ANTI-SYPHILITIC COMPOUND (SWEENY)

A specimen of Anti-Syphilitic Compound (Sweeny), sold by The National Laboratories of Pittsburgh, was received from a physician. The package (1 ounce size) has been opened by the sender and about three fourths of the contents removed.

From the rather indefinite statements in the literature of the manufacturer it is gathered that the preparation is claimed to be a “sterile, oily emulsion” which contains ¹⁄₂₀ grain of mercuric benzoate in each 5 minims, together with some sodium chlorid. According to information furnished by the Laboratory’s correspondent, the price asked for the preparation is $15 an ounce.

The quantity of the preparation received was too small to permit a complete examination, but, from the tests which it was possible to make, the preparation appears to be an aqueous solution containing some suspended matter and small quantities of mercuric benzoate and a chlorid, presumably sodium chlorid. There was no evidence of the presence of an “oily emulsion.” Quantitative tests indicated the presence of a mercuric salt, equivalent to about 0.2783 gm. of crystallized mercuric benzoate per 100 c.c. This corresponds to about 0.00086 gm. in each 5 minims, or about 26.5 per cent. of the amount claimed.—(From Reports A. M. A. Chemical Laboratory, 1916, p. 106.)

“AMBRINE” AND PARAFFIN FILMS [H]

Paul Nicholas Leech, Ph.D.

In the last year or so, the hot-wax or paraffin treatment of burns has been widely discussed both in medical and lay periodicals. Although the treatment is simply a modification of the well-known use of oil and ointments, it has received unusual attention, owing to the widespread sensationalism following the exploitation in France of a secret and therefore mysterious mixture, “Ambrine,” the formula of Dr. Barthe de Sandfort. Owing to this publicity, it seemed desirable to investigate the chemical composition, and to compare its physical properties with other waxlike substances.

“Ambrine” is promoted as a dressing for burns, frostbites, neuritis, varicose ulcers, phlebitis, neuralgia, rheumatism, sciatica, gout, etc. It is a smoky-appearing substance, resembling paraffin in consistency and without odor. For application, “Ambrine” is melted and applied to the wound either with a brush or with a specially devised atomizer. It cools quickly, and leaves a solid, protecting film.

“Ambrine” has been exploited in the United States for some time. To physicians it was sold under the name “Hyperthermine.” Above is a photographic reproduction (reduced) of a portion of a booklet describing “Hyperthermine,” which has been in The Journal office for some years.

Photographic reproduction (reduced) from the “Hyperthermine” (“Ambrine”) booklet recommending it for use in rheumatism, gout, pneumonia, buboes, dysmenorrhea, eczema, tuberculous ulcers, etc.

It is said that de Sandfort “stumbled on this treatment by accident.”[165] Being a sufferer from rheumatism, he had been benefited by hot mud baths; on returning home he sought a substitute, and finally made a mixture of paraffin, oil of amber and amber resin. This was applied hot, serving as a firm poultice. “Years later, he went on service to a railway in China and was in Yunnan at the time of the incendiary insurrection, and many badly burned Chinese were brought in for treatment. Remembering that Ambroise Paré treated such cases with hot oil, he tried the effect of covering the burn with his melted ambrine, which at once glazes over, forming a coat impervious to the air, and his patients ceased to suffer.”[166]

“Ambrine” has been sold in America under two names: “Hyperthermine,” as exploited to physicians, and “Thermozine,” as advertised to the public. Physical comparison alone shows that Ambrine as now sold differs from “Hyperthermine” of a few years ago; the probable reason is that “Ambrine” has changed its formula. This is borne out by Matas,[167] who states that de Sandfort “admitted that Ambrine was a compound of paraffin, oil of sesame and resins, but was not at liberty to divulge its exact composition, as the formula and manufacture of this substance was now the property of a private corporation, which was exploiting it as a proprietary and secret remedy.” The later formula differs from the original.

Besides the foregoing paraffin preparations, two others have recently been placed on the American market, “Parresine” (nonsecret) and “Mulene” (secret).

ANALYSIS OF AMBRINE

“Ambrine” comes in rectangular cakes, about 1¹⁄₂ inches wide, 6 inches long and ¹⁄₂ inch thick. It is moderately soft, but somewhat brittle at ordinary room temperature. A black substance is present, which evidently settles out during the compounding, as in one side of the cake these particles can be clearly discerned by holding it up to the light; in the other side there are no suspended particles. When melted, the solution is not clear, and a sediment forms. The melting point (U. S. P. method; see later) is 48.4 C. The plasticity and ductility [168] are 27 and 30.5, respectively. It is pliable and strong at body temperature. The saponification number and acid number are both very low, but a fatty oil is present. Tests indicated oil of sesame. Ninety-eight per cent. of “Ambrine” is soluble in ether; this soluble portion may be treated with low-boiling ligroin (petroleum ether), out of which, on standing, a black asphalt-like substance separates. Of the ether-insoluble substance, 65 per cent. is soluble in chloroform. The remaining insoluble substance contains a small amount of silica and vegetable fiber. The paraffin obtained from “Ambrine” melted at 48.6 C. As a result of various experiments, it appears that the composition of “Ambrine” is essentially as follows:

