Oro-Pharynx,” De Santi[15] quotes Rosenberg,[16] who reports the
successful use of Formamint in cases of streptococcus infections,
tonsillitis and acute symptoms of chronic sore throat. According
to Seifert,[17] Formamint is a chemical combination of formaldehyd
and milk sugar. When the tablets are dissolved in the saliva, 0.01
per cent. of formaldehyd in its “status nascendi” is liberated and
exercises a strong disinfectant action. Seifert states that the
preparation is markedly palatable, since it contains a little citric
acid to render the taste cool and refreshing. In some experiments with
streptococci, pneumococci, typhoid and diphtheria bacilli, Seifert
found that a solution of one tablet in 10 c.c. of water destroyed
these germs in from five to ten minutes. A solution of the same
strength was also added to culture tubes of broth, agar, and gelatin,
with the result that no growth occurred in them, while distinct and
characteristic development of the bacteria took place in control
tubes. He does not state, however, how much Formamint solution was
added to the mediums.
[15] De Santi: Medical Magazine =16=:141, 1907.
[16] Rosenberg: Lancet, London =2=:1871, 1905.
[17] Seifert: Pharmakol. u. therap. Rundschau, 1904, No. 14; quoted by
De Santi (Note 2).
Daus[18] reports successful treatment of tonsillitis, mumps and middle
ear diseases. In these cases no other gargles or mouth washes were
used. He states that no indication of irritant or other injurious
action made its appearance even after large doses. In the same article,
F. Levy reports experiments as follows: Agar plates were prepared with
a culture of streptococcus from a severe case of quinsy. One half of
the plate was rubbed with saliva containing Formamint in solution.
(The strength of the solution used is not given.) In twenty-four hours
streaks of growth had appeared on one portion of the plates while the
part on which the Formamint saliva had been rubbed remained sterile.
Daus also found that agar and broth cultures of streptococcus shaken
with Formamint saliva remained sterile.
[18] Daus: Med. Klin. =2=:4110, 1906.
Rheinboldt,[19] investigating the effects of Formamint and of ordinary
formaldehyd on animals, concludes that formaldehyd is toxic in action
while Formamint is not.
[19] Rheinboldt: Deutsch. med. Wchnschr. =32=:587, 1906.
[Illustration: How the exploiters of Formamint capitalize the medical
profession. Miniature reproductions of typical Formamint advertisements
appearing in the newspapers.]
Rosenberg[20] corroborates this statement. He also found that agar
plates of _Bacillus prodigiosus_ were killed by Formamint solutions
in about four hours. He fails, however, to give the strength of his
Formamint solutions.
[20] Rosenberg: Therap. d. Gegen. =7=:55, 1905.
Wingrave[21] suggests the use of Formamint for infants! He recommends
that a tablet be crushed and wrapped in “butter cloth.” The ends of the
cloth are to be tied with thread, the Formamint is to be moistened, and
the packet is to be held in the mouth of the baby several times each
day.
[21] Wingrave: Lancet, London =2=:1067, 1906.
Young[22] published the results of some experiments by himself and
Delépine on the human throat. They dissolved a tablet in the mouth and
made swab cultures with the following results:
Immediately after taking the tablet 0 colonies
10 minutes after taking the tablet 35 colonies
30 minutes after taking the tablet 150 colonies
[22] Young: Lancet, London =1=:975, 1908.
They found no staphylococci at any time. Other results of swabbing
various parts of the throat before and after the use of Formamint,
reported by these investigators, show enormous reductions in the count,
claimed to be due to the action of Formamint. The count was made on
agar at 37 C., but they fail to state the time elapsing between taking
the Formamint and making the swab. Young also reports favorable
clinical results in cases of scarlet fever, diphtheria, sore throat,
and the like. It must be noted, however, that they state that the mouth
and fauces must first be thoroughly cleansed by swabbing and douching
before Formamint is used.
THE “CHEMICAL COMPOUND” CLAIM
The claims made in the advertising literature of Formamint are very
extravagant. Many are highly improbable. These statements will be
discussed later.
The statement is made that Formamint is a new chemical compound:
“Formamint is Pentamethanallactose, 5 CHOH + C₁₂H₂₂O₁₁. It is an
original combination of Formaldehyde with Lactose, a definite
chemical compound. The Formaldehyde molecule is locked up in it
until solution in the saliva takes place, when the Formaldehyde is
liberated in its _nascent_ state and is therefore active without
being irritant.”
Furthermore the makers contend that this new chemical compound is
entirely harmless. For example, Daus,[5] in an article on “The
Disinfectant Action of Formic Aldehyde on Mucous Membranes,” declares:
“No indication of irritant or other injurious action made its
appearance even after large doses. The urine remained free from
albumin and sugar.”
Such statements as these are found in the advertising literature:
“Formamint tablets are absolutely harmless and innocuous, even to
little children.”
“When dissolved in the saliva, Formamint Tablets liberate slowly
Nascent Formaldehyde in a most active yet non-irritant form.”
They maintain that Formamint is not only absolutely harmless, but
actually beneficial to the tissues. It may be used “to tone up and
strengthen the tissues, prevent hoarseness, and allay irritation in
singers, public speakers,” etc.
The claims urged as to its germicidal power are indeed glittering. This
“new chemical compound” is claimed to liberate formaldehyd in some new
and peculiar condition which, while it has a soothing and tonic effect
on the cells of the human tissues, can at the same time quickly kill
any form of bacterial life.
“Dissolving readily, it releases its germicidal, antiseptic
qualities, which impregnate the saliva and are carried naturally
and easily around the mouth and in the deepest crevices of the
throat--destroying the germs where they are causing the mischief.
Formamint prevents and destroys infectious germ life in a soothing
grateful way.”
“In the saliva it frees a germicide, fatal to germs but harmless
to the most delicate membranes. And flowing into every tiny corner
of the gums, tonsils and throat, into places where no gargle ever
reaches, it most effectively _disinfects_ the throat.”
The claims as to the preventive and curative effects of the preparation
cover a large portion of the category of human ailments and distresses.
The following quotations indicate some of its supposed properties:
“... it is therefore self-evident that Formamint should be
looked upon as a necessary part of the treatment of all forms of
tonsillitis.”
“The value of Formamint is equally great in diphtheric tonsillitis,
or as a prophylactic ...”
“The extraordinary success which I had with Formamint in a
school epidemic of scarlet fever during May and June, 1907, was
the determining factor which induced me to abandon the use of
inhalations, gargles, local applications in the treatment of
diseases of the throat, and to use Formamint exclusively for the
future.”
“There are naturally many similar conditions in which Formamint
may be used as a prophylactic, notably scarlet fever, mumps,
streptococcal and staphylococcal sore throats, ‘milk outbreaks’ of
sore throat, drain throats, hospital throats, and the like.”
“Formamint Tablets are indicated in Angina, Tonsillitis,
Pharyngitis, Stomatitis, Gingivitis, Glossitis, ulceration, spongy
or bleeding gums, Pyorrhea Alveolaris, ‘Smoker’s Sore Throat,’
Abscess or Boils, etc.”
“As a _Prophylactic_ against Diphtheria, Scarlet Fever,
Influenza, Measles, Epidemic poliomyelitis, and other pathogenic
micro-organisms. To neutralize putrefaction products in and about
the teeth, correct fermentative processes, deodorize and purify the
breath, etc.”
“To _tone up_, and _strengthen_ the tissues, prevent _hoarseness_
and _allay irritation_ in singers, public speakers, neutralize the
effects of dust-infection or _disinfect the saliva or sputum_ in
Influenza, Tuberculosis, etc.”
One man declares that along with specific constitutional treatment he
“had the best results from the use of Formamint tablets” in a case of
syphilitic ulceration of the tongue.
In short, Formamint is recommended for the treatment or prevention
of almost everything, from a bad breath to such grave conditions as
scarlet fever, diphtheria and tuberculosis, conditions in which a
delay in proper treatment--for instance, in diphtheria, a failure to
administer antitoxin--may result in the death of the patient.
A series of investigations was therefore undertaken in order to
discover whether the extravagant claims regarding the germicidal power
of Formamint could be verified.
Experimental Data
Two fifty-cent bottles of Wulfing’s Formamint were purchased in the
open market and were kept well stoppered to prevent deterioration.
Qualitative tests showed the presence of formaldehyd and the amount was
determined quantitatively by the hydrogen peroxid method as given by
Sutton.[23] The results were respectively, 1.99 per cent. and 2.03 per
cent. of formaldehyd.
[23] Sutton: Volumetric Analysis, Edition 10, p. 390.
[Illustration: Two Formamint advertisements reproduced in miniature
typical of those appearing in a certain type of medical journals.]
Some determinations were made of the germicidal power of Formamint
in vitro, that is, under controlled laboratory conditions. A
twenty-four-hour plain agar culture of _Staphylococcus aureus_ was
washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid
solution. A 1:100,000 dilution of this was made in each of three flasks
containing 100 c.c. of sterile saliva. Flask 1 contained 1 per cent. of
Formamint, Flask 2, 5 per cent.; Flask 3, containing no Formamint, was
kept as a control. At intervals samples were removed and dilutions made
and plated in duplicate on standard agar. The plates were incubated
twenty-four hours at 37 C., and plates containing less than 200
colonies were counted. The results are given in Table 1. After seven
days there was no appreciable difference in the plates.
Another test was made by adding a 1 per cent. Formamint solution to
plain agar plates inoculated with _B. coli_. A twenty-four-hour plain
agar culture of _B. coli_ was washed off in 10 c.c. of sterile 0.85 per
cent. sodium chlorid solution. A 1:1,000,000 dilution was made of this
and 1 c.c. added to each plate. Varying amounts of 1 per cent. solution
of Formamint were added to each plate. They were incubated seventy-two
hours at 37 C. After seven days’ incubation the count was the same. The
results are given in Table 2.
Another experiment was made thus: One loopful of a twenty-four-hour
plain agar culture of _Streptococcus lacticus_ was mixed with a tube
of North medium. One loopful from the inoculated tube was mixed with a
second tube of North medium. Both tubes were poured into Petri dishes
and allowed to cool. One half of each plate was well smeared with a 10
per cent. solution of Formamint in saliva. After twenty-four hours’
incubation at 37 C., only a few colonies appeared on the side to which
the Formamint had been applied, while the other half was thickly
covered with colonies.
TABLE 1.--SHOWING TIME IN WHICH CULTURES OF STAPHYLOCOCCUS AUREUS WERE
KILLED BY DIFFERENT AMOUNTS OF FORMAMINT
===================+=================+=============+=================
Amount of Formamint| Period of |Average Count| Count on Flask
in Saliva |Standing at 37 C.| When Plated |of Saliva Without
(Per Cent.) | (Hours) | | Formamint
-------------------+-----------------+-------------+-----------------
1 | 3 | 32 | 3200
1 | 6 | 0 | 7000
5 | 1 | Few | 5000
5 | 2 | 0 | 4100
5 | 3 | 0 | 3200*
5 | 6 | 0 | 7000*
-------------------+-----------------+-------------+-----------------
* The last two observations were made at the same time as on the 1 per
cent. solutions.
This work so far corroborates that reported in the literature quoted
by the manufacturers. But the fact that a compound is a germicide when
brought into intimate contact with bacteria in a solution or medium in
a test tube or flask does not prove that it will be effective when used
in the human throat.
THE ALLEGED GERMICIDAL ACTION
An attempt was made to discover whether or not the claims advanced by
the manufacturers as to the perfect germicidal action of Formamint in
all the nooks and crannies of the mouth and throat could be confirmed.
TABLE 2.--COUNT OF B. COLI CULTURES WITH DIFFERENT AMOUNTS OF FORMAMINT
======================================================================
No. c.c. of 1 per cent. Formamint 0 0.1 0.3 0.5 0.7 1.0 1.5 2.0 3.0
Count 160 33 39 26 15 12 2 0 0
----------------------------------------------------------------------
The first step in attacking this problem was to make comparative counts
of the number of bacteria in the throat before and after the use of
Formamint. The methods employed were as follows: The throat was gargled
with 50 c.c. of sterile 0.85 per cent. sodium chlorid solution. In
each case the same length of time, as far as possible, was used in the
process. The liquid was collected in a sterile flask. The gargling in a
series of experiments was begun not less than two hours after a meal.
