Theobromine and sodium salicylate

Sodium salicylate, Diuretin. Equimolar mixture of sodium theobromine and sodium salicylate, containing 1H20-Theobromine 47.3%, sodium salicylate 42.1%. White, odorless or almost odorless, hygroscopic powder- Absorbs C02 from the air and becomes incompletely soluble. Soluble in ] part water slightly sol in alcohol the solns are strongly alkaline. pH about 10. 

Theobromine can be converted quantitatively into caffeine by the method of Self and Rankin with a slight excess of dimethyl sulphate in the presence of sodium hydroxide. The process has been found of general value for the determination of theobromine and is described in detail later under theobromine and sodium salicylate to which it was first applied. 

Theobromine and sodium salicylate consists of a mixture of sodium salicylate and sodium theobromine in approximately equimolecular proportions. 

Dissolve 0 5 g of theobromine and sodium salicylate in 100 ml of hot water, add 15 ml of 0-1N sulphuric acid and boil to remove carbon dioxide. C ool to 40, add 15 ml of phenol red solution and a measured quantity of O IN sodium hydroxide until the mixture is alkaline (2 to 3 ml required). Titrate with O IN sulphuric acid until the colour of the indicator changes to lemon yellow. The amount of 0 1 N sodium hydroxide deducted from the total 0-1N acid is a measure of the alkalinity. To this solution add 20 ml of O IN silver nitrate and titrate the liberated nitric acid with O IN sodium hydroxide to a deep red-violet colour. 1 ml O IN 001802 g theobromine. The approach of the endpoint is indicated by incipient precipitation of silver oxide. 

Dissolve 1 g of theobromine and sodium salicylate in 10 ml of water in a small stoppered flask, add 2 ml of N sodium hydroxide and 0-6 ml of dimethyl sulphate and shake continuously for five minutes. Allow to stand for half an hour, shaking frequently, then add 3 ml of N sodium hydroxide and 10 ml of water shake well for two minutes. Transfer to a separator w ith chloroform and a little water, and extract the caffeine immediately by shaking w ith successive portions of chloroform, washing each extract w ith about 10 ml of water contained in a second separator. Evaporate the chloroform, dry at 105° and weigh. 1 g anhydrous caffeine. 0- )278 g of theobromine (C7H8O2N4). 

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

Incompatible with alkalis, heavy metal ions, especially copper and iron, oxidizing materials, methenamine, phenylephrine hydrochloride, pyrilamine maleate, salicylamide, sodium nitrite, sodium salicylate, theobromine salicylate, and picot-amide. Additionally, ascorbic acid has been found to interfere with certain colorimetric assays by reducing the intensity of the color produced. ... 

Apart from the possible prevention of unwanted physiological effects, hydrotropes can have a direct action on efficacy. Theobromine is soluble in water to the extent of 1 in 2000 an equimolar mixture with sodium acetate has a solubility of 1 in 1.5, and a mixture with sodium salicylate, 1 in 1. Clinical evaluation of various theophylline and theobromine preparations in the treatment of angina pectoris [288] showed a theobromine-sodium acetate mixture to be the most effective. Ergotamine levels have been shown to be enhanced when the drug is administered in combination with caffeine, which increases the solubility and rate of solution of the ergotamine [289]. 

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