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Terpin Hydrate; Terpini Hydras; Terpin. Hyd.

Terpin Hydrate chemical structure

Terpin Hydrate; Terpini Hydras; Terpin. Hyd.
Terpin Hydrate sold for $0.55/lbs in 1906 (Lehn & Fink catalog New York, 1906)

The following information has been taken from the United Stated Dispensatory Wood-Osol 23rd Edition 1943. The information contained is for historical purposes only.

Common Names: Terpinum; Terpina; Terpirmm Hydratum. Fr. Terpine; Dihydrate de terebenthene; Hydrate de dipentene; Cisterpine; Hydrate de terpine. Ger. Terpinhydrat. It. Terpina idrata; Idrato di terpina. Sp. Terpina; Hidrato de terpina. Terpin Hydrate; Terpini Hydras; Terpin. Hyd.

Terpin hydrate is prepared by the action of nitric acid on oil of turpentine in the presence of alcohol, the resulting crystals being filtered off and crystallized from alcohol. The yield of crystallizable material is largely dependent upon the temperature at which the reaction is allowed to proceed. If the temperature be too high, polymerization of the turpentine takes place; if too low, the yield is insufficient. For a discussion of the chemical properties of terpin hydrate, seer Oleum Terebinthince.

Description and Tests.—"Terpin Hydrate occurs as colorless, lustrous crystals, or as a white powder. It has a slight odor, and is efflorescent in dry air. One Gm. of Terpin Hydrate dissolves in about 200 cc. of water, in 13 cc. of alcohol, in 140 cc. of chloroform, and in about 140 cc. of ether, at 25° C. One Gm. dissolves in 35 cc. of boiling water and in 3 cc. of boiling alcohol. When quickly heated, Terpin Hydrate melts between 115° and 117° C. with the loss of water.

"Identification.—Add a few drops of sulfuric acid to a hot, aqueous solution of Terpin Hydrate: the liquid becomes turbid and develops a strongly aromatic odor. Ash.—Terpin Hydrate yields not more than 0.1 per cent of ash. Reaction.—A hot aqueous solution of Terpin Hydrate (1 in 100) is not acid to litmus. Residual turpentine.—Terpin Hydrate has no odor of turpentine.
Anhydrous terpin hydrate has a melting point of 104.7° C. The melting point is considerably changed by small variations of water present. Terpin hydrate may be identified by the color reaction of Petenkoefer. A drop of sulfuric acid is added to a crystal of terpin hydrate. This produces a yellow color which changes to orange on heating. If a solution of levulose, 0.5 Gm. in 100 cc. of 25 per cent alcohol, is added a carmine red color develops. {Bull. Soc. Pharm. Bordeaux, 1922, 60, 49.)

Uses.—Terpin was first physiologically investigated by Lepine, in 1855, who stated that it acted in a manner similar to the oil of turpentine. It has since been used in chronic bronchitis and in the advanced stages of acute bronchitis, especially when the secretion is unusually free. As terpin hydrate is not volatile and is relatively nonirritant it seems impossible that, of itself, it can exert the characteristic effects of oil of turpentine. The theory on which it is employed is that it will be slowly decomposed in the body liberating the active terpenes. The evidence that this actually occurs is lacking; Matzel (A. I. P., 1905, 15, 331) took 4 Gm. daily without any obvious effects. Although it is very largely employed it is, in our opinion, a remedy of very doubtful utility.
Dose, two to five grains (0.13-0.32 Gm.).
Storage.—Preserve "in tight containers." U. S.

Off. Prep.—Elixir Terpini Hydratis; Elixir Terpini Hydratis et Codeinae, N. F.

