The Studies On The Pharmacokinetics,Pharmacodynamics And Safety Of The Complex Enzyme In Dairy Cows

As enzyme drugs for treatment of inflammation,trypsin and chymotrypsin have been widely used in clinics at abroad.In view of the wide application of typsin and chymotrypsin in medical clinics,we try to develop the enzyme complex to treat the mastitis-infected dairy cows.According to the compilation on guiding principle of veterinary drugs research,we start the test of pharmacodynamics?pharmacokinetics and safety to help veterinarian gather experience and provide theory evidence in veterinary clinics.To understand the pharmacokinetic properties of the enzyme complex in the dairy cows in vivo,as well as to provide a guarantee for using dose and method in the veterinary clinic,the pharmacokinetics of the enzyme complex in the dairy(milk)was studied in this paper.The results showed that the lowest detectable limit of trypsin in the tested milk was 72 mu/mL and the average recovery in the milk was 71.9%;The lowest detectable limit of chymotrypsin in the tested milk was 142 mu/mL and the average recovery in the milk was 70.1%.According to the detection method established in this study,after 1 branch of the enzyme complex was injected in the selected mammary region,the results showed that the activities of trypsin decreased to the lowest detectable limit in 12 h of enzyme complex injection and the lowest enzyme levels maintained until 24 h and 36 h later;The activities of chymotrypsin decreased to the lowest detectable limit in 8 h of enzyme complex injection and the lowest enzyme levels maintained until 12 h and 24 h later.It indicate that trypsin remove more slowly from the tested mammary region and the effect take a longer time.The proposed interval dose should be 12 h according to the elimination time of trypsin.To evaluate the therapeutic effects and using dosage of the enzyme complex in the mastitis-infected dairy cows,the therapeutic effects of the enzyme complex in the mastitis-infected dairy cows were evaluated in this paper by means of the test of the somatic cells,isolation and identification of bacteria,detection of the clinical parameters.The results showed that the therapeutic effective rate of the enzyme complex(8 mg of chymotrypsin + 8 mg of trypsin)for the mastitis-infected dairy cows was 88.2%and the cure rate was 70.6%,by intramammary administration with 1 branch of the enzyme complex in each mammary region for 3 times(12 hours each time);More than half of the pathogenic bacteria in the mastitis-infected mammary region were reduced;The standard average scores of the mastitis syndrome were increased from 2.80 to 4.30;The average somatic cells were reduced from 2.09×106/mL to 1.25×106/mL.It is recommended that the dosage of the enzyme complex should be 8 mg of chymotrypsin + 8 mg of trypsin,as a clinical recommended dose.In order to understand the tolerance(maximum tolerated dose)of dairy cows to the enzyme complex,as well as the effect and the harm,including clinical syndrome,breast local changes in breast,effects on the blood parameters and the somatic cell changes in dairy cows,caused by the enzyme complex,the safety of the enzyme complex to the target animals was evaluated with different dosage of the enzyme complex.The results showed that there was no significant unnormal clinic syndrome after administrated with 1,3,5 times of recommended dose of the enzyme complex in all experimental dairy cows.The parameters of the routine blood and the blood biochemistry were in the normal range after drug administration.Collecting milk samples for The detections of somatic cells which collected at the day 0,day 3,day 5,day 10,respectively showed that 3 and 5 recommended dose of drug had stimulating effects on the dairy breast,especially for 5 recommended dose of drug.The result indicate that the recommended using dosage of the enzyme complex should not be more than 3 times of the recommended dose each time.Although the average numbers of the somatic cells from 3 and times of the recommended dose groups increased to the levels of 5×105/mL at day 3 and day 5 after injection,it decreased to the normal levels of 2×105/mL at day 10 after injection.It indicate that the numbers of the somatic cell in the milk rise in the short period of time and reduce to the normal levels after the pesticide effect of the drug disappeared.The stimulation intensity could be tolerant by dairy cows and the enzyme complex can be used safely in veterinary clinics.