ITEM No. 24 
FILE No. XXIII—23 
•COPY No. 
PHARMACEUTICALS AND INSECTICIDES 
LG. FARBENINDUSTRIE A.G., HOCHST/MAIN 
COMBINED INTELLIGENCE OBJECTIVES 
SUB-COMMITTEE PHARMACEUTICALS AND INSECTICIDES AT THE 
I.G. FAKBENINDUSTRIE PLANT 
HOCHST A. MAIN 
10 - II April 1945 
Reported By 
H.M. HORACE, Major, M.C., A.U.S. 
PERGY J. LEVPER. It. D., U.S. CiYilian 
JOSEPH E. SMADEL, Lt.Col., M.C., A.U.S, 
LESTER M. WHITE, Ph. D., U.S. Civilian 
ERNEST H. YOLWILER, Ph. D., U.S. Civilian. 
Teaca Leader. 
CIOS Target Number 24/4 
COMBINED INTELLIGENCE OBJECTIVES SUB-COMMITTEE 
G-2 Division, SHAEF (Rear) APO 413 TABLE OF CONTENT^ 
Subject Page No* 
1, Introduction 3 
2, Personnel 3 
3, Pharmaceuticals 3 
a. Chemotherapy of Infectious and Neoplastic 4 
Diseases 
(1) General Remarks 4 
(2) Nitroacridine and Rutenol 4 
(3) Congasin and Preparation 7602 6 
(4) Preparation 96:9a 6 
(5) Penicillin 7 
b. Analgesics 7 
c. Pyramidon 8 
d. Rivanol and Surfcn 8 
e. Vitamins • 9 
f. Salvarsans 9 
g. Novocaine 9 
h. Analeptics q 
i. Enteric coatings o 
j. Suppository Base q 
k. Antispasmodics q 
l. Hypnotics 10 
m. Manufacturing methods 10 
n. Recommendations 10 
Appendices* 
1, Pharmaceutical and Scientific Staff. 11 
2, List of Hftchst Preparations 13 
3. Nitroacridine Preparation 35S2. - 19 
Article by Dr. R. Fussg&nger 
4. Rutenol - Article by Dr. R. Fussg&nger 28 
5• Photographs 34 
Composition of Team. 
(Note: Members actually engaged in the investigation of this 
target are indicated by an asterisk in the list on page l)• 
2 1. Introduction. 
This target is a large one, involving both industrial 
chemicals and pharmaceuticals, and the two day period to 
our team permitted interrogation relating to only a small portion of 
their activities. 
The Hoechst plant normally employed up to 12,000 persons. 
Near the end of the war they had 9,000 employees, of whom 2,900 were 
civilian Russian, French, Polish, and other displaced persons. The 
plant was practically untouched' by bombs, but due to lack of power, 
operations had almost ceased beginning in January, 1945. 
Normally, one third of the Hoechst output value was re- 
presented by pharmaceuticals, requiring about 3-400 workers. Their 
other activities were in the fields of dyes, alkalis, mineral acids, 
solvents derived from acetylene, plasticizers, color fixatives, 
glycerol, building material products, and vinyl plastics. Prof. 
Lautenschlaeger, the general Director, stated that the most important 
progress and research during the war was in the field of pharmaceutical 
products, Including compounds to combat colds and typhus; and vaccines, 
hormones, vitamins, antibacterial agents, and synthetic drugs. They 
had also done considerable work on nitro compounds to be used in 
explosives, but this phase was not gone into further. 
Hoechst has a large department for making packaged pharmace- 
utical products, such as tablets, ampoules, etc. 
The firm appears to have been well organized and capably 
managed by Prof. Lautenschlaeger and his staff. Our C.J.O.S. team 
was well received and we were given satisfactory cooperation in our 
interrogations. Lautenschlaeger is tall, dignified, correct, and some- 
what austere; his associates, Bockmuehl, Fussg&nger, Schaumann, Fehtle 
and others were more ready to volunteer information. Naturally, 
the principal concern of the entire staff was to obtain permission to 
resume operations, and to protect the physical plant from feared 
deprddatiohs and vandalism by displaced persons. 
2. Personnel. 
An organization chart of the Hoechst scientific personnel 
is attached as Appendix I. 
3. Pharmaceuticals. 
A complete list of the Hoechst Pharmaceuticals and insectic- 
ides i* given in Appendix B. a. Chemotherapy of Infection and Neoplastic Diseases. 
(l) General Remarks. 
gtudles on the chemotherapy of virus and rickettsial diseases 
at I.G. Hfcchst are carried out under the direction of Dr* R. Fuss- 
gftnger, chief of chemotherapy. Fussg8nger*s earlier work had to do 
with the chemical structure and synthesis of hormones. He was 
assigned to his present position several years ago when the former 
chief of chemotherapy resigned, presumably because he was of Jewish 
extraction. Fussgftnger is intelligent and conversant with the 
literature in the field of infectious diseases; he was cooperative 
during the visit of the CIOS team,. 
The general plan for the study of chemotherapeutic agents is the 
same at Fussgftnger*s laboratory in Hftchst as it is at Kikuth’s labor- 
atory at Elberfeld. (See report of CIOS Team No. 110. on I.G. 
Elberfeld and Leverkusen)• Various compounds prepared in different 
divisions of I.G. are submitted to the chemotherapy laboratory for 
testing* After the toxicity of the substances has been determined 
they are tested for their effectiveness against a number of Infectious 
and neoplastic diseases. Among the experimental virus diseases which 
are employed regularly in the testing of new drugs at HBchst 
are influenza A.,louping ill,lymphogranulona venereum; all the work 
is done in mice. Murine typhus is the only example of the rickettsial 
virus used in chemotherapeutic trials; mice are infected intraper:’ton- 
eally in these studies. Tumors employed in the experimental set ups 
arc the Broun - Pearce tumor, a sarcoma of rats, a fowl sarcoma, 
and occasionally the Shope papilloma. Several types of trypanosomal 
infections in mice ere also used in the testing. 
Many types of compounds are run through the gaunt of biological 
tests; however, no sulfa compounds are studied at Hbchst; these are 
all studied at Elberfeld. 
None of the studies at Hftchst on virus and neoplastic diseases 
have revealed new substances of chemotherapeutic value. Certain of 
the more interesting findings in other infectious diseases are 
summarized in the following paragraphs. 
Chemotherapeutic studies have gradually lessened during the 
past few years and during the last six months have almost ceased 
because of the shortage of animals. 
(2) Nttroacridine and Rutenol. Of the many compounds studied 
for the treatment of murine typhus, the only ones stated to have shown 
promise is nitroacridine, or mixtures containing this compound. It is 
made by the following synthesiss CH3°' of)0 
CH3O * — N02 
H2N CH2 CH OH CH2 N(C2H5) 
NH CH2 CH OH CH2 N(C2H5)2 
oh3o —fYY) 
OH3c —- {XK/w* 
Nitroacridine, 
The nitroacridine itself is not a new compound. The series of 
which it Is a member was originally used against streptococci and 
staphylococci. It was found that the acridine nucleus and the nitro 
group are necessary for effectiveness against typhus. The compound 
has been tested clinically in about 200 cases of R. mooseri. It is 
given orally and intravenously. The latter mode of administration 
causes some sclerosis of veins and oral administration causes 
vomiting, hence it is administered in divided doses. In 20-gram 
mice, the effective dose was found to be 3,3 to 5 mg. 