Taken from: Wood - Osol United States Dispensatory 23rd Edition 1943

Currently the FDA's final monograph for otc expectorants is guaifenesin (Glyceryl Guaiacolate) is the only agent approved for use as an expectorant in the USA. Formerly used expectorants like ammonium chloride, beechwood creosote, benzoin preparations, camphor, eucalyptol/eucalyptus oil, iodines, ipecac syrup, menthol/peppermint oil, pine tar preparations, potassium guaiacolsulfonate, sodium citrate, squill preparations, terpin hydrate, tolu and turpentine oil, must be reformulated.

Basic chemical structure of Terpin Hydrate

Current Terpin Hydrate Information

Current Terpin Hydrate Information
Cyclohexanemethanol, 4-hydroxy-a,a-4-trimethyl-, monohydrate; Terpinum; Terpinol
p-Menthane-l,8-diol monohydrate [2451-01-6] MW (190.28); anhydrous [80-53-5] (172.27).

Preparation—By hydration of the pinenes in turpentine oil (or pine oil) in the presence of a strong acid.

Description—Colorless, lustrous crystals, or as a white powder; slight odor, and efflorescent in dry air; a hot 1:100 aqueous solution is neutral to litmus; when dried over H2SO4 in a vacuum, it melts at about 103°.

Solubility—1 g in about 200 mL water, 13 mL alcohol, 140 mL chloroform or about 140 mL ether, at 25°; 1 g in about 35 mL boiling water or about 3 mL boiling alcohol.
Uses—In bronchitis as an expectorant. Terpin hydrate elixir contains too little of the compound to be effective alone and is employed mainly as a vehicle for cough mixtures such as Terpin Hydrate and
Codeine Elixir and Terpin Hydrate and Dextromethorphan Elixir. Dose—Usual, 125 to 300 mg every 6 hr.

Terpin Hydrate Elixir contains, in each 100 mL, 1.53-1.87 g. 

Terpin Hydrate and Codeine Elixir contains, in each 100 mL, 1.53-1.87 g of (terpin hydrate), and 180-220 mg of (codeine).

Terpin Hydrate and Dextromethorphan Hydrobromide Elixir contains, in each 100 mL, 1.53-1.87 g of (terpin hydrate), and 180-220 mg of (dextromethorphan hydrobromide).

Terpin Hydrate and Heroin Elixir, (Diacetylmorphine HCl, U.S.P. IX, Diamorphine Hydrochloride, B.P. C21H23NO5HCl, H2O MW=423.9) was formerly used in the United States as a cough syrup and contained 3 mg Heroin and 15 mg Terpin Hydrate/5 mL (teaspoon), and was dosed ½ to 1 teaspoonful every 4-6 hours. It was listed in the B.P.C. in 1949. This product was used in medicinally in the early 1900s until it became a controlled substance in 1914 under the Harrison Narcotic Act and has not been available in the United States since.

Terpin Hydrate Elixir was still available as an OTC in the US up until the late 1980's when it was removed from the market.

Terpin Hydrate Info from 1907
Various Names: Terpin Hydrate, Terpini Hydras. U.S., Terpine, Dihydrate de Terebenthene, Terpinum hydratum, Terpinhydrat, Terpina, Hydrate de Terpilene.

M.W. = 188.74

"The hydrate of the diatomic alcohol terpin. Terpin Hydrate should be kept in well-stoppered bottles." U.S.

