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Useful plants of dermatology. I. Hydnocarpus and chaulmoogra
COMMENTARY Useful plants of dermatology. I. Hydnocarpus and chaulmoogra Scott A. Norton, MD Honolulu, Hawaii
Before the development of dapsone, the standard remedy for Hansen's disease (HD) was chaulmoogra oil. This amber-colored oil was extracted from the seeds of the chaulmoogra or kalaw tree, Hydnocarpus kurzii, found in the jungles of north Burma. In much of southeast Asia, chaulmoogra was the traditional therapy for HD and other dermatoses. In the late nineteenth century, Western physicians began using it in oral, topical, and parenteral forms to treat HD. Hydnocarpus The 40 species in the genus Hydnocarpus (Hydno = truffle and carpus = fruit) are indigenous to Asia's tropical rain forests, ranging from India and Sri Lanka in the west to the Philippines and Indonesia in the east (Fig. 1). Many species in Hydnocarpus and related genera in the family F1acourtiaceae were tried in the treatment ofHD.I-4 The most important sources were kalaw in Burma, tuvaraka (Hydnocarpus pentandra) in southeastern India, and tai-fung-tsze (Hydnocarpus anthelmentica) in China. Only H. pentandra grew abundantly and accessibly in nature; therefore its oil was used extensively.P However, the original chaulmoogra, H. kurzii, was widely cultivated for its therapeutic oil. The kalaw tree stands 15 to 20 m tall and has large shiny green lanceolate leaves (Fig. 2). The fruits are orange-sized spheres with brittle, velvet-textured
From the Dermatology Service,DepartmenlofMedicine,TripierArmy Medical Center. Presented in part at the 52nd Annual Meetingof the AmericanAcademy of Dermatology, Washington, D.C., Dec. 4-9, 1993. The opinions andassertions containedhereinare theviews oftheauthor and not to beconsidered as reflecting the views of the Departmentof the Army or the Department of Defense. Reprint requests: Scott A. Norton, MD, Dermatology Service, Department of Medicine, Tripier Army Medical Center, Honolulu, HI. 96859. JAM ACAD DERMATOL 1994;31:683-6
16/1/57559
Fig. 1. Sourcesof chaulmoograoil.H. kurzii, Green; H. pentandra, yellow; H. anthelmentica, orange; Caloncoba echinata, blue; Carpotroche brasiliensis, red.
shells (Fig. 3). Inside are many large, hard, angular seeds embedded in a cream-colored pulp.? For years Western scientists did not know the identity of the true chaulmoogra tree. Botanists had only the seeds that had made it to Asia's herbal markets from which to identify the tree. Less durable parts, such as flowers, fruits, and leaves, that are also needed to classify plants were unavailable. Judging from markings on the seeds, botanists guessed the chaulmoogra tree was in the genus Gynocardia. However, they were wrong and the correct identity was finally determined early this century.I,2,6 Origin of chaulmoogra oil The use of chaulmoogra oil in the treatment of skin diseases, leprosy in particular, was part of two ancient pharmacopoeias-in India and in China. Its place in India's Ayurvedic medicine began more than 2000 years ago; it was based on the legend of King Rama (not the deity Rama) of Benares. He developed leprosy and fled to the forests where he lived in a hollowed kalaw tree. As he ate the kalaw's fruit, his leprosy cleared. A princess, Piya, also afflicted with leprosy, was banished to the same forest. Rama treated Piya with the kalaw fruit and
683
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Journal of the Americ an Academy of Dermatology October 1994
Fig. 2. Postage stamp from Fiji shows a mature chaulmoogra tree at the Central Leper Hospital, Makogai, Fiji, where patients from several isla nd groups who had HD in the southwest Pacific were sequestered. Stamp from Egypt shows a flowering branch and commemorates the International Congress of Leprology.
