A Note on Two New Creosote 
Compounds, Creosote Vale- 
rianate and Guaiacol 
Valerianate. 
BY 
FRANK WOODBURY, M. D., 
PHILADELPHIA. 
REPRINTED FROM THE 
Neto Yotfc JtSclrical journal 
for September 1897. Reprinted from the New York Medical Journal 
for September 4, 1897. 
A NOTE ON TWO NEW CREOSOTE COMPOUNDS 
CREOSOTE VALERIANATE 
AND GUAIACOL VALERIANATE* 
By FRANK WOODBURY, M. D., 
PHILADELPHIA. 
In these days of new remedies of ephemeral useful- 
ness and evanescent reputation, it is refreshing to take 
up for brief consideration a drug with an established 
record of more than half a century. We recall the fact 
that while experimenting with tar from beech wood, 
Reichenbach, in 1832, first obtained a fluid substance 
which, on account of its possessing preeminently the 
power of preventing putrefaction in organic substances, 
he termed “ creosote,” or “ flesh preserver.” That ex- 
pert chemist also fully recognized the fact that the new 
chemical agent was not a simple but a very complex sub- 
stance, being composed principally of hydrocarbons of 
the aromatic group. It also contains a variable quantity 
of water. According to a recent authority, Marasse, it 
contains phenol, cresol, phlorol, guaiacol, and creosol; 
also methylcreosol, and the methylic ethers of guaiacol, 
* Read before the Section in Materia Medica, Pharmacy, and Thera- 
peutics of the American Medical Association, June 3, 1897. 
Copyright, 1897, by D. Appleton and Company. 2 
TWO NEW CREOSOTE COMPOUNDS 
phlorol, etc. By fractional distillation, Hofmann sepa- 
rated the dimethylic ethers of pyrogallol,of methyl pyro- 
gallol, and of propyl pyrogallol, from that portion of the 
creosote which passes over at a temperature above 220°. 
Hofmann discovered a new body, which he named coeru- 
lignol, which possesses powerful toxic properties and 
which should be carefully removed from creosote that is 
to be used for medicinal purposes. Its presence may be 
detected by treating an alcoholic solution of creosote by 
a test solution of barium hydrate. If coerulignol is 
present the solution will turn blue or show a bluish 
tinge. Benzine may be substituted for alcohol, with the 
same result. The United States Pharmacopoeia has 
adopted this as one of the tests indicating the suitable- 
ness of a specimen of creosote for medicinal use. 
I have referred to the early studies of creosote by its 
discoverer, Beichenbach, in order to bring into marked 
prominence the fact that it was first obtained from tar 
from the beech wood, and the early experiments made 
upon this agent, not only chemically, but also physiologi- 
cally and clinically, were made with this form of creo- 
sote, which is still considered the best for medical use, 
and which is now used almost exclusively in therapeu- 
tics. An analogous substance obtained from coal tar is 
simply a mixture of phenol and cresylol of variable com- 
position, or, in other words, an impure carbolic acid. 
They differ chemically principally in the following 
characters: Creosote from wood tar, added to an equal 
quantity of glycerin, is precipitated upon the addition 
of water; added tocollodion,it does not coagulate it; and 
when treated with nitric acid and heat, by Clarke’s 
method, yields oxalic acid. The so-called creosote from 
coal tar is not precipitated by water from its gelatin so- TWO NEW CREOSOTE COMPOUNDS. 
3 
lution; it does coagulate collodion, and yields picric acid 
when treated with nitric acid. There are corresponding 
and equally well-marked differences between the two com- 
pounds in their physiological action, the most impor- 
tant being the comparative innocuousness of pure wood- 
tar creosote, which can be taken in large doses, not only 
without toxic symptoms, but with decided therapeutic 
results. 
It has unfortunately occurred that for many years 
the coal-tar compound was frequently dispensed for creo- 
sote, and the latter consequently fell into disrepute for 
a time on account of the accidents and untoward results 
from its use. Creosote, according to Dr. H. C. Wood, 
also, is liable to be adulterated with eupion. In the last 
edition of the United States Dispensatory, by Professors 
Wood, Remington, and Sadtler, the statement is made 
that “ commercial creosote almost always contains car- 
bolic and cresylic acids from coal tar; and, indeed, much 
of what is sold for creosote is nothing more than impure 
carbolic acid.” I can not, however, agree with these 
distinguished authorities in the statement contained in 
the sentence immediately following the above, which 
says, referring to carbolic acid, that “ this acid strongly 
resembles creosote, and this resemblance probably ex- 
tends also to their therapeutical effects, so that the sub- 
stitution is less to be regretted than might otherwise 
he the case.” This I regard as a most misleading and 
dangerous teaching. A patient may take as much as 
six hundred drops of creosote, as in Dr. Freudenthal’s 
case (Medical Record, 1892), and recover practically 
without the use of any antidote; but would this case 
have resulted so favorably had the same quantity of car- 
bolic acid been swallowed instead of creosote? 4 
TWO NEW CREOSOTE COMPOUNDS. 