Rutenol. is the name of the pharmaceutical product of 2 parts of nitro- 
acridlne plus 3 parts of arsenic trioxide, which forms a salt. A syn- 
ergistic effect is claimed. Rutcnol granulate contains % of this 
active material. Fussg&nger has not published his perimental data 
on this subject. However, in accordance with I.G. policy he prepared 
a prospectus on nitroacridin and on rutenol summarizing the available 
information. Such a prospectus is given to those clinicians who 
intend to subject I.G. drugs to clinical trial. Translations of 
Fussg&nger’s articles on nitroacridin and Rutenol are presented in 
Appendices 3 and 4. These data are quite convincing, (see charts 
in appendices dealing with mortality curves of treated and control 
mice). Examination of a large number of Fussgftnger’s protocols and 
summaries leads one to the conclusion that the examples chosen for 
illustration in his article are representative of the general exper- 
iences. The experiments are not reproducable with complete regularity, 
however, apparently because of two variables which Fussgftnger did not 
control adequately. These were variations in the infectivity of the 
innoculura and use of different strains of a suspension which contained 
a known number of minimal lethal doses of the infectious agent. Mice 
used in these experiments were obtained from different breeders. Mice 
from one of these breeders consistenly failed to survive infection 
when tested with amounts of the drugs which were adequate to protect 
the majority of mice supplied by another breeder. 
Guinea pigs Infected ?rith epidemic typhus richettsiae and 
treated with nitroacridin developed fever in the same way as untreated 
controls. The drugs have not been tried in arairaals injected with 
rickettsiae of Spotted Fever, Boutonneuse Fever or Scrub typhus 
5 Only three reports have been published on the use of these drugs 
on patients with rickettsial diseases. All three were by Holler/ 
two deal with epidemic typhus and the other with Trench Fever. Photo- 
stats of the original articles accompanied by English translations 
are filed with the Secretariat, These reports are of little or no 
scientific value since they present inadequate data for the reader 
to decide whether the authorfs contradltory and sweeping conclusions 
have any foundation in fact. For the record the references are 
as follows. 
(1) Kasuistiche Beltrftge zur Therapie der Kriegsseuchfen,> 
Holler, G,, Mathis A., and Ortner, E,, Wiener Klin, Woch. 1944, 
27-38. 345. 
(2) Eine sehr erfolgreich streng kausalpathogenetisch 
eingestellte Therapie des Fleckfiebers♦ Holler, G., and Zajitschck, 
R. Med. Klinik, 1944. 17-18, 247 
(3) Welche Erfahrungen liegen bel der Behandlung des 
Wolhynicnfiebers vor? Holler, G.,Med Klinik 1944, 2j> 374. 
In view of the good chemotherapeutic results obtained with 
nltroacridin and Rutenol in experimental murine typhus injection in 
mice it appears worthwhile to extend the studies on this grpup of 
drugs to determine their effects on other experimental ricksettsial 
infections, notably scrub typhus. It also appears desirable to 
obtain accurate information on the usefulness of this drug in 
epidemic typhus in human beings. 
Samples of Nitroacridin and Rutenol (active materials) and Rutenol 
granulosa (5% active material) are filed with the Secretariat. 
Informant Dr, R. Fussglnger. 
(3) OftngnfllB And fraparaMpp 7&>2 
These compounds which are related to Surfen and have a 
typanosomidal action are still considered of interest by Fussginger. 
Little or no experimental work has been done with them in the past 
three years. Reports entitled "Congasin," FussgUnger, R. 
Sonderdruck aus Medizin u Chemic Bd IV. 1942 and lfDie Behandlung 
der akuten Ohagas - krankheit mit 7602 (AC) Bayer Mazza, S., 
Deutsche. Trop Med. Zb it. 1941, 42 577 are filed with the Secretariat, 
Stitts Diagnosis, Prevention and Treatment of Tropical Disease 6th 
Edition 1943 discusses these drugs with comparatively little 
enthusiasm. 
(4) Preparation 9659a (Bismuth salt of glycolylaminophenyl 
arsenic acid) 
This bismuth-arsenic combination has been reported to be 
of value in the treatment of patients with amebic dyientery, The drug 
is discussed at length in the reoort of CIOS Team 110 on I.G. Elberfeld 
and Leverkusen. , 
6 (5) Penicillin research was begun about two years previously 
using strains from their own laboratory, and also one obtained from 
Euler in Sweden, None was particularly good. The best culture medium 
was from yeast, also whey. They used the surface method in flasks, 
and had just recently begun submerged growth experiments on a small 
■eftle, using bottles holding about 3 gallons* Their capacity by the 
surface growth method was million Oxford units per month. As 
a standard, they were employing a package of captured Burroughs-Wellcome 
penicillin tablets which had been turned over to th4m by the German 
War Ministry, 
A batch was Considered to be 300 liters of harvest. Butyl 
alcohol was used for extraction. The butyl alcohol extract was con- 
centrated by distillation, and after further processing to get it 
into ether solution, the latter was twice chromatographed, giving a 
60% overall recovery. The product was dried from the frozen state 
and was brown in color, with a potency they believed to be about 150 
Oxford units per milligram. None of this product was supplied to the 
German Army; most of it was intended for structural investigations, 
and for experiments on stabilization. Dr, Wegmann, in charge of this 
work, stated that they had not done any appreciable amount of structural 
research, as their product was too impure. 
The H&chst penicillin operations may be summary zed as followsI 
1 liter of harvest • 256,000 dilution units 
Ratio of dilution units to Oxford units » 25*1. 
256,000 dilution units = approx, 10,000 Oxford units. 
Loss in operation • about 5>000 Oxford units. 
Production per month r 1500 liters of harvest 
. 7,500,000 Oxford units 
* 200 million dilution units. 
Each dry ampoule ■ 15 m£. s 2000 Oxford units of sodium salt. 
HBchst has not worked much on other antibiotics. They studied 
quinones of the type , but found none having activity 
HC0 v 3 
comparable to penicillin. 
b. \r\*\p.p 
to 300 kg. per month. 
Dolantln was made at the rate of 200 Dr, Bockmlihl stated that considerable research has been carried 
on in this field. The meta-hydroxy derivative, which was made by 
analogy to morphine, is 
y c - - gooc2h5 
BO Ch/ CHp 
/ 1 
ch2 ch2 
N 
CH, 
J 
This compound is more, powerful than Dolantin. The corresponding ortho and 
para - hydroxy compounds are not efficient analgesics. 
The compound 
C6H5 —‘ c — coch3 
CH2/ CHo 
1 1“ 
ch2 ch2 
N 
ck3 
was stated by Bockm'CiM to be 3 times as effective as Dolantin. The 
corresponding ethyl analog is still better. This series is being 
tested clinically. 
analogy to Trasentin, 
(C6H5)2 CH COOC2H4 K(C2H5)2 
they prepared 
(c6h5)2 " C00C2 H 5 
CH2CH2N 2 
which has both analgesic and contispasraodic effects. 
* c, pyraagidon manufactured in a large plant, with a capac- 
ity of 54-0 metric tons per year* In 1938 their production was 200 
tons. It was stated that Germany produces 2 trillion Pyramidon tablets 
annually, and that practically no encountered. 
Combinations containing Pyramidon are also extensively employed. 
* d. Rlvanol is manufactured in quantity for wound disinfection. 
A newer product, about ten years old, is Surfen. 