After some preliminary work the following dilutions of the 50 c.c. of
salt solution were found sufficient: 1:1,000, 1:10,000 and 1:100,000.
Plates were made in duplicate from each dilution and incubated
seventy-two hours at 37 C. The counts were made on plates containing
less than 200 colonies. Except where otherwise noted standard agar was
used. The mediums were always prepared in the same way.
All the work was carried out under conditions as nearly natural
as possible. The Formamint was taken according to the directions
accompanying the trade package. Every opportunity was given the
Formamint to penetrate all the crypts and recesses about the mouth
and throat. The tablet was allowed to dissolve as slowly as possible,
the time usually being five to six minutes, and saliva was thoroughly
forced around the mouth before being swallowed. Plating was always
done immediately after gargling so that no growth could occur in the
salt solution. The results are given in Table 3. The numbers are
average counts from several plates and calculated to show the number of
bacteria washed out by the 50 c.c. of salt solution.
TABLE 3.--SHOWING THAT FORMAMINT DOES NOT GREATLY DECREASE THE NUMBER
OF BACTERIA IN THE THROAT
==========================+=========+=========+===========+===========
| | |No. Found |No. Found
| Time |Amount of|in Throat |in Throat
Conditions of Test | Since |Formamint| Before | After
|Preceding| Used | Use of | Use of
| Test | |Formamint |Formamint
--------------------------+---------+---------+-----------+-----------
Normal | ... | 0 | 15,600,000| ...
Normal | 1 hour | 0 | 38,500,000| ...
Normal | 1 hour | 0 | 30,500,000| ...
Normal | ... | 0 | 12,500,000| ...
Normal | 1 hour | 0 | 14,500,000| ...
| 1 hour | 0 | 23,500,000| ...
Tablet dissolved in mouth | 6 days | 1 tablet| ... | 15,000,000
and throat gargled one | | | |
hour later | | | |
Throat again gargled two | 1 hour | 0 | ... | 10,050,000
hours after Formamint | | | |
was used | | | |
Normal | 7 days | 0 | 62,000,000| ...
Normal | 1 hour | 0 | 72,500,000| ...
Normal | ... | ... | 61,000,000| ...
Tablets were taken, one | 2 days | 12 | ... | 39,100,000
per hour, and throat | | | |
gargled onehour after | | | |
last tablet was taken | | | |
Throat was again gargled 2| 1 hour | 0 | ... | 59,000,000
hours after taking last | | | |
tablet | | | |
Normal | 5 days | 0 | 35,000,000| ...
Normal | 1 hour | 0 | 62,000,000| ...
Normal | 1 hour | 0 | 72,000,000| ...
One tablet was taken each | 4 days | 24 | ... |175,000,000
half hour for 12 hours | | tablets | |
consecutively. Throat was| | | |
gargled one hour after | | | |
last tablet was taken | | | |
Throat was again gargled | 1 hour | 0 | ... |168,750,000
two hours after last | | | |
tablet was taken | | | |
Normal | 3 days | 0 |129,600,000| ...
Normal | 1 hour | 0 |177,000,000| ...
Normal | 1 hour | 0 |147,000,000| ...
Normal | 3 days | 0 | 79,000,000| ...
One tablet was taken | 1 hour | 1 | ... | 83,200,000
immediately after preced-| | | |
ing gargle. Throat was | | | |
again gargled at end of | | | |
one hour | | | |
Throat was again gargled 2| 1 hour | 0 | ... |134,750,000
hours after tablet was | | | |
taken | | | |
Normal conditions except | 19 days | 0 | 32,600,000| ...
that mouth and teeth were| | | |
throughly washed with | | | |
soap just before gargling| | | |
Same as above | 1 hour | 0 | 33,125,000| ...
Same as above | 1 hour | 0 | 40,375,000| ...
Teeth were not washed. | 2 days | 0 | 33,500,000| ...
Otherwise normal con- | | | |
ditions | | | |
Same as above | 1 hour | 0 | 43,330,000| ...
Same as above | 1 hour | 0 | 54,000,000| ...
Same as above | 1 hour | 0 | 50,000,000| ...
Same as above | 1 hour | 0 | 67,000,000| ...
Mouth and teeth thoroughly| 2 days | 0 | 5,270,000| ...
washed with soap just | | | |
before throat was gargled| | | |
Same as above | 1 hour | 0 | 10,916,000| ...
Same as above | 1 hour | 0 | 8,275,000| ...
Normal conditions, but 1 | 3 days | 0 |228,750,000| ...
c.c. of sterile rabbit’s | | | |
blood was added to each | | | |
plate | | | |
Count from the same gargle| 0 | 0 | 60,625,000| ...
as above. No blood used | | | |
in the plates | | | |
Normal conditions, but | 1 hour | 0 |431,250,000| ...
count was made on blood | | | |
agar | | | |
Count from the same gargle| 0 | 0 | 59,625,000| ...
asabove. No blood used in| | | |
the plates | | | |
Normal conditions, count | 2 days | 0 |683,300,000| ...
was made on blood agar | | | |
Same gargle as above, but | 0 | 0 | 58,500,000| ...
count was made on plain | | | |
agar | | | |
One tablet was taken just | 1 hour | 1 tablet| ... |558,300,000
after preceding gargle. | | | |
After one hour throat was| | | |
again gargled. Count on | | | |
blood agar | | | |
Same gargle as above, but | 0 | 1 tablet| ... | 55,875,000
count was made on plain | | | |
agar | | | |
Normal conditions | 2 days | 0 | 79,125,000| ...
One tablet was taken just | 1 hour | 1 tablet| ... | 56,250,000
ten minutes before gargle| 16 min. | | |
was made | | | |
Normal conditions | 2 days | 0 | 46,750,000| ...
One tablet was taken just | 1 hour | 1 tablet| ... | 38,500,000
ten minutes before throat| | | |
was gargled | | | |
Teeth and mouth were thor-| 5 days | 0 | 47,370,000| ...
oughly washed with soap | | | |
just before gargle was | | | |
made | | | |
Teeth washed as above and | 1 hour | 1 tablet| ... | 21,225,000
1 tablet taken 10 minutes| | | |
before gargle was made | | | |
--------------------------+---------+---------+-----------+-----------
Finally a determination was made of the number of streptococci in the
throat before and after the use of Formamint. The throat was gargled
in the manner previously described. The streptococcus count was made
by the dilution method as given by Heinemann.[24] Culture tubes were
used instead of fermentation tubes. One per cent. dextrose broth was
the medium employed. One cubic centimeter was added to each of a series
of ten tubes for each dilution and the following dilutions were used:
1:10,000, 1:100,000 and 1:1,000,000.
[24] Heinemann: Laboratory Guide in Bacteriology, p. 86.
The results given in Table 4 are the average count from a number of
dilutions and are reported as the total number washed out by the
50 c.c. of salt solution.
TABLE 4.--SHOWING THAT FORMAMINT FAILS TO REDUCE THE NUMBER OF
STREPTOCOCCI IN THE THROAT
==============+===========+===========+===========+==========
| | | No. Found | No. Found
| Time | Amount of | in Throat | in Throat
Conditions | Since | Formamint | Before | After
of Test | Preceding | Used | Use of | Use of
| Test | | Formamint | Formamint
--------------+-----------+-----------+-----------+----------
Normal | .... | 0 | 1,200,000 | ....
| | | |
One tablet was| | | |
taken and | | | |
throat gargled| | | |
one hour later| 4 days | 1 tablet | .... |14,750,000
| | | |
Normal | 3 days | 0 | 9,950,000 | ....
| | | |
One tablet was| | | |
taken and | | | |
throat gargled| | | |
ten minutes | | | |
later | 1 hour | 1 tablet | .... | 8,000,000
==============+===========+===========+===========+==========
Discussion
The contention that Formamint contains formaldehyd was confirmed by
analysis.
The manufacturers also maintain that Formamint is a new, definite
chemical compound, consisting of five molecules of formaldehyd and
one molecule of lactose, and that when dissolved in the saliva the
formaldehyd is liberated in some new and peculiar form, which they
call nascent formaldehyd. This new kind of formaldehyd is, according
to the advertising literature, especially powerful in its germicidal
properties and at the same time has absolutely no irritating or harmful
effects.
NOT A CHEMICAL COMPOUND
Thoms,[25] retained as an expert by the German government, decided,
after a series of chemical investigations, that Formamint was not
a definite chemical compound, but that it was probably a solid
solution of formaldehyd in lactose. He proved that when the process
of manufacture was carried out in exactly the way called for by the
Formamint patents, compounds containing a greater or less per cent. of
formaldehyd could be made while the other properties remained similar
to those of Formamint. The composition of the final product depended
on the proportion of the components used in the process. Therefore
Formamint did not form a safe means of uniform dosage.
[25] Thoms: Arb. a. d. Pharm. Inst. d. Universität, Berlin =11=:210,
1914.
As a result of Thoms’ work the German courts held that Formamint was
not a new chemical compound. Consequently the Formamint patent (Number
189036) was annulled in Berlin, Nov. 29, 1913.
Again the contention that formaldehyd in the nascent or active
condition is less poisonous and irritating than in its ordinary form is
contrary to what would be expected from the behavior of such compounds.
If it were liberated, as claimed, in the “nascent” condition, it would
be, for that very reason, not only more active but also more harmful.
As a matter of fact, Formamint did have an irritant effect on the
worker who carried out these investigations. When one tablet was
taken each hour for twelve consecutive hours, marked irritation of
the intestinal tract resulted. There was almost sufficient nausea to
cause vomiting and uneasiness in the alimentary canal following the
experiment. When the twenty-four tablets were taken the results were
similar but more pronounced. This is decidedly in contradiction to the
assertions of the manufacturers.
Otto Seifert,[26] moreover, cites the following:
“By Effects: Only a few patients complain of an unpleasant sharp
taste, burning of the tongue (Seifert, Sklarek). Among the general
symptoms observed are urticaria-like exanthems (Glaser, Roters),
which are accompanied by nausea, vomiting, headache, insomnia
and vertigo, burning and irritability especially in the larynx
(Meissner); phenomena of poisoning (Geissler); gastric disturbances
(Engelmann); renal irritation (Steinhard); unsuited for diabetics
(Voit).”
[26] Seifert, Otto: Die Nebenwirkungen der modernen Arzneimittel, 1915.
The contention that Formamint, when mixed directly with mediums
and left in contact with bacteria, will kill the organisms was
corroborated. Thus the statements and pictures in the booklet, “The
Gospel of Prevention,” which is enclosed with each bottle of Formamint,
showing the inhibition of growth of air bacteria on plates containing
Formamint are no doubt true and authentic.
Finally, the claim that Formamint is an almost perfect throat
disinfectant was by no means confirmed, as a glance at the tables will
show. One hour after it is taken, even when a tablet was used each
half hour for twelve hours, the number of bacteria in the throat was
practically the same as when Formamint was not used. Even ten minutes
after taking a tablet the number of bacteria in the throat was never
greatly reduced, as is maintained by the manufacturers.
HAS NO SELECTIVE ACTION
Formamint exerts no selective action in killing off the very delicate
organisms which are more apt to be pathogenic. When the comparative
counts were made on blood agar which would favor the growth of the
delicate parasitic organisms, no reduction whatever was shown by the
use of Formamint.
The number of streptococci was found to be the same, within limits of
experimental error, ten minutes after taking a tablet as it was before
the tablet was taken.
Therefore it seems that Formamint fails, as any such germicide would
be expected to fail, to kill bacteria in the crypts and recesses of
the throat, for when dissolved in the mouth it cannot reach and remain
in contact with the organisms long enough to kill them before it is
swallowed.
SUMMARY
Summed up, the investigation shows:
1. That the claims made for Formamint are extravagant and misleading.
2. That the recommendations for the use of these tablets may be, in
some cases, fraught with danger and are a menace, not only to the
health of the individual, but also to the safety of the community.
3. That the claim that Formamint is a definite chemical compound is
false.
4. That the use of Formamint may produce marked irritation of the
intestinal tract.
5. That Formamint is not a throat disinfectant, as the manufacturers
maintain, but its action on the bacteria of the throat is an almost
negligible one and dependence on Formamint for the prevention of
infection and for curing disease is not only unwise but dangerous.