cured her leprosy. The two, now free of disease, married and raised 16 sets of twin sons." Since then, kalaw fruits-or more specifically, the oilsextracted from their seeds-have served to fight leprosy. In view of this legend, one might think it has potential as a fertility drug, too. The earliest report from Chinese medical literature describes the use of oral preparations, probably fromH. anthelmentica introduced from Siam, in the fourteenth century. 1, 7 Chaulmoogra and Western medicine Chaulmoogra oil first became known to Western physicians in the 1850s with the reports of Dr. F rederic J . Mouat of the Bengal Medical Service.i-9 It gained acceptance as the best treatment and as a possible cure for lepromatous disease.l? Around 1900, leprosaria in the Hawaiian Islands and at Carville, Louisiana, adopted chaulmoogra as their main treatment. Oil supplies from Asian herbal markets were insufficient, expensive, and usually adulterated; therefore the United States Department of Agriculture decided to start Hydnocarpus plantations in Hawaii. Joseph Rock, who taught botany and Chinese at the University of Hawaii, was
Fig. 3. Fruit of H. anthelmentica are orange-sized spheres (A), with brittle, velvet-textured shells (B). Each fruit contains 10 to 20 angled seeds embedded in a moist, tan-colored flesh. (Fruits collected with permission of the Foster Botanical Gardens, Honolulu, Hawai'i.)
dispatched to southeast Asia to collect fresh seeds in the wild. For months, he trekked through the jungles of Siam , Burma, and Assam searching for scarce chaulmoogra trees. After encounters with man-eating tigers, rampaging elephants, and hostile tribesmen, he found stands of H. kurzii and H. anthelmentica. The seeds were collected and planted in a remote valley on O'ahu. After a decade, the new trees produced fruits and seeds and soon a supply of chaulmoogra oil was available for the leprosaria at Carville and Moloka'i.9, 11 Preparation and administration of chaulmoogra products The original source of chaulmoogra oil was the Burmese tree, H. kurzii, but oils obtained from related species were therapeutically indistinguishable.
Journal of the American Academy of Dermatology Volume 31, Number 4
Norton
685
CH
H( "'-cHICH.)'.COOH H2C- L 2
HYDNOCARPIC ACID
C16 H2S02
CH
H~ ~H(CH2112COOH
H~
/ CH2
CHAULMOOGRIC ACID C18 H3202
Fig. 4. Chaulmoogra acid (ClsH3202). Hydnocarpic acid (CI6H2S02).
Preparation of pharmaceutical-grade chaulmoogra oil requires pressure extraction of crude oilsfrom the seeds, followed by saponification of the oil with sodium hydroxide. Repeated washings with hot water allowed a purer oil to be decanted each time. The result contained two fatty acids, hydnocarpic and chaulmoogric acids, that differ slightly in their chemical composition (Fig. 4) and optical rotatory powers.': 12 These were prepared further for oral, topical, or parenteral administration (Fig. 5).13-16 A typical regimen for a patient was to receive subcutaneous injections of 15 ml of oil beneath lesions twice weekly for IO-week courses, repeated until the lesions were clinically clear. 16 Parenteral chaulmoogra was painful and caused fevers, sterile abscesses, and phlebitis.l'v 17 Because of the pain, many patients considered stopping the treatments. 18 Burroughs-Welcome marketed sodium hydnocarpate as Alepol and a creosoted ester of Hydnocarpus oil as Moogrol. Iodized ethyl esters of chaulmoogra oil, called Dean's derivative, reportedly had fewer side effects and were marketed by Bayer as AntileproLl518
Mechanism of action Proponents of chaulmoogra suggested several possible mechanisms of action. The lipolysis hypothesis suggested that the introduction of chaulmoogra oil, a foreign lipid, activated host lipases to destroy all foreign lipids including both the chaulmoogra oil and the cell wall of M. /eprae. The hypothesis held
Fig. 5. Oils from H. kurzii and H. venenata. (With permission of the Royal Botanic Gardens, Kew, England).
that once the bacillary cell wall was penetrated, regular immunologic processes could destroy the lepra bacillus. Proof was specious; after chaulmoogra injections, serum lipase levels often increased (rising to attack the foreign lipids) or decreased (depleted in combat against the foreign lipids). Another hypothesis invoked counterirritation, a sort of chemotaxis, in which the irritation caused by injected chaulmoogra drew phagocytes into proximity of the lepra bacilli. I, 16
The decline of chaulmoogra When the early successes of sulfones (e.g., promin and dapsone) were reported in the 1940s, proponents of chaulmoogra resisted a change in therapies. A standard text on leprosy written in 1947 admonished that "it cannot be too strongly stressed that no departure should as yet be made from the well-tried and accepted derivatives of hydnocarpus oil." 16 Others recommended the administration of both sulfones and chaulmoogra because their actions "on lepra bacilli are complementary, so a combination of the two is likely to furnish the most effective and rapid treatment ofleprosy." 19 However, most leprologists agreed with G. W. McCoy, former medical director of the U.S. Public Health Service, who in 1942 proclaimed "the oil and its derivatives are of little or no curative value, and [their] unpleasant side effects probably outweigh any advantage to the patient that might possibly accrue from their use.,,20 Although chaulmoogra was once the standard of care, we still do not know whether it had any effect on HD. No well-designed clinical trial of chaulmoogra was ever conducted. An Indian report from
686
Journal of the American Ac ademy of Dermatology October 1994
Norton
Table I. Members of the Flacourtiaceae family used to make antileprosy oils Binomial