8 NH0 
I 
/Nf'j —' NH Cfi NH 
NH2 
00 - -- 
N 
It Is a colorless substitute for Rivanol, used as a wound antiseptic 
and gargle. 
* e. Vitamins. Ascorbic Acid output at Hftchst was 12,000 
kg. per year. Vitamin £ was made solely by the extraction of wheat 
germ, and it had a good market. Synthetic Vitamin K was also manufact- 
ured* Experimental work was under way to develop an oil solution 
for injection. HBchst made no B vitamins, nor vitamin A. 
* f. S&Avarsans. No unusual methods of manufacture appeared to 
be involved. The filled ampoules were evacuated from a vacuum line 
manifold; the vacuum line contained a Gelsler tube to indicate by 
color the degree of vacuum, A. Tecla Field was used for the final 
vacuum inspection of the ampoules. 
The salva&san base is made in wooden kettles, and silver lined 
kettles are used for the preparation of the hydrochloride salts. 
♦ C. Novocaine is made by condensing ethyl p - aminobenzoate with 
diethyl - aminoethanol at 150°C. in the presence of sodium. An 80% 
yield is obtained. Nov6caine solution for sale are made as follows* 
A sodium chloride solution is made i* a closed vessel under hydrogen; 
this solution is filtered into a closed porcelain vessel of about 20 
gallon capacity, using a closed system. This solution is forced 
through a glass tube containing the required amount of crystalline 
Novocaine and epinephrine. Filling into ampoules is done in a closed 
system, using alternate vacuum and hydrogen pressure; no preservative 
is used in the solution. 
* h. Analeptics were not made by HBchst. It was stated that 
Amphetamine, Neospiran and Pervitin were not extenwively used in 
Germany, except perhaps for Amphetamine in aviation. 
* i. Enteric Coatings for tablets are made from polysterol 
maleic acid anhydride, and applied as a 7% acetone solution. 
* j. Suppository Base called "Postonal" is polyethylene oxide, 
to be used in place of cocoa butter* It does not melt at body 
temperature but 5s soluble in water. 
* k. Antlspasmodics. Aspasan is a new product, synthesized as 
follows: 
9 This intermediate is isolated, then 
treated with excess sodamide, whereby the CN group is removed and 
replaced by H, to g5ve Aspasan, (6^5)2 OH 2. 
Aspasaniis marketed in combination with dihydroxy-ephedrine and mono- 
hydroxy e phedrine (Suprafen)• 
* 1 Hypnotics These are made at Elberfeld. Formerly 
Novonal (diethylallytacetannid) and Nirvanol were manufactured at 
Hftchst, but they are no longer being produced* 
No digitalis or strophanthus preparations are made. 
* *m Manufacturing methods. 
Manufacturing directions for the following products were obtained 
and have been given to the Secretariat: Penicillin, Dolantin, Nltro- 
acrldin (No, 3582), Novalgin, Novocain Pantocain, Preloban, Progest- 
erone, Cortenil, Pjramidon, Racedrin, Rivanol, Salyrgan, and Sup- 
rarenin. 
* n Recommendations* This is one of the most outstanding drug 
and chemical units in Germany, and merits much more detailed study 
than this C,T.O.S, team was able to devote to it in the two days we 
had available. It is therefore recommended that a qualified pharm- 
aceutical team be assigned for a further and more intensive study. 
Interviewed s 
Drs* Lautenschltger, Max Bockrauehl, R. Fussginger, 
Schauraann, Alfred Fehrle (pharmaceutical manufacturing), Wegmann, and 
Stephan. 
10 APPENDIX I 
professor Dr. Lautenschlgger - General Director of the 
Entire Plant and Director of the Pharmaceutical Division. 
Dfc*. Dr. M. Bockmtthl - Director of the Research Phermaceutial 
Division. 
a. Dr. G. Ehrhart - Director of the Laboratory for Drug 
Synthesis. 
Dr. S. BartholomBus 
Dr. C. Eislob 
Dr. L. Stein 
Dr. E. Uonsch 
Dr. E. Huschig 
Dr. P. Eartmann 
Dr. A. Schmidt 
Dr. W. Krohs 
Dr. H. Loditschko 
Dr. W. Aumfi.ller 
Dr* W. Schneider 
Dr. H. PStz 
Dr. W* Persoh 
b* Dr. W» Ludwig - Director of the Biochecd cel Laboratory* 
Dr. F. Lmdnor 
Dr. H. Coppinger 
Dr. A. Magor 
Dr .Th .Wegmann 
Dr. H. Vetter 
c. Dr. 0* Schaumann - Dozent in the University of Frank- 
furt /Main and Director of the 
Pharmacological and Physiecological 
Laboratories. 
Pharmacist Dug. DOrzbach 
Dr. R. Eigler Dr„ R. Boucholt 
d. Dr. 0. Y/agner - Dozent in the University of Giessen 
and Director of the Parasitological 
Laboratory. 
Dr. W. Eohorst 
e« Dr. £. Fussggnger - Director of the Chemotherapeutic 
Laboratory. 
f* Dr. J> Stephan - Director of the Sero-bacteriological 
Laboratory. 
g. Dr. K. Pfaff - Director of the Laboratory for Plant 
Protection. 
Dr. M. Erlenbsch 
Dr. W. Finkanbrink 
(Entomologist) 
Dr* W. Staudermann 
(Botanist) 
Dr. W* Gelmroth 
ho Dr. Wo Hermann - Director of the Salvarson Laboratory- 
Dr* Fr. Plampe Dr. Hilraer 
11 1* Apoth* Lo Hlddendorf - Director of the Galenical 
Laboratory. 
Dr. J» Eisenbrand - Director of the Pharmaceutical- 
analytical Research Laboratory 
including physical methods. 