6. That Formamint conflicts with the rules of the Council. False
statements are made with regard to its composition (Rule 1); grossly
unwarranted claims are made for its therapeutic properties (Rule 6),
and therefore its exploitation to the public (Rules 3 and 4) is a
public danger.
It is recommended that this report be published, to call attention not
only to the falsity of the claims made for, and the danger in the use
of, Formamint, but also to emphasize the utter inefficiency of all such
methods of “disinfecting” the throat.--(_From The Journal A. M. A.,
Aug. 28, 1915._)
HYDRAGOGIN
Report of the Council on Pharmacy and Chemistry
Hydragogin (C. Bischoff & Co., New York, selling agents) is advertised
as “a most powerful diuretic and cardiac tonic.” The composition given
is:
“Fifteen parts of the remedy contain 0.5 parts oxysaponin, 1.5
parts tincture of digitalis, 2.5 parts tincture of strophanthus,
scillipicrin and scillitoxin, the active principles of scilla
maritima, and alcohol.”
It is not clear from this statement whether 15 parts of Hydragogin
contain 2.5 parts of tincture of strophanthus, plus unspecified
amounts of scillipicrin and scillitoxin, or 2.5 parts of a mixture,
in unspecified proportions, of tincture of strophanthus, scillipicrin
and scillitoxin. The activity of strophanthus, after it enters the
blood stream, is about fifty times that of digitalis; hence, if the
former proportion is the true one, in giving an amount of Hydragogin
which ensures the full therapeutic effect of the digitalis, one would
administer an almost certainly fatal amount of strophanthus. Whatever
the proportion of strophanthus may be, however, the administration
of a mixture of digitalis and strophanthus in fixed proportions is
indefensible. At times it is advisable to follow one of these drugs
with the other in the treatment of cardiac disease. The simultaneous
administration of the two continuously in fixed proportions, however,
is injudicious, because of the great difference between their rates of
absorption and in their activity after they enter the blood stream. The
action of digitalis, moreover, persists much longer than does that of
strophanthus.
An advertising circular contains the following claim:
“The well-known diuretic properties of digitalis, strophanthus and
squills are greatly enhanced by the addition of the oxysaponin.”
This is not true. Saponins are not synergistic with digitalis
therapeutically; on the contrary, they exert a purely deleterious
action on the heart when they enter the circulation.
The symptoms of cardiac disease are often difficult to distinguish
from the toxic actions of the digitalis bodies. Since these bodies
must often be given to the point of beginning toxic action in order
to induce the full therapeutic effects, it is obvious that the
administration of a mixture of digitalis, strophanthus, saponin and
active principles of squill is especially liable to induce serious
toxic effects which cannot be distinguished from the symptoms of the
disease.
Hydragogin is a shotgun mixture of semisecret composition; it is
marketed under a therapeutically suggestive name, and advertised by
means of unwarranted therapeutic claims. It is therefore in conflict
with Rules 1, 6, 8 and 10. The Council held Hydragogin ineligible for
New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 4,
1915._)
FILUDINE
Report of the Council on Pharmacy and Chemistry
Filudine is said to be prepared by J. L. Chatelain, Paris, and is
sold in this country by Geo. J. Wallau, Inc., New York. It is offered
as a remedy for “biliary insufficiency,” “hepatic insufficiency,”
“intestinal dyspepsia,” “all affections of the liver (diabetes,
cirrhosis, cancer, etc.),” “malaria,” “obesity” and “tuberculosis.”
No quantitative information is furnished as to the composition of the
preparation and there are noteworthy discrepancies in the various
statements regarding the ingredients. In one number of “Treatment,”
a self-styled “Review” of medical literature (actually devoted to
advertising the preparations sold by Wallau), we are told that
“This product [Filudine] is a more concentrated and potent extract
of the liver, with which is combined an extract of the spleen. The
liver and the spleen are so intimately interdependent, that the
addition of a splenary extract to the liver extract is a signal
improvement from which a synergistic action results. Thiarféine is
also added, as it helps somewhat to combat the anaemia from which
all diabetics suffer more or less.”
Thiarféine is said to be
“Thiomethylarsinate of Caffein, a new salt discovered by M.
Chatelain.”
Another circular, which gives an imposing formula for “thiarféine” or
“thiomethylarsinate of caffein,” states that
“Sulphurated methylarsinate is an arsenical preparation devoid of
all toxicity on account of the intimate joining of its composing
parts.”
And that
“Filudine can never be contraindicated.”
A statement of composition in a later number of “Treatment,” however,
says that biliary extracts are components, in addition to the liver and
spleen extracts. Moreover, thiarféine, the “new salt discovered by M.
Chatelain,” is no longer “thiomethylarsinate,” but “thiocinnamate of
caffein”; and a new formula is furnished for it.
We are told that
“Methyl-arsinate cannot be used in cases where fever is present....”
“M. Chatelain at first studied the action of thiomethylarsinate;
clinical and physiological experimentation led him, however, to
adopt thiocinnamate of caffein, of greater activity and with no
contraindications.”
Nevertheless the same absence of contraindications was urged in
favor of Filudine when it was said to contain the now discarded
thiomethylarsinate of caffein.
The following are some of the unwarranted and even absurd claims:
“Filudine restores the liver’s functions. It is to the liver what
digitalis is to the heart; it overcomes the insufficiency and
stimulates the debilitated organ.”
In malaria “it is the only true specific when associated with
quinine.”
“Filudine is ... the ideal medication for tuberculosis, conforming
as it does with the most recent researches in the therapeusis of
this affection.”
“We will not go as far as to say that Opotherapy _completely
restores_ unhealthy livers, for although the lesions of the hepatic
parenchyma may be obliterated by regeneration, the lesions of
the connective tissues are permanent, and may be observed at the
postmortem examination. The new cells, however, do not present the
same unhealthy conditions as those of the former diseased gland
which they have replaced, and the liver can therefore function
normally, so that the patient lives on; and he is satisfied with
that.”
“Therefore, while regenerating the liver with Filudine, we cleanse
it and combat its congested state with Urodonal. We cause it to
produce urea from the excess of uric acid which it contains.”
“By the judicious and harmonious combination of the beneficial
effects of Filudine and Urodonal, physicians not only possess the
means of treating by rational methods Cirrhosis of the Liver in its
various forms (which is one of the most terrible diseases which can
afflict anyone) but what is still better, _they can cure it_.”
“The liver of a person suffering from obesity being incapable
of fulfilling its functions in regard to the fatty tissues, the
rational and up-to-date method of treatment is therefore to restore
to the system, in the form of Filudine, the liver extracts which
are lacking.”
Filudine is a mixture of semisecret composition. The therapeutic
claims are manifestly unwarranted. The name is not indicative of the
composition, whatever that may be, and no rational excuse is offered
for the combination of liver and spleen extracts (with or without bile
extracts) with “thiomethylarsinate” or “thiocinnamate” of caffein.
The Council therefore held Filudine ineligible for New and Nonofficial
Remedies.--(_From The Journal A. M. A., Sept. 18, 1915._)
LACTOPEPTINE AND ELIXIR LACTOPEPTINE
Report of the Council on Pharmacy and Chemistry
Mixtures of pepsin and pancreatin are therapeutically irrational;
the two substances are not indicated in the same conditions, nor can
they act together. Under physiologic conditions, such mixtures are
chemically impossible: in a liquid medium the ingredients destroy each
other.
Lactopeptin is manufactured by the New York Pharmacal Association,
Yonkers, N. Y. It is sold under the claim that it contains, pepsin,
diastase, pancreatin, lactic acid and hydrochloric acid. This product
was among the first proprietary preparations examined by the Council on
Pharmacy and Chemistry. The report of the investigation was published
in The Journal, March 16, 1907, p. 959. The preparation was found to be
practically inert--“essentially a weak saccharated pepsin,” devoid of
tryptic activity.
Six years later it was still widely advertised with the same irrational
claims. A referee (A) therefore examined Lactopeptine (powdered) for
the Council in 1913, and confirmed the previous findings. The referee’s
report was published in The Journal, Aug. 2, 1913, p. 358.
Nearly four months after this publication, the manufacturer protested
against the report, maintaining, contrary to the findings of the
Council, that Lactopeptine possesses pancreatic activity and contains
“loosely combined” hydrochloric acid. Referee A therefore repeated
his examination, and a second referee (B), independently, examined
specimens of Lactopeptine (powder) purchased on the open market for the
purpose shortly before.
A few specimens examined by these two referees showed a slight tryptic
activity; most of them showed none. The amount of hydrochloric acid
present was insignificant.
The reports of the two referees were referred to the manufacturers, who
again protested vehemently against these findings, this time on the
ground that the specimens were old. The manufacturers also cited the
work of three chemists to disprove the findings of the referees, and
demanded that the Council reexamine Lactopeptine, making use of fresh
specimens. The Council refused for the following reasons:
1. So long as the packages of Lactopeptine are not dated, the activity
of specimens known to be fresh is of no practical importance. The
activity of the actual market supply is the only question of interest
to the profession. The only fair test is that made on specimens
representative of the product sold to the ultimate consumer.
2. The evidence presented by the manufacturers did not warrant
a reexamination, since the work of two of the chemists cited
substantially corroborates the results obtained by the Council’s
referees from the fresher specimens. The figures for tryptic activity
obtained by the third chemist cited by the manufacturers could not be
accepted by the Council, since it was at variance with all other known
results of investigations of Lactopeptine.
3. As stated at the outset, whatever the tryptic activity of the
mixture, it is therapeutically useless. A demonstration of tryptic
activity in a mixture containing both pepsin and pancreatin is of
merely theoretical interest.
Such activity, of course, cannot be expected, even on theoretical
grounds, in liquid mixtures like Elixir Lactopeptine.
The Council therefore again declared Lactopeptine (powder and tablets)
and Elixir Lactopeptine ineligible for New and Nonofficial Remedies and
authorized publication of the following statement.
W. A. Puckner, Secretary
_THE COUNCIL’S REPORT_
Lactopeptine powder (New York Pharmacal Association, Yonkers, N. Y.)
was examined by the Council in 1907. At that time it was claimed to
contain
“... the five active agents of digestion--pepsin, diastase (veg.
ptyalin), pancreatin, lactic acid and hydrochloric acid--combined
in the proper proportion to insure the best results.”
The examination showed that the preparation was essentially “a weak
saccharated pepsin,” containing but small amounts of pepsin, no
hydrochloric acid, or mere traces only, and no diastase or pancreatin
(The Journal, March 16, 1907).
In 1913, the product was reexamined, because the claims, as to both
composition and therapeutic value, were still being made. Samples
were tested both of the American product, and of a British product
from John Morgan Richards & Sons, London. The original findings were
confirmed and the results were published in The Journal, Aug. 2,
1913, p. 358. Nearly four months later (November 24) the New York
Pharmacal Association wrote to the Council, objecting to the findings
and maintaining that Lactopeptine possesses pancreatic activity and
contains (“in loose chemical combination”) hydrochloric acid. In
accordance with the custom of the Council, the work was sent back for
review to the referee (A), whose conclusions were then tested by a
second referee (B), a physiologic chemist, not a member of the Council,
selected because of his special knowledge of the subject.
In December, 1913, Referee A made a large number of new tests to
determine proteolytic and amylolytic power. His results show that
the ferment activity of the preparation is so low as to merit no
recognition in practical use. The tests also show that the amount of
lactic acid or “loosely combined HCl” (or both) present is too small to
have any appreciable physiologic activity and therefore to be of any
therapeutic value.
Nine samples of Lactopeptine purchased in the open market in December,
1913, and January, 1914, were examined by Referee B early in 1914. His
studies show absence of amylase in all samples; presence of pepsin,
giving weak reactions even when compared with those of old pepsin
preparations; complete absence of trypsin in seven out of nine samples,
tryptic reaction being obtained in two samples, in one of which the
reaction, “slight at best and of no practical import,” was obtained
only after treatment for twelve hours or more.
The presence of tryptic activity in two out of the nine samples may
be due to the fresher condition of these specimens, as indicated
by the serial numbers. The evidence shows that it is a commercial
impossibility to market mixtures of pepsin, pancreatin and lactic acid
so that they can display any material tryptic activity.
It should be reaffirmed that mixtures combining peptic and pancreatic
activities are not feasible, because pepsin cannot act except in the
presence of acid, and pancreatin is destroyed by acid and by peptic
activity. Furthermore, in conditions in which pancreatin is called
for, pepsin is not, and vice versa; therefore the administration of
mixtures of pepsin and pancreatin would be unjustified, even if both
constituents could be expected to exert activity.
