改性Cu/LDPE纳米复合材料的释放行为与生物相容性研究
|
摘要
含铜宫内节育器(简称Cu-IUD)是目前使用最广泛的活性节育器,具有很高的避孕率,但容易引起经血过多、疼痛、异常出血和炎症等副作用。这些副作用严重影响了Cu-IUD的应用和发展。为了降低Cu-IUD引起的副作用,本课题组在前期工作中制备了铜/低密度聚乙烯(Cu/LDPE)纳米复合材料,在此基础上,本论文引入了能够降低副作用的锌、氧化锌和吲哚美辛等活性物质,制备出了新型的用于IUD的改性Cu/LDPE纳米复合材料。
锌和氧化锌溶解后产生的锌离子具有避孕、抗菌、恢复创伤等功能。纳米锌和氧化锌具有很强的抗菌能力,纳米氧化锌还具有优良的抗凝血性能,因此在降低副作用方面,纳米锌和氧化锌具有广阔的应用前景。吲哚美辛(简称IDM)是减轻月经过多副反应的有效药剂。本研究在Cu/LDPE纳米复合材料的基础上加入纳米锌、纳米氧化锌和吲哚美辛,应用热模压法制备了Cu/Zn/LDPE、Cu/ZnO/LDPE和Cu/IDM/LDPE纳米复合材料,并对复合材料的离子释放性能、抗菌性能和血液相容性能进行了研究。
模拟宫腔液的血清白蛋白能显著影响锌和氧化锌颗粒的溶解。血清白蛋白通过与锌离子结合形成络合物而促进了锌和氧化锌的溶解,增大了锌离子转化率。但结合了锌离子的血清白蛋白在变性和沉淀之后,对锌离子转化率会产生反作用。
通过对Cu/Zn/LDPE和Cu/ZnO/LDPE三元纳米复合材料的Cu~(2+)和Zn~(2+)释放进行研究后发现,纳米铜和纳米锌(或纳米氧化锌)颗粒既相互抑制对方的溶解,又相互为对方离子的释放提供扩散通道。在经历了初期的快速释放后,复合材料能持续稳定地释放Cu~(2+)和Zn~(2+),而且通过调整纳米铜和纳米锌或氧化锌的含量,可以获得合适的Cu~(2+)和Zn~(2+)释放速率。因此以这种复合材料制备成的IUD在保证避孕率的同时,还可望降低疼痛、生殖系统感染和异常出血等副作用。
应用振荡烧瓶法进行的抑菌实验结果表明,对于铜含量35%,锌或氧化锌含量15%的纳米和微米复合材料,Cu/ZnO/LDPE复合材料的抗菌能力最强,其次为Cu/LDPE复合材料,Cu/Zn/LDPE复合材料最差。对纳米复合材料和微米复合材料进行对比后发现,由于纳米抗菌剂具有很强的抗菌活性,纳米复合材料的抑菌能力远高于微米复合材料,其中Cu/ZnO/LDPE和Cu/LDPE纳米复合材料,尤其前者在浸泡一个月后仍能保持较好的抗菌活性。
应用血浆复钙化时间实验、溶血率实验和血小板黏附实验对复合材料的血液相容性进行了评估。研究结果表明,在纳米颗粒含量为15%的ZnO/LDPE、Zn/LDPE和Cu/LDPE纳米复合材料中,ZnO/LDPE复合材料的溶血率最低,复钙化时间最长。在纳米铜含量35%的Cu/LDPE纳米复合材料中加入15%的纳米氧化锌后,其溶血率降低,复钙化时间延长。血小板黏附实验结果显示,ZnO/LDPE纳米复合材料表面黏附了少量血小板,而Zn/LDPE纳米复合材料表面黏附了大量血小板,且严重聚集、变形,容易引发血栓的形成。
对Cu/IDM/LDPE三元纳米复合材料的性能研究表明,基材中铜溶解后留下的孔道可为吲哚美辛的溶出提供扩散通道,促进吲哚美辛的释放。当IDM在纳米复合材料表层集中分布时,这种纳米复合材料可提高IDM的利用度、延长药效,并能够减轻Cu~(2+)暴释带来的副作用。
The copper-bearing intrauterine device (Cu-IUD) is the most popularly used IUD at present. However, after Cu-IUDs insertion, some side effects such as pelvic inflammatory disease, pain and bleeding have been observed by some researchers. Concerns about side effects remain stubborn obstacles to a wider use of modern IUDs. In order to decrease the side effects of Cu-IUD, Cu/LDPE nanocomposites were prepared for IUD in our previous study. Further, zinc, zinc oxide and indomethacine were added into Cu/LDPE nanocomposites in this study to decrease the side effects more effectively.
Zinc ion has the function of contraceptive action, antibacterial effects, wound healing and tissue repair of the endometrium. Compared with zinc and zinc oxide bulk, zinc and zinc oxide nanoparticles shew much stronger antibacterial properties. Furthermore, the anticoagulant properties of zinc oxide nanoparticles are excellent. It indicates that nanoparticles of zinc and zinc oxide could decrease the side effects of IUD more effectively. At the same time, indomethacine (IDM) can alleviate menorrhagia that is responsible for the extraction of Cu-IUD. Therefore, by using low-density polyethylene as the carrier , composites of Cu/Zn/LDPE、Cu/ZnO/LDPE and Cu/IDM/LDPE were prepared by method of compressing molding. And the properties of the composites were deeply investigated.