Apoth. Sionz 
Dr. Picher 
Dr. J. Eisenbrand 
k® Dr® Jo Vfefrer - Director of the Scientific Bureau 
Dr ® l£8pp 
Apothekor JTischmann 
Frankfurt a/Main-Hoechst 
den 4 April 1945/G APPENDIX 2 
List of the Pharmaceutical Remedies of the I®G* Works, 
Hflchst 
!• Remedies for Human Use 
eH Anaesthetics 
Anaesthesin 
Novocain 
Novocain-Corbasil 
Nosuprin (local-anaesthetic for dentistry) 
Pantocain 
Impletol (complex combination of Novocain and 
Caffeine) 
b. Sedatives 
(l) AniTpyretics, Antirheumatics and Antiarthritlcs 
Antipyrin~ 
MigrSnin 
iWelubrin, Malgin y 
Garden (Novalgin-Pyremidon) Pyrazolon-group 
Novelgin-^uinine 
Pyramldon 1 
Trigemin (Pyramidon+Butylchloralhydrete J 
Hexophan (combination of quinoline ana 
carboxylic acidj 
12) Analgesics and Spasmolytics 
Dolentin 
Aspasan (remedy for asthma) 
c» Eormon-Preparations 
Lutren (Corpus-luteum-hormon) 
Gortenil (synthetic cortical-hormon) 
Corteniletten 
Suprarenin (synthetic horraon of suprarenal gland) 
Slityran (preparation of the thyroid gland) 
Elityran K (a substance having the action of the 
thyroid gland and made of non-specific albumen 
by iodation)* 
Emanal (a preparation of the thyroid gland, 
enriched with iodine)* 
Erugon (testical-hormon-preparation) 
Festal (pancreas-enzyme-preparation with hemi- 
cellulase) 
Hypophysin (labour-exciting drug and tonic of the 
vessels) 
Iliren (an Adrenalin-free preparation of the supra- 
renal cortex) 
Orasthin (a constituent of the posterior lobe of 
the pituitary gland, with a specific action on 
the uterus) Preloban (active principle of the posterior pitui- 
tary Lob©) 
Tonephin (a bormon of the pituitary gland (pars 
posterior) acting as a tonic on the intestine and 
checking diuresis)* 
Torantil (obtained from the intestinal mucrous 
membrane and possessing anti-allergic and detoxi- 
cating properties)^ 
Insulin (Normal - Insulin 
(Depot - Insulin, turbid 
( M M clear 
(Native - Insulin 
Lacarnol (a nucleoside preparation acting on the 
circulation)* 
d* Vitamins 
Cantan (Vitamin C) 
Citrin (permeability-vitamin, factor P) 
Hemodal (Vitamin K-Preparation) 
Priovit (water-soluble vitamins of the B and C-group) 
Ereton (natural Vitamin E-preparation)* 
e* Ghemotherepoutical and Antiseptical Remedies 
(1) keta]-combinations * 
Cashis (a bismuth preparation for injections) 
Ebesal (organo-ccpper combination for combating 
tuberculosi s)* 
Lopior (organo-gold combination for combating 
tuberculosis)* 
Salyrgan (crgano-mercury combination 
(2) Non-metal-combinations 
Trypeflavin (antiseptic for treating wounds, 
antlgonorrhoic and internal chemotherapeutic) 
Trypaflavetten 
Pan-flavin-pastils 
Surfen (a colorless chemical substance for use 
in surface and deep antisepsis)* 
Surfen-preparations : "Revasa-Tablets • 
'Rivanol (a specific for use in deep and surface 
antisepsis) • 
Rivanol-prsparations; Rivanol granulate 
Kivanoletten 
(3) Arsenic preparations 
Salvarsan 
Salvarsan-Sodium 
Myosalvarsan 
Meosalvarsan 
Neo-Silbersalvarsan 
Solu-Salvarsen 
Spirocid (a compound of arsonic acid), 
f<.• Synthetics acting on the circulation 
Icoral icirculatory and respiratoryrestorative) Hacedrin (Raceme-£phe dr ine) 
Rephrin (Racedrin 4* Eeceme-Suprarenin) 
Suprarenin (compare Eonnon-proparatlons) 
Suprifen (a circulatory tonic and antileptic) 
g# Stomachics 
Hydronal (The antacid for conditions of gastric 
irritation and disorders of secretion)* 
Orexin (for improving the secretion of the gastric 
juice)• 
h* Narcotics 
Solaesthin (inhalation anesthesia) 
Stickoxydul (narcotic gas) 
i* Eczema Remedies 
Sellidol, in form of: Bellidol ointment, 
Bellidol bougies 
Turn©no1-Ammonium (an antiphlogistic dermatological 
preparation) 
j* Remedies for indications not enumerated in a* - 1* 
(1) Synthetics 
Lublsan (anthelmlnt1cj 
3ajodinetten(a llpotr0pic iodille Preparation; 
Salyrgan (organo-mercury-comblnation,diuretic) 
Yaron (labour exciting drug) 
Tonophosphan (for assisting metabolism) 
(2) Biochemical Remedies 
Devegan (for the treatment of loucorrhoea) 
k* Others 
3^ostonal (ground-mass for suppositories) 
Ninhydrin (diagnostic) 
21 April 1945/G 
Sera and Vaccines 
Anti-cholera Vaccine 
Anti-Dysenteria-Polyfagin 
Febris-Undulans Vaccine of "Behringwerke" 
Gonargin (Gonococcus Vaccine) 
Mixed Gonorrheal Vaccine Behringwerke 
Anti-Influenza Vaccine Mixed Behringwerke 
Gripcaline-drops (mixture of antigens for the early therapy 
and prophylaxis of influenza) 
Anti-catarrh Vaccine and Mixed Behringwerke 
Anti-whooping cough-Vaccine Behringwerke 
Leukogen (antistaphylococcic Vaccine) 
Omnadin (an non-specific Vaccine) 
paragen (immune therapeutic) 
Anti-whooping cough Vaccine Mixed Behringwerke 
15 Phytossan (monovalent antiwhooping cough Vaccine) 
Anti-Pneumococoic Vaccine Behringwerke 
Anti-Streptococcic and Anti-Staphylococcic Vaccine Mixed 
Behringwerke 
Tetra-Vaoclne Behringwerke (a mixed Vaccine of Typhoid, 
paratyphoid and cholera A ♦ B Bacilli)® 
Trichophytin (a polyvalent extract prepared from trichophyton 
fungus o 
Tuberculin-Preparations 
Anti-Typhoid Vaccine Behringwerke 
Anti-Tghoid and Anti-paratyphoid Vaccine T.A®Bo Behringwerke 
Typhoral (a polyvalent antityphoid Vaccine) 
Anti-tjrphoid - Anti-paratyphoid B Folyfagin 
Dermotubin (a skin-tuberculin)e 
Zp Remedies for Veterinary-Medical Use 
eZ Anaesthetics 
Anaesthesia 
Novocain 
Novocain-Suprarenin (local anaesthetic) 
Pantocain (surface anaesthetic) 
b* Analgesics and Antispasmodlcs 
Novalgin 
Co Hormone Preparations 
Elityran (preparation of the thyroid gland) 
Erugon (testioal hormon preparation) 
Postal (pancreas-enzyme preparation with hemi-cell- 
ulase) 
Hypophysin 
Insuiin 
Orasthln (a constituent of the posterior lobe of 
the pituitary gland, with a specific action on 
the uterus) 
Suprarenin (synthetic hormon of suprarenal gland) 
d* Vitamins 
Eviabit (oil from wheat germ with standardized 
Vitamin-E content) 
Centan (Vitamin C) 
ee Chemotherapeutical and antiseptioal Remedies 
Methylene-blue medicinal "Bayer” 
Methyl-violet medicinal "Bayer" 
Trypanblue (Specific for various kinds of piro- 
plasmosis) 
Bovoflavin ointment (incubation infection of the 
female and male cattle) 
Gongasin (for combating diseases in cattle and 
horses caused by Tryp. oongolense and Tryp* 
vivax) 
Sntozon-Granulate (chemotherapeutical soothing 
antiseptic) 
Entozon-rods 
Entozon-studs 
Entozon-ointment 16 - Hivanol (a chemotherapeutic for use in surface and 
deep antisepsis) 
Trypaflavin 
Reosalvarsan 
Spirocid-Sodium (for spirochaetosis of fowl and oth- 
ers) 
Ratrolets (a disinfecting of virus) 
Osmaron (disinfecting and sliding agent to be used 
in milking - germicidal) 
fo Synthetics acting on the circulation 
Rephrin (Raceme Sphedrin){and Raceme-Suprarenin)• 
Suprarenin (compare Hormone preparations) 
go Anthelmintics and other effective remedies for 
combating intestinal parasites' 
Allegan-plates (anthelmintic and roborant) 
Avomin (anthelmintic) 
Ciff-capsules (Anthelmintic) 
Remural (anthelmintic) 
Igitol-powder and pills (for treatment of liver-rot) 
h* Remedies for combating ectoparasites» horn-flies 
and others 
Malix (Dusting powder obtained from derris) 
Derrophen (a preparation obtained from derris and 
to be used for combating larvae of horn-flies on 
cattle, scab, mange, vermin, Herpes tonsurans in 
cattle end horses) 
io Others 
J'ellidol ointment (used to promote epitheliation) 
Salyrgan (a diuretic) 
Tonophosphan-Solution (for assisting metabolism) 
SI April 1945/G 
Sera end Vaccines (for veterinary use) 
Amblosin (Bangfs bacillus of abortion) 
Antidiplococcic and Formol-Vaccine Behringwerke 