The foregoing observations apply to Lactopeptine in powder and tablet
form.
While mixtures of pepsin and pancreatin are unscientific and
unjustified, theoretically the two substances may coexist in a solid
preparation, and the activity of such a preparation is consequently a
proper subject of investigation. Theoretically as well as practically,
however, pepsin and pancreatin cannot exist together in solution. The
claims made for Elixir Lactopeptine and all other liquid preparations
sold as mixtures of pepsin and pancreatin are therefore impossible.
The Council has previously taken action (The Journal, Feb. 2, 1907,
p. 434) refusing to approve for inclusion with New and Nonofficial
Remedies such preparations, calling the attention of the medical
profession and of manufacturers to their worthlessness, and requesting
the American Pharmaceutical Association to instruct its committee on
the National Formulary to omit from the next edition of that work a
liquid preparation of pepsin and pancreatin recognized under the title
of “elixir digestivum compositum.”
It is recommended that the Council reaffirm this previous action,
and that Lactopeptine and Elixir Lactopeptine be declared ineligible
for New and Nonofficial Remedies because of conflict with Rule 10
(“No article will be admitted which, because of its unscientific
composition, is useless or inimical to the best interests of the public
or of the medical profession”).
Manufacturers’ Protest and Council’s Answer
The foregoing was submitted, together with the findings of the two
referees, to the manufacturers. They protested again, alleging that:
AGE OF SPECIMENS
_First._--The specimens of Lactopeptine examined by the second referee
were old. The dates of manufacture corresponding to the several batch
numbers are supplied by the manufacturers as follows:
2275 (Powder) September, 1908
2301 (Powder) June, 1909
2312 (Powder) December, 1909
2348 (Powder) October, 1911
2352 (Powder) December, 1911
2364 (Powder) July, 1912
2374 (Powder) March, 1913
2383 (Powder) October, 1913
1638 (Tablets) October, 1911
The manufacturers assert that they do not understand how specimens of
these ages could have been purchased on the open market in 1913 and
1914, inasmuch as their agents are and long have been instructed to
take up from the druggist all lots of Lactopeptine which, as indicated
by the batch numbers, have attained “any appreciable age.” The age of
the specimens, the manufacturers declare, deprives the table in the
second referee’s report of “all significance or interest.”
As previously stated, however, the specimens of Lactopeptine examined
were purchased on the open market in various localities in unbroken
packages, in December, 1913, and January, 1914. They thus represent
stock used in filling physicians’ prescriptions or sold to the
public. Neither the referees nor any one connected with the Council
had any means of knowing the age of the specimens until the dates of
manufacture were furnished by the New York Pharmacal Association. The
first tests of the second referee were made in February, 1914, on
Specimens 2374 and 2383, which were then, it would appear, about one
year old and four months old, respectively. The Council has repeatedly
urged that pharmaceutical substances which are subject to deterioration
should be dated by the manufacturer, and a similar suggestion has
been made by the Bureau of Chemistry of the U. S. Department of
Agriculture concerning mixtures containing enzymes. Notwithstanding
the instructions which the New York Pharmacal Association claims to
have given its agents, the market supply of Lactopeptine in December,
1913, and January, 1914, was not composed of new stock, and until
the manufacturers adopt the practice of dating packages, there can
be no assurance that it will be fresh. In this connection, it is of
interest to note that the Bureau of Chemistry of the U. S. Department
of Agriculture has issued a warning that it will judge such products by
the degree of their activity when they reach the consumer, i. e., as
they are found on the market.
REPORTS OF OTHER CHEMISTS
_Second._--The New York Pharmacal Association cites the work of several
chemists, who have examined Lactopeptine and report the presence of
tryptic activity. Dr. S. R. Benedict in December, 1913, reported to
the Council “distinct” tryptic activity (digestion in twelve hours by
Lactopeptine of 4.2 times its weight of fibrin containing 50 per cent.
moisture) in specimens examined by him. These specimens were numbered
2382, and were therefore probably manufactured in October, 1913;
compare the dates furnished by the manufacturer for the specimens used
by the second referee. No tests against other preparations possessing
tryptic activity are reported, and Dr. Benedict expressly disclaims
any opinion as to the therapeutic value of the preparation.[27] Dr.
P. B. Hawk, whose report was submitted by the manufacturers, found in
Lactopeptine by Fermi’s method one-fifth tryptic activity of that of
Merck’s pancreatin, and by Grützner’s method an activity of 18 per
cent. of the pancreatin. A test for the production of tryptophan was
reported positive. The New York Pharmacal Association also submitted
a report from Dr. A. W. Balch, who found pepsin, rennin, trypsin,
steapsin, amylopsin and lactic acid present in Lactopeptine; also
an amount of combined hydrochloric acid in 1 gm. the equivalent of
1.05 c.c. tenth normal solution or 0.00383 gm. hydrochloric acid. (He
reports digestion in twenty-four hours by Lactopeptine of 25 times its
own weight of fibrin. “An active extract of pancreas reacted exactly
like the Lactopeptine solution.”) The serial numbers of the specimens
tested by Hawk and Balch are not given, but no doubt they were fresh.
[27] Dr. Benedict’s personal communication to a member of the Council
is as follows:
“In the report of the Council upon Lactopeptine which you sent to me,
I find the following statement: ‘Careful examination failed to show
the presence of either diastase or pancreatin.’ In this connection
I will cite to you the following experiment carried out by myself:
A package containing a 1-ounce bottle of Lactopeptine (powder) with
seal unbroken was purchased in the open market and opened in this
laboratory. The label bore the special Number 6 2382. Two hundred
milligrams of this product was dissolved in 50 c.c. of a 0.25 per cent.
solution of sodium carbonate in water. This solution was divided into
two portions of 25 c.c. each. One of these portions was boiled at once,
and after cooling was added to 1 gm. of moist fibrin contained in a
flask. The other portion (unboiled) was also added to 1 gm. of moist
fibrin contained in a flask. Both flasks (after addition of 5 c.c.
of toluene to each) were stoppered and placed in an incubator at 37
degrees, and left there for twelve hours. Examination of the two flasks
at the end of this period showed that the one to which the unboiled
solution of Lactopeptine [powder] had been added contained much less
solid protein than did the other. Although this fact was obvious to
the naked eye, the exact extent of digestion in the two flasks was
determined by heating both to boiling, acidifying with acetic acid,
diluting to definite volume, filtering and determining the nitrogen in
the filtrate by Kjeldahl’s method. Subtracting the trace of nitrogen
contained in the filtrate of the control flask, the results showed
that 42 per cent. of the original fibrin present had been dissolved
by the unboiled Lactopeptine solution. This can be ascribed only to
tryptic activity under the conditions of this experiment. Furthermore,
this is not simply a ‘trace’ of activity, but is at least sufficiently
marked to warrant a statement that this sample showed a distinct
tryptic activity. Inasmuch as I have obtained exactly similar results
with two other samples of Lactopeptine (powder) (these being the only
ones I have examined), I am inclined to question the correctness of
the Council’s statement regarding the absence of trypsin from this
preparation. [As noted above, a fresh preparation was used.--Ed.]
“May I again add that I am making no statement regarding therapeutic
value of preparation, and that I have no opinion upon that matter one
way or the other? My work was undertaken solely out of interest to
see whether trypsin could exist in the powder (which gives a markedly
acid solution when dissolved in water). The Elixir Lactopeptine could
theoretically show no tryptic activity, nor have I found any trace of
such activity in one sample of the Elixir examined.
“In making use of any of the contents of my letters kindly include the
statement that my work upon Lactopeptine was done without remuneration
of any kind, and was done only for the scientific interest attached to
the question.”
CONCLUSIONS
The New York Pharmacal Association demanded that the referee reexamine
Lactopeptine, making use of fresh specimens. The Council held that this
was unnecessary, for the following reasons:
1. The previous finding of the Council, that specimens of Lactopeptine
found on the open market are essentially weak saccharated pepsins, is
not to be refuted by examination of fresh specimens. Even if it be
assumed that all old specimens of Lactopeptine have been withdrawn
from the market since the last purchase of specimens for the use of
the Council’s referee, there can be no assurance that the stock will
be constantly kept fresh. Unless the manufacturers date their product,
physicians cannot know that their prescriptions are filled with fresh
material. Nor is it reasonable to ask that the Council examine the
market supply of any given proprietary at a time selected by the
manufacturers.
2. Without entering into all questions of detail in the analyses,
the Council is willing to accept the reports of Drs. Benedict and
Hawk as representative of fresh Lactopeptine powder. It is therefore
unnecessary for the Council to make further experiments along this
line. The results of these two chemists in no wise contradict the
conclusions of the Council’s referees, being comparable with those
obtained by the referee on the fresher specimens used by them. The
experiments of Drs. Hawk and Benedict show a degree of tryptic
activity which, though chemically not negligible, is quite without
significance practically, even if it could be assumed that the trypsin
in the fresh Lactopeptine escaped destruction in the stomach. The
figures for tryptic activity given by Dr. Benedict do not differ
materially from those of the first referee. Those of Professor
Hawk show a tryptic activity of from 18 to 20 per cent. of that of
commercial pancreatin--and commercial pancreatins ordinarily are of
low tryptic activity, if not inert (see Long and Muhleman: _Arch.
Int. Med._, February, 1914, p. 314.) The reports of these chemists
present no reason for changing the conclusion that “it is a commercial
impossibility to market mixtures of pepsin, pancreatin and lactic acid
so that they can display any material tryptic activity.”
The results which Dr. Balch obtained in a test for tryptic activity
show a marked discrepancy with those obtained by Drs. Hawk and
Benedict, not to mention the Council’s referees, and also with the
fact that only about 11 per cent. of “pancreatin” is claimed in the
published formula of Lactopeptine. The Council is unable to accept Dr.
Balch’s result for trypsin or rennin as reliable. His other results are
without significance and call for no special comment.
3. Even if tryptic activity were conceded to Lactopeptine, the
preparation, like all preparations containing pepsin and pancreatin,
would still be, as previously stated, therapeutically irrational.
The Council approved the report.
Report of Referee A
In view of the manufacturer’s reiteration of the claims for
Lactopeptine powder, I have carried out further experiments to
determine its proteolytic and amylolytic power.
For the proteolytic test I used fresh, well washed fibrin and examined
samples of Lactopeptine powder numbered as follows:
No. 1. A part of the English product examined and reported on last
spring.
No. 2.--A fresh bottle obtained at a Chicago retail drug store in
December, 1913.
No. 3. A fresh bottle obtained at a Chicago retail store in December,
1913.
Portions of 1 gm. each of these samples were mixed with 5 gm. fibrin,
100 mg. of sodium carbonate and 50 c.c. of water in flasks. A little
toluene was added to each flask, which was then closed with a tuft
of cotton and the mixtures were incubated at 40 degrees through
twenty-four hours. At the end of that time there was no marked change
in the quantity of the fibrin remaining in each flask, the larger part
by far being undigested.
As a control I used the sample of an active commercial trypsin, of
which I added 500 mg. to the same quantity of water, fibrin and sodium
carbonate. This was digested in the same bath at the same time. The
digestion was practically completed in less than ten minutes, only
minute flakes of the fibrin remaining.
It is evident that the digestive power of the Lactopeptine must be
extremely low, and only a small fraction of that exhibited by a
commercially good trypsin.
In an experiment with the English sample carried out through nineteen
hours as above, using 2 gm. of fibrin and 100 mg. of ferment, it was
found by nitrogen tests on the filtrate that about 12.2 per cent.
of the protein had been brought into solution, an amount which is
practically without importance in a digestion of such duration.
To test the starch digestive power I have made a large number of
experiments. In a series just completed I mixed 1 gm. portions of
Samples 1 and 2 with water to make 100 c.c. volumes. Before making
up to the final volumes 0.5 c.c. of normal sodium hydroxid was
added to neutralize the slight acidity of the ferment as shown by
phenolphthalein.
Of these mixtures 4, 6, 8 and 10 c.c. portions were mixed with 50 c.c.
of 1 per cent. starch paste and incubated at 40 degrees to find the
colorless end-point in the starch digestion, by the iodin test.
At the end of twenty-two hours the iodin reaction was as strong as at
the beginning, indicating no appreciable starch digestion.
