market is as much as price Rs. 720 per pound, a dose of 3 single grains costing nearly a rupee. As the drug is used largely in this country for the treatment of Ascaris and Oxyuris infections rs well as in sprue, it is of economic importance. Practically all the santonin used in India is of Russian manufacture and is imported from Europe. It is obtained from Artemisia cina there are Berg but many allied species, such as A. maritima L., var. Stechmanniam Besser (A. le'rchcana Karel and Kiril), A. panciflora, Stechm, etc., which are indigenous to the vast uncultivated plains of the Kirghiz in Turkestan. A number of species of Artemisia are also widely distributed over different parts of Europe, Asia, and America. Some years ago, large quantities of the strongly aromatic flower heads were col- lected and sent to the European markets, especial- ly to Moscow and Petrograd; some also found their way to Bombay via Afghanistan and Persia. Such is not the case now, as factories have been established in some of the large towns in Turkes- tan where santonin is extracted, and mainly the is now purified product exported. Of late years there has been a great scarcity of santonin owing to political and economic disturbances in Russia; also, owing to wasteful and destructive methods of harvesting in Turkestan, the plant is in serious danger of extermination there. Efforts have been made therefore to find other sources of the drug with a view to increasing the output. Van Laren has successfully cultivated /a. cina in Holland, which has yielded as much as 1.3 per cent, of santonin. Some of the American species of Artemisia, A. mexicana and A. ncomcxicana, which grow wild in Mexico, and in New Mexico and the neighbouring states, also Professor yield santonin. Greenish has sug- gested the possibility of India supplying not only her own needs but also having a good deal of surplus for export and Dr. J. L. Simonsen of the Forest Research Institute and College, Dehra Dun. has given strong support to this view.

Indian Spccics of Artemisia?A. maritima. Artemisia maritima. Linn (A. brevifolia Wall', jrrovvs in the dry inner valleys of the Western Himalayas from Kumaon to Kashmir (Baltis- of INDIAN SANTONIN. tan) at'an altitude 4,000 to 12,000 feet above the sea level. According to Dr. Parker, the Extracted from the Indian spccics of Artemisia Forest Botanist, it grows more abundantly and maritima. uniformly in Baluchistan, Chitral and Afghani- stan than in the Himalayas. It is used as a R. N. CHOPRA, m.a., m.d. (Cantab.), By packing material for fruit which is imported from I. M.S., MAJOR, Kandahar. The drug is called kirmala or kir- Professor of Pharmacology, mani in Hindi; skill, sarifun and afsantin-el- and bahcr in Persian and Arabic. It is a very ancient and was used the ASA C. CHANDLER, rh.D., remedy by Greeks and Romans to expel intestinal worms. The old Arabian and In Hookworm Research Laboratory, Calcutta char

