白鼠感染 肝吸蟲幼蟲에 대한 Praziquantel(Biltricide^(�))의 殺蟲效果에 대하여

林漢鍾,梁元容,宋寅喆,金洙鎭 최신의학사 1981 最新醫學 Vol.24 No.4

吸蟲類感染의 化學療法에 關한 硏究

林漢鍾 고려대학교 의과대학 1975 고려대 의대 잡지 Vol.12 No.2

Trematode infections, especially clonorchiasis, paragonimiasis, heterophyidiasis and fasciolopsiasis are the most important public health problems in certain countries in the Far East and South Eastern countries. Three common species of trematodes of medical importance have been reported in Korea, namely, Clonorchis stnensis, Paragonimus westermani and Metagonimus yokogawai. These trematode infections have long been recognized as an important public health problem in Korea. There is no report of human infection of Fasciola hepaiica and Eurytrema pancreaticum which common in Korean cattle. The occurrence of Fasciolopsis buski in Korea has not yet been reported. Some other small intestinal flukes, such as Echinostoma spp., Echinochasmus sp. And Heterophyes spp. Are also found in animals, however there are of no medical importance in Korea. Since last 10 years, there is no practically any big changes on the chemotherapy for the trematode infections except schistosomiasis. Bithionol is the drug of choice in the chemotherapy for paragonimiasis and tetrachlorethylene is the drug of choice for heterophyidiasis and fasciolopsiasis. However, there is none of the drug of choice for the treatment of clonorchiasis and opisthorchiasis up to now. In the present study several new drugs were attempted to the clinical trials for the treatment of clonorchiasis, paragonimiasis and metagonimiasis. The results are as follows: 1. Study on the chemotherapy for clonorchiasi Many earlier investigators have studied the treatment of clonorchiasis with various drugs, however none has proved to be effective as well as non-toxic to the host. Clonorchiasis is the most important disease in Korea, and this disease has been known to be of public health concern in many areas of southern part of Korea, but there is not any specific treatment for clonorchiasis. It would be desirable to find a therapeutic agent in the treatment of this disease. (1). Activity of drugs on Clonorchis sinensis infection of rabbits. In order to find a highly efficient compound against Clonorchis infection, the anthelmintic activiy of hetol (1,4 bis-trichloromethyl-benzol), dehydroemetine and bilevon (niclofolan) were tested against C. sinensis experimentally infected rabbits. All drugs showed a progressive increase in efficacy as the dose rate. They were highly efficient against Clonorchis infection if sufficiently high, potentially toxic doses were given. The efficacy was evaluated by the number of detected worms with vital condition at autopsy after the treatment with above drugs. The high efficacy was observed at the following dose rates of each drugs, i. e. hetol at the daily doses from 50 to 100㎎/㎏ for 5 to 10 consecutive days, dehydroemetine at the daily dose of 10㎎/㎏ for at least 10 consecutive days, and a single dose of 8 ㎎/㎏ of bilevon. (2). Clinical obser vation on the chemother apeutic effect of hetol. The therapeutic effect of hetol in various dosages and duration of medication was observed in 32 cases were treated with hetol at the dosage of 50 ㎎, 100 ㎎ and 150 ㎎ per ㎏ body weight daily or every other day for 5 to 12 medication days. The dosage of 50 ㎎ per ㎏ daily for 5 medication days can obtain complete cure in the light infection cases (1-1999 EPG), but the dosage for the treatment of the moderate infection(1,000-9,999 EPG) and heavy infection cases (10,000 and over EPG) require at least 50 ㎎ per ㎏ body weight daily for 12 medication days or 100 ㎎ per ㎏ daily for 7 medication days. However a dosage of 50 ㎎ per ㎏ daily for 5 to over 12 medication days depending on the severity of infection appears to be safe and appropriate for the treatment of clonorchiasis sinensis. (3) Clinical observation on the chemother apeutic effect of dehydroemetine Forty-five clonorchiasis patients were treated with dehydroemetine late-release tablets. These patients were divided into 5 groups and each group was given different dosages of dehydroemetine. In the results, high effectiveness showed at the dose of 2.5 ㎎/㎏ every other day for 25 to 30 days. In most of cases the EPG of faeces turned negative from the 30th day to the 40th day of treatment, but a very small number of eggs was detected again by concentration method at their follow up for over 6 months. During and after treatment, most patients showed marked improvement, usually with disappearance of upper abdominal pain and recovery of appetite. Some side effects such as diarrhea, anorexia, weakness and headache were reported in the most treated cases. However dehydroemetine should not be given to patients with