Obsolete names
Vernacularnames
H. kurzii (King) Warb.
Taraktogenos kurzii
Kalaw, chaulmoogra
H . pentandra (buch.-Ham.) Oken H . anthelmentica Pierre ex Lanessan H. venenata Gaertn H. alcolce C.DC. H . castanea Hook f. & Thomson H . macrocarpa (Beddome) Warb Coloncoba enchinata (Oliver) Gilg Carpotroche brasiliensis End!. Gynocardia odorate R. Brown
H. laurifolia, H. wight iana H. alpina
Tuvaraka Tai-fung-tsze, krabao Maku lu Dudo's
Asteriastigma macrocarpa Oncoba echinata
1973 continued to advocate its use.!? but otherwise the medicine has been dropped from our formularies and memories. Conclusion Chaulmoogra emerged from traditional pharmacopoiea to attain a prominent role in the fight against RD. It has been replaced today, but its reign as the treatment of choice was longer than the period that dapsone has been used. The rain forests in which chaulmoogra trees grow were so poorly explored that for half a century scientists could neither identify nor locate the tree from which this medicine was obtained. Jack Norton translated portions of Sleumer's monograph . Fruits of H. anthelmentica were collected from the Foster Botanical Gardens, Honolulu, Hawai'i. Samples of chaulmoogra oil were examined and photographed at the Royat Botanic Gardens, Kew, England. REFERENCES 1. Cole HI. Chemistry of leprosy drugs. Int J Leprosy 1922;1:159-4. 2. Sleumer H. Monographie der gattung Hydnocarpus Gaertner. Botanische Jahrbucher 1939;69:1-93. 3. Mabberley DJ. The plant book. Cambridge: Cambridge University Press, 1987:283.
Location
Thailand, Burma, northeast India Malabar coast of southwest India Tha iland, Cambodia , Laos, Vietnam Sri Lanka Philippines Burma, Malay peninsula Southern India
Godi Sapucainha
Sierra Leone, Ivory Coast , Guinea East coast of Brazil Burma, northeast India
4. de Souza-Araujo HC. The Brazilian chaulmoogra: Carpotroche brasiliensis. Int J Leprosy 1935;3:49-66. S. Joseph We. Hydnocarpus Wightiana. Leprosy Rev 1932; 3:22-4. 6. Anonymous. Chaulmugra seed. 4th series. Pharm J 1901;12:596. 7. Wong KC, Wu L-T. History of Chinese medicine. Sh anghai: National Quarantine Service, 1936:114-7. 8. Mouat Fl. Noles on native remedies. Indian Ann Med Sc i 1854;1 :646-52. 9. Kreig MB. Green medicine: the search for plants that heal. Chicago: Rand McNally, 1964:242-54. 10. Schujman S. Therapeutic value of chaulmoogra in the treatment ofleprosy. Int J Leprosy 1947;15:135-43. II. Rock JF. Hunting the chaulmoogra tree. National Geographic 1922;16:243-76. 12. Rogers L, Muir E. Leprosy. Bristol:John Wright, 1925:25869. 13. Dean AL, Wrenshall R. Preparation of chaulmoogra oil derivatives for the treatment of leprosy. Public Health Rep 1922;37:1395-9. 14. Cole HI, Cardoso HT. Purification and esterification of chaulmoogra oils. Int J Leprosy 1936;4:455-68. 15. Cole HI, Cardoso HT. Analysis of chaulmoogra oils. Int J Leprosy 1941;9:215-28. 16. Cochrane RG. A pract ical textbook of leprosy. Ox ford: Oxford University Press, 1947:117-32. 17. Chaudhuri SK, Ghosh S. Review on chaulmoogra oil. Indian J Dermatol 1973;18:55-61. 18. Wilson RM. Leprosy in Korea with special reference to the Soochun Leprosy Colony. Leprosy Rev 1932;3:81 -3. 19. Rogers L. Comb ined chaulmoograte and sulphone treatment of leprosy and tuberculosis. Lancet 1948;1:515-7. 20. McCoy G W. Chaulmoogra oil in the treatment ofleprosy. Public Health Rep 1942;57:1727-33.