The principal constituent of creosote is guaiacol, the 
methyl ether of pyrocatechin, which is said to be present 
in the proportion of sixty to eighty per cent, in the best 
specimens. Guaiacol, in a pure state, is crystalline, but 
as commonly met with is an oily-looking fluid with a 
peculiar pungent, smoky odor. It can be obtained, how- 
ever, in an absolutely pure condition from a commercial 
sample, by cooling with a mixture of ice and salt, and 
then separating the crystals which have formed, as stated 
by S. Winghoffer (Pliarmaceutische Zeitung, Berlin, 
1894). 
On account of the liability to adulteration in com- 
mercial guaiacol and its variable composition, various 
compounds have been introduced into the practice of 
medicine as substitutes for creosote and guaiacol. Among 
the more prominent of these are the carbonate of guaia- 
col; guaiacol salol, benzoyl guaiacol, or benzosol; cinna- 
myl guaiacol, or styracol; guaiacol phosphite, guaiacol 
biniodide, and most recently the guaiacol valerianate, or 
geosot. These various compounds are administered with 
the view of their undergoing decomposition in the in- 
testinal tract and yielding guaiacol at the point where 
it can be most readily absorbed into the blood-vessels. 
In this way the administration of chemically pure guaia- 
col is accomplished more surely than by any other 
method. Moreover, these compounds, generally speak- 
ing, are more agreeable to the palate than the guaiacol 
itself. 
Chemistry.—The following is Dr. Wendt’s process 
for the manufacture of the valerianic-acid esters of creo- 
sote, eosote, and geosote: 
The description of the process of manufacture and 
of the physical and chemical properties of these esters TWO NEW CREOSOTE COMPOUNDS. 
5 
can properly be confined for the purpose in question to 
the esters of the two most important constituents of the 
wood-tar creosote, the guaiacol and creosol. 
To fifteen parts of creosol and twenty parts of valeri- 
anic acid seven parts of oxychloride of phosphorus are to 
be added. The mixture is then gently heated and boiled 
for the beginning in the water bath, and later on the 
open flame, until the development of hydrochloric acid 
has ceased. Afterward the mixture is washed with a 
three-per-cent, solution of caustic soda, well shaken with 
benzol, separated from the solvent medium and from 
water. 
The ester represents an indifferent, slightly yellow, 
oily liquid, and boils in the vacuum (two to three milli- 
metres pressure) between 117° and 121° C. The creosol 
used in the process is distilled in vacuum (two to three 
millimetres pressure) for the greater part between 81° 
to 85° C. 
The ester is easily soluble in alcohol, ether, and ben- 
zole, and has an aromatic odor. 
The process for the manufacture of guaiacol va- 
lerianate (geosote) is slightly different: 
Five parts of guaiacol are mixed with seven parts 
and a half of chloride of valeryl and gently heated until 
boiling occurs, at first over tbe water bath and later 
on the open flame, and until the development of hydro- 
chloric acid ceases. Then the mixture is washed with a 
cold three-per-cent, solution of caustic soda, diluted 
with benzol, separated from the solvent medium, and 
exsiccated. 
The physical and chemical properties of this ester 
are practically the same as those of the analogous creosol 
ester. The boiling point of both of them under the 6 
TWO NEW CREOSOTE COMPOUNDS. 
regular atmospheric pressure is stated to be about 260° 
C. Other compounds of the esters resulting from the 
process of esterification of commercial creosote with 
valerianic acid begin to distill at a temperature of about 
240° C. 
Physiological Action.—The valerianic-acid esters of 
the wood-tar creosote, especially of the most important 
constituents—that is, of guaiacol and creosol—are dis- 
tinguished by their special property of being easily ab- 
sorbed by the human system, and particularly by the 
fact that the heart and nerve tonic property of the 
valerianic acid is entirely preserved in these prepara- 
tions. 