cardiac insufficiency. (4) Clinical observation on the chemother apeutic effect of bilevon(niclofolan) A new drug which is bilevon (niclofolan, menichlofolan) has been used in the treatment of clonorchiasis. In order to obtain a minimum effective dose, various dosages and duration of medication of bilevon were applied for the treatment of clinical cases with different degree of infection. Bilevon was given at the dosages of 0.2, 0.4, 0.8, 1.0, and 2.0 ㎎/㎏ body weight in once or twice equally divided doses for one to 15 medicaion days in 35 cases consistiog all degree of infection. In each 5 cases received bilevon at the doses of 0.2 ㎎/㎏ and 0.4 ㎎/㎏ body weight for 15 consecutive days, the mean egg reduction rates at 6 months after treatment were shown 69.1 per cent and 94.4 per cent respectively. On the other hand, in each 5 cases received a relatively higher doses at 0.8㎎/㎏ body weight for 5 consecutive days, 1.0 ㎎/㎏ for 3 consecutive days and 2.0 ㎎/㎏ for 2 consecutive days, the mean egg reduction rates were shown 95.4%, 98.9% and 99.5% respectively at 3 or 6 months after treatment. In the most cases the EPG falled rapidly in the number of Clonorchis ova within 20 days after the beginning of treatment. On follow-up examination on 3 to 5 months after treatment, most patients showed marked clinical improvement. And also in the cases previously affected liver, much improvement of their liver function test showed after treatment with bilevon. Bilevon was well tolerated, but some side effects were noted such as with weakness, muscle pain on sacral region and lower extremities. The possibility that human clonorchiasis could be successfully treated with a few doses of bilevon can be promised from this study. Therefore, bilevon is a very promising drug for mass treatment against Clonorchis sinensis infection. Ⅱ. Study on the chemotherapy for paragonimiasis Paragonimiasis has been known as a medically important endemic disease linked with eating habit of fresh water crustaceans, particularly in Far East Asian countries for a long time. Bithionol is the drug of choice in paragonimiasis and has been used extensively in the past 15 years. However, the multiple doses and it's side reactions are hampered in mass treatment with bithionol in the field. In the present study bilevon has been used in the treatment of paragonimiasis for the first time. The experimental chemotherapy with bilevon for the infected dogs and cats with P. westermani were carried out. It was proved that a single or two doses of 20. ㎎/㎏ of bilevon were evidently effective for the infected dogs or cats with the lung fluke. In the clinical trial 25 paragonimiasis cases who have shown the eggs in their bloody sputa were treated with bilevon at a single dose of 2.0 ㎎/㎏ body weight. The number of eggs and the amounts of sputa were gradually decreased until 3 weeks after medication. The eggs in sputa of all cases were disappeared within one month after medication, and no relapses were found from the results of the follow-up investigations during the period from 6 to 12 months after medication. Fifteen out of 25 cases were examined periodically chest X-ray. Among them 5 cases who have shown abnormal X-ray shadows disappeared between the period from 2 to 4 months after medication. Bilevon was well tolerated and side effects were noted as transient weakness and muscle pain on sacral region in some cases but did not require treatment. There was no significant alteration in ECG, blood counts, blood biochemistry and urine analysis of all 15 cases before and after medication. The possibility that human paragonimiasis could be successfully treated with a single dose of bilevon can be presumed from this study. Therefore, bilevon is a very promising drug for mass treatment against paragonimiases as well as clonorchiasis. Ⅲ. Study on the chemotherapy for metagonimiasis The heterophyids are extremely small flukes inhabiting the intestine of man and fish eating mammals and birds. The infection of Metagonimus yokogawai has been known to be present nationwidely and endemic in some parts of Korea. In order to select a highly effective compound against Metagonimus infection, the therapeutic effects were observed in 101 cases were treated with several anthelmintics, i. e. terachlorethylene, bephenium hydroxynaphthoate(alcopar), pyrantel pamoate(combantrin), oxantel and pyrantel pamoate mixture and niclosamide(yomesan). Among the above drugs Metagonimus was removed by tetrachlorethylene and niclosamide at a single dose. From the results niclosamide was well tolerated, and no side effects were observed. Overall egg reduction rate was 96.2 per cent and radical cure was obtained by using a dosage of 100-125㎎/㎏ body weight in children.

