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Division C of the acute toxicity of erythromycin_3136

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Division C of the acute toxicity of erythromycin_3136

Division C of the acute toxicity of erythromycin

     Author: Pan Jing-yuan QIU Yin-Sheng YAN Han-chi

    LING Sa

     Key Words Division C erythromycylamine

     Abstract: Objective: To observe the Division C of erythromycin on acute toxicity in mice and death. Methods: Three different routes of administration in Kunming mice, acute toxicity studies. Results: The intragastric administration of LD50 of 21346 (1761.8 ~ 2586.4) mg / kg, intraperitoneal injection of LD50 dose of 305.5 (272.2 ~

    341.9) mg / kg, intravenous administration of LD50 of 121.2 (115.3 ~ 127.3) mg / kg . Conclusion: The Secretary for clinical use of erythromycin C is more secure.

     Keywords: Division C erythromycin; mice; acute toxicity

     Division C erythromycin (erythormycin propionate | N | acetylcysteinate, EPAC) for the erythromycin derivative, in comparison with erythromycin, which is characterized by high blood concentration after oral administration, long half-life.

    This product is mainly caused by susceptible strains of

    erythromycin for the treatment of various acute and chronic infection. Safe dose for clinical use of drugs to provide experimental basis for the study of its acute toxicity was studied.

     1 Materials and methods

     11 subjects materials

     Division C erythromycin (EPAC): white powder, the content 980%, batch number 980,907, from hospital rooms to provide synthesis. In Pro, when used with 05% CMC prepared into

various concentrations of suspension.

     12 experimental animals

     Kunming mice, weighing 19 ~ 21g, male and female in half, provided by the Tongji Medical University. Animals at room temperature for 22 ? 2 ? after the experiment to adapt to

    3d.

     13 test method [1,2]

     131 gavage acute toxicity in mice

     Mice were 50, fasting 16h were randomly divided into five groups of 10 male and female in half, the ratio of 1:07 between agents, namely, dose, respectively

    4200,2940,2058,1440,1008 mg / kg, by 20ml/kg gavage, animals after administration 7d, observe the animals, toxic reactions

    and death, with Bliss method LD50.

     Intraperitoneal injection of 132 acute toxicity in mice administered

     60 mice were taken, fasting after 16h were randomly divided into six groups of 10 male and female in half, the ratio of 1:08 between agents, namely, dose, respectively 5000,4000,3200,2560,2048,1638 mg / kg by intraperitoneal injection 20ml/kg administration, after administration animals 7d, observe the animals, toxic reactions and death situation, experimental results using Bliss method LD50.

     Intravenous administration of 133 acute toxicity in mice

     Mice were 40, after 16h fasting were randomly divided into four groups of 10 male and female in half, the ratio of 1:09 between agents, namely, dose, respectively 1372,1235,1110,1000 mg / kg, according to 10ml / kg tail vein injection of administration, after administration animals 7d, observe the animals, toxic reactions and death situation, experimental results using Bliss method LD50.

     2 Results

     21 intragastric administration acute toxicity in mice

     After the mice were gavage 1h autonomous activity started to decrease, apathetic, arched vertical hair, unresponsive to outside stimuli, poor feeding, respiratory depression until death, animal death is generally between 12 ~ 48h after

    administration. Autopsy of dead animals, the naked eye no obvious abnormalities in major organs. Survival of animals poisoned to the first 2 ~ 3d later disappeared. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence

    limit range. The experimental results shown in Table 1. Table 1 Division C of erythromycin on the LD50 in mice gavage results (omitted) reposted elsewhere in the paper for free download http://

     Intraperitoneal injection of 22 acute toxicity in mice

    administered

     Minutes after intraperitoneal injection of mice with an animal excitement, anger, jumping, the final death spasm. Dead animals, mostly occurs in 48h between the autopsy of dead animals, the naked eye no obvious abnormalities in major

    organs. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence limit range. The results in Table 2. Table 2 Division C of erythromycin administration on mice by intraperitoneal injection of the LD50 results (omitted)

     23 Intravenous administration of acute toxicity in mice

     Tail intravenous injection, the mice immediately appear restless, vertical tail, the final death convulsion. Dead animals, mostly occurs in 12h between the autopsy of dead animals, the naked eye no obvious abnormalities in major

    organs. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence limit range. The results in Table 3. Table 3 Division C of intravenous administration of erythromycin on the LD50 in mice results (omitted)

     3 Conclusion

     Division C of erythromycin in mice gavage LD50 for 21346mg/kg (1761.8 ~ 2586.4mg/kg); intraperitoneal injection of LD50 dose of 305.5mg/kg (272.9 ~ 341.9mg/kg); intravenous administration of LD50 To 121.2mg/kg (115.3 ~ 127.3mg/kg). [3

    ~ 5]

     4 Discussion

     EPAC is a synthesis of erythromycin and acetyl-cysteine,

    both similar to the antibacterial effect of erythromycin, has a certain mucus dissolution. There is a small water-soluble

    erythromycin plasma concentration is low, after oral

    administration easily destroyed by stomach acid, gastrointestinal side effects. N-acetylcysteine as a good

    phlegm dissolving drugs, a large number of mucus obstruction due to breathing difficulties caused by significant effect, but the use of penicillin, when respiratory inflammation, but also can not use the acetyl-cysteine, because failure to make

    penicillin . EPAC is the Red enzymes prime the formation of ester and acetylcysteine salts, acid stability, high serum concentration, half-life long, that is a significant

    antibacterial activity, but also has a good mucus dissolution [3 ~ 5]. Therefore, the drug for respiratory infections to provide a new treatment.

     The experiment carried out three pairs of EPAC acute toxicity studies showed that, EPAC mice gavage LD50 for

    21346mg/kg, the equivalent of the clinical recommended dose per day (37mg/kg) of 58 times; EPAC mice intraperitoneal injection of LD50 dose of 305.5mg/kg, the equivalent of the clinical recommended daily dose of 8 times; EPAC in mice

    administered intravenous LD50 for 121.2mg/kg, the equivalent of the clinical recommended daily dose of 3 times. EPAC for clinical oral preparation, indicating EPAC for clinical use is more secure.

     References

     The People's Republic of China Ministry of Health

    Pharmaceutical Council, a new drug (Western) pre-clinical

    study of the guiding principles 1993,143

     2 Shu-Yun, Bian Lian, Chen Xiu-pharmacology experiments

    Methodology 3rd edition, Beijing: People's Publishing House, 2002,1871 ~ 1885.

     3 BernardiM.D, et al. Human pharmacokinetics of erythromycin propionate | N | acetylcysteinate: comparative evaluation with erythromycin stearate and N | acetylcysteine.

Int. J. Clin. Pharmacol. Ther. Toxical. 1988,26 (9): 444

     4 Ricevuti G, et al. Serum, Sputum and Bronchial Concentrations of Erythromycin in chronic bronchitis after single and multiple treatments with either Propionate | N | Acetylcsteinate of Stearate Erythromycin. Chemotherapy, 1988,34:374 ~ 379

     5 Stubbs. C, et al. Determination of Erythromycin in Serum and Urine by Highperformance Liquid Chromatography with Ultraviolet Detection. Joumal of Pharmaceutical Sciences. 1985,74 (10): 1126 ~ 1128. Reposted elsewhere in the paper for free Download Center http://

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