drugs 0.000 claims description 4
229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 4
235000019731 tricalcium phosphate Nutrition 0.000 claims description 4
235000015112 vegetable and seed oil Nutrition 0.000 claims description 4
239000008158 vegetable oil Substances 0.000 claims description 4
241000416162 Astragalus gummifer Species 0.000 claims description 3
229920000084 Gum arabic Polymers 0.000 claims description 3
229920002230 Pectic acid Polymers 0.000 claims description 3
239000002202 Polyethylene glycol Substances 0.000 claims description 3
229920001615 Tragacanth Polymers 0.000 claims description 3
235000010489 acacia gum Nutrition 0.000 claims description 3
239000000205 acacia gum Substances 0.000 claims description 3
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 claims description 3
235000010443 alginic acid Nutrition 0.000 claims description 3
239000000783 alginic acid Substances 0.000 claims description 3
229920000615 alginic acid Polymers 0.000 claims description 3
229960001126 alginic acid Drugs 0.000 claims description 3
150000004781 alginic acids Chemical class 0.000 claims description 3
150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 3
125000001931 aliphatic group Chemical group 0.000 claims description 3
150000005215 alkyl ethers Chemical class 0.000 claims description 3
239000003963 antioxidant agent Substances 0.000 claims description 3
235000006708 antioxidants Nutrition 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
239000000872 buffer Substances 0.000 claims description 3
235000010410 calcium alginate Nutrition 0.000 claims description 3
239000000648 calcium alginate Substances 0.000 claims description 3
229960002681 calcium alginate Drugs 0.000 claims description 3
229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
239000008116 calcium stearate Substances 0.000 claims description 3
235000013539 calcium stearate Nutrition 0.000 claims description 3
OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims description 3
239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
239000005018 casein Substances 0.000 claims description 3
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims description 3
235000021240 caseins Nutrition 0.000 claims description 3
229920003086 cellulose ether Polymers 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
235000014113 dietary fatty acids Nutrition 0.000 claims description 3
GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 claims description 3
150000002170 ethers Chemical class 0.000 claims description 3
239000000194 fatty acid Substances 0.000 claims description 3
229930195729 fatty acid Natural products 0.000 claims description 3
235000019256 formaldehyde Nutrition 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
235000010445 lecithin Nutrition 0.000 claims description 3
229940057995 liquid paraffin Drugs 0.000 claims description 3
LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 claims description 3
239000006187 pill Substances 0.000 claims description 3
239000010318 polygalacturonic acid Substances 0.000 claims description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
235000000346 sugar Nutrition 0.000 claims description 3
229930003799 tocopherol Natural products 0.000 claims description 3
235000019149 tocopherols Nutrition 0.000 claims description 3
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
235000010487 tragacanth Nutrition 0.000 claims description 3
239000000196 tragacanth Substances 0.000 claims description 3
229940116362 tragacanth Drugs 0.000 claims description 3
239000001993 wax Substances 0.000 claims description 3
QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 claims description 3
230000003078 antioxidant effect Effects 0.000 claims description 2
BMQVRJOWNGSIEG-UHFFFAOYSA-L calcium;icosanoate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCCCC([O-])=O BMQVRJOWNGSIEG-UHFFFAOYSA-L 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
150000002334 glycols Chemical class 0.000 claims description 2
239000006210 lotion Substances 0.000 claims description 2
229920001451 polypropylene glycol Polymers 0.000 claims description 2
229960001484 edetic acid Drugs 0.000 claims 6
229910052739 hydrogen Inorganic materials 0.000 claims 6
239000001257 hydrogen Substances 0.000 claims 6
229960003609 cathine Drugs 0.000 claims 4
150000002431 hydrogen Chemical group 0.000 claims 4
229960000395 phenylpropanolamine Drugs 0.000 claims 4
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 4
WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical group CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims 4
239000008274 jelly Substances 0.000 claims 3
239000008194 pharmaceutical composition Substances 0.000 claims 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
241000978776 Senegalia senegal Species 0.000 claims 2
125000005907 alkyl ester group Chemical group 0.000 claims 2
125000000217 alkyl group Chemical group 0.000 claims 2
125000003118 aryl group Chemical group 0.000 claims 2
125000001589 carboacyl group Chemical group 0.000 claims 2
239000003085 diluting agent Substances 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 2
229960004279 formaldehyde Drugs 0.000 claims 2
150000002500 ions Chemical class 0.000 claims 2
125000006501 nitrophenyl group Chemical group 0.000 claims 2
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 claims 2
239000001267 polyvinylpyrrolidone Substances 0.000 claims 2
230000002335 preservative effect Effects 0.000 claims 2
238000010189 synthetic method Methods 0.000 claims 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
239000004743 Polypropylene Substances 0.000 claims 1
OBFQBDOLCADBTP-UHFFFAOYSA-N aminosilicon Chemical compound [Si]N OBFQBDOLCADBTP-UHFFFAOYSA-N 0.000 claims 1
239000012928 buffer substance Substances 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
229930195733 hydrocarbon Natural products 0.000 claims 1
239000003186 pharmaceutical solution Substances 0.000 claims 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
DLNKOYKMWOXYQA-CBAPKCEASA-N (-)-norephedrine Chemical compound C[C@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-CBAPKCEASA-N 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
230000000694 effects Effects 0.000 abstract description 3
208000002972 Hepatolenticular Degeneration Diseases 0.000 abstract description 2
208000018839 Wilson disease Diseases 0.000 abstract description 2
206010027439 Metal poisoning Diseases 0.000 abstract 1
208000010501 heavy metal poisoning Diseases 0.000 abstract 1
VVNCNSJFMMFHPL-GSVOUGTGSA-N L-penicillamine Chemical compound CC(C)(S)[C@H](N)C(O)=O VVNCNSJFMMFHPL-GSVOUGTGSA-N 0.000 description 63
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000003814 drug Substances 0.000 description 18
229940079593 drug Drugs 0.000 description 15
239000004472 Lysine Substances 0.000 description 11
235000019766 L-Lysine Nutrition 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
230000003287 optical effect Effects 0.000 description 8
238000003756 stirring Methods 0.000 description 8
230000000875 corresponding effect Effects 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000013543 active substance Substances 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000000306 component Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
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235000011167 hydrochloric acid Nutrition 0.000 description 5
229960000443 hydrochloric acid Drugs 0.000 description 5
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239000008013 pharmaceutical fillers and diluents Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
230000001830 phrenic effect Effects 0.000 description 1
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
235000019448 polyvinylpyrrolidone-vinyl acetate copolymer Nutrition 0.000 description 1
229940072033 potash Drugs 0.000 description 1
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
238000003825 pressing Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
229960001404 quinidine Drugs 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
235000003441 saturated fatty acids Nutrition 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
231100000430 skin reaction Toxicity 0.000 description 1
230000035483 skin reaction Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
229940083466 soybean lecithin Drugs 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 1
229930003945 thebaine Natural products 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
229960001295 tocopherol 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
239000011573 trace mineral Substances 0.000 description 1
235000013619 trace mineral Nutrition 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
150000004670 unsaturated fatty acids Chemical class 0.000 description 1
235000021122 unsaturated fatty acids Nutrition 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
- 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
- A61K31/60—Salicylic acid; Derivatives thereof