Druse Vaccine Behringwerke 
Fowl-Cholera Vaccine Behringwerke 
Fowl-Diphtheria and smallpox Vaccine Behringwerke 
Mixed Vaccine Behringwerke for Paralysis of foals 
Oumadin 
Mother Vaccine Behringwerke 
Pig Paratyphoid Vaccine Behringwerke 
Rieumonia Vaccine Behringwerke 
Pullorura-Antigen Behringwerke 
Anti-streptococcic Vaccine Behringwerke for veterinary use 
Tuberculins (Old Tuberculin, Bovine Tuberculin, Tuberculin- 
Diagnostic for ophthalmic reaction) 
17 List of Commercial Products of the Fungicide and Insecticide 
Department of the I» G» Works» Hoechst 
Tritlsan - a dry seed dressing free from metals for the 
treatment of Bunt or Stinking Smut in Wheat 
Titigran - a fungicide containing copper oxide and having 
a particularly good adherence 
2317 W • a fungicide free from metals against Peronospora 
Nosprasit - the cuprous and arsenical fungicide and insec- 
ticide for the simultaneous treatment of 
fungus and insect pests in fruit culture® 
Bulbosan - to cure brown patch disease of tomatoes 
Brassisan - against Plasmodiophora brassicae 
Brassicol - against botrytis (sclerotinia) 
Nirosan-Spraying Agant-Free from Arsenic 
Nirosan Dust 
against Clysia 
ambiguella and 
Polychrosis botrana 
Copper Nirosan Spraying Agent 
Copper Nirosan Dust 
for the simultaneous treatment 
of Peronospora and Clysia am- 
higuella and Polychrosis 
botrana 
Aresin - against Leptinotarsa decemlineata 
Gralit - dusting agent against eating insects 
Nicropren new - a nicotine-saving product against sucking 
insects 
Gix - against flies 
Dizan - an insecticide against cockroaches 
Grodyl new - a spray against Calendra granaria 
Synthetic caterpillar lime Hoechst - against all creeping 
insects 
Agrotin - a product for improving the wetting power of 
fungicides 
18 APPENDIX 3 
Nitroacridine preparation 3588 (Chemisch-Pharmazeutische 
und Sero-Bakteriologische Abteilung, I.G* Farbenindustrie 
A.G.. Frankfurt/Main - HCchst - R. Fussgftnger) 
Chemotherapeutic remedies for true typhus with specific 
efficacy have not been known until this time* During the last 
tan years systematic experiments to find such remedies have 
been undertaken. Otto, Wohlrab, and Schlfer especially 
have worked out extensive experimental series, but it has 
never been possible to determine anything more than mere 
traces of an influence upon the disease in mice* As a 
causative agent, these investigators used a rlckettsia 
strain, isolated by Mooser, of Mexican typhus (tarbadillo 
fever), on whose suitability for chemotherapeutic experi- 
mental series Wohlrab reported in Berlin in 1937 at the 
17th congress of the Yereingung f«r Mikrobiologie* 
The danger of an increased incidence of typhus, cauoed 
by the Eastern Campaign, caused the author to initiate very 
extensive laboratory tests in quest of a chemotherapeutic 
substance for medicinal therapy of typhus, since the manu~ 
facture of vaccines in quantities required for protective 
inoculation of the entire military and civilian personnel 
in the Eastern area cannot be carried through even with 
the best type of organization* 
Since work with the causative agent of true typhus 
in large experimental series is difficult and since the 
study of immunity conditions showed the close relationship 
of genuine typhus with the causative agent of Mexican 
typhus, the chemotherapeutic test series were performed 
with Mooser* s strain* Extraordinarily many preparations 
from a multiplicity of chemical groups were tested for 
their efficacy by means of this model test* Above all 
many of the classical chemotherapeutic remedies were 
examined; in most cases they proved to be totally ineffec- 
tive* Certain indications of an effect were found in oral 
administration of some arsenic acids* In the further 
course of these large-scale experiments a substance was 
found which has a very regular, strong influence upon the 
course of the disease in regard to intensity and lethal 
outcome, and in experimental animals were kept alive and 
were cured* This substance is No* 3582 in extensive 
clinical tests in genuine typhus, Yolhynian fever, and 
other rickottsioses. It is a nitx*oacridine derivate of 
complicated structure, and it is readily soluble in water# 
19 Toxicologioal data 
The toxicity of the substance is but slight# The 
maximum tolerated dose is in the mouse (per kg) 0.15 gm 
in subcutaneous and 0.5 gm in oral administration. Rabbits 
tolerate intravenously 25 mg per kg. In the animal experi- 
ment, No. 3582 never showed any recognizable injury of the 
gastric and intestinal mucosae even in great overdpsage. 
For biological tests of the new typhus remedy on the 
causative agent of Mexican or murine typhus, mice were used 
in large test series, as experience had shown that uniform 
results can only be obtained if each preparation, each 
individual dosage, and each manner of administration 
(subcutaneous, oral,1rfcravenous) are applied to as large a 
group of mice as possible, in order to reduce the giological 
stray results occurring in this infection to a minimum. 
For the infection of the series of mice, the author used 
the emulsified brains from gravely diseased passage animals, 
in certain dilutions, which caused an 80 - 100$ mortality 
in the untreated control animals. In spite of frequent 
adjustment of the optimal dilution of the emulsified brains 
there appear fluctuations in virulence, evidently of 
seasonal causation, of the causative agent, which render 
the determination of effective remedies difficult. After 
substance No. 3582 had excelled time and again in all 
tests, the author began in all large-scale tests to treat 
a collective group with this substance, in addition to the 
untreated control animals, and thus he was able to determine 
the degree of efficacy of a new substance in comparison with 
No. 3582 as a standard substance. 
The aspect of the disease in intraperitoneally infected 
mice had approximately the following course; On the 4th 
or 5th day after infection the first symptoms of the disease 
became visible. They were a lack of motion and raised fur; 
as the disease continued, there appeared uni- or bilateral 
conjunctivitiss, and extensive edemas developed in the head 
of the animal. Before death occurred — generally between 
the 8th and the 10th day of the test — the author observed 
occasionally symptoms of paralysis, and frequently diarrhea 
and spasms. While the mice in the control series had, with 
very few exceptions, died by the end of the 10th day of the 
test, the disease in the majority of the animals treated 
with substance No. 3582 orally had a distinctly milder 
course. In most instances these animals did not even show 
any symptoms while the control animals already displayed 
very grave symptoms of disease. Lack of motion and raised 
fur appeared several days later. Many mice recovered very 
20 rapidly from this condition. Only a part of the experimental 
animals succumbed to the infection, however much later than 
the control animals«' 
From a juxtaposition of the percentages of the mice 
surviving every day of the experiment it was possible to 
obtain a standard for determining the efficacy of a prepara- 
tion. The best result was obtained by oral administration 
of No0 3582 for a period of several days. The greatest 
number of survival were obtained with 5 times 5 mg per 
20 gm mouse, administered orally. With smaller daily doses 
the effect was smaller, likewise the substance appeared 
less effective in subcutaneous and-intraperitoneal applica- 
tion, evidently because of the greater toxic effect in this 
type of application. 