Locally, guaiacol acts like solutions of carbolic acid 
to produce limited surface anaesthesia. Dr. Newcomb, 
of New York, at the recent meeting of the American 
Laryngological Association, recommended a five-per-cent, 
solution in olive oil as a substitute for cocaine for nasal 
operations. I have myself used tbe guaiacol valerianate 
for this purpose, both in full strength and diluted, and 
found it to possess, after a slight sensation of heat, de- 
cided anaesthetic effects, which are slower in appearing 
than after the application of cocaine, and which are not 
followed by secondary hyperaemia. The antiseptic power 
of guaiacol is also of great value in throat and nose 
operations. We know of the frequency of the presence 
of virulent bacilli in the nasal chambers of apparently 
healthv individuals, and the routine use of determent 
remedies, followed hv a decided antiseptic, such as guaia- 
col in oily solution, or the more agreeable valerianate of 
guaiacol, is now almost necessarv in the conduct of our 
hospital and private work. I should have stated that 
the valerianate has a strong odor of valerian, which al- TWO NEW CREOSOTE COMPOUNDS. 
7 
most masks the guaiacol, and produces a combination 
the odor of which is suggestive of walnuts. Guaiacol 
valerianate is a local anaesthetic to the skin when ap- 
plied in full strength. 
The temperature-reducing power of guaiacol, discov- 
ered by Sciolla in 1894,* is one of the most remarkable 
observations in the whole realm of pharmacology. This 
is not likely to occur in persons of good health with a 
normal temperature, but it is very marked in conditions 
of pyrexia. Caporali f has found that the external appli- 
cations of guaiacol not only relieve pain and reduce ab- 
normal temperature, but also increase the utilization 
of albuminoids by the organism and the absorption of 
fat and diminish oxidation. 
Administered internally, guaiacol and creosote both 
exert a powerful antiseptic action upon the contents of 
the alimentary canal. The temperature reduction ap- 
pears to be due to a special action of guaiacol upon the 
peripheral end organs of the nerves in the skin and mu- 
cous membranes. Upon the heart and blood-vessels there 
are no obvious effects from moderate doses of creosote 
or guaiacol. In larger doses it acts as a cardiac de- 
pressant, producing diaphoresis from relaxation of the 
blood-vessels, also giddiness and a tendency to fainting 
or collapse, convulsions, or coma, but these disagreeable 
effects are more likely to occur from commercial creosote 
or guaiacol than from a chemically pure article. In 
escaping from the blood by the bronchial mucous mem- 
brane and urinary organs, guaiacol exerts a local stimu- 
lant and antiseptic action. 
* Cronica di din. med. di Geneva for 1894, vol. i, p. 171. 
\ Riforma medica, Naples, No. 175, 1894. 8 
TWO NEW CREOSOTE COMPOUNDS. 
From this very brief review of the physiological 
action of guaiaeol I turn to the therapeutic use. 
As my time is limited, I will confine my remarks to 
the guaiaeol valerianate and creosote valerianate (for 
brevity, denominated eosote and geosote) which were re- 
cently introduced by Dr. Gustav Wendt, of Berlin, and 
which I have used, to some extent, for the past three 
months in private and dispensary practice. For the same 
reason I will omit notes of cases, and simply summarize 
some of the results of the use of these agents. Both of 
them are liquid and have characteristic odors, the guaia- 
col valerianate being more agreeable to patients than the 
creosote compound. 
In painful affections of the skin, attended by hyper- 
emia, such as inflamed acne, or abscess in the external 
auditory canal, pin boils, etc., applications of pure guaia- 
col valerianate (geosote) relieved pain and checked fur- 
ther pus formation. In chilblains this agent promptly 
relieved the annoying symptoms. Small compresses wet 
with guaiaeol and applied over the painful spots of 
Vallein afford almost immediate relief in neuralgia. 
In an acute erythema of the face, apparently ery- 
sipelatous, but possibly the result of rhus poisoning, a 
single application of this agent for ten minutes, followed 
by applications of zinc ointment containing creosote (one 
drachm to the ounce), afforded immediate relief and 
prompt disappearance of the inflammation. In the cases 
of children, however, or where larger areas are involved, 
the antithermic effect should be borne in mind, and not 
more than twenty-five to thirty drops applied at one 
time. I have already alluded to the use of guaiaeol 
valerianate in the treatment of affections of the nose. 
In acute rhinitis it should be diluted with three or more TWO NEW CREOSOTE COMPOUNDS. 