Before the development of dapsone, the standard remedy for Hansen's disease (HD) was chaulmoogra oil. This amber-colored oil was extracted from the seeds of the chaulmoogra or kalaw tree, Hydnocarpus kurzii, found in the jungles of north Burma. In much of southeast Asia, chaulmoogra was the traditional therapy for HD and other dermatoses. In the late nineteenth century, Western physicians began using it in oral, topical, and parenteral forms to treat HD. Hydnocarpus The 40 species in the genus Hydnocarpus (Hydno = truffle and carpus = fruit) are indigenous to Asia's tropical rain forests, ranging from India and Sri Lanka in the west to the Philippines and Indonesia in the east (Fig. 1). Many species in Hydnocarpus and related genera in the family F1acourtiaceae were tried in the treatment ofHD.I-4 The most important sources were kalaw in Burma, tuvaraka (Hydnocarpus pentandra) in southeastern India, and tai-fung-tsze (Hydnocarpus anthelmentica) in China. Only H. pentandra grew abundantly and accessibly in nature; therefore its oil was used extensively.P However, the original chaulmoogra, H. kurzii, was widely cultivated for its therapeutic oil. The kalaw tree stands 15 to 20 m tall and has large shiny green lanceolate leaves (Fig. 2). The fruits are orange-sized spheres with brittle, velvet-textured
From the Dermatology Service,DepartmenlofMedicine,TripierArmy Medical Center. Presented in part at the 52nd Annual Meetingof the AmericanAcademy of Dermatology, Washington, D.C., Dec. 4-9, 1993. The opinions andassertions containedhereinare theviews oftheauthor and not to beconsidered as reflecting the views of the Departmentof the Army or the Department of Defense. Reprint requests: Scott A. Norton, MD, Dermatology Service, Department of Medicine, Tripier Army Medical Center, Honolulu, HI. 96859. JAM ACAD DERMATOL 1994;31:683-6
16/1/57559
Fig. 1. Sourcesof chaulmoograoil.H. kurzii, Green; H. pentandra, yellow; H. anthelmentica, orange; Caloncoba echinata, blue; Carpotroche brasiliensis, red.
shells (Fig. 3). Inside are many large, hard, angular seeds embedded in a cream-colored pulp.? For years Western scientists did not know the identity of the true chaulmoogra tree. Botanists had only the seeds that had made it to Asia's herbal markets from which to identify the tree. Less durable parts, such as flowers, fruits, and leaves, that are also needed to classify plants were unavailable. Judging from markings on the seeds, botanists guessed the chaulmoogra tree was in the genus Gynocardia. However, they were wrong and the correct identity was finally determined early this century.I,2,6 Origin of chaulmoogra oil The use of chaulmoogra oil in the treatment of skin diseases, leprosy in particular, was part of two ancient pharmacopoeias-in India and in China. Its place in India's Ayurvedic medicine began more than 2000 years ago; it was based on the legend of King Rama (not the deity Rama) of Benares. He developed leprosy and fled to the forests where he lived in a hollowed kalaw tree. As he ate the kalaw's fruit, his leprosy cleared. A princess, Piya, also afflicted with leprosy, was banished to the same forest. Rama treated Piya with the kalaw fruit and
683
684
Norton
Journal of the Americ an Academy of Dermatology October 1994
Fig. 2. Postage stamp from Fiji shows a mature chaulmoogra tree at the Central Leper Hospital, Makogai, Fiji, where patients from several isla nd groups who had HD in the southwest Pacific were sequestered. Stamp from Egypt shows a flowering branch and commemorates the International Congress of Leprology.
cured her leprosy. The two, now free of disease, married and raised 16 sets of twin sons." Since then, kalaw fruits-or more specifically, the oilsextracted from their seeds-have served to fight leprosy. In view of this legend, one might think it has potential as a fertility drug, too. The earliest report from Chinese medical literature describes the use of oral preparations, probably fromH. anthelmentica introduced from Siam, in the fourteenth century. 1, 7 Chaulmoogra and Western medicine Chaulmoogra oil first became known to Western physicians in the 1850s with the reports of Dr. F rederic J . Mouat of the Bengal Medical Service.i-9 It gained acceptance as the best treatment and as a possible cure for lepromatous disease.l? Around 1900, leprosaria in the Hawaiian Islands and at Carville, Louisiana, adopted chaulmoogra as their main treatment. Oil supplies from Asian herbal markets were insufficient, expensive, and usually adulterated; therefore the United States Department of Agriculture decided to start Hydnocarpus plantations in Hawaii. Joseph Rock, who taught botany and Chinese at the University of Hawaii, was
Fig. 3. Fruit of H. anthelmentica are orange-sized spheres (A), with brittle, velvet-textured shells (B). Each fruit contains 10 to 20 angled seeds embedded in a moist, tan-colored flesh. (Fruits collected with permission of the Foster Botanical Gardens, Honolulu, Hawai'i.)