간디스토마 감염 관리사의 진전

林漢鐘 대한의학협회 1992 대한의학협회지 Vol.35 No.11

肺吸蟲症에 대한 Niclofolan 및 Praziquantel의 治療效果에 關한 硏究

林漢鍾,張維臣 고려대학교 의과대학 1980 고려대 의대 잡지 Vol.17 No.1

Since 1961 bithionol has been extensively for the treatment of paragonimiasis westermani and it was proved as a drug of choice for the paragonimiasis caused by all kinds of Paragonimus. However, the multiple doses and it's side reactions are hampered in mass treatment with bithionol in the field. In the present study, two new drugs, niclofolan and praziqunatel, were attempted to the clinical trials for the treatment of paragonimiasis. The disappearance of eggs and chest X-ray improvement as well as the disappearance of clinical symptoms served as criteria for evaluating the therapeutic effects of the two drugs were compared. A total number of 40 paragonimiasis cases were treated with niclofolan at a single dose of 2.0㎎/㎏ body weight. The eggs in sputa of all cases except two were disappeared after one month of the medication and never relapsed during the follow up period, but in 2 cases the eggs were found in their sputa from the results of the follow up investigations. Therefore, the cure rate was shown as 95.0 percent. On the other hand, 50 paragonimiasis cases were treated with praziquantel at the dosages of 3×25㎎/㎏ bwt in a single day, 2 days and 3 days. 15 out of 21 cases who received 3×25㎎/㎏ bwt in a single day shoed negative eggs in their sputa or stools during the follow up period of 4 months after medication. The cure rate was 71.4 percent. In 19 cases who received 3×25㎎/㎏ bwt for 2 days, all cases except two showed complete negative egg in the follow up study. The cure rate was shown as 89.5 percent. However, in 10 cases received 3×25㎎/㎏ bwt for 3days, complete cureness was obtained at the follow up examinations. The treatment with niclofolan and praziquantel were found to be highly effective in pulmonary paragonimiasis. In treated cases disappearance of eggs and clinical symptoms were observed after one month of the mediation, and regressions in size of the lesions by chest X way finding were reviewed within 4 months after treatment. The laboratory tests were performed before and immediately after treatment in order to study for the drug influences on hematology, blood biochemistry and urnalysis. In some cases who received niclofolan, a transient marginal or slight rise of SGOT, SGPT, and BUN levels were seen, but no toxic nor abnormal effects were revealed. Adverse reactions consisted mainly muscle tenderness at the sacro-iliac region and the extremities, sweating and lassitude. But none of these symptoms was so severe to require bed-rest or withdrawal of the drug. On the other hand, none of the causes with laboratory abnormalities and unwanted side effects attributable to praziquantel were observed. Consequently both niclofolan and praziquantel are highly effective for the treatment of paragonimiasis, but praziquantel is more effective and safe drug than niclofolan. Therefore, praziquantel is the most promising drug for the treatment of paragonimiasis as well as clonorchiasis.

