本文選題：旋毛蟲病 + 三苯雙脒��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的 評價口服不同劑量三苯雙脒(TBD)和不同療程口服TBD300mg/(kg-d)抗小鼠橫紋肌中旋毛蟲成囊期幼蟲的療效,比較口服TBD的三種不同溶液抗小鼠旋毛蟲成囊期幼蟲的效果。 材料與方法 實驗1：88只小鼠隨機均分為11組,每鼠口服感染成囊期幼蟲50條。感染后29d,分別口服TBD0-500mg/(kg-d),連服6d。觀察小鼠的不良反應(yīng)。治療后7d,肌肉壓片法計數(shù)膈肌、咬肌、胸肌和腓腸肌中成囊期幼蟲,以每克肌肉平均幼蟲數(shù)評價療效。 實驗2：40只小鼠隨機均分為5組,每鼠口飼感染成囊期幼蟲50條。感染后29d,以不同療程(2、4、6、8d)口服TBD300mg/(kg-d)治療,對照組不治療。停藥后7d,肌肉壓片法計數(shù)膈肌、咬肌、胸肌、腓腸肌中幼蟲。另40只小鼠隨機均分為5組,進行反證實驗,分別用上述不同療程治療后的小鼠膈肌幼蟲50條口飼感染,感染后29d,肌肉壓片法計數(shù)膈肌中幼蟲。 實驗3：40只小鼠隨機均分為4組,每鼠口服感染成囊期幼蟲50條。感染后29d,分別用不同溶劑的三苯雙脒治療,溶劑分別為：7%吐溫-80和3%乙醇(吐溫組),1%羧甲基纖維素和3%乙醇(羧纖組),7%羥丙基-p-環(huán)糊精和3%乙醇(羥環(huán)組)。劑量均為200mg/(kg-d),連續(xù)給藥6天,對照組不治療。治療后14d,肌肉壓片法計數(shù)膈肌和腓腸肌的活蟲數(shù)和死蟲數(shù),以每克肌肉平均幼蟲數(shù)評價療效。 結(jié)果 實驗1：50～300mg組小鼠無藥物有不良反應(yīng)；350和400mg組小鼠有重度不良反應(yīng),分別死亡25%和50%；450和500mg組小鼠在給藥4～5d全部死亡。50mg組無療效,隨TDB劑量增高,4個部位肌肉的總蟲數(shù)和活蟲數(shù)下降,而死蟲數(shù)升高,其中300mg組4個部位肌肉的活蟲數(shù)顯著少于對照組(P0.01),而350和400mg組4個部位肌肉中幼蟲全部死亡(P0.01)。 實驗2：所有小鼠未見藥物不良反應(yīng)。隨療程天數(shù)的增加,4部位肌肉中幼蟲總蟲荷和活蟲數(shù)下降,而死蟲數(shù)升高。與對照組相比,2d及2d以上療程組膈肌、咬肌和腓腸肌中總蟲數(shù)和活蟲數(shù)顯著減少(P0.05、P0.01),6d和8d療程組胸肌總蟲數(shù)顯著減少(P0.05、P0.01)。隨著療程增加,4部位肌肉的幼蟲死亡率升高,6d和8d療程組分別達96.16%～99.13%和99.62%～100%(P0.01)。療效驗證性感染表明,6d(37.5%)和8d(12.5%)的感染率顯著低于對照組(100%)和2d(100%)療程組(P0.01)。 實驗3：所有小鼠無藥物不良反應(yīng)。與對照組相比,3個治療組膈肌和腓腸肌中幼蟲總蟲數(shù)和存活蟲數(shù)均顯著減少(P0.05,P0.01),死蟲數(shù)顯著增加(P0.05,P0.01),羥環(huán)組的療效最高。以吐溫組TDB的相對藥效率為1.0,按減蟲率計算,羧纖組對膈肌和腓腸肌中幼蟲相對藥效率分別為1.61和2.46,羥環(huán)組相應(yīng)為2.13和2.49：而以死蟲率計算,羧纖組分別為1.55和1.79,羥環(huán)組分別為2.51和2.16(P0.01)。 結(jié)論 口服TBD50mg/(kg-d),給藥6天,對肌肉中蟲荷無影響。300mg/(kg-d)可有效殺死肌肉中的成囊期幼蟲,為適宜劑量。而350mg/(kg-d)或更高劑量TBD對小鼠有毒性作用或致死。 口服TBD300mg/(kg-d),連續(xù)給藥6d或8d,無不良藥物反應(yīng),可有效殺死肌肉中的成囊期幼蟲,連續(xù)給藥6d為適宜療程。 3%乙醇加1%羧甲基纖維素或7%羥丙基-β-環(huán)糊精配制TBD的相對生物藥效率和抗成囊期幼蟲效果顯著提高,以3%乙醇加7%羥丙基-β-環(huán)糊精配制的TBD溶液的效果更佳。
[Abstract]:objective
The efficacy of different doses of three benzamid (TBD) and oral TBD300mg/ (kg-d) oral administration of different doses of TBD300mg/ (kg-d) on the larva of Trichinella Trichinella in mice was evaluated, and the effect of three different solutions of oral administration of orally on mouse Trichinella cysts was compared.