dispatched to southeast Asia to collect fresh seeds in the wild. For months, he trekked through the jungles of Siam , Burma, and Assam searching for scarce chaulmoogra trees. After encounters with man-eating tigers, rampaging elephants, and hostile tribesmen, he found stands of H. kurzii and H. anthelmentica. The seeds were collected and planted in a remote valley on O'ahu. After a decade, the new trees produced fruits and seeds and soon a supply of chaulmoogra oil was available for the leprosaria at Carville and Moloka'i.9, 11 Preparation and administration of chaulmoogra products The original source of chaulmoogra oil was the Burmese tree, H. kurzii, but oils obtained from related species were therapeutically indistinguishable.
Journal of the American Academy of Dermatology Volume 31, Number 4
Norton
685
CH
H( "'-cHICH.)'.COOH H2C- L 2
HYDNOCARPIC ACID
C16 H2S02
CH
H~ ~H(CH2112COOH
H~
/ CH2
CHAULMOOGRIC ACID C18 H3202
Fig. 4. Chaulmoogra acid (ClsH3202). Hydnocarpic acid (CI6H2S02).
Preparation of pharmaceutical-grade chaulmoogra oil requires pressure extraction of crude oilsfrom the seeds, followed by saponification of the oil with sodium hydroxide. Repeated washings with hot water allowed a purer oil to be decanted each time. The result contained two fatty acids, hydnocarpic and chaulmoogric acids, that differ slightly in their chemical composition (Fig. 4) and optical rotatory powers.': 12 These were prepared further for oral, topical, or parenteral administration (Fig. 5).13-16 A typical regimen for a patient was to receive subcutaneous injections of 15 ml of oil beneath lesions twice weekly for IO-week courses, repeated until the lesions were clinically clear. 16 Parenteral chaulmoogra was painful and caused fevers, sterile abscesses, and phlebitis.l'v 17 Because of the pain, many patients considered stopping the treatments. 18 Burroughs-Welcome marketed sodium hydnocarpate as Alepol and a creosoted ester of Hydnocarpus oil as Moogrol. Iodized ethyl esters of chaulmoogra oil, called Dean's derivative, reportedly had fewer side effects and were marketed by Bayer as AntileproLl518
Mechanism of action Proponents of chaulmoogra suggested several possible mechanisms of action. The lipolysis hypothesis suggested that the introduction of chaulmoogra oil, a foreign lipid, activated host lipases to destroy all foreign lipids including both the chaulmoogra oil and the cell wall of M. /eprae. The hypothesis held
Fig. 5. Oils from H. kurzii and H. venenata. (With permission of the Royal Botanic Gardens, Kew, England).
that once the bacillary cell wall was penetrated, regular immunologic processes could destroy the lepra bacillus. Proof was specious; after chaulmoogra injections, serum lipase levels often increased (rising to attack the foreign lipids) or decreased (depleted in combat against the foreign lipids). Another hypothesis invoked counterirritation, a sort of chemotaxis, in which the irritation caused by injected chaulmoogra drew phagocytes into proximity of the lepra bacilli. I, 16
The decline of chaulmoogra When the early successes of sulfones (e.g., promin and dapsone) were reported in the 1940s, proponents of chaulmoogra resisted a change in therapies. A standard text on leprosy written in 1947 admonished that "it cannot be too strongly stressed that no departure should as yet be made from the well-tried and accepted derivatives of hydnocarpus oil." 16 Others recommended the administration of both sulfones and chaulmoogra because their actions "on lepra bacilli are complementary, so a combination of the two is likely to furnish the most effective and rapid treatment ofleprosy." 19 However, most leprologists agreed with G. W. McCoy, former medical director of the U.S. Public Health Service, who in 1942 proclaimed "the oil and its derivatives are of little or no curative value, and [their] unpleasant side effects probably outweigh any advantage to the patient that might possibly accrue from their use.,,20 Although chaulmoogra was once the standard of care, we still do not know whether it had any effect on HD. No well-designed clinical trial of chaulmoogra was ever conducted. An Indian report from
686
Journal of the American Ac ademy of Dermatology October 1994
Norton
Table I. Members of the Flacourtiaceae family used to make antileprosy oils Binomial
