FORMAMINT
Report of the Council on Pharmacy and Chemistry
The following report has been authorized for publication.
W. A. Puckner, Secretary.
Formamint is a proprietary medicine manufactured by the A. Wulfing Company (New York, London and Berlin), which is affiliated with the Bauer Chemical Company.
It has been widely advertised in Europe for several years, and is now on the American market;[14] it is advertised in this country both in newspapers and medical journals.
Following is a brief review of the more important alleged investigations that have been reported from time to time in various European journals.
In “The Therapeutical Value of Foramint in Septic Affections of the 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.
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.
Rheinboldt,[19] investigating the effects of Formamint and of ordinary formaldehyd on animals, concludes that formaldehyd is toxic in action while Formamint is not.
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.
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.
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 |
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,[18] 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.
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.
TABLE 1.—SHOWING TIME IN WHICH CULTURES OF STAPHYLOCOCCUS AUREUS WERE KILLED
BY DIFFERENT AMOUNTS OF FORMAMINT
| Amount of Formamint in Saliva (Per Cent.) | Period of Standing at 37 C. (Hours) | Average Count When Plated | Count on Flask of Saliva Without 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.
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.
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 |
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.
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.
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
| Conditions of Test | Time Since Preceding Test | Amount of Formamint Used | No. Found in Throat Before Use of Formamint | No. Found in Throat After Use of 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 and throat gargled one hour later | 6 days | 1 tablet | ... | 15,000,000 |
| Throat again gargled two hours after Formamint was used | 1 hour | 0 | ... | 10,050,000 |
| Normal | 7 days | 0 | 62,000,000 | ... |
| Normal | 1 hour | 0 | 72,500,000 | ... |
| Normal | ... | ... | 61,000,000 | ... |
| Tablets were taken, one per hour, and throat gargled one hour after last tablet was taken | 2 days | 12 | ... | 39,100,000 |
| Throat was again gargled 2 hours after taking last tablet | 1 hour | 0 | ... | 59,000,000 |
| 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 half hour for twelve hours consecutively. Throat was gargled one hour after last tablet was taken | 4 days | 24 tablets | ... | 175,000,000 |
| Throat was again gargled two hours after last tablet was taken | 1 hour | 0 | ... | 168,750,000 |
| 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 immediately after preceding gargle. Throat was again gargled at end of one hour | 1 hour | 1 | ... | 83,200,000 |
| Throat was again gargled two hours after tablet was taken | 1 hour | 0 | ... | 134,750,000 |
| Normal conditions except that mouth and teeth were throughly washed with soap just before gargling | 19 days | 0 | 32,600,000 | ... |
| Same as above | 1 hour | 0 | 33,125,000 | ... |
| Same as above | 1 hour | 0 | 40,375,000 | ... |
| Teeth were not washed. Otherwise normal conditions | 2 days | 0 | 33,500,000 | ... |
| 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 washed with soap just before throat was gargled | 2 days | 0 | 5,270,000 | ... |
| Same as above | 1 hour | 0 | 10,916,000 | ... |
| Same as above | 1 hour | 0 | 8,275,000 | ... |
| Normal conditions, but 1 c.c. of sterile rabbit’s blood was added to each plate | 3 days | 0 | 228,750,000 | ... |
| Count from the same gargle as above. No blood used in the plates | 0 | 0 | 60,625,000 | ... |
| Normal conditions, but count was made on blood agar | 1 hour | 0 | 431,250,000 | ... |
| Count from the same gargle as above. No blood used in the plates | 0 | 0 | 59,625,000 | ... |
| Normal conditions, count was made on blood agar | 2 days | 0 | 683,300,000 | ... |
| Same gargle as above, but count was made on plain agar | 0 | 0 | 58,500,000 | ... |
| One tablet was taken just after preceding gargle. After one hour throat was again gargled. Count on blood agar | 1 hour | 1 tablet | ... | 558,300,000 |
| Same gargle as above, but count was made on plain agar | 0 | 1 tablet | ... | 55,875,000 |
| Normal conditions | 2 days | 0 | 79,125,000 | ... |
| One tablet was taken just ten minutes before gargle was made | 1 hour 16 min. | 1 tablet | ... | 56,250,000 |
| Normal conditions | 2 days | 0 | 46,750,000 | ... |
| One tablet was taken just ten minutes before throat was gargled | 1 hour | 1 tablet | ... | 38,500,000 |
| Teeth and mouth were thoroughly washed with soap just before gargle was made | 5 days | 0 | 47,370,000 | ... |
| Teeth washed as above and one tablet taken ten minutes before gargle was made | 1 hour | 1 tablet | ... | 21,225,000 |
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.
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
| Conditions of Test | Time Since Preceding Test | Amount of Formamint Used | No. Found in Throat Before Use of Formamint | No. Found in Throat After Use of 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.
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).”
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.)