To the flasks in which no digestion had taken place under these
conditions, 5 mg. of a pancreas ferment was added. This gave an almost
immediate conversion to the colorless end-point. This ferment was a
sample of Holadin which had been in the laboratory about a year. The
5 mg. completed the reaction to the colorless end-point in less than
ten minutes.
In a similar test I used 2 gm. of Lactopeptine No. 3, made up to
100 c.c. with 1.2 c.c. of normal alkali. Ten and 15 c.c. portions were
incubated with 50 c.c. of 1 per cent. starch paste through twenty hours
at 40 degrees with no apparent result. The Holadin then added, 5 mg.
being used, completed the conversion in less than ten minutes.
This shows that the medium was a proper one for the test and that the
Lactopeptine must be extremely weak. No sugar tests were made because
the Lactopeptine contains milk sugar to the extent of about 60 per cent.
Similar results for both protein and starch digestives have been
obtained in a large number of experiments. These here quoted show
that the ferment activity of the preparation is so low as to merit no
recognition practically. The digestion of a few milligrams of fibrin or
starch after many hours of contact, while being perhaps scientifically
possible, is of no value when we come to a consideration of the use of
such bodies as digestive ferments in medicine.
The amount of lactic acid or “loosely combined HCl” present in
Lactopeptine is very small, since the total acid which may be titrated
by sodium hydroxid and phenolphthalein is measured by 0.5 c.c. of
the normal hydroxid for 1 gm. of the Lactopeptine powder, in the
mean. In different samples examined the range was found to be from
0.41 c.c. to 0.6 c.c. Tests with methyl orange, methyl red and other
indicators showed that the free acidity is but trifling; if the whole
of this acid, as measured by phenolphthalein, were calculated to HCl,
the amount would be too small to have any appreciable physiologic
activity, in view of the daily dose recommended, 10 to 20 grains of the
powder.
Report of Referee B
The following table gives a summary of the results of my investigations
on Lactopeptine. The numbers in the extreme left-hand column are the
manufacturer’s identifying marks. These, it is assumed, run serially,
the higher numbers indicating fresher specimens.
TABLE SHOWING ENZYMIC POWER OF LACTOPEPTINE PREPARATIONS
Amylase Pepsin Rennin Trypsin Lipase
2275 - + + - -
2301 - + + - -
2312 - + + - -
2348 - + + - -
2352 - + + - -
2364 - + + +(?) -
2374 - + + - +(?)
2383 - + + + +(?)
1638 (tablets) - + + - -
Pancreatin (Old) - .. .. ++ -
The conclusions in the foregoing summary depend on the following
criteria:
_Amylase_: removal of starch (paste), _small in proportion to begin
with_.
_Pepsin_: solution of small shreds of _fresh_ fibrin in acid media.
_Rennin_: curdling of milk in moderate excess.
_Trypsin_: solution of small shreds of _fresh_ fibrin in neutral and
alkaline media, and tryptophan test.
_Lipase_: coloration of litmus-milk; exact _color_ controls.
All tests were suitably controlled. The responses for pepsin were weak
even when compared with those of old pepsin preparations.
In the table above, the interrogation points in parentheses (?) refer
to results that were obtained after treatment for from twelve to
twenty-four hours and indicates that the change was slight at best and
of no practical import.--(_From The Journal A. M. A., Oct. 23, 1915,
with additions._)
IODUM-MILLER AND IOD-IZD-OIL (MILLER’S)
Report of the Council on Pharmacy and Chemistry
The Council adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
A referee has submitted to the Council the following report of the
Chemical Laboratory of the American Medical Association on Iodum-Miller
and Iod-Izd-Oil (Miller’s) (Iodum-Miller Co., Kansas City, Mo.):
The unsatisfactory statements made in regard to the composition of
Iodum-Miller and the far-reaching therapeutic recommendations for
it induced the laboratory to make a chemical examination of the
preparation. It claimed more or less directly that the preparation is
entirely new and possesses novel characteristics.
It is asserted that
“Iodum-Miller is made from Soot Iodine, which is our own product.
This Soot Iodine is SOLUBLE IN WATER before being combined with its
base C.P. Glycerine.”
No information regarding “soot iodine” is offered and an inquiry sent
to the proprietors by a physician brought only the noncommittal reply
that “soot iodine”
“is made from Resublime [resublimed?] Iodine by a chemical process
which renders it soluble in water before being combined with its
base.”
Iodum-Miller is said to contain
“Active Free Iodine 2.2 grams per 100 c.c., 10. grains per fluid
ounce, 1.7% by weight.”
“In addition to the active free iodine ... IODUM-MILLER carries a
still greater per cent of Iodine in its basic combination....”
According to the label, the preparation is
“An Iodine for External and Internal use ... 45 drops equals 1 dr.
by weight. Each drop equals the per cent. of iodine in 1 gr. potas.
iodide.”
Iodum-Miller is a heavy, dark liquid having an odor characteristic
of ether (ethyl oxid). Qualitative tests revealed the presence of
glycerin, free iodin, iodid and potassium. The specific gravity at 25
degrees was 1.284. Direct titration with sodium thiosulphate solution
indicated the presence of 1.68 per cent. of free iodin. A determination
of the total iodin content by the Hunter method indicated 3.06 per
cent. Subtraction of the amount of free iodin found from the total
amount of iodin present, gives 1.38 per cent. combined iodin. Assuming
this to be present as potassium iodid, as appears probable from the
qualitative examination and from the quantitative determination of
potassium, 1.80 per cent. potassium iodid is indicated. From this
examination it is concluded that Iodum-Miller is, essentially,
a solution of iodin and potassium iodid in glycerin, containing
1.68 per cent. free iodin and 1.80 per cent. potassium iodid. The
examination contradicts the assumption that Iodum-Miller is either
novel in principle or new. Moreover, accepting the firm’s statement
that 45 drops weigh 1 dram (60 grains) the examination shows that one
drop equals not “the per cent. of iodine in 1 gr. potas. iodide” but
instead, the per cent. of iodin in only 1/20 grain potassium iodid. As
the statement that “Each drop equals the per cent. of iodine in 1 gr.
potas. iodide” appears on the label of the trade package, Iodum-Miller
would seem to be misbranded under the federal Food and Drugs Act.
The recommended internal dosage of Iodum-Miller (from 1/2 to 20 drops)
is equivalent to from 1/40 to 1 grain of potassium iodid. Its external
efficacy in comparison with that of other iodin preparations may be
estimated by comparing the respective free iodin contents, since the
germicidal power of combined iodid is negligible. While Iodum-Miller
contains 2.15 gm. free iodin in 100 c.c., tincture of iodin contains
7 gm. per 100 c.c. and compound solution of iodin (Lugol’s solution)
contains 5 gm. free iodin in 100 gm.
Among the advertising literature is a circular which purports to be
a “Certificate from Kansas City Testing Laboratory, by Roy Cross,
Secretary.” The “certificate” attempts to prove that Iodum-Miller is
vastly superior to the official tincture of iodin as a germicide,
asserting that “In the process of dissolving [tincture of iodin] in
water, a very large amount of the iodin is lost by precipitation....”
This is not true of the tincture of iodin which is now official,
though it is true of the tincture official in former editions of the
Pharmacopeia. The report ignores completely the widely used aqueous
solution of iodin.
Iod-Izd-Oil (Miller’s) is said to be an “Iodine Combination” made
“from the same Soluble Soot Iodine as is IODUM-MILLER.” It is said
to “liberate Free Soluble Iodine” when applied to the skin, mucous
surfaces, etc. It is further defined as “Soluble Iodine combined
with water-white Hydrocarbon Oil” and is said to liberate “Soluble
Iodine 2 per cent.” While these statements suggest that Iod-Izd-Oil
(Miller’s) contains the iodin-potassium iodid combination contained in
Iodum-Miller, analysis indicated the oil to be a simple solution of
iodin in liquid petrolatum. Quantitative determinations indicated, not
2 per cent. of iodin, as claimed, but only 0.42 per cent. and all of
this was present as free iodin.
REFEREE’S REPORT
The following therapeutic claims appear on the label of a bottle of
Iodum-Miller:
“EXTERNAL INDICATIONS
“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea,
Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any
Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood
Poison, Diseases of Uterus and appendages (apply full strength on
cotton wrapped applicator), Gonorrhea, acute or chronic in both
sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands,
Etc.”
“INTERNAL INDICATIONS
“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis,
Catarrh of Mucous surface of Alimentary Canal, Autotoxemia,
Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic
Affections.”
The “certificate” from the Kansas City Testing Laboratory, mentioned
above, states that Iodum-Miller was found to have a germicidal value
nineteen times greater than carbolic acid--a somewhat remarkable
finding in view of the fact that iodin dissolved by means of potassium
iodid in alcohol or water, when tried on the typhoid bacillus has
recently been found to possess only four times the germicidal value
of carbolic acid in a solution of the same strength (Maben and White:
_Chem. and Drug._, Jan. 30, 1915, p. 144). The “certificate” further
states that the test “shows available iodine as found in IODUM-MILLER
to have the greatest bactericidal power of any substance that we have
ever tested that can be used medicinally.” There is no reason to
believe that the desire to please its patrons has led the “testing
laboratory” astray from the literal truth. The laboratory’s experience
may be limited and the statement therefore entirely correct as far
as it goes. No mention, however, is made of any tests comparing the
germ-destroying power of Iodum-Miller with that of tincture of iodin,
which contains 7 per cent. free iodin, unless the casual statement that
“Iodum-Miller sterilized [the skin] more quickly” than tincture of
iodin, be taken to imply such tests. It is not clear, however, by what
means the laboratory was able to determine that there were no bacteria
left alive in the skin after application of tincture of iodin and
Iodum-Miller; no details are given of the methods used in arriving at
this conclusion.
A circular says that Iodum-Miller
“... gives the Greatest Bactericidal and Therapeutic Action,
whether used Internally, Externally, Hypodermically or
Intravenously.”
In the light of the preceding report of the Chemical Laboratory of the
Association, these claims require little comment. The laboratory has
shown that the free iodin content (and consequently the germicidal
efficiency) of Iodum-Miller is less than half that of Lugol’s solution,
and less than a third of that of the official tincture of iodin. As
for the advice to use Iodum-Miller internally in diseases ranging
from pneumonia to syphilis and from typhoid to tuberculosis, in order
to be convinced of its dangerous character, it is necessary only to
recall that this treatment is equivalent to the administration of
small doses of iodid--from 1/40 to 1 grain of potassium iodid. The
mystery being removed from the composition of Iodum-Miller, the absurd
extravagance of the claims made for it becomes manifest. The criticisms
of the Council on the recommendations for Burnham’s Soluble Iodine
(The Journal A. M. A., May 15, 1915, p. 1673) apply in almost every
particular to Iodum-Miller.
Unwarranted therapeutic claims are made for Iodum-Miller; incorrect
statements are made with regard to its composition and that of
Iod-Izd-Oil (Miller’s); and the application of a trade name to both
of these products is unjustifiable, since neither is original. It is
therefore recommended that Iodum-Miller and Iod-Izd-Oil (Miller’s) be
held ineligible for New and Nonofficial Remedies--(_Abstracted in The
Journal A. M. A., Oct. 2, 1915._)
ELIXIR IODO-BROMIDE OF CALCIUM COMP. “WITHOUT MERCURY”
AND “WITH MERCURY”
Report of the Council on Pharmacy and Chemistry
The Tilden Company, New Lebanon, N. Y., and St. Louis, Mo., sells
“Elixir Iodo-Bromide of Calcium Comp. without Mercury” and “Elixir
Iodo-Bromide of Calcium Comp. with Mercury.” The latter is said to
contain, in addition to the ingredients of the former, 1/100 grain
mercuric chlorid in each fluidram. According to the label the formula
of the elixir “without mercury” is:
“_Formula_--Salts of Iodine, Bromine, Potassium, Sodium, Calcium,
Magnesium with Stillingia, Sarsaparilla, Rumex, Dulcamara, Lappa,
Taraxacum, Menispermum.”
A recent circular declares that the elixir contains:
“... a number of the most powerful alteratives of the pharmacopeia
such as chemically pure iodin, magnesium, potassium with
sarsaparilla, stillingia, prickly ash, burdock, taraxacum, etc. ...
