恩诺沙星聚乳酸—聚三亚甲基碳酸酯的体内外降解和释药研究
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摘要
本实验用新型可降解高分子材料聚乳酸-聚三亚甲基碳酸酯(PLA-PTMC)聚合物,在其中加入兽类专用喹诺酮类抗菌药恩诺沙星,制成薄块状试件(En-PLA-PTMC),埋植入兔脊柱两侧的肌肉内,观察其在体内的降解速度、对组织生长的影响和缓慢释放药物情况。同时,在体外中性环境(PBS液)中同步观察试件的降解情况和释放药物情况,以研究其在体内的降解性、缓释性和生物相容性等特性。试验结果表明:
降解性:体内降解比体外稍快。体外降解中,第110天时, PLA-PTMC试件降解率为32.65%,En-PLA-PTMC试件降解率为48.0%。体内降解中,第42天时, PLA-PTMC试件降解率为10.71%,En-PLA-PTMC试件降解率为18.57%;第70天时, PLA-PTMC试件破碎不完全,中心留有部分未破碎试件,En-PLA-PTMC试件破碎完全,组织完全长入,无法分离。
缓释性:缓释试件中,聚合物和药物质量比为2:1,药物包埋率达到30%。体外中性环境(pH为7.0的PBS液)中,试件在前两周释药速度缓慢,从2周后释药加快,且之后降解率呈直线上升。到第10周释药率达到79.68%。体内环境中,从第2周开始血药浓度始终能检测到,且逐渐增加,第8周时血药浓度达到最大。恩诺沙星在体内部分代谢为环丙沙星,且环丙沙星的浓度大于恩诺沙星的浓度。
生物相容性:试件植入体内后,所有兔子术后活动正常,伤口无感染,愈合良好。2周至4周时,试件周围肌肉有肉眼可见炎性反应,但未影响动物活动和生活。试件周围形成包膜,第6周后消失,并且试件开始破碎,组织长入,炎性反应逐渐消失。组织切片观察,整个过程表现为异物引起的无菌性慢性炎症的修复过程,肉芽组织、成纤维细胞大量增生,包裹异物和坏死组织。
This experimentation used new biodegradable polymer Polylactide-Poly trimethylene carbonate(PLA-PTMC),in which we added in veterinary medicine Enrofloxacin,and made it to thinness test pieces and embedded it into muscle of rabbits, back bone,then we observing the speed of degradation、the effect to the growth of organization and the condition of delayed release medicine of these test pieces in vivo,and meanwhile we observing the speed of degradation、the condition of slow release drug of these test pieces in neutrol environment(PBS fluid) in virto,through which we studied the degradation、delayed release and biocompatibility of PLA-PTMC . The result of this experimentation as follow:
Degradation:The degradation in vivo was quicker than in virto. In virto,the degradation rate of PLA-PTMC test pieces was 32.65%,and that of En-PLA-PTMC test pieces was 48.0% at the 110th day. In vivo,the degradation rate of PLA-PTMC test pieces was 10.71%,and that of En-PLA-PTMC test pieces was 18.75% at the 42th day. At the 70th day,PLA-PTMC test pieces were not completely break into pieces,but En-PLA-PTMC test pieces were completely break into pieces,and tissues grown into test pieces,we could not separate them.
Delayed release:In delayed release test pieces,the proportion of polymer and medicine quality is 2:1,the ratio of embedding medicine is 30%. The delayed release speed of test pieces was very slowly at the first two weeks in neutrol environment(PBS fluid) in virto,after the 2th week,delayed release speed started to speed up,and the delayed release rate was shoot up at fllowing time. The ratio of delayed release medicine was up to 79.68% at the 10th week. In vivo,form the second week,the blood drug level could be detdcted and was increasing,the blood drug level was up to maxlmum at the 8th week. Part Enrofloxacin metabolism to Ciprofloxacin in vivo and the Ciprofloxacin concentration was higher than the Enrofloxacin concentration.
Biocompatibility:The activity of all rabbits was normal after test pieces were implanted into rabbits body. The cut were free from infection and the condition of heal was good. Form the seciend week to the forth week,muscles by the surrounding test pieces had inflammatory reaction that could be see by naked eyes,but which was not effect the activity and living of rabbits. Amicula were formed surrounding the test pieces and amicula disappeared at the sixth week,meanwhile test pieces started to break into pieces,tissues grown into test pieces,inflammatory reaction disappeared gradually. We observed tissue section and found the all process was reparative process of chronic inflammation which originated by foreign object,granulation tissue and collagenoblast multiplicitly accrementited and packed foreign object and necrotic tissue.