The use of No. 3582 as standard substance in almost 
all test series made it possible to calculate the average 
course of the disease in treated and untreated mice from 
a very large number of experimental animals, and to present 
it in an unequivocal curve. In this the control animals 
participating in the same large-scale.experiment were 
contrasted with the series treated with substance No. 3582. 
The following curve I is based on 8 experimental series 
with 79 treated and 150 untreated mice# The form of the 
course presented in curve II —untreated control animals 
infected with rickettsia — represents an average of 675 
infected mice* In juxtaposition to this is the curve of 
555 mice vfaich all had received orally the standard dose 
of 4, mostly 5 times 5 mg of substance No. 3582* While 
of the control animals only 8.4$ had survived the infection 
at the end of the 17th day of the test, in 31 large-scale 
experiments with No. 3582 an average of3# of the experimen- 
tal animals had survived, in spite of the fluctuations in 
virulence. Extension of the period of observation hardly 
changes this quotient at all; on the other hand the juxta- 
position of the two curves shows that a premature inter- 
ruption of the experiment on about the 10th or 11th day 
and an evaluation based thereon causes an overestimation 
of the efficacy of the substances tested. Ultimately, 
curve III represents the result of 70 experimental series, 
in which 1234 mice had received the standard dose of 5 
times 5 mg substance No. 3582 orally and in which 1257 mice 
had been infected as control animals, without receiving 
any treatment. In spite of the fluctuating virulence of 
the causative agent, an average of 58$ of the animals 
treated with No. 3582 survived, whereas only 19$ of the 
control animals survived. Extending the period of obser- 
21 vation does not change the curves in any appreciable manner® 
Experiences lasting more than one year have taught that 
the percentage of mice surviving after treatment with No* 
3582 fluctuates according to the virulence of the rickettsia; 
i.e®, when the virulence was high, all control animals died 
rapidly, and only a small percentage of the 3582-treated mice 
remained alive® If, on the other hand, virulence was low and 
20-30$ of the control animals remained alive, up to 100$ of 
the 3582-treated animals survived. There always was a certain 
distance between the two curves, which enabled the author to 
establish an efficacy quotient. If I represents the percen- 
tage of surviving animals after treatment, and II represents 
the percentage of surviving control animals, based on the 
animals at the beginning of the test, the efficacy quotient, 
i.e*, the percentual number of the mice which is preserved 
alive by chemotherapeutic treatment after subtraction of the 
control animals, is calculated from the formula: 
I - II 
Q, s 
. 100 
Application of this formula yields from curve II an 
efficacy quotient of 47*6$ and from curve III an efficacy 
quotient of 48.2$. In spite of great fluctuations of 
virulence this efficacy quotient thus remained almost 
unchanged in the two halves of the year® 
100 - II 
Tested in the same manner, Rivanol, Trypaflavin. Atabrlne, 
and numerous other chemotherapeutics proved ineffective® 
The fact that after treatment with substance No.3582, on basis 
of the large amount of experimental material at hand more than 
48$ (after subtraction of the surviving control animals) ware 
cured represents a great success in view of the fact that most 
of the chemotherapeutic tests always had negative results® 
This success justifies clinical tests of applying the substance 
in true typhus. These tests are even more justified as it is 
known from other chemotherapeutic model tests that even a 
delay of the course of the disease in the animal may be con- 
sidered as an indication for good chemotherapeutic efficacy in 
the human organism* 
Studies on the clarification of the mode of action of 
the substance are in progress. One must assume that the 
preparation changes into a more effective form when it passes 
through the intestinal wall; in any case, it appears in the 
urine as an amido-compound which is characterized by pro- 
nounced fluorescence. This amido-oompound possesses slight 
spasmolytic properties which are perhaps eiiplained by the 
clinically observed antidiarrheal effect. Tests on dogs and cats shown that in oral administration there was distinct 
excretion of the substance through the bile* 
Besides the effect upon the murine typhus strain, the 
substance possesses additional, very considerable there** 
peutic properties* In subcutaneous and oral application 
it is characterized by a very pronounced effect upon general 
streptococcus infections, which is distinguished from the 
indirect effect of the sulfonamides by the fact that the 
streptococci are killed rapidly in vivo. Even in great 
dilutions it prevents the development of many types of 
bacteria. In tests on mice it caused, upon oral adminis- 
tration, spontaneous lemtOlosis to disappear completely® 
Application in the human organism 
Tolerance. Substance No. 3582 has a repulsive taste 
which causes sensitive individuals to vomit. In ingestion 
of the substance one must see to it that it does not remain 
too long in the mouth and that no No* 3562 enters into 
solution from the granular state. Thus the substance 
is best ingested in the dry state, and followed by much 
water or other beverage. It is not recommended to ingest 
the substance into an empty stomach, because thus possibly 
irritations of the mucosa by the substance might cause 
nausea. Healthy individuals who ingett the granulated No. 
3582 observing these precautions will tolerate it as a rule 
for weeks without any disturbing effects. In typhus patients 
there may, however, occur vomiting even after correct in- 
gestion of the substance; this vomiting is, however, 
probably of cerebral causation, and less connected vdth 
the substance then with the disease. Many typhus patients 
tolerate No. 3582 in granular form without difficulty. 
Experiences with typhus patients 
Already at this time substance No* 3582 has proved its 
worth in the treatment of typhus in a number of cases; it 
is especially effective in the treatment of the early stages 
of the disease. In general, one administers individual doses 
of 0.25, corresponding to one teaspoonful of the granulated 
substance, in consecutive intervals of 6 hrs. One course 
of treatment requires as a rule 6 individual doses, a maxi- 
mum of 10 doses. The results of the treatment generally 
become evident after about 2 days. At this point in cases 
with pronounced diarrhea t e stools are distinctly affected® 
The lowering of temperature is not the result of an anti- 
febrile effect of No. 3582, but it is a specific effect, 
since in experimental tests in febrile animals the substance 
23 has no antifebrile effect. In the same sense one must also evaluate 
the observation that after 3532-treatment in typhus patients the 
lowering of the temperature takes place before the exanthem becomes 
pale* 
If after a longer administration of #3532 there occur symptoms of 
stomachal irritation, or if the patient vomits a dose of the substance 
the 3532-therapy may be continued after a pause of a few hours. One 
often succeeds in stopping cerebral vomiting by administration of 
0*3 gm chloretone. 
3* Substance #3532 used in other diseases. 
#3582 proved successful also in the treatment of Volhynian fever. 
In this a smaller number of individual doses will generally suffice. 
Because of its general chemotherapeutic properties, #3582 is suitable 
for the treatment of bacillary dysentary and non-specific intestinal 
affections. For amebas, #3582 has a specific efficacy corresponding 
to that of Rivanol; thus it is useful in the treatment of amebic 
dysentary. 
4. Form of application. 
Substance #3582 is used in granular form, of which a heaping 
teaspoon corresponds to the customary individual dosage of 0,25, 
it is not to be ingested in an empty stomach. The granular substance 
is ingested in a dry state, and it is washed down immediately with 
a generous amount of liquids. 
5, Packing, 
Bottles containing 100 gm of the granular substance. One heaping 
teaspoon corresponds to 0,25 gm. Chemotherapeutic test with mice, infected with Rickettsia Moosori. 