Each fluidounce contains seventy-two grains of the combined salts.”
The same circular also alleges that each dram of the preparation
contains:
“... the equivalent of one and one-half grains of the combined
iodids, potassium and calcium ...”
It will be observed that, (1) the two statements quoted from the
circular make no reference to bromids; (2) the statement that each
dram contains “the equivalent” of 1-1/2 grains of the combined iodids,
potassium and calcium, accounts for but 12 of the 72 grains of “the
combined salts” per fluidounce declared in the preceding quotation;
(3) the circular mentions the presence of a drug--prickly ash--not
declared on the label and, finally (4) none of the “formulas” gives the
quantities of all of the several constituents.
It is evident from these “formulas” that the Tilden Company continues
its policy of concealment and mystification as exemplified in the cases
of Hydrocyanate of Iron, Tilden (discussed in The Journal, June 19,
1909, p. 2008), Febrisol (The Journal, June 29, 1912, p. 2043) and
Respirazone (The Journal, June 14, 1913, p. 1899).
In the circular just quoted (“The Conquest of Syphilis”), all hope for
the syphilitic is declared to rest in mercury and iodin, and it is
implied that only through Elixir Iodo-Bromide of Calcium Comp. is it
possible to obtain the greatest good from these drugs.
“Were the cleansing influences of these two drugs [mercury and
iodin] unavailable to the luetic patient, he, truly, would be as
pitiable an object as the leper ...
“Modern Pharmacy has devised no better means of utilizing these
anti-syphilitics than Elixir Iodo-Bromide of Calcium Comp. (Tilden)
with or without mercury.... The Elixir, in proper dosage, acts
in specific fashion and is adapted for use in all stages of the
disease.
“In the early months ... Elixir Iodo-Bromide of Calcium Comp.
(Tilden) with mercury is a trustworthy weapon and the physician
need have no fear but that it will subjugate the disease ...
“When ... the virulent stage is passed ... Elixir Iodo-Bromide of
Calcium Comp. (Tilden) without mercury may be given the patient
with every assurance that medicine’s most aggressive measures are
being resorted to ... From time to time, up to the very end of the
time honored three years’ period of treatment, it is well to put
the patient back on the bichloride, using for this purpose the form
of the Elixir administered in the first stages of the disease ...
“This regime ... will indubitably antidote the virus of syphilis
and eradicate from the organism its every vestige.”
While it seems incredible that any physician would jeopardize the
health--even the life--of a patient by accepting this boastful
magniloquence as sound therapeutic advice, still the fact that certain
medical journals lend their advertising pages to advertisements for
Tilden’s Elixir with the caption “The Conquest of Syphilis” makes it
incumbent on the Council to record its condemnation of the employment
of this unscientific, semisecret mixture.
It is recommended that Elixir Iodo-Bromide of Calcium Comp. “without
mercury” and “with mercury” be held in conflict with Rule 1 (secrecy
of composition), Rule 6 (unwarranted therapeutic claims) and Rule 10
(unscientific composition).--(_From The Journal A. M. A., Nov. 6,
1915._)
LECITHIN PREPARATIONS OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report was sent to the manufacturers of the various
lecithin preparations mentioned therein. As the replies of the
manufacturers were obviously written from the commercial point of
view and did not affect the Council’s conclusion that lecithin, when
indicated, would be given more advantageously in the form of yolk of
egg than in the less pure manufactured product, the Council directed
that the report be published, together with extracts from the replies
of the manufacturers.
W. A. Puckner, Secretary.
Commercial lecithin preparations are at best very impure substances;
all are more or less altered from the original composition. Even
with great care, the methods of extraction and drying always produce
considerable decomposition; and in some cases the phosphorus and
nitrogen contents bear but little relation to the theoretical values.
(Long, J. H.: _Jour. Am. Chem. Soc._, xxx, 881. McLean, Hugh: _Chem.
Abstracts_, May 20, 1915). There is not the slightest reliable evidence
that commercial lecithin has any advantage over the lecithin contained
in natural foods; the weight of probability is on the other side.
The doses recommended, moreover, are absurdly small; and the amount
thus administered is without practical value. Why administer a few
milligrams of a more or less decomposed lecithin when it is possible to
give a far larger weight of a purer substance in the form of yolk of
egg?
In view of these considerations the Council voted that the following
proprietary products be omitted from the next edition of N. N. R.:
Glycerole of Lecithin
Lecibrin
Lecithin Solution
Lecithol
Neuro-Lecithin-Abbott
and that the general article on “Lecithin Preparations” be transferred
to the annual Council Reports as a matter of record.
The report was submitted to the manufacturers. Their replies were
evidently based on commercial consideration, and called for no
modification in the report.
The referee recommended that the preceding report be published together
with the following extracts from the replies of the manufacturers:
From Armour and Company:
“We are selling a good deal of Lecithol and it seems to be giving
satisfactory results in some quarters.... We shall continue to
advertise Lecithol along the lines we have employed heretofore.”
From the Abbott Laboratories:
“We can assure you of our confidence in the therapeutic value of
Neuro-Lecithin. This has been attested by the reports of favorable
results sent us by many physicians, as well as by the periodical
literature of the last few years which contains a considerable
number of very encouraging references to lecithin therapy.”
From Fairchild Bros. & Foster:
“We would like simply to say that the physician and the Council
must be aware of the circumstances and the purposes which actuated
us in placing lecithin at disposal, viz., the studies--research--of
lecithin and the properties attributed to it and which led to
inquiry for and consideration of it. The _quantities_ proposed for
medicinal use were not suggested by us; the suggestion of lecithin
in small quantities as a therapeutic agent was obviously directed
by those who proposed it.... The question whether lecithin, per se,
has therapeutic properties in contrast to lecithin as naturally
contained in food substances, is something we do not undertake
to decide. The Council, on purely theoretical grounds, decides
in the negative notwithstanding clinical experience--internal
and hypodermic--and thus would deny lecithin the status of a new
and nonofficial remedy, worthy of at least tentative progressive
clinical consideration. We can only say that we offered bona fide
lecithin and that we did not make the investigation of lecithin
a pretext for the sale of all sorts of lecithin ‘jumbles’ with
lecithin in small proportions, taking their name and making their
bid on lecithin.”
Below appears the general article which has been omitted from N. N. R.:
Lecithin Preparations
Lecithins are fat-like bodies belonging to the group of phosphatides.
They all consist of glyceryl esters containing two fatty acid radicals
and the phosphoric acid radical in which one of the residual hydrogens
is replaced by the choline group. The fatty acid may be palmitic, oleic
or stearic and various combinations are known to exist; for example,
distearyl lecithin, stearyl palmityl lecithin and so on. The commercial
lecithins usually include the closely related kephalins.
On saponification the lecithins split more or less readily into
choline, the fatty acids and glycerophosphoric acid, and by fusion with
alkali nitrate and carbonate they yield alkali phosphate. They occur,
free or in combination as lecithoproteins, most abundantly in certain
animal tissues, but there are also vegetable lecithins. The lecithins
of commerce are obtained usually from yolks of eggs or from calves’ or
sheep’s brains.
Numerous processes have been devised for the preparation of lecithin
from egg-yolk or animal tissue. From egg-yolk it may be obtained by
making an alcoholic extract and precipitating by cadmium chloride. The
precipitate is washed with alcohol and ether, mixed with 80 per cent.
alcohol and warmed with the proper amount of ammonium carbonate to
remove the cadmium. After filtering hot and concentrating the filtrate
the lecithin is thrown down by cooling to a low temperature--10 C. or
below. The precipitate is taken up in chloroform and reprecipitated by
acetone.
From tissues it is obtained by extracting with warm alcohol and ether,
concentrating the extract, precipitating with acetone and repeating the
operations.
Pure lecithin is white, but the commercial preparations are
yellowish-brown wax-like solids, which are not soluble in water but
form milky emulsions which exhibit the myeline figures under the
microscope. The solubility in cold alcohol or ether is slight, but heat
aids it. Lecithins are not soluble in acetone. They are hygroscopic and
the water mixtures undergo decomposition on standing. They darken on
exposure to air and light.
The alcoholic solution is precipitated by platinum or cadmium
chloride. It is decomposed by alkalies with the formation of choline
and trimethylamine. The ash contains phosphoric acid. The different
lecithins contain from 3.84 to 4.12 per cent. of phosphorus and 1.73 to
1.86 per cent. of nitrogen. The ratio of nitrogen to phosphorus should
be at 1 to 2.21.
Lecithin is incompatible with alkalies; it should be kept in
well-stoppered bottles and should be protected from the light.
The content of lecithin (plus kephalin) in tissues is about as follows:
Per Cent.
Egg-yolk 8 to 12
Egg-white 0.1 to 0.2
Liver 2.0 to 3.0
Kidney 2.0 to 3.6
Lung 2.0 to 3.0
Pancreas 2.0 to 3.0
_Actions and Uses._--The lecithin preparations have been recommended
in many pathologic conditions, especially in malnutrition and sexual
debility. Moderate doses are said to bring about a marked retention of
nitrogen and phosphorus, but satisfactory proof of this is lacking. It
is extremely unlikely that the small doses which have been recommended
in pill or tablet form or in emulsions can have any perceptible action,
in view of the fact that many of our natural foods contain much greater
weights of available lecithins than the medicinal doses provide. There
is no good basis for the statement that the free lecithin has a greater
food value or is more readily assimilated than is the substance as
found in eggs or tissue. The reverse proposition is much more likely
to be true, especially when it is considered that the commercial
preparations are usually somewhat altered or decomposed in the process
of separation.
_Dosage._--Given by the mouth in the form of pills, tablets or
glycero-alcoholic emulsions. The amount of actual lecithin ingested
in this way is usually small because of the doubtful purity of the
original preparation. Several doses, as commonly administered, would
be required to furnish the amount of lecithin present in a small
egg.--(_From Reports of Council on Pharmacy and Chemistry, 1915,
p. 122._)
PROPRIETARY NAMES FOR LIQUID PETROLATUM
Report of the Council on Pharmacy and Chemistry
The Council has accepted the following report and authorized its
publication.
W. A. Puckner, Secretary.
A former report of the Council (Liquid Petrolatum or “Russian Mineral
Oil,” Report Council Pharm. and Chem., The Journal, May 30, 1914,
p. 1740) called attention to the large number of concerns that were
placing on the market liquid petrolatum as a proprietary under coined
names. Since then the number of such products has increased. The
Council has been requested by several concerns to consider their
products put out under proprietary brand names.
The rules of the Council affirm that “the application of ‘trade names’
to official or established nonproprietary substances tends to confusion
and fosters many abuses.” In accordance with this general ruling,
the Council has invariably refused to countenance proprietary names
applied to liquid petrolatum. The Council holds that proprietary or
coined names for this substance are detrimental to medical progress,
since they are sure to foster the impression that the particular
product is different from liquid petrolatum. Manufacturers have been
advised that there is no objection to distinguishing their products
by the addition of their firm name or the initial representing the
firm name; for instance, “Liquid Petrolatum, A. B. and Co.” or “Liquid
Petrolatum, Smith.” The Council also believes that such designations
as “Star Liquid Petrolatum” or “Liquid Petrolatum, Anchor Brand,”
may be regarded as unobjectionable, provided that the words “Liquid
Petrolatum” are always used in connection with the brand designation
and given equal prominence.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 127._)
SENG
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Seng (Sultan Drug Co., St. Louis) is called by the manufacturers:
“... a palatable preparation of Panax (Ginseng) in an aromatic
vehicle.”
Regarding ginseng (_Panax quinquefolia_) the United States
Dispensatory, nineteenth edition, page 1603, says:
“The extraordinary medicinal virtues formerly ascribed to ginseng
had no other existence than in the imagination of the Chinese.
It is little more than a demulcent, and in this country is not
employed as a medicine.”
No discussion of ginseng is to be found in the more recently published
books on pharmacology, materia medica and therapeutics, evidently
because their authors agree with this estimate.
On the other hand, physicians are told through the medium of
advertisements appearing in medical journals that Seng is:
“An efficient remedy in all affections in which the
gastro-intestinal glands need stimulating.
“Exceptionally useful in atonic indigestion, malnutrition,
convalescence from the acute diseases, and all digestive disorders
characterized by deranged or depressed functions.” (_Woman’s
Medical Journal_, July, 1914.)
