EP 4 EP-1 4 mg /ml 0. 5 mg /ml 2 2 mg /kg EP-1 HPCD EP-1

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1 Acta Theriologica Sinica EP * EP 2 - -β- HPCD EP 4 EP % HPCD 4 mg /ml 0. 5 mg /ml 2 2 mg /kg EP-1 HPCD EP-1 EP-1 EP 2- -β- Q494 A Preparation of hydroxypropyl-β-cyclodextrin inclusion with Levonorgestrel and Quinestrol EP-1 and its influence on the reproductive organs Brandt s voles Lasiopodomys brandtii WANG Dawei 1 2 LIU Qi 3 LIU Ming 2 LI Ning 1 HUANG Baohuan 1 LIU Xiaohui 1* 1 Key Laboratoryof Weed and Rodent Biology and Management Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing China 2 State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of Zoology Chinese Academy of Science Beijing China 3 Key Laboratory of Dryland Farming and Water-saving Agriculture MOA Institute of Environment and Sustainable Development in Agriculture Chinese Academy of Agricultural Sciences Beijing China Abstract EP series rodent contraception is mainly composed of levonorgestrel and quinestrol. However neither component do not readily dissolves in water which limits the precision of research and application. In the present study solubilization was measured in hydroxypropyl-β-cyclodextrin HPCD inclusion complexes of levonorgestrel and quinestrol respectively. Afterwards the effects of treatment times after 2 and 4 weeks and doses mg /kg of EP-1 inclusion complexes on reproductive organs were investigated using a gastric gavage method. The results showed that the solubility of levonorgestrel and quinestrol reached 4 mg /ml and 0. 5 mg /ml in 20% aqueous HPCD solution respectively. For females there were no significant differences after 2 or 4 weeks between the control and treatment groups that received gavage. For males the average weight of reproductive organs of the group that received gavage for 2 weeks of 2 mg /kg group was less than that of the control group. Our results indicate that the solubility of EP-1 was significantly enhanced by forming inclusion complexes with HPCD the suppressive effects on reproduction in male Brandt s voles is more obvious than those in females. Moreover inclusion did not affect the anti-fertility effect of EP-1. Key words Antifertility control HPCD Inclusion complex Lasiopodomys brandtii Levonorgestrel Quinestrol CB ChineseIPM YW * Corresponding author lxiaohui2000@ 163. com

2 μg /ml ml ml Knipling Davis ml ml ml ml ml 25 ml Marsh μg /ml ml ml ml ml ml ml ml ml 280 nm A C HPCD EP 10 min EP-1 48 h μm ph = g /ml g /ml g /ml g /ml HPCD 2- -β- HPCD β- ph = 7. 0 β-cd 10 min 20 Szetjli μm 240 nm 280 nm 2006 Trapani et al HPCD 1. 2 EP-1 EP > 25 g mg /kg C HPCD 1. 0 mg /kg Ⅰ 2. 0 mg /kg Ⅱ UV-2550 HPCD 99% 4. 0 mg /kg Ⅲ 6 Wako EP λ max 240 nm 20% HPCD nm HPCD mg /ml 240 nm A C 48 h 14L 10D 96 20% HPCD 4

3 1 EP-1 81 Δλ = 2. 0 nm 5 d ph = 7. 0 g /100 g 4π 2 /3cm 3 HPCD 1 cm HPCD HPCD X 1. 3 SPSS Oneg /ml Y μg /ml Y = X R 2 = Way ANOVA EP Y = 20460X R 2 = P < % HPCD 4 mg /ml 0. 5 mg HPCD ~ μg /ml A C A = C R 2 = ~ μg /ml A C A = C R 2 = Fig. 1 λ max ph = 7. 0 HPCD The solubility curve of levonorgestrel and quinestrol of HPCD solution ph = 7. 0 Table 1 1 EP-1 HPCD 2 4 ± The reproductive organs of male Brandt s voles 2 and 4 weeks after treated by HPCD inclusion with EP-1 Mean ± SE 2 Two weeks Testis g ± a ± a ± a ± a Epididymides g ± a ± a b ± b ± a b Seminal vesicle g ± a ± b ± b ± a b Volume of testicle cm ± a ± a b ± b ± a b 4 Four weeks Testis g ± a ± a ± a ± a Epididymides g ± a ± a ± a ± a Seminal vesicle g ± a b ± a ± b ± a b Volume of testicle cm ± a ± a ± a ± a P < C Ⅰ 1. 0 mg /kg Ⅱ 2. 0 mg /kg Ⅲ 4. 0 mg /kg Different superscripts in each row indicate significant differences P < C Control Ⅰ 1. 0 mg /kg Ⅱ 2. 0 mg /kg Ⅲ 4. 0 mg /kg

4 EP-1 HPCD EP-1 HPCD mg /kg mg /kg 2 4 P = EP - 1 P = P = HPCD mg /kg 4 Table 1 2 EP-1 HPCD 2 4 ± The reproductive organs of female Brandt s voles 2 and 4 weeks after treated by HPCD inclusion with EP-1 Mean ± SE 2 Two weeks Ovaries mg ± 1. 4 a ± 2. 0 a ± 1. 9 a ± 1. 6 a Uterus g ± a ± a ± a ± a Length of Uterus cm ± a ± a ± a ± a 4 Four weeks Ovaries mg ± 1. 0 a ± 2. 1 a ± 3. 2 a ± 1. 3 a Uterus g ± a ± a ± a ± a Length of Uterus cm ± a ± a ± a ± a P < C Ⅰ 1. 0 mg /kg Ⅱ 2. 0 mg /kg Ⅲ 4. 0 mg /kg Different superscripts in each row indicate significant differences P < C Control Ⅰ 1. 0 mg /kg Ⅱ 2. 0 mg /kg Ⅲ 4. 0 mg /kg β EP-1 EP-1 HPCD Cricetulus migratorius Meriones meridianus Tscheskia triton Meriones unguiculatus Phodopus campbelli EP-1 HPCD Szetjli mg /kg 2006 EP-1 HPCD Zhao 2007 EP-1 Zhao et al EP-1 HPCD EP-1 - -

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