9 
parts of oil of sweet almonds, or liquid albolene, and in 
this form it acts as a protective as well as an analgetic 
and antiseptic application. In chronic rhinitis, especially 
the purulent form, as well as in some varieties of atrophic 
rhinitis, it is used in full strength with advantage, as 
many of these cases are kept up by the presence of viru- 
lent micro-organisms, the action of which is inhibited by 
the guaiacol. In ulcerated conditions, even of supposed 
tuberculous origin, a few applications of pure guaiacol 
or creosote valerianate materially promote the healing 
process, at the same time relieving pain. This observa- 
tion also applies to the larynx. I have not yet employed 
it in lupus, but it might be of service here for its local 
anassthetic effects, prior to scraping and the application 
of lactic acid and the subsequent use of a twenty-per- 
cent. guaiacol spray, as recommended by Dr. P. Watson 
Williams.* In tuberculosis of the air-passages external 
applications of pure guaiacol have been recommended 
by Dr. J. Solis-Cohen and others, and for this purpose 
the valerianate (geosote) would have especial advantage 
Internally, guaiacol valerianate is given either in milk 
or dilute alcohol, or, better, in the form of capsules. It 
checks bronchorrhcea and reduces the number of tuber- 
cle bacilli in the sputum, at the same time that it tends 
to prevent reinfection from the intestinal tract. It is 
well borne in moderate doses, ten to thirty minims daily, 
or one to three capsules, each containing two grains, ot 
three minims and a third, three times a day. 
In the treatment of gastric catarrh, chronic gastritis 
with gastrectasia, and other conditions associated with 
or producing fermentation of the contents of the stom- 
ach, I have used creosote valerianate (eosote) in prefer- 
* Medical Annual, London, 1897. 10 
TWO NEW CREOSOTE COMPOUNDS. 
ence to the guaiacol valerianate (geosote), as I believe it 
to exert stronger antiseptic action. It also overcomes 
nausea, and in connection with lavage favors return to 
a healthy condition of the mucous membrane and the 
reestablishment of appetite and normal digestion. 
Fifty years ago Dr. Fahnestock * used pure creosote 
as an application to erysipelas with remarkable success. 
I have already referred to the use of guaiacol valerianate 
as a local application for erythema, and would suggest 
its use as a topical agent in erysipelas and also in small- 
pox. 
In cases of pulmonary phthisis the remedy has been 
well borne, but I have had it too brief a time under 
observation to report decided results. Very favorable 
results, however, have been observed by Dr. Rieck, of 
Dassum, Germany,f who reports increase of appetite and 
powers of digestion, and of physical strength under *its 
use. In cases of the initial stage of tuberculosis of the 
lungs this improvement was quite marked, with a de- 
cided diminution of the cough; the expectoration not 
only became more free, but it also decreased steadily in 
quantity. The night sweats disappeared. 
This report was based upon the study of twenty-three 
cases (sixteen of catarrh of the apices and seven of 
developed tuberculosis) which were markedly bene- 
fited. 
I have found the guaiacol valerianate (geosote) of 
decided value in the treatment of the so-called catarrhal 
state which is sometimes considered as the pre-tubercu- 
lous stage of phthisis pulmonalis. It seems especially 
* American Journal of the Medical Sciences, 1848. 
f Deutsche Medizinal-Zeituny, Berlin, December 24, 1896. TWO NEW CREOSOTE COMPOUNDS. 
11 
suited, when properly diluted with some bland oil, for 
intratracheal injection in cases of advanced phthisis 
with or without ulceration in the larynx or cavity in the 
lung. 
Inhalation of creosote in combination with oil of 
peppermint is alleged by Ur. Carasso to cause a disap- 
pearance of the tubercle bacilli from the sputum, and he 
reports good results, clinically, after nearly ten years’ 
experience with it. Certainly this form of aerial medi- 
cation is worthy of extended trial, and guaiacol va- 
lerianate would be preferable to creosote for this pur- 
pose. 
I am of the opinion that in guaiacol we have the best 
remedy known at present to counteract the pernicious 
activity of the tubercle bacillus, and 1 may repeat the 
words of Dr. Jacobi: “ No one treatment of all forms of 
tuberculosis ever satisfied me to the same degree as has 
that of guaiacol.” When introduced into the stomach 
the guaiacol valerianate is decomposed and the effects of 
pure guaiacol, with the sedative action of valerianic acid, 
are obtained simultaneously, which may be expected to 
have a favorable effect upon the nervous manifestations 
of the disease, reducing cough and restlessness. In pneu- 
monia, Malderesco used applications of guaiacol to the 
thorax, posteriorly, over the affected area of lung, 
with reduction of temperature and a diminished 
mortality. 
I have thought that these few notes on a recent form 
of an old remedy might be of interest to the members 
of the section, and I beg to present, for their inspection, 
samples of the guaiacol valerianate (geosote) and creo- 
sote valerianate (eosote), the valerianic-acid esters of 
guaiacol and of creosote respectively. For further and 12 
TWO NEW CREOSOTE COMPOUNDS. 
more detailed information I may refer those interested 
to reports from the medical clinic of the Royal Charity 
Hospital, of Berlin, by Dr. Grawitz, and of Dr. Rieck, 
already referred to, which have appeared in the Deutsche 
Medizinal-Zeitung and the Therapeutische Monatshefte 
for 1896.