In making terpin hydrate a mixture of four parts of rectified oil of turpentine, three parts of alcohol (sp. gr. 0.863), and one part of nitric acid is put in large, shallow porcelain dishes and allowed to stand for three or four days. The crystals which have formed are then collected and allowed to drain thoroughly; they are then pressed between sheets of absorbent paper, and recrystallized in a cold solution of 95 per cent, of alcohol. The product is about 12 per cent, of the original turpentine oil. E. T. Hahn proposed the use of methyl alcohol (sp. gr. 0.801) in place of alcohol, in making terpin hydrate. ( A. J. P., 1897, 73.) Terpin hydrate is officially described as in "colorless, lustrous, rhombic prisms, nearly odorless, and having a slightly aromatic and somewhat bitter taste. Permanent in the air. Soluble in about 200 parts of water, and in 10 parts of alcohol at 25° C. (77° F.); in 32 parts of boiling water, and in 2 parts of boiling alcohol; also soluble in about 100 parts of ether, 200 parts of chloroform, or 1 part of boiling glacial acetic acid. Terpin Hydrate melts when quickly heated at 116° to 117° C. (240.8° to 242.6° F.), with the loss of water, and, at the temperature of boiling water, sublimes in fine needles. When heated in a flask adapted for distillation, it first loses water. At 258° C. (496.4° F.) anhydrous terpin distils over without decomposition, soon solidifying to a crystalline, hygroscopic mass, which melts at 102° to 105° C. (215.6° to 221° F.). When strongly heated on platinum foil, it burns with a bright, smoky flame, leaving no residue. If to its hot, aqueous solution a few drops of sulphuric acid be added, the liquid will become turbid and develop a strongly aromatic odor. Terpin Hy-drate should not have the odor of turpentine, and its hot, aqueous solution should not redden blue litmus paper." U.S. The anhydrous terpin obtained from it by the loss of water has the characters of a glycol. Dipentene dihydrochloride is its hydrochloric acid ether. By the loss of water the terpin then becomes terpineol and finally yields dipentene, terpinene, or terpinolene, according to the conditions of its treatment. Bouchardat and Voiry obtained terpineol in crystals which melt at 35° C. and remain in superfusion for long periods. (Ann. Ch. Ph., 1893, 103.) For Wallach's researches on crys-tallized terpineol, see P. J., 1893, 2.

L. Krentmann states that good results are obtained by replacing the alcohol in the process with hydrogen dioxide solution and subjecting the mixture poured into shallow dishes to light and air. The temperature should be carefully regulated so that the range will be between 15° and 20° C.
Uses.—Terpin was first physiologically investigated by Lepine, in 1855, who found it to act both upon the mucous membranes and upon the nervous system in a manner similar to the oil of turpentine. It has since been used in chronic bronchitis and in the advanced stages of acute bronchitis, especially when the secretion is unusually free; also in chronic cystitis and gonorrhea.

Dose, two to three grains (0.13 to 0.2 Gm.), from four to six times a day, in pill or in emulsion.

Terpin Hydrate Preparations National Formulary 1907
Elixir Terpini Hydratis. N.F. 
Elixir of Terpin Hydrate
This is a new elixir introduced into the 3rd Edition of the N.F. It contains terpin hydrate, tincture of sweet orange peel, solution of saccharin, alcohol, glycerin and syrup. The solution of saccharin might well have been omitted. About 1 grain of terpin hydrate is contained in 1 fluidrachm of the finished elixir. It is used as a stimulant and expectorant.
Average dose: 4 Cc. (1 fluidrachm).

Elixir Terpini Hydratis Cum Codeina. N.F.
Elixir of Terpin Hydrate with Codeine
This is a new elixir introduced into the 3rd Edition of the N.F. It contains about 1 grain of terpin hydrate and J grain of codeine in 1 fluidraehm of the finished elixir. It is used as an expectorant and sedative.
Average dose: 4 Cc. (1 fluidrachm).

Elixir Terpini Hydratis Cum Heroina. N.F.
Elixir of Terpin Hydrate with Heroine
This is a new elixir introduced into the 3rd Edition of the N.F. It contains 1 grain of terpin hydrate and l-24th of a grain of heroine in 1 fluidrachm of the finished elixir. It is used as an expectorant and sedative.
Average dose: 4 Cc. (1 fluidrachm).

Taken from; The Dispensatory Of The United States Of America. Nineteenth Edition. By Dr. Geo. B.Wood And Dr. Franklin Bache. Thoroughly Revised, Largely Rewritten, And Based Upon The Eighth Decennial Revision Of The United States Pharmacopoeia Issued June 1, 1907.