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Chemistry (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000167082A 1972-03-25 1973-03-26 Methode de preparation de d-penicillamine et preparation qui en renferme Expired CA1138776A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE2214814A DE2214814A1 (de)	1972-03-25	1972-03-25	Zubereitungen, die vollsynthetisch hergestelltes d-penicillamin enthalten
DEP2214814.7		1972-03-25

Publications (1)

Publication Number	Publication Date
CA1138776A true CA1138776A (fr)	1983-01-04

Family

ID=5840274

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000167082A Expired CA1138776A (fr)	1972-03-25	1973-03-26	Methode de preparation de d-penicillamine et preparation qui en renferme

Country Status (6)

Country	Link
BE (1)	BE797282A (fr)
CA (1)	CA1138776A (fr)
DE (1)	DE2214814A1 (fr)
HU (1)	HU170551B (fr)
SE (1)	SE394175B (fr)
ZA (1)	ZA731909B (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20070134277A1 (en) *	2005-12-09	2007-06-14	Children's Medical Center Corporation	Pharmaceutical formulation for sulfur-containing drugs in liquid dosage forms

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB585413A (en) *	1944-06-19	1947-02-06	Wellcome Found	Improved method for the resolution of penicillamine
CH540234A (de) *	1968-09-06	1973-08-15	Degussa	Verfahren zur Herstellung von Penicillamin
US3793462A (en) *	1970-10-16	1974-02-19	M Kludas	Treatment of scleroses

1972
- 1972-03-25 DE DE2214814A patent/DE2214814A1/de not_active Ceased
1973
- 1973-03-19 ZA ZA731909A patent/ZA731909B/xx unknown
- 1973-03-23 BE BE6044072A patent/BE797282A/fr not_active IP Right Cessation
- 1973-03-23 SE SE7304165A patent/SE394175B/xx unknown
- 1973-03-24 HU HUDE814A patent/HU170551B/hu unknown
- 1973-03-26 CA CA000167082A patent/CA1138776A/fr not_active Expired

Also Published As

Publication number	Publication date
SE394175B (sv)	1977-06-13
BE797282A (fr)	1973-09-24
DE2214814A1 (de)	1973-09-27
HU170551B (fr)	1977-07-28
ZA731909B (en)	1973-12-19

Legal Events

Date	Code	Title	Description
2000-01-04	MKEX	Expiry

Publication	Publication Date	Title
DE3881489T2 (de)	1993-09-16	Peptide mit collagenase hemmender wirkung.
EP0830863B1 (fr)	2000-05-10	Médicaments améliorateurs de l'irrigation sanguine gastrointestinale
DE69310475T2 (de)	1997-09-04	Benzokondensierte Lactame
DE3786250T2 (de)	1993-10-07	Phosphinsäure-Derivate.
DE69524114T2 (de)	2002-07-18	Naphthyridinonderivate
EP0608759B1 (fr)	2001-08-22	Dérivés de pipérazines
DE2445584C3 (de)	1979-05-10	L- bzw. DL-2-Methyl-3- (3', 4'-dihydroxyphenyl)-alanin-ester, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
EP0236872A2 (fr)	1987-09-16	Dérivés hydroxylamine, leur préparation et emploi comme médicaments
DE3508251A1 (de)	1986-09-11	Dipeptide
DE69832268T2 (de)	2006-07-13	Peptidyl2-amino-1hydroxyalkansulfonsäuren als zysteinprotease-inhibitoren
DE3210496A1 (de)	1983-10-06	Neue derivate bicyclischer aminsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue bicyclische aminosaeuren als zwischenstufen und verfahren zu deren herstellung
DE4443390A1 (de)	1996-06-13	Neue dipeptidische p-Amidinobenzylamide mit N-terminalen Sulfonyl- bzw. Aminosulfonylresten
DE69628360T2 (de)	2004-03-25	Azepinonverbindungen zur Anwendung bei der Hemmung von ACE und NEP
DE69610145T2 (de)	2001-06-07	Benzo-kondensierte Azepinon-und Piperidinonverbindungen, nützlich als ACE-und NEP-Inhibitoren
DE2332837A1 (de)	1974-01-24	Amine, verfahren zu ihrer herstellung und sie enthaltende arzneimittel
EP0243645B1 (fr)	1994-03-16	Composés à activité nootrope, les agents les contenant et leur emploi pour le traitement prophylactique des dysfonctions cognitives
DE1795022C3 (de)	1981-06-19	Lysergsäurederivate
EP0110224A2 (fr)	1984-06-13	Composés benzoylthio, leur préparation et emploi comme médicaments
JPS6251A (ja)	1987-01-06	シス，エンド−２−アザビシクロ〔３．３．０〕オクタン−３−カルボン酸誘導体およびその製法
DE3872213T2 (de)	1993-01-28	5-substituierte ornithin-derivate.
DE60010711T2 (de)	2005-06-09	Amido-spiropiperidine promovieren die freisetzung von wachstumshormonen
CA1138776A (fr)	1983-01-04	Methode de preparation de d-penicillamine et preparation qui en renferme
DE69826881T2 (de)	2005-12-01	Neue indolcarboxamide, pharmazeutische zusammensetzungen und methoden zur hemmung von calpain
US4587250A (en)	1986-05-06	Thiazaspirane derivatives, process for their preparation, and medicaments
DE69838686T2 (de)	2008-08-28	Tripeptidylpeptidaseinhibitoren