Surviving in % after treatment with substance #3582 
% Surviving 
10C 
9o 
80 
70 
60 
50 
40 
30 
20 
10 
I. Substance #3532 \ 
4 times 5 mg (per 20\gm 
mouse) average of \ 
79 mice \ 
II. Control group, un* 
treated. Average pf 
150. \ 
1 2 3 4 5 6 7 8 9 10 11 12 13 U 15 16 17 Average life of mice infected with Rickettsia Mooseri and 
treated with substance #35&2, 
% Surviving 
100 
90 
80 
70 
60 
50 
40 
30 
20 
10 
Treatments 
I. Substance #3552 \ 
5 times 5 mg per 20 gm mouse 
orally. \ 
Average of 555 mice \ 
II. Control group, un- \ 
treated. Average of 675 mice 
1 2 3 4 5 6 7 8 9 10 11 12 13 U 15 16 17 
Day of test Chemotherapeutic effect of substance #3582 in mice infected with 
Rickettsia Mooserl. 
Surviving 
100 
90 
80 
70 
60 
50 
'40 
30 
20 
10 
I• Substance #35Bfe 
Average from 12$4 mice 
treated with 5 tipies 5 mg 
per 20 gm mouse orally. 
II, Control group 
Average from 1267 un- 
treated mice. 
12 3 4 5 6 7 8 9 10 11 12 13 U 15 16 17 
Day of test APPENDIX L 
RUTENOL 
I.G. Farbenindustrie A.G. Frankfurt (Main)- Hftchst, 
Chemisch-Pharmazeut. u. Bero-Bakteriologische 
Abteilung. 
R. Fussg&nger. 
Chemotherapeutic remedies for true Ijyphus with specific efficacy 
have not been known until now. For the last 10 years systematic inve- 
stigations have been undertaken for the discovery of such remedies. 
Above all, Otto, Wohlrab, and Sch&fer have conducted extensive series 
of tests, but it was not possible to find anything more than just indi- 
cations of an affect upon the disease in the mouse. For a causative 
agent, these investigators used a rickettsia-transmitted strain of 
Mexican typhus tabardillo fever), isolated by Mooser, on whose suit- 
ability for chemotherapeutic experimental series Wohirab reported in 
1937 at the 17th meeting of the Vereinigung ffcp Mikrobiologie, 
The danger of increased incidence of typhus occasioned by the 
Eastern campaign caused the author to take up very extensive laboratory 
experiments to discover a chemotherapeutic substance for medicinal 
therapy of typhus, since the manufacture of vaccines in quantities 
necessary for the protective inoculation of the entire military and 
civilian personnel in the Eastern area could not be performed even 
with the best organization. 
Since work with the causative agent of true typhus in large 
experimental series is difficult and since the study of immunity con- 
ditions showed the close relationship of genuine typhus with the caus- 
ative agent of Mexican typhus, the chemotherapeutic test series were 
performed with Mooser's strain. Extraordinarily many preparations from 
a multiplicity of chemical groups were tested for their efficacy by 
means of this model test. Above all many of the classical chemothera- 
peutic remedies were examined; in most cases they proved to be totally 
ineffective. Certain indications of an effect were found in oral 
administration of some arsinic acids. In the further course of these 
large-scale experiments a substance was found which has a very regular, 
strong influence upon the course of the disease in regard to intensity 
and lethal outcome, and in the application of which a very large 
percentage of the infected experimental animals were kept alive and 
were cured. This substance is No 3582, in entensive clinical tests in 
genuine typhus, Wolhynian fever, and other rickettsioses. It is a 
nitroacridine derivative of complicated structure. A further intens- 
ification of the effect was obtained by the combination of the base 
of substance 3582 with an arsinic acid. RutenoJ. is a salt from the 3582- base with this arsinic acid, and it has been used since in clin- 
ical tests. 
Toxicology* 
Rutenol is only slightly toxic. The dosis tolerata maxima is 
per kg mouse 0.5 gm with subcutaneous and 1.5 gm in oral administration. 
Rabbits tolerate 35 mg per kg intravenously. 
Chemotherapeutic data! 
For biological tests of the new typhus remedy on the causative 
agent of Mexican or murine typhus, mice were used in large test series, 
as experience had shown thqt uniform results can only be obtained if 
each preparation, each individual dosage, and each manner of administ- 
ration (subcutaenous, oral, intravenous) are applied to as large a 
group of mice as possible, in order to reduce the biological stray 
results occurring in this infection to a minimum. For the infection 
of the series of mice, the author used the emulsified brains from 
gravely diseased passage animals, in certain dilutions, which caused 
a 90 - 100 % mortality in the untreated control animals. In spite of 
frequent adjustment of the optimal dilution of the emulsified brains 
there appear fluctuations in virulence, which render the determination 
of effective remedies difficult. After the basic substance, namely 
preparation #3582, had excelled time and again in all tests, the author 
began in all large-scale tests to treat a collective group with this 
substance, in addition to the untfeated control animals, and thus he 
was able to determine the degree of efficacy of a new substance in 
comparison with No. 3582 as a standard substance. 
The aspect or the disease in intraperitoneally infected mice 
had approximately the following courses On the 4-th or 5th day after 
infection the first symptoms of the disease became visible. They 
were a lack of motion and raised fur; as the disease continued, there 
appeared uni- or bilateral conjunctivitis, and extensive edemas 
developed in the head of the animal. Before death occurred — gen- 
erally between the 8th and 10th day of the test — the author obser- 
ved occasional symptoms of paralysis, and frequently diarrhea and 
spasms. While the mice in the control series had, with very few excep- 
tions died by the end of the 10th day of the test the disease in the 
majority of the animals treated with substance # 3582 orally had a 
distinctly milder course. In most instances these animals did not 
even show any symptoms while the control animals already displayed 
very grave symptoms of disease. Lack of motion and raised fur 
appeared several days later. Many mice recovered very rapidly from 
this condition. Only a part of the experimental animals suwumbed to 
the infection, howecer much later than the control animals. 
From a juxtaposition of the percentages of the mice surviving 
every day of the experiment it was possible to obtain a standard for 
determining the efficacy of a preparation. The best r«ilt was 
obtained by oral administration of #3582 for a period of several days. 
29 The greatest number of survivals was obtained with 5 times 5 nig per 
20 gm mouse, administered orally*. With smaller daily doses the effect 
was smaller, likewise the substance appeared less effective in sucu- 
taneous and intraperitoncal application, evidently because of the 
greater toxic effect in this type of application. 
The use of ft 3582 as standard substance in almost all test ser- 
ies made it possible to calculate the average course of the disease in 
treated and untreated mice from a very large number of experimental 
animals, and to present it in an unequivocal curve* In this the cont- 
rol animals participating in the same large-scale experiment were 
contrasted with the series treated with substance #3582. The curve 
depicting this represents the average of 675 mice infected with rick 
ettsias but not treated with any remedy (control animals)• Contrasted 
to this is the curve of 555 mice which all had received at least the 
standard dosage of 4, but most mostly 5 times 5 mg substnace #3582 
orally. While of the control ani als only 8*4$ survived the infection 
by the end of the 17th day of the experiment, in 31 large-scale exper- 
iments with #3582 an average of 52$ of the experimental animals surv- 
ived, in spite of the fluctuations in virulence. Extension of the 
period of observation hardly changes this quotient at all; on the other 
hand the juxtaposition of the two curves shows that a premature 
interruption of the experiment on about the 10th or 11th day and an 
evaluation based thereon leads to an overestimation of the efficacy 
of the substances tested. 