quoted by the authors of this system are to stop santonin as compared with the variety imported hiccough and as a remedy for dropsy. Extern- from Europe. It will be seen that it comes ally it is recommended for application to boils practically up to the same standard of purity. and inflammatory swellings and to promote the The small differences are due to traces of impuri- growth of the hair. A decoction made from the ties, which cannot be removed by recrystallisa- plant, which would consist mainly of the essen- tion. These, however, have neither any delete- tial oil, is used as a cardiac and respiratory stimul- rious effects, nor do they interfere with the action ant. An oleaginous extract made from the plant, of the drug. The Indian santonin (Smith, which contains both the essential oil and santonin, Stanistreet brand") satisfied all the tests of purity is used for application to wounds and internally laid down by both the British and the United in ascites. No mention of this drug is made by States Pharmacopoeias. the old writers and it is not included Ayurvedic Imported santonin. Indian santonin. in their materia tnedica. A. maritima grows in (Smith, Stanistreet certain parts of Kashmir State .and the author- (Standard). brand) ities are making efforts to collect the plant and 1. Very sparingly soluble in Same as the standard. give facilities for extracting santonin. Messrs. cold water. Soluble in 40 parts of cold rectified Smith, Stanistreet & Co., one of the firms leading spirit, in 3 parts at the of chemists in manufacturing pharmaceutical boiling point and in 4 Calcutta, have experimentally extracted a quan- parts of chloroform. Same as tity of the drug and we are very grateful to this 2. Crystallises in flattened the standard. in fea- firm and to .their head chemist, Mr. C. S. Cooper, rhombic prisms, thery radiating groups. for us a of this supplying with sufficient quantity Odourless. Tasteless at Indian santonin for purposes of chemical, physio- first, but afterwards de- logical and clinical investigations. velops a bitter taste. The cold alcoholic solu- Chemical composition of A. maritima. tion has an extremely The active consist of:? bitter taste. principles 3. On sublimation becomes Same as the standard. 1. A an odour resembl- volatile oil, which has reddish brown, evolves ing cajuput oil and camphor. The physiological white fumes and on cool properties and pharmacological action of this oil ing sets to a clear brown which is are under vitreous mass, investigation. reddened on treatment 2. A neutral is principle?santonin?which with a little dry alkali responsible for the anthelmintic properties, and an e.g., slaked lime. allied body, artemisin. The amount of santonin 4. On exposure to light, espe- Same as the standard extracted from the Russian Artemisia usually is cially to direct sunlight, santonin a yel- 1.2 to 1.4 be as as 2.3 to acquires per cent., but may high low colour. The hot 3.6 per cent. The yield from the Kashmir alcoholic solution of this variety is comparatively small, and even by the altered substance is yel- improved method devised by Smith, Stanistreet low, but deposits crystal? of colourless santonin on & Co., it did not go 0.5 per cent. This beyond cooling. be due to the fact the santonin content may that 5. Lrevo-rotatory in chloro- Lrevo-rotatory in chloro- of A. maritima is naturally low, or the plant may form = 171.4. form. = ? 161.2 r.ot have been collected at the right time of year. 6. Melts at 169? to 171? C. It softens at 169? C. It is a well known fact that santonin dis- and melts completelv appears after flowering of the plant, and if the at 171? C. specimens are collected at such a time the yield is 7. Sp. Gr. 1.1866. small. that 8. of C. R. C = 70.4 cent. Simonsen has shown the plants col- Percentage , per C = 73.17 cent. H = 6.5 cent. lected in June in Kashmir (Ourez") showed no per per H = 7.31 cent. santonin content at those collected in and per all, July 9. Leaves no appreciable ash 0.1 grm. incinerated. August showed from 0.1 to 1.0 per cent., the No ash remained. latter being the maximum yield; in the first half of was September 0.1 per cent.; and after that it Pharmacological action of Indian Santonin. entirely absent, or only slight traces present. An- The behaviour in vitro of ascari- other factor which may possibly be responsible earth-worms, is that the A. maritima used for extraction had des, etc., in solutions of Indian santonin in oil is been collected and stored for some time and the the same as with the European variety. We tested the of the on a series of cats and leaves, which contain most of the santonin, may toxicity drug have fallen off, leaving mostly the stalks, which found that this variety was not more toxic than have no santonin. the European variety, and as much as 90 mgm. could be given to a cat. weighing 2 kilogrammes and Chemical Physical properties of Indian without producing any untoward effects.- A Santonin. series of cats whose stools were previously exa- The following table gives a description of the mined and found to contain ova of Belascaris and physical and chemical properties of the Indian hookworm were :riven the drug in doses ranging Nov., 1924.] INDIAN SANTONIN: CHOPRA AND CHANDLER. 539

in? X b0 3 0J ? U V. c V! ?

Hospital 1 N one None Pr e v i o 427 (16) 4500 None. Santonin 10 p.m. Mag. sulph. 6 a. m usly gr. 3, calo- 1 oz. passed 3 female As- mel gr. 2, Sod.bicarb, caris after c h e n o- gr. 4. op dium. 428 (ad.; 2450 j No food 10 p.m. 6 a.m None Left hospi- stools 1 after tal,so I 4 p.m. saved only I Mag. 24 hours. sulph. 1 oz. 430 (ad.) 10 p.m. 6 a.m. Stools lost 2nd da y; patient noticed worms. 436 (ad.) 1837 10 p.m. 6 a.m. 444 (4) No food Santonin 10 p.ni, Mag. sulph. 6 a.m. after gr. 2'5, 2 dr. 4 p.iri. calomel gr. 0'5, Sod. bicarb, gr.4. Present 452 (5) No food Santonin 10 p.m. Mag. sulph. 6 a.m. J after gr. 3, calo- 2 dr. 5 p.m. mel gr. 1, Sod.bicarb, 4. 453 ^gr. 1 (ad.) Santonin 10 p.m. Mag. sulph, 6 a.m. gr. A, calo- 1 Oz. mel gr. 5, Sod.bicarb. gr. 4. 454 None (2J) Santonin 10 p.m. Mag. sulph. 6 a.m. None; gr. 2, calo- 2 dr. mel gr. I, Sod. bicarb, gr. 2. Jail 1 8700 (ad.) Liquid S a n t o n i n j 5 p.m. Ma?. sulph, 8 a.no. diet 24 oz. gr. 4, calo- j 1 hours. mel gr. 5, I Sod.bicarb. gr. 5. 3550 4 5750 5 6600 6 100 7 300 8 30V 9 6100 10 2600 11 450 12 500 1 Nausea dur- ing night; v omit e d twice. Vo- mited seve- ral times after purge. Giddiness; cramps in fingers. 13 ? 5000 1 None

