autolysis of comminuted tissue parts, heating with ammonium sulfate in alkaline solution, filtration and acidification yield heparin as complex with protein, removal of fat with alcohol
Trang 1Heparin H 1001 Uzara plus (Uzara)-comb.; GB: Quixalin (Squibb); wfm
Use: anticoagulant, antithrombotic RN: 9005-49-6 MF: [C,,H,,N,O,sS,]x MW: unspecified EINECS: 232-681-7
LD,,,: 500 mglkg (M, i.v.);
1950 mglkg (R, p.0.)
CN: mucopolysaccharide polysulfuric acid ester
sodium salt
RN: 9041-08- 1 MF: unspecified MW: unspecified
LD,: 2800 mgikg (M, i.v.); >5 g k g (M, p.0.);
391821 i d k g (R, i.v.); >779000 i d k g (R, p.0.);
I glkg (dog, i.v.)
calcium salt
RN: 37270-89-6 MF: unspecified
LD,,: A 0 g k g (M, i.v.);
>40 gikg (R, i v.)
magnesium salt
RN: 54479-70-8 MF: unspecified
MW unspecified
MW: unspecified
(molar mass 6000-20000, according to origin)
From animal tissue, especially bovine lung and liver (e g autolysis of comminuted tissue parts, heating with ammonium sulfate in alkaline solution, filtration and acidification yield heparin as complex with protein, removal
of fat with alcohol and treatment with trypsine for the purpose of decomposition of proteins, precipitation with alcohol and various purification methods)
Reference(s):
review:
Hind, H.G.: Manuf Chem (MACSAS) 34,510 (1963)
purification:
US 2 884 358 (Southerm California Gland Co; 28.4.1959; appl 22.4.1957),
US 2 989 438 (Uclaf; 20.6.1961; appl 29.12.1958)
DE 1 195 010 (Ormonoterapia Richter; appl 12.5.1962)
US 3 016 331 (Ormonoterapia Richter; 9.1.1962; I-prior 28.1.1960)
US 4 119 774 (AB Kabi; 10.10.1978; appl 2.3.1977)
GB 1 539 332 (AB Kabi; appl 4.3.1977; S-prior 5.3.1976)
Formulation(s): amp 12500 iu, 20000 iu, 50000 iu, 60000 iu; cream, eye drops and eye ointment 30000 iu,
60000 iu, 150000 iu (as sodium salt or calcium salt); syringe 5000 iu, 7500 iu
Trang 2Trade Name(s):
D: Calciparin (Sanofi
Winthrop)
Heparin-lnjekt (Immuno)
Heparin-Na (Braun
Melsungen; medac;
Nattermann; ratiopharm)
Heparin Novo (Novo)
Heparin POS (Ursapharm)
Heparin Riker (Riker)
Liquemin (Roche)
Thrombareduct
(Azuchemie)
Thrombophob (Knoll)
Traumalitan (3M M e d ~ c a ;
as sodium salt)
Vetren (Klinge)
numerous generic and
combination preparations
F: Calciparin (Sanofi
Winthrop; as calcium salt)
Dioparine (ThCa; as sodium
salt)
NCoparyl Framycttine
(CIBA Vision
0phthalmics)-comb
numerous generic and
combination preparations
GB: Canusal (CP Pharm.) Clexane (RhGne-Poulenc Rorer)
Fragmin (Pharmacia &
Upjohn) Hepsal (CP Pharm.) Monoparin (CP Pharm.) generic and combination preparations
I: Ateroclar (Mediolanum) Chemyparin (SIT) Clarisco (Schwarz) Disebrin (Allergan) Eparina (Tariff Integrativo;
Bristol-Myers Squibb;
Manetti Roberts; Parke Davis)
Eparinovis (Intes) Essaven Gel (RhGne- Poulenc Rarer)-comb
Flebs Crema (Pierre Fabre Phar.)-comb
Heparin Collirio (Farmigea) Idracemi Eparina (Farmigea)-comb
Lioton (Menarini)
Liquemin (Roche; as sodium salt) Luxazone Eparina (Allergan)-comb
Normoparin (Opocrin) Venotrauma (Also)-comb Viteparin (Teofarma)- comb
numerous generic preparations J: Caprocin (Mitsui; as
calcium salt) Depo-Heparin (Upjohn- , Kodama; as sodium salt) Hepacarin (Eisai) Heparigen (Mukasa-Torii) Heparin Sodium (Tokyo Tanabe)
Novo Heparin (Novo- Kodama)
Panheprin (Nippon Abbott) numerous generic preparations USA: Heparin-Sodium (Wyeth- Ayerst)
Hep-Lock (Elkins-Sinn)
Use: vasodilator RN: 7237-81-2 MF: C2,H3,N,06 MW: 505.57
LD,,,: 5 glkg (M, p.0.)