肝吸蟲症에 대한 Praziquantel (Embay 8440)의 治療效果에 關한 硏究

林漢鍾,柳光司 고려대학교 의과대학 1979 고려대 의대 잡지 Vol.16 No.3

A total of 162 patients with proven Clonorchis sinensis infection were treated by 8 different dosages with praziquantel at a single dose and 2 or 3 divided doses on a single or two days. A single dose of 40 ㎎/㎏ bwt and 50 ㎎/㎏ bwt of praziquantel were given to 28 and 15 patients respectively and each 15 patients were treated with a single dose of 20 ㎎/㎏ bwt and 30 ㎎/㎏ bwt for 2 days. Follow-up examinations were carried out at about 30 and 60 days after treatment. Two months after therapy, the results were shown 82.6 to 99.1% in the egg reduction rates but only 6.7% (in dosage group of 20 ㎎/㎏×2 days) to 33.3% (in dosage group of 50 ㎎/㎏×1 day) in cure rates. On the other hand, two doses of 25 ㎎/㎏ bwt (50 ㎎/㎏ bwt) and 3 doses of 25 ㎎/㎏ (75 ㎎/㎏ bwt) of praziquantel with the interval of 6 hours on one or two days were given to the other patients. The dosage of 2×25 ㎎/㎏×1 day and 2×25 ㎎/㎏×2 days were given to 15 and 24 patients respectively. The high egg reduction rates of 97.4% and 99.9% were shown in the follow-up examinations, however 46.7% and 75.0% of cure rates were obtained. Considerably high egg reduction rate (99.7%) and cure rate (85.7%) were obtained in 35 patients received 3×25 ㎎/㎏ bwt in a single day. However in 15 patients received 3×25 ㎎/㎏ bwt for two days complete cure was obtained at the follow-up examinations. In case eggs were found at the first or second follow-up examination, patients were treated again with the same dosage of praziquantel and another follow-up period of 60 days was required. Six of 24 patients received 2×25 ㎎/㎏×2 days and 5 of 35 patients received 3×25 ㎎/㎏×1 day treated again with the same dosage of praziquantel and all were completely cured. After a single dose of 40 ㎎/㎏×1 day, only 7 of 28 patients were cured at 30 and 60 days after therapy, and 21 patients received for another time 40 ㎎/㎏ once on a single day and 7 of these 21 patients (33.3%) were cured. The remaining 14 patients showed egg reduction rates of over 90%. Therefore 50.0% of cure rate was obtained after the 2nd medication. Eight of 15 cases received 2×25 ㎎/㎏×1 day were treated again with the same dosage, and only 4 cases were cured. In the final result, 73.3% of cure rate with 99.4% of egg reduction rate was shown at 60 days follow-up examination after the second medication. The assessment of tolerance recorded only a few side effects, such as headache, dizziness and nausea etc. Extended hematological and biochemical tests showed no abnormal findings after thereapy which might be due to the medication. It was evidently shown that the human clonorchiasis could be successfully treated with a few doses of praziquantel without any serious side effects. Therefore praziquantel is the most promising drug for the treatment against Clonorchis sinensis infection.

肝吸蟲症과 최신 化學療法

林漢鍾 대한기생충학열대의학회 1986 The Korean Journal of Parasitology Vol.24 No.4

우수선수에 있어서 기생충감염률 조사

임한종 中央醫學社 1982 中央醫學 Vol.42 No.4

십이지장충 알레르기

임한종 中央醫學社 1978 中央醫學 Vol.35 No.1

土壤媒介性 ?蟲症의 臨床檢査法 및 治療

林漢鍾 한국의 현대의학사 1969 한국의 현대의학 Vol.1 No.3

寄生蟲疾患의 化學的 療法

林漢鍾 대한의학협회 1979 대한의학협회지 Vol.22 No.11