After it had become evident that experimental typhus may also 
be Influenced effectively by some arsinic acids, the author began to 
produce a series of arsinic acid salts of the basic substance #3582, 
which was found to be so effective, and to compare them with the 
latter. These tests were conducted in such a manner that lit the 
experiment always the same parts of the nitroacridine base of sub- 
582 were administered with the corresponding quantities 
of the arsinic acid, in order to compare quantitatively the increase 
of the effect by the addition of the arsenic acid. One of the most 
effective of the arsinic acid salts received the name "rutenol". It 
contains about 50$ of the nitroacridine base. The added curve 
shows for comparison, besides the course of the experiment in the 
untreated controls and in those treated with standard preparation #3582 
the curve No I which is the average of several experiments with rutenol 
(5 times 10 mg orally per 20 gm mouse) from 115 mice. According to 
this curve on the 10th day of the experiment still 96$ of the experi- 
mental animals were surviving, whereas only 25$ of the control animals 
remained alive at that time. For the 17th day of the experiment the 
corresponding numbers were 71 $ with rutenol and 8*4 $ with the control 
animals. From this curve it is seen that there is a most considerable 
influence upon the experimental typhus infection. This result repres- 
ents a great success, in consideration of the many chemotherapeutic 
tests in experimental typhus, which nearly always had a negative 
course; this success justifies the clinical testing of the applicat- 
ion of rutenol in true typhus. 
30 Work on clarifying the mechanics of the effect of this substaucw 
is in full progress. It must be assumed that rutenol when passing 
through the intestinal wall is changed to a more effective form- The 
nltroacrldine component reappears in urine as an araido-coinpound charac- 
terized by pronounced fluorescence. This amido-compound possesses 
weak anti-spasmotic (?) spasmolytic properties, probably explained by 
the clinically observed antidiarrheal effect. In oral administration, 
tests performed with dogs and cats showed a distinct excretion through 
the bile. 
Besides the effect upon the murine typhus strain, rutenol possesses 
very considerable additional therapeutic properties. In subcutaneous 
and oral administration it is characterized by a powerful effect 
upon general streptococcus infections, which is distinguished from the 
indirect effect of the sulfonamides by the fact the streptococci 
are rapidly killed in vivo. Further even in greatest dilutions it 
possesses the property of impeding the development of numerous bact- 
eria, In experimental tests on mice it causes, in oral administration, 
spontaneous lambliosis to disappear completely. 
Application in the human organism. 
1. Tolerance, 
Healthy individuals tolerate rutenol without any disturbance of 
their well-being. In patients with gastric disease and also in patients 
with grave typhus cases it amy, especially in continuous application, 
lead to irritations of the gastric wall; thus it is recommended that 
the substance never be ingested into the empty stomach and always be- 
washed down by means of some beverage, soup, or oatmeal, and if neces- 
sary one-half to one day of intermission is to be interpolatad in the 
course of therapy. 
2, Experiences with typhus patients. 
Rutenol has already proved its worth in the treatment of typhus 
in a number of cases and it seems to be especially effective in the 
early stages of the disease. Success of the treatment is generally 
preceived after 2 days. At this point, a distinct effect also is 
noticed in the stools of cases with pronounced diarrhea. The decrease 
in fever is not the result of an antifebrile effect of rutenol, but 
it is a specific effect, since rutenol in experimental tests in 
febrile animals did not have an antifebrile effect. In the same sense 
one must evaluate the observation that after rutenol treatment the 
lowering of the fever in typhus patients takes place before the dis- 
appearance of the exanthema» 
In general one administers individual doses of O.A gm continually 
in 6 -hr. intervals. If that is not possible one may administer the 
same dose three times daily. A cure requires as a rule 6-10 indiv- 
idual doses. 
31 If after longer administration of rutenol there occur stomachal 
Irritations, they manifest themselves by the fact that the patient 
vomits the substance. However, there is no further injury to the 
patient. In the animal experiment even with large over-dosage rutenol 
never causes a recognizable injury of the gastric and intestianl muc- 
osas. Thus there should be no hesitations to continue the administr- 
ations of rutenol as long as the symptoms of stomachal irritation can 
be overcome, possibly by some pause in the treatment. 
3. Rutenol in other diseases. 
Rutenol also proved successful in the treatment of Wolhynian 
fever. Here as a rule a smaller number of doses will, suffice. Because 
of its general chemotherapeutic properties rutenol is also suitable 
for the treatment of bacillary dysentery and non-specific intestinal 
affections. Toward amebas rutenol has a specific effect of the type 
of that of rivanol and it is thus also useful for the treatment of 
amebic dysentery. 
4. Forms of application. 
Rutenol is used in form of a % granulate, of which 2 tea- 
spoons correspond to the customary individual dose of 0.4- gm. Rutenol 
is not to be ingested into an empty stomach; it is best administered 
in combination with oatmeal, soup, or some beverage. It must be poi- 
nted out expressly that sympto s of stomachal iracompatibility are ex- 
ceptional cases and that they, due th their harmless nature, in no 
wise exclude the continuation of the treatment after some interruption. 
5. Packing. 
Bottles containing 100 gm of the granular substance. 
Two teaspoons of granular substance equal to 0.4- gm. 
Parenteral rutenol therapy: 
Rutenol is not to be administered intramuscularly and subcuta- 
neously, as it causes very great irritations in the tissues. Also the 
intravenous injection of aqueous solutions causes difficulties as very 
great dilutions must be chosen to avoid vascular thromboses. However, 
if one applies rutenol in solution with 25 % alcohol addition, there 
generally appear no injuries to the veins, so that the author recommends 
for intravenous injections an alcoholic special solution which can eas- 
ily be prepared by means of an iso-double-ampule. 
Rutenol is injected intravenously in thA dosages of 0.1 - 0.25 
daily or three times per week. Since in wartime conditions the acqui- 
sition of iso-double-ampules for the 0.25 dosage is difficult, the pre- 
paration is issued in a dry-ampule with foot, into which the contents 
of the accompanying ampule of solvents is injected. In this manner 
one obtains the solution ready for use in intravenous injection. Comparison of the chemotherapeutic effect of rutenol with 
that of substance 35B2 in mice infected with 
Rickettsia Mooseri. 
% surviving 
100 
90 
BO 
70 
60 
$0 
40 
30 
20 
10 
treatments 
I. Rutenol 
5 times 10 mg 
per 20 gm mouse, 
orally 
II. Substance 3582 
5 times 5 mg 
per 20 gm mouse, 
orally 
III, Control animals 
untreated 
1 2 3 4 5 6 7 B 9 10 11 12 13 14 15 16 17 
Day of test 
33 APPENDIX 5 
Photographs of I. G. Parboil Headquarters, Prankfurt 
a. Main, and of the HSchst Plant. 
I. G. HEADQUARTERS, PRANKFURT a. MAIN I. G. HEADQUARTERS, THANKPURT a. MAIN 
I. G. HEADQUARTERS, FRANKFURT a. MAIN HOCHST PLANT - STREET VIEW 
EOCHST PLANT eSchst plant 
hScHST S2MI-GQIftMBfiCIAL LABOKATOHY HOChST TABLET MACHINE 
kScHBT SALVARSAH fILLBE 
38