Paraffin (M. P. 48.6 C.)	97.0 per cent.
Fatty oil (sesame?)	1.5 per cent.
Asphalt-like body	0.5 per cent.
Coloring matter, and undetermined	1.0 per cent.
	——
	100.0

OTHER PROPRIETARY FILMS

A cursory examination of “Mulene,” manufactured by the Mulene Company, Pittsburgh, was also made. This appears to contain paraffin, beeswax, a fat-soluble red dye and considerable rosin. When heated carefully in a beaker, the rosin “sticks” to the bottom, and does not go into solution readily.[169]

“Paresine,”[170] according to the manufactures, is a mixture composed of paraffin, 94 to 96 per cent.; gum elemi, 0.20 to 0.25 per cent.; Japan wax, 0.40 to 0.50 per cent.; asphalt, 0.20 to 0.25 per cent., and eucalyptol, 2 per cent., the whole being colored with alkannin and gentian violet.[171]

FORMULA FOR PARAFFIN FILM

In a recent article, Sollmann [172] presented various suggestions for the compounding of paraffin films. Some of the formulas were promising and others were not, but all were simple. He did not try to imitate “Ambrine.” Lieut.-Col. A. J. Hull [173] of the Royal Army Medical Corps, after experimenting with different combinations, concluded that a mixture of “1 part resorcin, 2 parts eucalyptus oil, 5 parts olive oil, 25 parts soft paraffin [petrolatum][174] and 67 parts hard paraffin” served the purpose as well as “Ambrine.” The following formula, which might be called Asphalt-Paraffin No. 21, much more closely resembles “Ambrine,” and it seems to have certain advantages, due to the use of a more suitable grade of paraffin:

Paraffin [175] (M. P. by U. S. P. method 47.2 C.)		97.5	gm.
Asphalt	from 3	to 5 drops
Olive oil		1.5	c.c.

Photographic reproduction from a booklet on “Thermozine” showing that it is identical with “Ambrine.”

About 10 c.c. of “asphalt varnish” (B. Asphaltum)[176] is placed in a beaker and heated on the steam bath for one-half hour. From 3 to 5 drops, delivered from a 1 c.c. pipet, are then placed in a casserole, and 1.5 c.c. of olive oil added. The mixture is heated and stirred for a few minutes until perfect solution is effected. To this is then added, with stirring, the paraffin, which has been previously melted. When it is cooled, a brown solid is obtained.[177] The physical factors of this paraffin mixture are, melting point 45.4 C. (U. S. P. method); plasticity, 28.5; ductility, 29; it is very pliable and strong at 38 C., and adheres exceedingly well to the skin, although it detaches easily. This mixture, which is easy to prepare, is inexpensive, the cost of the materials being approximately 10 cents a pound.

Both Hull and Sollmann noticed that tarlike substances and melted paraffin do not mix well. This is noticeable in “Ambrine,” which cannot be called an “elegant” preparation. The difficulty may be overcome by first mixing hot olive oil and asphalt; the asphalt will then go into solution. It is interesting to note that the suggested formula (as well as others which were also prepared) is not as plastic as the paraffin itself.[178] This is also true of “Ambrine.” On the other hand, the melting point of the paraffin is higher. The important point, however, in compounding all paraffin preparations, is to select a proper grade of paraffin as elaborated below.

EXAMINATION OF PARAFFINS AND PARAFFIN PREPARATIONS

Photographic reproduction (greatly reduced) of a full page magazine advertisement of “Thermozine,” the name under which “Ambrine” was sold to the public.

The name “paraffin” generally applies to a colorless and tasteless waxlike substance that is solid at ordinary temperature. It is composed of saturated hydrocarbons, that is, they are unable to take up any more hydrogen, and thereby are quite stable; the hydrocarbons in paraffin have the general formula of C_nH_2n+2, ranging as high as C₂₄H₅₀ to C₂₇H₅₆. Paraffin may be found in crude form in coal, from which source the first paraffin candles were made. It may be produced from the distillation of brown coal, as in Germany, or from bituminous shale. In America, it is obtained chiefly from the distillation of crude petroleum, being in the residue after the distillation of such products as naphtha (gasoline), kerosene and the lubricating oils. The residue is treated by one of a number of processes causing the unpurified solid paraffin to be made available. The crude paraffin is either sold as such, or is refined. Paraffin or “paraffin waxes”[179] are designated in the trade by their melting points (which in the “American standard” is expressed in Fahrenheit degrees), and as to their state of refinement as “crude,” “semirefined” and “fully refined” paraffin. There are certain chemical and physical differences so that two refined waxes having the same melting point would not have the same plasticity. The higher melting point varieties of paraffin are hard and tough at room temperature: when melted, paraffin expands and forms a thin mobile liquid.

Photographic reproduction from a booklet on “Thermozine” giving the conditions in which the stuff was alleged to be “very useful.”