CN: 3-pyr~d~necarboxylic acid 2-hexyl-2-[[(3-pyr1d1nylcarbonyl)oxy]methyl]-1,3-propaned1yl ester
octanol
0
H 0
2-hexyl-2-hydroxy- methyl- 1,3-
proponediol (I)
chloride
Trang 3Heptabarb H 1003
Reference(s):
U S 3 384 642 (Yoshitomi; 21.5.1968; J-prior 18.11.1964, 12.10.1965)
Formulation(s): tabl 100 mg
Trade Name(s):
I: Megrin (Yoshitomi)
(Heptabarbital; Heptabarbitone; Heptamalum) Use: hypnotic sedative
RN: 509-86-4 MF: Cl3HI8N2O3 MW: 250.30 EINECS: 208-107-6
LD,,: 180 mglkg (M, i.v.); >800 mglkg (M, p.0.);
>S glkg (R, p.0.);
105 mglkg (dog, i.v.)
H$"B~ , N O O C H ~
-+I
cyanaacetate
Reference(s):
FR 870 714 (Geigy; appi 1941 ; Palestine-prior 1940)
DE 756 489 (Geigy; appl 1941 ; Palestine-prior 1940)
Forrnulation(s): tabl 200 mg
Trade Name(s):
D: Medomin (Geigy); wfm F: Medomine (Geigy); wfm GB: Medomin (Gcigy); wfm
Use: cardiotonic, sympathomimetic RN: 372-66-7 MF: C8Hl9NO MW: 145.25 EINECS: 206-758-0
LD,,,: 1250 mgikg (M, i.p.)
CN: 6-amino-2-methyl-2-heptanol
hydmchloride
RN: 543-15-7 MF: C,H,,NO HCI MW: 181.71 EINECS: 208-837-5
LD,,: 900 mglkg (M, i.p.)
Trang 41004 H Hetacillin
5-hepten-2-one
~ejizrence(s):
Dceuvre, I.; Pozat, I.: C R Hebd Seances Acad Sci (COREAF) 224,286 (1947)
Formulation(s): amp 250 mg, 500 mg; drg 50 mg; drops 50 mg/ml;tabl 150 mg (as hydrochloride)
Trade Name(s):
D: Normotin (0TW)-comb DCbmmyl (Pierre Fabre numerous combination
F: Amptcyclal (Sargel) Sureptil (SynthClab0)- I: Coreptil (Delalande
Use: antibiotic RN: 3511-16-8 MF: C,,HZ3N3O4S MW: 389.48 EINECS: 222-512-5
azabicyclo[3.2.0]heptane-2-carboxylic acid
monopotassium salt
RN: 5321 -32-4 MF: C,,H,KN,04S MW: 427.57 EINECS: 226-182-3
LD,,,: 650 mglkg (M, i.v.); >15 g k g (M, p.0.);
>1400 m g k g (R, i.v.); > I 0 gikg (R, p.0.);
2200 m g k g (dog, 1.v.); >4 g k g (dog, p.0.)
ONa
(q v )
Reference(s):
US 3 198 804 (Bristol-Myers; 3.8.1965; appl 6.1.1965; prior 25.1.1963)
Formulation(s): amp 250 mg, 500 mg, 1 g; tabl 5 0 mg (as potassium salt)
Trade Name(s):
D: Penplenum (Bristol); wfm Etadipen (Ghimas)-comb J: Natacillin (Banyu)
F: Versapen (Allard); wfm with dicloxacillin; wfm USA: Versapen (Bristol); wfm
I: Dicloeta (Lusopharma)- Versaclox (Bristo1)-comb
comb with dicloxacillin; with dicloxacillin; wfm
Trang 5Heteronium bromide H 1005
Use: anticholinergic
RN: 7247-57-6 MF: C , *H,,BrN03S MW: 41 2.35
LDs,,: 3576 mgkg (R, p.0.)