According to the label, Seng is indicated in “indigestion,”
“malassimilation,” “malnutrition” and “wasting diseases.” It is also
stated--though the preparation is admitted to contain 18 per cent. of
alcohol--that to give babies “ten to fifteen drops in water or milk
during feeding” is a proper procedure and that “For Colic, Flatulency,
etc., the dose for an adult or child may be repeated every half hour
until relieved.”
The following are some of the exaggerated therapeutic claims made for
this preparation of a worthless drug:
“As a result of its administration the gastro-intestinal secretions
are augmented, the digestion of food is substantially increased,
and fermentative processes are promptly overcome.”
“Seng will specifically encourage the secretion of the juices in
the entire alimentary tract ...”
The formula furnished for Seng is non-quantitative and therefore
meaningless. The preparation is exploited in a manner to encourage
its ill-advised use by the public, and exaggerated and unwarranted
therapeutic claims are made for it. The use of an inefficient or
worthless drug like ginseng, moreover, is detrimental to rational
therapeutics. The Council therefore voted that Seng be refused
recognition for conflict with Rules 1, 4, 6 and 10.--(_From Reports of
Council on Pharmacy and Chemistry, 1915, p. 129._)
FROSST’S BLAUD CAPSULES
Report of the Council on Pharmacy and Chemistry
Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine
Capsules were submitted to the Council by C. E. Frosst & Co., Montreal,
Canada. This firm claims, on the authority of the report of a firm of
analytical chemists, that:
“... of three leading Blaud preparations bought by us on the open
market, the iron in Frosst’s Blaud Capsules showed the highest
percentage of _Ferrous_ carbonate.”
The Chemical Laboratory of the American Medical Association found this
claim unjustified. The laboratory reported that there was no especial
difference in the ferrous iron content of the various Blaud pills found
on the market, and that among ten specimens examined, the total iron
content was the lowest in the Frosst specimen. In view of this the
Council refused recognition to Frosst’s Blaud Capsules and Frosst’s
Blaud, Arsenic and Strychnine Capsules.--(_From Reports of Council on
Pharmacy and Chemistry, 1915, p. 164._)
TYREE’S ELIXIR OF BUCHU AND HYOSCYAMUS COMPOUND
Report of the Council on Pharmacy and Chemistry
Each dessertspoonful of this preparation is said to represent
Buchu Leaves 3-1/2 grains
Uva Ursi 1-1/8 grains
Pareira Brava 1-1/8 grains
Hyoscyamus 1-1/2 grains
Hops 1-1/2 grains
Acetate Potash 7-1/2 grains
Spirits Nitre 5 grains
Alcohol 5 per cent. (by volume)”
The manufacturer, J. S. Tyree, Washington, D. C., offers this formula
to the medical profession with the following claim:
“Approximate composition made [sic] by quantitative and qualitative
analysis of the finished product.”
It is also claimed that
“An even greater advantage of Tyree’s Buchu and Hyoscyamus Compound
over other drugs, lies in the fact that every constituent of
the former is required to conform to a fixed standard of active
principle strength; hence the results derivable from it are
absolutely uniform.”
These pretentious claims of scientific accuracy look rather absurd to
chemists. Many of the substances present in buchu, hops, hyoscyamus,
uva ursi and pareira brava are also present in other drugs; hence it
would never occur to a pharmaceutical chemist to try to ascertain the
composition of such a mixture as Tyree’s Elixir by “quantitative and
qualitative analysis of the finished product,” much less to determine
the “active principle strength” of each ingredient, for no methods are
known by which this can be done.
It is claimed that, because of the care exercised in making Tyree’s
Elixir
“... the results derivable from it are absolutely uniform.”
A moment’s reflection, however, must compel any physician to attribute
this statement, on the most charitable construction, to sheer
ignorance. Of course, even a definite chemical principle, such as
quinin, does not exert uniform clinical action, for clinical conditions
vary, and accordingly the patient may or may not be cured. It is simply
preposterous to claim that the clinical results obtained from such
substances as hops, pareira brava, buchu and uva ursi are absolutely
uniform.
A peculiarly vicious claim is that the elixir renders the mucous
surfaces of the genito-urinary tract “hostile to the multiplication of
the gonococci.” Since infection with the gonococcus produces the direst
results, any claim which means in plain English that the remedy assists
in producing a cure or in preventing infection with that organism
cannot be condemned too strongly. Uva ursi, to be sure, has some slight
antiseptic action but it is devoid of any curative action in gonorrhea
and the minute amounts that are present in the Tyree elixir are of no
more protective value against gonorrheal infection than a grain of
hexamethylenamin would be.
It is further claimed that the elixir is a “specific” for “Inflammation
of the Bladder, Bright’s Disease, Renal Colic, Suppurative Nephritis,
Acute Cystitis, Urethritis, Catarrh of the Bladder [it would be
interesting to know what distinction the manufacturer draws between
‘Inflammation of the Bladder,’ ‘Cystitis’ and ‘Catarrh of the
Bladder’], Acidemia, Edema, Vesical Catarrh of Old Age, Lithemia” and
that ascites and anasarca “can be reduced greatly to the satisfaction
of the patient, and honor of the physician” by using a mixture of
Tyree’s Elixir and infusion of digitalis. Such claims as these do not
merit serious discussion, for they carry their own refutation.
It is recommended that Tyree’s Elixir of Buchu and Hyoscyamus Compound
be held in conflict with Rules 5, 6 and 10 and that publication of
this report be authorized.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 167._)
HYDROLEINE
Report of the Council on Pharmacy and Chemistry
Hydroleine (Charles N. Crittenton Company, New York) is a cod liver
oil emulsion said to contain 45 per cent. of cod liver oil, a trace of
salicylic acid and 18-1/2 grains of “Pancreatin, Etc.,” per ounce. The
advertising claims are based largely on the theory that cod liver oil
is “that particular fat which dietetic experience and physiological
chemistry have proved to be most digestible.” As a matter of fact,
while the superior digestibility of cod liver oil over other oils has
often been asserted, neither “dietetic experience” nor “physiological
chemistry” have “proved” this by definite observations. The Crittenton
Company claims that it is more readily split than other oils. This
is probably not true, easy emulsification of the raw oil being often
confounded with easy splitting. This latter claim, however, is offered
in justification of the name “Hydroleine,” which the Crittenton Company
interprets as “hydrated oil.” A circular wrapped around the bottle
contains the assertion that “Cod Liver Oil has long been held in high
esteem by the medical profession for the treatment of a large number of
serious diseases.” This recommendation is likely to lead the public to
place undue reliance on Hydroleine in the grave conditions mentioned.
The preparation is in conflict with the rules of the Council inasmuch
as its name does not indicate its composition, unwarranted therapeutic
claims are made for it, and the exploitation is likely to give the
public unwarranted confidence in its value. The Council therefore held
Hydroleine ineligible for New and Nonofficial Remedies.--(_From Reports
of Council on Pharmacy and Chemistry, 1915, p. 171._)
CURATIVE VACCINE, BRUSCHETTINI
Report of the Council on Pharmacy and Chemistry
Curative Vaccine, Bruschettini, manufactured by A. Bruschettini, Genoa,
Italy, is claimed to have the properties “of acting directly on the
tubercular bacillus, bringing directly into the field and determining a
hyperproduction of antibacillar and antitoxic substances.” The use of
the preparation is said to be indicated in “all forms of tuberculosis.”
A referee reported to the Council that he had examined the available
information and believed that the use of this product had no
satisfactory experimental basis. The method of preparation appears to
be based more on theoretical considerations than on experimental basis.
On the recommendation of the Committee on Serums and Vaccines the
Council voted that Curative Vaccine, Bruschettini, be not accepted
because (1) the method used for the production of the vaccine was not
satisfactorily stated; (2) the theory on which its use is based has not
been satisfactorily confirmed, and (3) the value of the product is not
upheld by satisfactory clinical evidence.
The Council’s findings, in accordance with its procedure, were sent
to the manufacturers for comment. His reply was considered by a new
referee who found that the matter presented did not warrant a revision
of the Council’s conclusions. Accordingly the Council directed
publication of its findings.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 176._)
STEARNS’ WINE
Report of the Council on Pharmacy and Chemistry
Frederick Stearns & Co. market a preparation known as “Stearns’ Wine,”
“Stearns’ Wine of Cod Liver Ext. with Peptonate of Iron,” and as “Vinum
Ext. Morrhuae, Stearns.” The constituents are said to be “concentrated
extract of fresh cod livers,” “Peptonate of Iron” and a “fine quality
of prime Sherry Wine” containing 18 per cent. of alcohol.
This preparation was at one time marketed through the medical
profession, but is now advertised direct to the public in typical
“patent medicine” style. The label on a recently purchased bottle of
Stearns’ Wine contains the following statements:
“STEARNS WINE is an ideal tonic for elderly people, for weak, pale
and delicate children and convalescents.
“STEARNS WINE has for many years been successfully prescribed
in the treatment of general or nervous exhaustion, anemia,
malnutrition, loss of appetite, loss of sleep, faulty circulation
and impoverished blood supply.”
The scope of the recommendations for the preparation is further
indicated in a booklet accompanying the bottle, which begins:
“STEARNS’ WINE, What It Is and Why It Is Good for You.”
The conclusion is:
“STEARNS’ WINE is a safe medicine for the young, middle-aged and
old. It is a safeguard to the family health.”
It is not necessary to discuss either these all-embracing claims as
to the therapeutic efficacy of the mixture or the fallacies presented
in favor of cod-liver extract and peptonate of iron. The Council
reaffirms the opinion that whatever therapeutic value cod liver may
have resides chiefly, if not entirely, in its fatty constituents
(The Journal, Oct. 9, 1909; Reports Council Pharm. and Chem., 1909,
p. 115). A confirmation of this opinion has recently been furnished by
the investigations of Prof. J. P. Street (The Journal A. M. A., Feb.
20, 1915, p. 638) of several cod liver cordials, one of which (Vinol)
like Stearns’ Wine, is described as a wine of cod liver extract with
peptonate of iron.
Stearns’ Wine is essentially an alcoholic stimulant. It is not “a
safe medicine for the young, middle-aged and old.” The unwarranted
therapeutic claims and the recommendations for its indiscriminate use
bring it into conflict with Rules 4 and 6. The Council voted that
Stearns’ Wine be held ineligible for inclusion in N. N. R.--(_From
Reports of Council on Pharmacy and Chemistry, 1915, p. 177._)
PROTONUCLEIN AND PROTONUCLEIN BETA
Report of the Council on Pharmacy and Chemistry
The Council had adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Protonuclein, with other products of Reed and Carnrick, was examined
by the Council in 1907 and found ineligible for admission to New and
Nonofficial Remedies. According to the patent specifications, it is
prepared “from the thyroid and thymus glands, brain (pineal glands
and pituitary body), bone-marrow, pancreas, spleen, liver, salivary
glands, Brunner’s glands, Lieberkühn’s follicles and peptic glands.”
These various glandular bodies, it is said, are dried at a temperature
below 130 F. (preferably between 100 and 110); the fat is removed by
ether, the dried glands disintegrated, the connective tissue removed
by sifting and the resulting powder coated with an ether solution of
benzoin and mixed with milk sugar. The dose is three to ten tablets (9
to 30 grains) daily.
Protonuclein Beta is said to be produced by the addition to
Protonuclein of an equal amount of nucleoplasm and protoplasm of the
spleen. The dose is from two cubes (each 5 grains) three times a day to
three cubes four times a day (30 to 60 grains daily).
Special advantages over ordinary nuclein are attributed to
Protonuclein, in which, it is claimed, certain unaltered cells remain
that are more easily assimilated by the leukocytes than are ordinary
proteins, thus leading to a multiplication of cells. In the early
advertising Protonuclein was claimed to be:
“... an exact physiological product derived from the lymphoid
structures of the body without the use of chemical agents.... So
delicate is Protonuclein that any chemical agent is liable to
disturb its cellular activity.”
After its examination of the product in 1907 (The Journal, Oct. 5,
1907, p. 1198), the Council concluded that any distinction between
the action of Protonuclein and that of ordinary nuclein was purely
speculative and highly improbable. “If the active ingredients are
really so unstable that they are destroyed by all chemical agents, as
claimed, it seems impossible that the activity would be preserved when
Protonuclein is given by mouth and therefore subjected to the very
profound changes of digestion.”