The significant requirements of paraffin for surgical dressings are that it should be solid at body temperature, at the same time having flexibility and adhesiveness, together with a certain amount of strength. A number of brands of paraffin are sold in the United States, so that it seemed advisable to examine some of them and compare them with certain paraffin-film preparations. They were tested as to their melting points, plasticity, ductility, strength of film, etc.

Melting Point Determination.—The melting point was determined by the method of the U. S. Pharmacopeia IX, p. 596. The melting point as obtained by this method is lower than the melting point used by manufacturers of paraffin (after conversion to Fahrenheit).

Pliability and Ductility, Limit Temperature.[180]—A little of the melted wax was poured from a teaspoon on the surface of the water at about 40 C., in a tin pan (bread mold). This formed a fairly thin film. The temperature of the water was then lowered by the addition of cold water. At each temperature the pliability and ductility were tested thus:

Pliability Test.—The film, immersed in water, was doubled on itself, note being taken whether or not it broke.

Ductility Test.—The film was pulled under water, note being taken whether it stretched on being pulled and broke with a ragged fracture; or whether it broke sharp without stretching. It is desirable that the pliability and ductility be preserved at as low a temperature as possible.

Cotton Films, Adhesives and Detachability.[180]—The melted wax was applied as it would be for burns; namely, a thin layer was painted on the inner surface of the forearm with a camel’s hair brush,[181] a transverse strip about an inch wide being made. This was covered with a very thin layer of absorbent cotton, and over this another layer of melted wax was painted. As soon as this had cooled a little, it was covered by a few layers of bandage and left on for at least an hour. At the end of that time, the bandage was removed. The cotton film should be found at the place at which it was applied, showing that it is sufficiently adherent. It should detach without “pulling” the skin.

Photographic reproduction (greatly reduced) of the carton in which “Ambrine” is now sold.

The results of these tests are given in the accompanying table. It can be seen that nearly all the paraffins examined have properties which would make them useful, the notable exceptions being Nos. 8, 15 and 16. The more satisfactory products would be those having a melting point about 47 C., ductility of 30 or below, and plasticity of 28 or below. The paraffin described in the U. S. Pharmacopeia is not so satisfactory, the required melting point being between 50 and 57 C.

The use of paraffin bandages has been suggested by Fisher [182] and Sollmann.[183] In such cases, it may very likely be that a paraffin of higher melting point would be more satisfactory, owing to its greater resistance and tougher fiber.

SUMMARY

1. “Ambrine” is essentially paraffin in which a small amount of fatty and asphalt-like body is incorporated; like most secret mixtures, its composition varies.

2. A simple formula for a paraffin film, similar in chemical composition but superior in physical properties to “Ambrine,” is that described as Formula 21. The superiority is due to using a grade of paraffin that is better adapted to the purpose. The cost of materials is about 10 cents a pound.

3. The properties of the paraffin used for a surgical dressing are important. A number of different grades have been examined, in order to determine the ones that appear most promising. Paraffins Nos. 3, 4, 10, 11 and 25 are the best in the table, and surpass “Ambrine” itself.

4. It is exceedingly probable that further experience will show that for most purposes simple paraffin will serve just as well as the mixtures—if, indeed, not better.

Addenda

(Reprinted from the Annual Report of the Chemical Laboratory of The American Medical Association, Vol. 10 (1917), p. 32)

Since the foregoing was published, two other products—“Cerelene” and “Stanolind Surgical Wax”—were submitted to the Council on Pharmacy and Chemistry for investigation as to their acceptability for inclusion in New and Nonofficial Remedies. In this connection the Laboratory was requested to examine them.

“Cerelene” is manufactured by the Holliday Laboratories, Pittsburgh. According to the manufacturers, “Cerelene” is a compound composed of 84 per cent. paraffin, 15 per cent. myricyl palmitate and 1 per cent. elemi gum. As ordinarily marketed, “Cerelene” contains the following materials: To the beeswax is added Oil of Eucalyptus, U. S. P., 2 per cent., and Betanaphthol, U. S. P., 0.25 per cent. The manufacturer further states that the myricyl palmitate is a purified form of beeswax, free from all impurities, acids, etc., which is solely manufactured by this company and for which patents are pending. The properties described for “Cerelene” were as follows:

When cold, Cerelene is a solid wax-like cake of a fine yellow brown color. On exposure to air for long periods, the amber color darkens to some extent. It is entirely free from solids, odorless and tasteless; does not separate or change when melted repeatedly, and cannot in the melted state be separated by fractional crystallization. It is entirely neutral to indicators being perfectly free from both acids and bases.

Tests:	Melting Point, U. S. P. method, 126 F.
	Density, U. S. P. method, 0.907.
	Iodin value, 0.5.
	Saponification number, 0.9.

“Stanolind Surgical Wax” is manufactured by the Standard Oil Company of Indiana. In the submission of the product to the Council on Pharmacy and Chemistry, it was stated that the product was a specially prepared paraffin “free from dirt or other deleterious matter.... It has been steamed and resteamed to drive out any free oil and repeatedly filtered.”

The examination of the foregoing products yielded the figures described in Table “B.”—(From The Journal A. M. A., May 19, 1917.)