CN: 3-[(hydroxyphenyl-2-thienylacety1)oxyl-1 ,l-dimethylpyrrolidinium bromide
NaOCH,, n-C7HI6
I-methyl- phenyl-
3-pyrrolidinol (2-thieny1)-
glycolic
acid
H,C-Br
methyl
bromide
I Heteroniurn bromide
u s 3 138 614 (Eli Lilly; 23.1.1964; prior 18.12.1961, 3.8.1960)
slarting material:
US 2 830 997 (A H Robins; 1958; prior 1956)
Formulation(s): tabl 1 mg
Trade Name(s):
I: Quentar (Ravizza)-comb USA: Hetrum Bromide (Lilly);
Use: topical antiinfective, disinfectant, parasiticide
RN: 70-30-4 MF: C,,H6c160, MW: 406.9 1 EINECS: 200-733-8
LD,,: 67 mgkg (M, p.0.);
7500 @kg (R, i.v.); 56 mglkg (R, p.0.)
Trang 61006 H Hexafluronium bromide
2 NaOH
+ (CH,O),
Refirence(s):
US 2 250 480 (B T Bush; 1941; appl 1939)
US 2 435 593 (B 1Bush; 1948; appl 1945)
US 2 8 12 365 (Givaudan Corp.; 1957; prior 1951, 1954)
2,4.5-trichloro- poroform-
Forniulation(s): cream 0.5 g1100 g; emulsion 0.5 gt100 g; lotion 0.5 gt100 g
Hexachlorophene
Trade Narne(s):
D: Aknefug (Wolff) GB: Dermalex (Sanofi Phisohex disinf (Magg~om-
with estrad~ol Ster-Zac D.C (Seton) Vestene (Eurospital); wfm
F: Acnestrol (Po1rier)-comb 1: Etaproctene (Ange1ini)- USA: pHisoHex (Sanofi)
comb.; wfm
f
RN: 3 17-52-2 MF: C,,H,,Br2N2 MW: 662.55 EINECS: 206-265-0
Hexafluronium bromide
US 2 783 237 (Irwin, Neisler & Co.; 1957; prior 1953)
F r t i o ( ) : amp 20 mgln~l
1
Trade Name(s):
J : Mylaxen (Nippon Shoji); USA: Mylaxen (Mallinckrodt); Mylaxen (Wallace); wfm
Trang 7Hexamethonium chloride H 1007
Use: ganglionic blocker, antihypertensive RN: 60-25-3 MF: CI2H3,Cl2N2 MW: 273.29 EINECS: 200-465-1
LD,,,: 26.7 mglkg (M, i.v.);
35 mgkg (dog, i.v.)
CN: N, N, N,N,N,N-hexamethyl- 1,6-hexanediaminium dichloride
CH3
Reference(s):
DE 900 097 (May & Baker; appl 195 1 ; GB-prior 1950)
H3C\+
Formulation(s): oral: 0.5 gld
Trade Name(s):
D: Raucombin forte (Voigt); Gastrometonio (Fabo; as
1: Gastrometonio (Fabo); J: Methobromin
Hexcarbacholine bromide
(Carbolonium bromide)
ATC: M03 Use: muscle relaxant
RN: 306-41-2 MF: C,,H,,,Br,N,O, MW: 536.35
H
thionyl
methylene- carbonate
diamine
Trang 81008 H Hexestrol ":
1 potassium bromide
2 trimelhylamine
H
1 Hexcorbacholine bromide 1
Reference(s):
DE 1 021 842 (Osterr Stickstoffwerke; appl 1954; A-prior 1953)
Formulation(s): amp 2 mglml
Trade Narne(s):
D: lmbretil (Hormon-
Chemie); wfm
Use: estrogen, antineoplastic (hormonal) RN: 84-16-2 MF: C1XH2202 MW: 270.37 EINECS: 201-518-1
LDs": 1 g/kg (M, p.0.);
>2 glkg (R, p.0.)