At that time the importance of thyroid as an ingredient had not been
emphasized. The following year, however, Hunt and Seidell (The Journal
A. M. A., Oct. 24, 1908) reported the results of an investigation
which showed that Protonuclein was a diluted thyroid preparation, as
skilfully disguised as in the antifats Rengo and Marmola. Hunt later
pointed out (The Journal, Feb. 1, 1913, p. 384) that the amount of
nuclein contained in a dose of Protonuclein probably would not have the
slightest effect, especially when given by mouth.
The following are extracts from the Protonuclein advertising matter:
“For cancer, infectious fevers (measles, scarlet fever, typhoid and
septicaemia) and as a prophylactic.”
“Protonuclein: An ideal prophylactic for all infectious Diseases.”
“A true alterative and tissue builder.”
“The value of Protonuclein depends upon its ability to increase
cell power and promote tissue strength. It is therefore needed
whenever the organism is below the normal standard, more especially
in Anaemia, Typhoid, Neoplasms and as a Prophylactic.”
All the foregoing claims and recommendations are supposed to be based
on certain alleged discoveries which the Council has previously
characterized as “a tissue of vague speculations ... in direct conflict
with the known facts of physiologic chemistry.” As for the third claim,
Hunt and Seidell have commented on the danger of recommending thyroid,
the most powerful tissue-destroying drug known, as a “tissue builder.”
Protonuclein Beta, it is said:
“... combines the reconstructive action of Protonuclein with the
action of the vital principle of the spleen, making it a distinct
product for use in all tubercular troubles, including phthisis,
localized joint affections and scrofular conditions.”
This product, according to the manufacturers, is based on the work of a
certain Dr. Bayle of Cannes, France. Dr. Bayle said that he had treated
tuberculous patients with fresh ground up spleen of hogs (25-100 grams
per day), mixed with fruit preserve or bouillon; in cases in which this
brought on gastro-intestinal disorders, extract of the spleen pulp was
administered hypodermically. Bayle reported extraordinary improvements
in the physical and mental conditions of his patients even after a few
days of this treatment; over 90 per cent. of his tuberculous patients,
according to him, improved or were cured. This applied to all types
and stages of tuberculosis in man. “With the spleen pulp treatment
tuberculous glands disappear like syphilis lesions on administration of
mercury and iodids.”
This “spleen specific” of Bayle lacks scientific foundation; Bayle’s
own cases were not adequately controlled, and no notice has been taken
of Bayle’s report by experts on tuberculosis. Hence it practically
lacks both confirmation and contradiction.
The spleen is invaded by tubercle bacilli quite as frequently as are
the kidneys and the liver; it has no special toxic action on these
bacilli. Nor is there any reason to believe that the end products of
gastric and intestinal digestion of spleen pulp, after absorption into
the blood, exert such toxic action. It cannot be assumed that these
end products indirectly aid the healing processes through improved
metabolism, for there is no evidence that they have any specific
nutritive or stimulating action after such absorption. Altogether, what
we know of the physiology and pathology of the spleen does not warrant
us in looking for a “specific” against tuberculosis in this organ.
If, however, the known facts did justify any hope that the spleen
might furnish such a specific, manufacturers would not be warranted in
exploiting or physicians in prescribing spleen products as a remedy
for tuberculosis until control experiments on animals had confirmed
the therapeutic value of these products. In a chronic disease like
tuberculosis, no conclusions that are scientifically valid can be drawn
from clinical cases until many cases have been observed for years
under suitable conditions. Right here it may be said that the clinical
“evidence” offered in favor of Protonuclein Beta is worthless. The
observations which have been reported on this product are not such as
to permit any valid final conclusions to be drawn with regard to its
value.
The rational method of proving the worth of an alleged new specific
such as this is by animal experimentation. So far as we know, neither
Dr. Bayle nor the Reed and Carnrick company has performed any such
experiments with “spleen pulp” or Protonuclein Beta; nor are we aware
that any competent investigator has done so. There is, to the best of
our knowledge, no scientific evidence on which to base the claims for
Protonuclein Beta.
The Council reaffirms its former action with regard to Protonuclein.
The objections made to Protonuclein apply with equal force to
Protonuclein Beta. In view of the lack of evidence, the claims for
Protonuclein Beta are unwarranted and the product is ineligible to
N. N. R. on account of noncompliance with Rules 1, 6 and 8.--(_From The
Journal A. M. A., Jan. 1, 1916._)
HYDROPSIN
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Hydropsin is marketed by the Ernst Bischoff Company, Inc., New York.
Its composition is thus described:
“Hydropsin is the standardized dialysate of Digitalis purpurea,
Betula alba, Scilla maritima, Juniperis communis, and Herniaria
glabra; or, stated otherwise, it is the juice of these drugs,
dialyzed and physiologically standardized.”
“Each fluid dram represents Digitalysatum 7 gtts., and 2 gtts. each
of the dialysates of Betula, Herniaria, Juniper and Scilla.”
The composition of Hydropsin must be considered essentially secret
since the amounts of the several constituent drugs in a given amount
of “dialysate” are not disclosed. The active principle of juniper is a
volatile oil which is practically insoluble in water; it is difficult
to believe that the “juice” of juniper submitted to dialysis could
contain any material amount of the active constituent. No information
is given as to the method used whereby the several dialysates are
“physiologically standardized.” It therefore remains to be proved
that the manufacturer of Hydropsin possesses any method whereby the
dialysates of juniper (Juniperis communis), birch (Betula alba,
the common European birch) and knot weed (Herniaria glabra) are so
standardized. The claim is made that:
“Herniaria has long been recognized as one of the most valuable
drugs in the treatment of dropsical affections due to cardiac
impairment.”
On the contrary, Herniaria belongs to that large class of drugs
which have been tried, found wanting and abandoned. It is a very old
remedy, and the claims made for it are an inheritance from the early
herbalists, with whom it was very popular. According to King’s American
Dispensatory, it was “principally employed to cure _hernia_ (hence its
name) and to increase the flow of urine. It was also said to increase
the flow of bile.... Internally and externally, it was praised in
_snake-bites_, and the powdered plant was employed to kill maggots
on unhealthy _sores_ of horses. It was reputed to ‘crush’ and expel
calculi from the kidneys and bladder....”
The Ernst Bischoff Company says that:
“Betula exerts both an antiseptic and stimulating influence
on the urinary passages and is particularly serviceable where
a catarrhal condition of the bladder exists. When combined
with other diuretics, as in Hydropsin, the drug affords highly
satisfactory results in the treatment of ascites, cardiac dropsy
and hydrothorax.”
Birch is another drug which has been discarded. Few textbooks on
materia medica even mention it. That it can materially affect the
action of such powerful drugs as squill and digitalis is exceedingly
doubtful.
An unwarranted implication--that in this preparation the powerful
drugs digitalis and squill have been deprived of their dangerous
qualities--is the assertion:
“Dialysis, removing all resins and colloidals, results in better
tolerance on part of sensitive patients, and in more rapid
absorption and elimination; which, in turn, means early therapeutic
effects and little or no fear of toxic accumulation.”
That removal of colloids and resins materially affects the tolerance
of these drugs is improbable. To claim that because of their removal,
there need be “little or no fear of toxic accumulation” is utterly
without warrant. The claim that one preparation containing digitalis
is less likely to produce cumulative effect than any other digitalis
preparation is contradicted by a mass of evidence.
It is claimed that Hydropsin affects “favorably all forms of dropsy
or Edema that are at all amenable to medical treatment.” There can be
no question but that squill and digitalis, or, better, either singly,
used in suitable cases, may relieve dropsical effusions; but to claim
that such a complex mixture as Hydropsin can favorably affect all
forms of dropsy that are amenable to medical treatment is on its face
unwarranted.
The claim is made that:
“By reason of its unusual potency and relative harmlessness,
Hydropsin may be employed to great advantage in all cases where it
is desirable to increase the volume of urine without injury to the
renal structures.”
On the basis of the claimed composition, the action of Hydropsin
must be essentially that of digitalis or of digitalis and squill.
Consequently, if it possesses “unusual potency,” it cannot possess
“relative harmlessness,” and vice versa. Neither digitalis nor
squill should be employed “in all cases” of nephritis, even if it is
“desirable to increase the volume of urine.”
The composition claimed for Hydropsin brands it as an irrational
mixture in which potent drugs are combined with, and more or less
covered up by, others that are obsolete and inefficient. The name,
instead of indicating its composition, suggests diseases in which it
may be thoughtlessly and indiscriminately used. The claim that the
danger of toxic or cumulative action has been removed, if accepted by
physicians, tends to uncritical use with possible disastrous results.
Hydropsin is ineligible for New and Nonofficial Remedies because of
conflict with Rules 1, 2, 6, 8 and 10.--(_From The Journal A. M. A.,
Jan. 8, 1916._)
DIGITALYSATUM
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Digitalysatum is sold in the United States by Ernst Bischoff Company,
Inc., New York. The firm claims that it is a dialysate prepared from
the juice of freshly gathered digitalis, containing all the active
principles, and representing the fresh plant weight for weight. It is
said to be standardized physiologically and to contain 12 per cent.
alcohol. Sterisol-Digitalysatum, intended for injection, appears
to be the “dialysate” without alcohol, diluted with equal parts of
physiologic sodium chlorid solution. The Council some years ago found
both products ineligible for New and Nonofficial Remedies because
of unwarranted therapeutic claims. The preparations are still being
advertised to physicians under claims which imply superiority to all
other digitalis preparations. For instance:
“Digitalysatum is the diuretic _par excellence_ in cardiac
insufficiency ...”
“Digitalysatum as a diuretic and cardiac stimulant is in a class
by itself, being quick of action, uniform in strength, and well
tolerated.”
“Digitalysatum differs from other forms of digitalis in these
respects:... Digitalysatum is free from fat, resins and colloids,
and is therefore well-borne by sensitive patients--the young and
the feeble--and is quickly absorbed and eliminated....”
The Council has elsewhere[28] expressed the conviction that tincture
of digitalis produces the full therapeutic effects of digitalis; that,
when properly made, the tincture is as stable as any liquid preparation
of digitalis now available, and that attempts to enhance the reputation
of proprietary products by exaggerating the disadvantages of the
official preparation are to be deplored. No adequate evidence is
offered of the claimed superiority of action of Digitalysatum.
[28] Report on Proprietary Digitalis Preparations, J. A. M. A., Dec. 4,
1915, p. 2024.
By implication, the claim is made that Digitalysatum is superior to
other digitalis preparations in respect to toxicity:
“Free from fat, resins and colloidals, it is always well borne and
is quickly absorbed and eliminated. No case of toxic accumulation
(faulty elimination) has ever been reported.”
That Digitalysatum is free from the dangers of toxic cumulation is
highly improbable; in fact, it is inconsistent with the statement
that the preparation contains all the constituents found in the fresh
plant. Even if instances of cumulative action have not been reported
this does not prove that such cumulative action does not occur. The
tincture of digitalis has the systemic side-effects of digitalis in no
greater degree than the various proprietary preparations. Attempts to
create the impression that Digitalysatum possesses all the virtues of
digitalis without its chief disadvantage are to be condemned as likely
to lead to incautious use of the preparation.
These exaggerated claims are in the main made indirectly, but they are
none the less inimical to sound therapy. The Council therefore declared
Digitalysatum ineligible for New and Nonofficial Remedies and voted
that this report be published.--(_From The Journal A. M. A., Jan. 8,
1916._)
SO-CALLED SECRETIN PREPARATIONS
Report of the Council on Pharmacy and Chemistry
The Council authorized the following report for publication, and voted
to endorse the work of Professor Carlson discussed therein.
W. A. Puckner, Secretary.
The Council has not accepted for inclusion in New and Nonofficial
Remedies any preparations said to contain secretin or prosecretin as
their active ingredient. A report giving the reasons for the rejection
of one (the first of the so-called secretin preparations marketed) was
published early last year;[29] an article on secretin, based on work
undertaken at the request of the Council on Pharmacy and Chemistry, is
now published.[30]
[29] Secretogen, J. A. M. A., May 1, 1915, p. 1518.
[30] Carlson, A. J.; Lebensohn, J. E., and Pearlmann, S. J.: Has
Secretin a Therapeutic Value? J. A. M. A. =66=:178 (Jan. 15) 1916.