Materials and methods
Experimental 1:88 mice were randomly divided into 11 groups, each mouse was infected with 50 cystocyst larva orally. After infection, 29d, TBD0-500mg/ (kg-d) was taken orally, and the adverse reaction of mice was observed with 6D.. After treatment, 7d was used to count the phrenic, masseter, pectoral and gastrocnemius myocytocyst, and the average number of muscle larvae per gram of muscle was evaluated.
The mice were randomly divided into 5 groups at 2:40 in the experiment. 50 mice were infected by the mouth of each mouse. After infection 29d, TBD300mg/ (kg-d) was taken orally with different courses of treatment (2,4,6,8d), and the control group was not treated. After stopping the drug, the muscles of the diaphragm, the masseter muscle, the pectoral muscle and the gastrocnemius were counted by 7d. The other 40 mice were randomly divided into 5 groups and carried out the reverse experiments, respectively. After treatment, the diaphragm muscles of mice were infected by 50 different ways. After infection, 29d was used to count the larvae in diaphragm.
The mice were randomly divided into 4 groups at 3:40. Each mouse was infected with 50 cystocyst larvae. After infection, 29d was treated with three benzamiprid in different solvents. The solvents were 7% Twain -80 and 3% ethanol (Twain group), 1% carboxymethyl cellulose and 3% ethanol (carboxyl group), 7% hydroxypropyl -p- cyclodextrin and 3% ethanol (hydroxyl group). The dose was 200mg/ (kg- D), after 6 days of continuous administration, the control group was not treated. After the treatment, the number of live worms and the number of dead worms were counted by 14d, and the average number of larva per gram of muscle was evaluated.
Result
The mice in the 350 and 300mg group had no adverse reactions. The 350 and 400mg mice had severe adverse reactions, which died 25% and 50%, respectively. 450 and 500mg mice had no curative effect in all.50mg groups of 4 to 5D, with the increase of TDB dose, the number of total insects and the number of live worms in the 4 parts of the muscles were reduced, and the number of dead insects in the 300mg group was increased, among which the 300mg group 4 parts muscle was muscle. The number of live insects in meat was significantly less than that in the control group (P0.01), while in the 350 and 400mg groups, all the 4 parts of the muscle larvae died (P0.01).
Experiment 2: no adverse drug reaction was found in all mice. With the increase of the duration of the course of treatment, the number of total larvae and live worms in the 4 parts of the muscles decreased, but the number of dead worms increased. Compared with the control group, the number of total worms and the number of live worms in the 2D and 2D groups were significantly reduced (P0.05, P0.01), and the number of the total pectoral muscles in the 6D and 8D courses was significantly reduced. Less (P0.05, P0.01). As the course of treatment increased, the mortality of the 4 muscle larvae increased, and the group of 6D and 8D was 96.16% to 99.13% and 99.62% to 100% respectively (P0.01). The efficacy of confirmatory infection showed that the infection rate of 6D (37.5%) and 8D (12.5%) was significantly lower than that of the control group (100%) and 2D (100%) course group (P0.01).
Experiment 3: All mice had no adverse drug reactions. Compared with the control group, the total number of larvae and the number of surviving worms in the 3 treatment groups were significantly decreased (P0.05, P0.01), the number of dead worms increased significantly (P0.05, P0.01), the effect of the hydroxyl group was the highest. The drug efficiency of the TDB in the Twain group was 1, and the carboxyl fiber group was calculated on the diaphragm and fibula according to the rate of worm reduction. The relative efficacy rates of larva in the intestinal muscle were 1.61 and 2.46, respectively 2.13 and 2.49 in the hydroxyl group, and 1.55 and 1.79 in the carboxyl group and 2.51 and 2.16 in the hydroxyl group (P0.01), respectively.
conclusion
Oral TBD50mg/ (kg-d), for 6 days, did not affect.300mg/ (kg-d) in the muscles of the muscle, which could effectively kill the cyst stage larva in the muscle, which was the appropriate dose. 350mg/ (kg-d) or higher dose TBD had toxic effect or death to mice.
Oral administration of TBD300mg/ (kg-d), continuous administration of 6D or 8D, has no adverse drug reaction, and can effectively kill the cystic stage larvae in muscle. Continuous administration of 6D is an appropriate course of treatment.
The effect of 3% ethanol plus 1% carboxymethyl cellulose or 7% hydroxypropyl - beta cyclodextrin on the relative biologic efficiency of TBD and the effect of anti cystic larva increased significantly, and the effect of TBD solution prepared with 3% ethanol plus 7% hydroxypropyl - beta cyclodextrin was better.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R532.14

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