Clinical Test Of Guixiong Yimu San For Treatment Retained Fetal Membranes In Cows With Blood Stasis Syndrome

Blood stasis syndrome is the main type of retained fetal membranes in dairy cows,and Guixiong Yimu San prepared from a combination of Herba Leonuri,Angelicae Sinensis Radix,Ligusticum wallichii,Sparganii Rhizoma,Curcumae rhizoma,Flos Cartham,and Glycyrrhiza uralensi,is an innovative herbal preparation with activating blood circulation and removing blood stasis,promoting qi circulation to relieve pain for treatment retained fetal membranes in cows with blood stasis syndrome.Previous clinical trial has suggested that an oral adminstration dosage of 400g/cow of Guixiong Yimu San has a beneficial clinical efficacy for treatment retained in cows with blood stasis syndrome,and cure rate is 85.9%.Clinical efficacy evaluation is the basic contents of new drug,and the key researches of new drug registration.Based on the preliminary exploratory clinical trials,the target animal safety test,experimental clinical test,expanded clinical test and the clinical pharmacodynamics were to carry out to evaluate the clinical efficacy of Guixiong Yimu San,and the results as following:?1?Target animal safety test of Guixiong Yimu San on dairy cowsTwenty healthy cows were randomly divided into one of three treatment groups?n=5?with animals receiving either an oral dose of 400g/cow?recommended dosage?,1200g/cow?3times recommended dosage?and 2000g/cow?5 times recommended dosage?once daily for three consecutive days,respectively,or no treatment in the control group.During the experiment,clinical symptoms,daily yielding,hematology and blood biochemical indexes was tested at the 0,4th,7th,14th days after treatment.The results showed that Guixiong Yimu San had no significant effects on clinical symptoms,daily yielding and hematology indexes.But the level of ALT,TG and CRE were higher?P<0.01?,the level of AST,BUN were higher?P<0.05?on the 4th day after treatment in cows in the 5 times recommended dosage group than the controls;the level of TG were significantly elevated?P<0.01?,the level of ALT,AST,BUN,CRE were higher on the 7th day after treatment in cows in the 5 times recommended dosage group than the controls;Compared with the control group,5 times recommended dosage group blood biochemical indexes were not significant?P>0.05?on the14th day after treatment.The results showed that target animal was safe when receiving Guixiong Yimu San owder with an oral dose less than 3 times recommended dosage?1200g/cow?.?2?Experiment clinical test by Guixiong Yimu SanAccording to the diagnositic criteria inclusion criteria and exclusion criteria,45 cows were diagnosed retained placenta by blood stasis and allocated into four groups.The animals were treated with Guixiong Yimu San with an oral adminstration of 800g/cow in the high dose group?n=11?,400g/cow in the middle dose group?n=12?or 200 g/cow in the low dose group?n=11?once daily for 1-3 days respectively,and with an oral adminstration of 250g/cow in Yimu Shenghua San group.Additionally,10 haelty cows received no treatment were included into healthy control group.During the experimental period,the clinical symptoms,release of retained placenta,milk performance before treatment and 4th,7th,14th days after treatment,occurrence of puerperal metritis,reproductive performance were tested.The results showed that the milk yield increased,the somatic cell count decreased and reproductive performance index increased in the cows in Guixiong Yimu San groups,there is no significantly difference compared with healthy control group?P>0.05?;the cure rate and the total effective rate increased by 18.2%and 19.7%respectively,the incidence of the puerperal metritis decreased by 9.1%and the reproductive performance index increased in the high and middle dose groups than positive drug group?P>0.05?;the milk protein in the middle dose group significantly increased,the milk fat significantly increased in high and middle dose groups.?P<0.01?,the milk fat significantly higher?P<0.05?in low dose group on 14th day after treatment?P<0.05?,the milk fat in the high and middle dose groups increased significantly?P<0.05?on 21th day after treatment.The levels of IL-2,TNF-?had up-regulated,the levels of IL-4,IL-10 had down-regulated to balanced Th1/Th2 type cytokines,the level of GSH-Px had increased,the level of MDA had decreased to improved the antioxidant capacity of cow,the level of progesterone estradiol and PGF_2?had reduced to regulate hormone imbalance,the level of TXB₂ had reduced,the level of 6-keto-PGF_1?had increased to make TXB₂/6-keto-PGF_1?tend to balance after treatment.The present results provided evidence for a beneficial clinical effect of Guixiong Yimu San on retained placenta in cows with blood stasis syndrome.?3?Expanded clinical test on Guixiong Yimu SanOne hundred and ninety-three cows were diagnosed retained placenta by blood stasis and allocated alternatively into Guixiong Yimu San group?n=97,400g/cow?and control group?n=96,250g/cow?,respectively.The expulsion rate of the placenta following treatment as the primary efficacy end point,the proportion of puerperal metritis consequent to retained placenta and the profermance fertility within 180 days postpartum as the second end points were used to evaluate the efficacy of Guixiong Yimu San.Compared with the positive drugs group,the cure rate?80.4%vs.63.5%,P<0.01?and total effective had increased,?89.7%vs.72.9%,P<0.01?.Guixiong Yimu San tended to have superior clinical efficacy in metritis prevention compared to the control drug for tratment retained placenta in cows affected with blood stasis syndorme?15.5%vs.24.0%,P<0.01?.The calving-to-first-service interval?68.9±17.7 days vs.80.5±26.6 days,P<0.01?,service per conception?1.8±1.3 vs.2.6±1.3,P<0.01?and days open?87.3±42.7 days vs.120.9±47.3 days,P<0.01?were shorten for cows in Guixiong Yimu San group than the controls.Additionally,Guixiong Yimu San treatment effectively elevated the first AI conception proportion?70.6%vs.26.4%,P<0.01?and proportion of cows that were pregnant within 180 days postpartum?71.9%vs.90.6%,P<0.01?compared with that of controls.The present results provided evidence for a beneficial clinical effect of Guixiong Yimu San with the recommended dosage of 400 g/cow for treatment retained placenta,including facilitated the expulsion of the placenta,lowered the risk of occurrence of puerperal metritis and improved the subsequent fertility of cows with retained placenta.