THE THERAPEUTIC VALUE OF THE GLYCEROPHOSPHATES

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Glycero­phosphates are the salts of glycero­phosphoric acid, H2[C3H5(OH)2]PO4. This acid is produced by the interaction of glycerin and phosphoric acid. In general, only sodium glycero­phosphate, Na2[C3H5(OH)2]PO4 +512H2O, and calcium glycero­phosphate, Ca[C3H5(OH)2]PO4 +H2O, are used in medicine, though the glycero­phosphates of lithium, potassium, manganese, magnesium, iron, quinin and strychnin are claimed as constituents of proprietary preparations. At a time when certain disorders were assumed to be due to a deficiency of phosphorus in the nerve structure in the body, glycero­phosphates were introduced as “nerve foods” and “tonics” on the theory that they would be assimilated more readily than hypo­phosphites or ordinary phosphates. What led to this assumption was the fact that the lecithins, which form a part of the nerve structure, were known to contain the glycero­phosphate radical in the molecule. The belief that inorganic phosphates cannot supply the body’s need of phosphorus is implied or expressed in most of the “literature” devoted to proprietary phosphorus preparations.

Thus, Schering and Glatz quote G. Meillière as saying that “the organism is incapable of assimilating inorganic forms of phosphorus.”

Again, when exploiters of glycero­phosphates admit that the body can synthesize its phosphorus compounds from inorganic phosphates, they attempt to counterbalance the admission by contending that the use of organic compounds “spares” the system the necessity of making such synthesis. This assumption rests on the theory that the organic phosphorus compounds are absorbed and stored as such.

This theory is contradicted by evidence which has been presented[97] that the organic phosphorus compounds are split up into inorganic phosphates before absorption.

The Council requested E. K. Marshall, Jr., to review the evidence for and against the therapeutic value of organic phosphorus compounds. Marshall’s study[98] brings out the following points:

1. In various tissues of the animal body, enzymes have been found which hydrolyze complex organic phosphorus compounds so as to liberate the phosphorus in the form of inorganic phosphates.

2. Metabolism studies of the phosphorus balance with diets containing inorganic phosphorus compounds, as compared with diets containing organically bound phosphorus, are somewhat conflicting in their results. The balance of evidence, however, is in favor of the view that there is no difference between organically combined phosphorus and inorganic salts with respect to the phosphorus balance.

3. Experiments indicate that the organism thrives on and supplies its phosphorus needs quite as well from inorganic phosphorus compounds as from organically bound phosphorus.

Marshall concludes:

“We see that the evidence is very convincing of the view that the animal organism can synthesize its complex organic phosphorus constituents from inorganic phosphates, and that organic phosphorus is of no more value as a food than inorganic.”

In view of this report, the Council deemed it advisable to take up the consideration of certain glycero­phosphate preparations on the market. As the therapeutic claims are all similar, it is not necessary to quote them extensively.

TONOLS (SCHERING’S GLYCEROPHOSPHATES)

Tonols (Schering and Glatz, New York) comprise iron, lime, lithium, magnesium, manganese, potassium, quinin, sodium and strychnin “Tonols” or glycero­phosphates; also Duotonol Tablets, said to contain equal parts of calcium and sodium glycero­phosphates; Triotonol Tablets, each said to contain “Sodium Tonol 212 grains, Lime-Tonol 212 grains, Strychnine-Tonol 160 grain”; Quartonol Tablets, said to contain “Sodium and Lime-Tonols, each 214 grains, Quinine Tonol 12 grain, Strychnine-Tonol 1200 grain”; Sextonol Tablets, said to contain “Sodium and Lime-Tonols, each 2 grains, Iron-Tonol, 12 grain, Manganese and Quinine-Tonols, each 14 grain, Strychnine-Tonol, 1200 grain.”

The name “Tonols” is objectionable in that it is not only nondescriptive of the composition, but also thera­peutically (and falsely) suggestive. The composition of the more elaborate Tonols is particularly unscientific; there is no justification for combining quinin, strychnin, iron, manganese, etc., in one formula.