降解性:体内降解比体外稍快。体外降解中,第110天时, PLA-PTMC试件降解率为32.65%,En-PLA-PTMC试件降解率为48.0%。体内降解中,第42天时, PLA-PTMC试件降解率为10.71%,En-PLA-PTMC试件降解率为18.57%;第70天时, PLA-PTMC试件破碎不完全,中心留有部分未破碎试件,En-PLA-PTMC试件破碎完全,组织完全长入,无法分离。
缓释性:缓释试件中,聚合物和药物质量比为2:1,药物包埋率达到30%。体外中性环境(pH为7.0的PBS液)中,试件在前两周释药速度缓慢,从2周后释药加快,且之后降解率呈直线上升。到第10周释药率达到79.68%。体内环境中,从第2周开始血药浓度始终能检测到,且逐渐增加,第8周时血药浓度达到最大。恩诺沙星在体内部分代谢为环丙沙星,且环丙沙星的浓度大于恩诺沙星的浓度。
生物相容性:试件植入体内后,所有兔子术后活动正常,伤口无感染,愈合良好。2周至4周时,试件周围肌肉有肉眼可见炎性反应,但未影响动物活动和生活。试件周围形成包膜,第6周后消失,并且试件开始破碎,组织长入,炎性反应逐渐消失。组织切片观察,整个过程表现为异物引起的无菌性慢性炎症的修复过程,肉芽组织、成纤维细胞大量增生,包裹异物和坏死组织。
This experimentation used new biodegradable polymer Polylactide-Poly trimethylene carbonate(PLA-PTMC),in which we added in veterinary medicine Enrofloxacin,and made it to thinness test pieces and embedded it into muscle of rabbits, back bone,then we observing the speed of degradation、the effect to the growth of organization and the condition of delayed release medicine of these test pieces in vivo,and meanwhile we observing the speed of degradation、the condition of slow release drug of these test pieces in neutrol environment(PBS fluid) in virto,through which we studied the degradation、delayed release and biocompatibility of PLA-PTMC . The result of this experimentation as follow:
Degradation:The degradation in vivo was quicker than in virto. In virto,the degradation rate of PLA-PTMC test pieces was 32.65%,and that of En-PLA-PTMC test pieces was 48.0% at the 110th day. In vivo,the degradation rate of PLA-PTMC test pieces was 10.71%,and that of En-PLA-PTMC test pieces was 18.75% at the 42th day. At the 70th day,PLA-PTMC test pieces were not completely break into pieces,but En-PLA-PTMC test pieces were completely break into pieces,and tissues grown into test pieces,we could not separate them.
Delayed release:In delayed release test pieces,the proportion of polymer and medicine quality is 2:1,the ratio of embedding medicine is 30%. The delayed release speed of test pieces was very slowly at the first two weeks in neutrol environment(PBS fluid) in virto,after the 2th week,delayed release speed started to speed up,and the delayed release rate was shoot up at fllowing time. The ratio of delayed release medicine was up to 79.68% at the 10th week. In vivo,form the second week,the blood drug level could be detdcted and was increasing,the blood drug level was up to maxlmum at the 8th week. Part Enrofloxacin metabolism to Ciprofloxacin in vivo and the Ciprofloxacin concentration was higher than the Enrofloxacin concentration.
Biocompatibility:The activity of all rabbits was normal after test pieces were implanted into rabbits body. The cut were free from infection and the condition of heal was good. Form the seciend week to the forth week,muscles by the surrounding test pieces had inflammatory reaction that could be see by naked eyes,but which was not effect the activity and living of rabbits. Amicula were formed surrounding the test pieces and amicula disappeared at the sixth week,meanwhile test pieces started to break into pieces,tissues grown into test pieces,inflammatory reaction disappeared gradually. We observed tissue section and found the all process was reparative process of chronic inflammation which originated by foreign object,granulation tissue and collagenoblast multiplicitly accrementited and packed foreign object and necrotic tissue.
引文
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