14 ? 2150 1 Nausea dur- ing night; v o m i t e d afterpurge. 15 ,, | 100 None 16 ,, j No count made. 17 | 150 Vomited in night. Gid- diness and drowsiness next day up to 3 p.m. 18 ,, No count None j made. 19 ,, 50 540 THE INDIAN MEDICAL GAZETTE. [Nov., 1924. from 45 to Ascarides were ex- 90 mgm. The if it is worked on a larger scale we have no doubt pelled and their ova disappeared from the stools. it could be considerably reduced. We have much pleasure in expressing our Clinical Trials. indebtedness to Dr. A. K. Mukerji, Capt. With the assistance of Dr. A. K. Mukerji, P. De and Mr. N. R. Chatterjee for their help in assistant in the Hookworm Research Laboratory, this research. To- Messrs. Smith, Stanistreet & Co. of Calcutta we are for we have tested the drug as an anthelmintic on a grateful supplying few cases infected with Ascaris and hookworm Indian santonin, and to the Kashmir State in the Carmichael Hospital for Tropical Diseases, Council, and especially to Mr. D. Nagerketti, and on a series of 18 cases infected with Ascaris Member in charge of Industry and Commerce, in the Alipore -Central Jail, Calcutta. We wish for supplying sufficient quantities of A. maritima Linn here to express our appreciation of the whole- (A. Brevifolia Wall). hearted co-operation received from the Superin- tendent of the Jail, Lieut. H. A. Young, i.m.d. References. The Indian santonin was accompanied in all 1. Watts' "Dictionary of Economic Products in cases calomel and sodium bicarbonate. The India." / by " amounts given and the details of preliminary and 2. Pharmacographia Indica." Vol. II. 3. Viehoever and Capen. American Jl. of purges are in the table. Pharma- subsequent given ceutical Association, May 1922, p. 393. All cases were on a of the jail kept liquid diet 4. Greenish. Eastern and Indian Drugs." /4, 1923, on the day that the drug was given. The stools p. 225. from the hospital cases were saved and washed 5. Greenish. Pharmaceutical Journal and Pharmacist, for 72 hours after the administration of the 1921, Vol. 10. 6, p. 2: 1922, Vol. 109, p. $5: 1923, drug, Vol. Ill, p. 94. those from the cases for 48 hours All " jail only. 6. Caius, J. F. and Mhaskar, K. S. Note/ on Ascari- of the patients' stools were re-examined for ova cides." Ind. J I. Med. Res., Vol. XI, 1923, pI 377-392. by the Kofoid and Barber technique 10 days later. As will be seen by reference to the table, the re-* suits compare very favourably with those ordina- rily obtained with European santonin. Caius and Mhaskar (1923) gave 5 gr. doses of the latter to 19 men, curing 6 out of 9 who were given the drug in the morning, followed by a purge two hours later, and 8 out of 10 were given the drug in the evening followed by a purge next morning. Caius and Mhaskar obtained only 52.1 per cent, of cures with 48-minim doses of oil of chenopodium, but we have succeeded in curing 56.7 per cent, of 37 cases with 30 minims given in divided doses of 10 minims each at one hour intervals. Santonin is, therefore, more effective than chenopodium, though much more expensive. Two of our hospital cases harboured hook- worms as well as Ascaris ; case No. 427 passed 15 Ancylostoma duodcnale, but was subsequently still positive for hookworm; case No. 436 passed 11 Ancylostoma d'wdenale, but on subsequent treatment with carbon tetrachloride passed 178 Ancylostoma duodcnalc and 146 Necator ameri- canus. The apparent differential effect on Ancylostoma is very interesting. Two other hookworm cases were treated with santonin but passed no hookworms, though both passed a few Oxyuris.

Conclusion. Santonin extracted from A. maritima Linn (A. brevifolia Wall), which grows in the mount- tains of Kashmir (Baltistan), closely resembles in its physical, chemical and physiological pro- perties the santonin imported from Europe. It satisfies all the tests laid down in the British and United States Pharmacopoeias. Its therapeutic ' efficacy is just as good. The present market price of the Indian santonin is Rs. 670 per pound, but