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제목 |
Studies on the Treatment of Leprosy With a Synthesized Thiocarbanilide Derivative L-4 |
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저자 |
Joon Lew, Chai Hoon Chang, and Tae Kyung Choi |
소속 |
Dept. of Microbiology, College of Medicine, Yonsei University |
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년도 |
1968 |
권 |
5 |
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호 |
1 |
번호 |
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시작페이지 |
25 |
끝페이지 |
46 |
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첨부 |
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요약 |
Though Chaulmoogra oil (Mouat 1854) had been used empirically in the treatment of
leprosy from the ancient time, the very beginning of modern chemotherapy of leprosy
was initiated by the work of Faget et al. (1943) who originated the Promin treatment of
leprosy, Promin was a less toxic derivative of the parent sulphone, ie., DDS
(Diaminodiphenyl sulphone) which was synthesized by Fromm and Whittmann (1908).
However, Promin itself was too toxic to be given orally or subcutaneously, and
therefore, it had only to be given intravenously. By the introduction of other derivatives
of DDS such as Sulfoxone sodium, U.S.P (Diasone sodium), Solapsone, B.P.
(Sulphetrone), Acetosulphone (Promacetin) and Thiazolsulphone that could be given
orally in similar doses with safety, Promin was eventually replaced by those drugs.
Meanwhile, the pioneering works done by Cochrane et at. (1949), Lowe and Smith
(1949) and Lowe (1950) firmly established that DDS, the parent sulphone of those
derivatives, did possess activity against Mycobacteria, and DDS has become the choice
of drug in the treatment of leprosy since then on.
Today, it is well recognized that DDS is the drug having the virtues of low cost,
general efficacy, suitability of outpatient treatment, rarity of drug resistance, and its
prophylactic effectiveness. However, as Davey (1964) pointed out, DDS has still many
limitations such as 1) its rather strong toxicity, 2) the existence of idiosyncrasy, 3) the
precipitation of hypersensitive state, 4) the development of leprosy reactions, 5) the
prolonged time of medication, 6) occasional occurrence of non-responding patients and
etc. Those limitations of DDS indicate that it could not be a sole and the most ideal
antileprosy chemotherapeutic.
Extorts (Buu-Hoi 1954, 1955a, 1955b, Buu- Hoi et al. 1955a, Buu-Hoi et at. 1955b,.
Buu-Hoi et at. 1955c, bfayer 1941, 1954, Mayer et al. 1953, Mayer et at. 1959) have been
made to produce alternative, ideal drugs that would exert lesser toxicity, speedier action
and smoother progress during the treatment in addition to the virtues of DDS. Following
representative of several classes of various organic compounds hale been discovered and
have been shown to possess activities against Mycobacterium leprae at more than one
institute throughout the world; Diami-nodiphenylsulfoxide (Buu-Hoi et al. 1955a)
Sulfamethokypyrazine (Lederkyn; Schneider et al. 1958, Schneider et al. 1960),
Sulfamethoxydiazine (Barclay and Wilkinson 1963), Acetylsulphomethxypyrazine
(Schneider and Languillon 1963), P-acetamidoben-zaldehyde thiosemicarbazone
(Ainithiozone or TB1/689;Ryrie 1950, Lowe 1952, Lowe 1954, Dharmendra and Chatterjee
1952), 4-butoxy-4'-dimethylaminodiphenyl thiourea (DPT or Ciba 1906; Davey and
Currie 1956, Davey et at. 1958, Davey 1960) and Diethyldithiolisophthalate (Ditophal or
Etisul; Devey arid Hogerzeil 1959).
All of those chemical compounds have been developed in the hope that they could be
administered siglely or in combination with DDS to surpass or to improve the
limitations of DDS. Recently, there have been some reports which provided additional
data in support of the general efficacy and advantages of DDS administration for the
treatment of patients and for the control of leprosy. Such reports include the
effectiveness of low dose DDS treatment and its advantages (Browne 1965, Leiker and
Carling 1965 Ramu and Ramanujam 1965), and the sensitivity of Mycobacterium leprae
to low levels of DDS in mice (Shepard et al. 1966).
Choi and Lew (1965) synthesized a series of thiocarbanilide derivatives in the efforts
of developing new antileprosy and antitubercolosis chemotherapeutics. Among the
synthcsized derivatives, L-4 Ivas shown to possess a significant activity against taurine
leprosy (Choi and Lew 1965). Following their original study, Kim and Lew (1967)
demonstrated that L-1 and L-4 exerted potent antifungal activity in in-vitro experiment,
and Chang and Lew(1967) also reported that the activities of L-1 and L-4 against
mycobacteria and superficial mycoses wore specific and selective ones.
These evidences clearly indicated the possibility of clinical treatnlent of leprosy with
L-4, a synthesized thiocarbanilide derivative.
In this study, domiciliary leprosy patients who had registered at the World Vision
Leprosy Research Center there included. The results of clinical trial of L-4 in the
treatment of leprosy patients were assessed clinically and bacteriologically in comparison
with patients under ordinary DDS treatment. |
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