Obsolete names
Vernacularnames
H. kurzii (King) Warb.
Taraktogenos kurzii
Kalaw, chaulmoogra
H . pentandra (buch.-Ham.) Oken H . anthelmentica Pierre ex Lanessan H. venenata Gaertn H. alcolce C.DC. H . castanea Hook f. & Thomson H . macrocarpa (Beddome) Warb Coloncoba enchinata (Oliver) Gilg Carpotroche brasiliensis End!. Gynocardia odorate R. Brown
H. laurifolia, H. wight iana H. alpina
Tuvaraka Tai-fung-tsze, krabao Maku lu Dudo's
Asteriastigma macrocarpa Oncoba echinata
1973 continued to advocate its use.!? but otherwise the medicine has been dropped from our formularies and memories. Conclusion Chaulmoogra emerged from traditional pharmacopoiea to attain a prominent role in the fight against RD. It has been replaced today, but its reign as the treatment of choice was longer than the period that dapsone has been used. The rain forests in which chaulmoogra trees grow were so poorly explored that for half a century scientists could neither identify nor locate the tree from which this medicine was obtained. Jack Norton translated portions of Sleumer's monograph . Fruits of H. anthelmentica were collected from the Foster Botanical Gardens, Honolulu, Hawai'i. Samples of chaulmoogra oil were examined and photographed at the Royat Botanic Gardens, Kew, England. REFERENCES 1. Cole HI. Chemistry of leprosy drugs. Int J Leprosy 1922;1:159-4. 2. Sleumer H. Monographie der gattung Hydnocarpus Gaertner. Botanische Jahrbucher 1939;69:1-93. 3. Mabberley DJ. The plant book. Cambridge: Cambridge University Press, 1987:283.
Location
Thailand, Burma, northeast India Malabar coast of southwest India Tha iland, Cambodia , Laos, Vietnam Sri Lanka Philippines Burma, Malay peninsula Southern India
Godi Sapucainha
Sierra Leone, Ivory Coast , Guinea East coast of Brazil Burma, northeast India
4. de Souza-Araujo HC. The Brazilian chaulmoogra: Carpotroche brasiliensis. Int J Leprosy 1935;3:49-66. S. Joseph We. Hydnocarpus Wightiana. Leprosy Rev 1932; 3:22-4. 6. Anonymous. Chaulmugra seed. 4th series. Pharm J 1901;12:596. 7. Wong KC, Wu L-T. History of Chinese medicine. Sh anghai: National Quarantine Service, 1936:114-7. 8. Mouat Fl. Noles on native remedies. Indian Ann Med Sc i 1854;1 :646-52. 9. Kreig MB. Green medicine: the search for plants that heal. Chicago: Rand McNally, 1964:242-54. 10. Schujman S. Therapeutic value of chaulmoogra in the treatment ofleprosy. Int J Leprosy 1947;15:135-43. II. Rock JF. Hunting the chaulmoogra tree. National Geographic 1922;16:243-76. 12. Rogers L, Muir E. Leprosy. Bristol:John Wright, 1925:25869. 13. Dean AL, Wrenshall R. Preparation of chaulmoogra oil derivatives for the treatment of leprosy. Public Health Rep 1922;37:1395-9. 14. Cole HI, Cardoso HT. Purification and esterification of chaulmoogra oils. Int J Leprosy 1936;4:455-68. 15. Cole HI, Cardoso HT. Analysis of chaulmoogra oils. Int J Leprosy 1941;9:215-28. 16. Cochrane RG. A pract ical textbook of leprosy. Ox ford: Oxford University Press, 1947:117-32. 17. Chaudhuri SK, Ghosh S. Review on chaulmoogra oil. Indian J Dermatol 1973;18:55-61. 18. Wilson RM. Leprosy in Korea with special reference to the Soochun Leprosy Colony. Leprosy Rev 1932;3:81 -3. 19. Rogers L. Comb ined chaulmoograte and sulphone treatment of leprosy and tuberculosis. Lancet 1948;1:515-7. 20. McCoy G W. Chaulmoogra oil in the treatment ofleprosy. Public Health Rep 1942;57:1727-33.