PHOSPHORCIN COMPOUND

Phosphorcin Compound, called “The Elementary Phosphorus indicated in all forms of Nervous Diseases” and the “Perfect Formula,” is said to be manufactured by the Organic Products Company, Wetzlar an der Lahn, Germany, and Greenwich, Conn. It is sold in the United States by Eimer and Amend, New York, according to whom:

“Each two fluidrachms contain:

“Acidulated Bone Phosphor O. P. Co.

2    grains

“Calcium Glycerinophosphate, Merck & Co.

112 grains

“Magnesium Glycerinophosphate, Merck & Co.

112 grains

“Sodium Glycerinophosphate, Merck & Co.

212 grains

“Lactated Pepsin

2    grains

“Ignatia Extract

120 grain

“C. P. Glycerin (Special Process) O. P. Co.

50 per cent.

“Acidulated bone phosphor” presumably is acid phosphate of calcium. This formula is an unscientific shotgun combination.

ROBINOL

Robinol, manufactured by John Wyeth and Brother, Philadelphia, is called a “Universal Tonic.” It is said to be:

“A preparation of the glycero­phosphates of lithium, calcium, sodium, iron, manganese, quinine, with 1-16 gr. strychnine glycero­phosphate in each fluidounce.”

This is a semisecret preparation, since the quantities of most of the ingredients are not given and the vehicle is not named. This complex combination, too, is unwarranted.

PHOSPHOGLYCERATE OF LIME (CHAPOTEAUT)

This is said to be prepared by the Laboratories de Pharmacologie Générale, Dr. Ph. Chapelle, Paris and New York. It is sold in this country by E. Fougera and Co., Inc., New York. It is offered in several forms, especially in that of wine, which is called the “Medicinal Wine and Tonic Par Excellence.” The alcohol is no doubt the constituent to which this preparation is indebted for such popularity as it has attained, for it is much more freely advertised than the syrup, capsules or granulated form. The usual claims are made with regard to the efficacy of calcium glycero­phosphate “during convalescence, in cases of enfeebled vitality, and nervous affections associated with an excessive elimination of phosphates.”

ELIXIR GLYCEROPHOSPHATES, NUX VOMICA AND DAMIANA

This is manufactured by Sharp and Dohme, Baltimore. The manufacturers’ statement of composition is:

“Each fluidounce represents Nux Vomica 8 grains, Damiana 64 grains, combined with Glycero­phosphates of Calcium and Sodium.”

“Alcohol 20 per cent.”

Sharp and Dohme call this mixture a “Reconstructive Nerve Stimulant, Aphrodisiac,” and claim that:

“Phosphorus in elemental form has long been prescribed under the title of Elixir Phosphorus, Nux Vomica and Damiana, but due to the rapidity of chemical change occurring in preparations containing this form of Phosphorus, much of the Physiologic action is lost. The Glycero­phosphates present Phosphorus in its most available form—the form in which it exists in the brain and nervous system. They powerfully stimulate the functions of nutrition and are rapidly assimilated by the system.

“Nux Vomica is a general Nerve Tonic. Damiana exerts a stimulant effect upon the sexual appetite and function.”

The claim that the glycero­phosphates may be substituted for elementary phosphorus is, at least, novel.

The elixir is an unscientific semisecret combination.

RECOMMENDATIONS

All of the preparations mentioned violate Rule 6 (unwarranted therapeutic claims). In addition, Robinol and Elixir Glycero­phosphates, Nux Vomica and Damiana violate Rule 1 (secrecy of composition) in that not all the quantities of the ingredients are declared; Tonols, Phosphorcin Compound and Robinol violate Rule 8 (objectionable names). It is recommended that the Council endorse Marshall’s findings[98] and declare that Tonols (Schering and Glatz), Phosphorcin Compound (Eimer and Amend), Robinol (John Wyeth and Brother), Phospho­glycerate of Lime Chapoteaut (E. Fougera and Co.), and Elixir Glycero­phosphates, Nux Vomica and Damiana (Sharp and Dohme) are ineligible for New and Non­official Remedies.—(From The Journal A. M. A., Sept. 30, 1916.)