@ W 3 r , ether, toluene, CoCI2
b
1 -bromo-1-(4-meth-
oxypheny1)propone (I)
(cf diethylstilbestrol
synthesis)
HI
11 -*
hydrogen
iodide
1 metals (Na Mg Ai, or Fe)
2 HI
1
1 (sodium, magnesium, aluminum, or iron)
2 hydrogen iodide
Trang 9Hexetidine H 1009
Reference(s):
a Kharasch, M.S.; Kleimann, M.: J Am Chem Soc (JACSAT) 65,491 (1943)
b Dodds, E.C et a].: Proc R Soc London, Ser B (PRLBA4) 218,253 (1940)
Bernstein, S.; Wallis, E.S.: J Am Chem Soc (JACSAT) 62, 2871 (1940)
Buu-Hoi', N.G.; Hoan, N.G.: J Org Chem (JOCEAH) 14, 1023 (1949)
US 2 357 985 (Research Corp; 1944; appl 1940)
GB 523 320 (Boots; appl 1938)
FR 855 879 (Lab Franc; de ChimiothCrapie; appl 1939)
starting material:
Bemstein, S.; Wallis, E.S.: J Am Chem Soc (JACSAT) 62,2871 (1940)
alternative syntheses:
Dockcn, A.M.; Spielman, M.A.: J Am Chem Soc (JACSAT) 62,2163 (1940)
US 2 392 852 (Lilly; 1946; prior 1941)
US 2 402 054 (Lilly; 1946; prior 1941)
US 2421 401 (Hoffmann-La Roche; 1947; S-prior 1943)
review:
Solmssen, U.V.: Chem Rev (Washington, D C.) (CHREAY) 36,481 (1945)
Fonulation(s): pessaries 10 mg
Trade Name(s):
D: Malun (Temm1er)-comb.;
F: Cycloestrol (Bruneau); J:
wfm
Micro-cristaux Cycloestrol USA:
(Bruneau); wfm
Synthrogene (Gerda); wfm Hexestrol and Phenorbital Synthovo (Boots); wfm (Jenkins)-comb.; wfm Robal (Chugai; as Hexestrol WlButabarb
Estra-Plex (Rowell); wfm Vagi-Plex (Rowell)-comb.;
wfrn
Use: antiseptic antifungal RN: 141-94-6 MF: C2,H4,N3 MW: 339.61 EINECS: 205-513-5
Reference(s):
US 2 415 047 (Commercial Solvents; 1947; appl 1945)
US 3 054 797 (Commercial Solvents; 18.9.1962; prior 1 1.10.1961),
Senkus, M.: J Am Chem Soc (JACSAT) 68,161 1 (1946)
Trang 101010 H Hexobarbital
pur$cation:
DE 2 01 1 078 (Godecke; appl 9.3.1970)
DAS 2 355 917 (Meditest; appl 8.1 1.1973)
DOS 2 709 929 (Dolorgiet; appl 8.3.1977)
DOS 2 310 337 (Wiilfing; appl 1.3.1973)
DAS 2 323 150 (Wiilfing; appl 8.5.1973)
salts with aromatic acids:
GB 1 538 603 (Doll; appl 5.1 1.1976; D-prior 6.11.1975, 3.6.1976, 16.6.1976)
US 4 141 968 (Doll; 27.2.1979; D-prior 16.6.1976)
US 4 142 050 (Doll; 27.2.1979; D-prior 6.1 1.1975,3.6.1976)
nicotinate:
DOS 2 310 338 (Wiilfing; appl 1.3.1973)
Fortnulation(s): sol 100 mg1100 ml, 200 mg1100 ml; spray 0.1 d l 0 0 g; vaginal tabl 10 mg
Trade Namc(s):
D: Anginasin Spray
(0pfermann)-comb
De-menthasin (Scheurich)-
comb
Doreperol (Rentschler) F:
Givalex (Norgine)-comb
Hexetidin Gurgellosung
(ratiopharm)
Hexoral (Warner-Lambert) Nifluril (UPSA) Hcxoral Spray (Warner- GB: Oraldene (Wamer-
Collu-Hextril (Warner- USA: Sterisil (Warner Chilcott);
Givalex (Norgine)-comb
Hextril (Warner-Lambert)
Use: hypnotic, sedative RN: 56-29- 1 MF: C,,Hl6N,O3 MW: 236.27 EINECS: 200-264-9
LD,,,: 133 mglkg (M, i.v.); 468 mglkg (M, p.0.)
CN: 5-(1 -cyclohexen- 1 -yl)- 1,s-dimethyl-2,4,6(1 H,3H,SH)-pyrimidinetrione
sodium salt
RN: 50-09-9 MF: C12H1,N,Na0, MW: 258.25 EINECS: 200-009-1
LD,,,: 165 mglkg (M, i.v.); 1325 mglkg (M, p.0.);
1 gikg (R, p.0.)
O+ /O'CH~
H ~ c ~ / ~ + ~ , NoOCH3
hexonone cyono- 1 -cyclohexenyl-
acetate cyonoocetate
H + H2NKN\CN
methyl 2-cyano- dicyono-
2-(1 -cyclohexenyl)- diomide