Investigation on Zn~(2+) transformation ratios of zinc and zinc oxide in the simulated uterine solution shows that the Zn~(2+) transformation ratios are affected by human serum albumin in the simulated uterine solution. By the binding of zinc ions with human serum albumin, the dissolutions of zinc and zinc oxide and the transformation ratio of Zn~(2+) can be obviously accelerated in initial stages. But after denaturalization of human serum albumin in later time, Zn~(2+) transformation ratio becomes lower.
It has been found that the release rates of Cu~(2+) and Zn~(2+) of Cu/Zn/LDPE and Cu/ZnO/LDPE nanocomposites can keep stable during the experimentation time after a burst release at beginning. So IUD prepared with this composite should not only have high contraceptive effect but also reduce the side effects like infection, pain and bleeding. With the variation of one kind of nanoparticle content, the ion rate of the other kind of nanoparticles decreases or unchange. The reason is that the copper and zinc nanoparticles (or zinc oxide nanoparticles) can inhibited the dissolution mutually and at the same time provide the pathways for iron release to each other. So the proper release rate of Cu~(2+) and Zn~(2+) in the nanocomposites can be achieved by adjusting the relative contents of copper and zinc.
Shake flask test was employed to evaluate the antibacterial activity of the composites with 35wt% copper particles and 15wt% zinc or zinc oxide particles. The results show that the antibacterial activity of these composites, in descending order of strength, is as follows: Cu/ZnO/LDPE composite, Cu/LDPE composite and Cu/Zn/LDPE composite. The antibacterial activity of all the composites becomes worse if they are immersed in the simulated uterine solution for a month. Furthermore, the antibacterial activity of the nanocomposites is better than that of the microcomposites. Among all the composites, only Cu/ZnO/LDPE and Cu/LDPE nanocomposites, especially the latter, can keep good antibacterial activity even for a month.
The blood compatibility of the nanocomposites with 15% nanoparticles was evaluated in terms of the plasma recalcification time,the hemolysis rate and platelets adhesion. Among ZnO/LDPE、Zn/LDPE and Cu/LDPE nanocomposites, ZnO/LDPE nanocomposite has the lowest hemolysis rate and the longest plasma recalcification time. The results show that a small amount of platelets on the surface of ZnO/LDPE are detected. However, a lot of activated platelets on the surface of Zn/LDPE aggregate and spread out, which may trigger the formation of thrombus. Consequently, compared with zinc nanoparticles, zinc oxide nanoparticles show good antibacterial effect and blood compatibility. The above results indicated that zinc oxide nanoparticles are more suitable for the material of IUD with low side effects.
Cu~(2+) release and IDM release from Cu/IDM/LDPE nanocomposites were studied. IDM in the composites diffuses out through pore channels. Some of the pores created by the dissolution of copper nanoparticles provide diffusion path for IDM release and enhance the release rate of IDM. The preparation process of the nanocomposite was improved in this study by distributing IDM in the surface layer of the nanocomposite. This nanocomposite exhibits much higher release rate of IDM after incubation for 3 months and lower initial burst of Cu~(2+) than the matrix-type nanocomposite, implying that it can enhance the availability ratio of IDM, prolong the service life of IDM, and reduce the burst effect of Cu~(2+).
锌和氧化锌溶解后产生的锌离子具有避孕、抗菌、恢复创伤等功能。纳米锌和氧化锌具有很强的抗菌能力,纳米氧化锌还具有优良的抗凝血性能,因此在降低副作用方面,纳米锌和氧化锌具有广阔的应用前景。吲哚美辛(简称IDM)是减轻月经过多副反应的有效药剂。本研究在Cu/LDPE纳米复合材料的基础上加入纳米锌、纳米氧化锌和吲哚美辛,应用热模压法制备了Cu/Zn/LDPE、Cu/ZnO/LDPE和Cu/IDM/LDPE纳米复合材料,并对复合材料的离子释放性能、抗菌性能和血液相容性能进行了研究。
模拟宫腔液的血清白蛋白能显著影响锌和氧化锌颗粒的溶解。血清白蛋白通过与锌离子结合形成络合物而促进了锌和氧化锌的溶解,增大了锌离子转化率。但结合了锌离子的血清白蛋白在变性和沉淀之后,对锌离子转化率会产生反作用。
通过对Cu/Zn/LDPE和Cu/ZnO/LDPE三元纳米复合材料的Cu~(2+)和Zn~(2+)释放进行研究后发现,纳米铜和纳米锌(或纳米氧化锌)颗粒既相互抑制对方的溶解,又相互为对方离子的释放提供扩散通道。在经历了初期的快速释放后,复合材料能持续稳定地释放Cu~(2+)和Zn~(2+),而且通过调整纳米铜和纳米锌或氧化锌的含量,可以获得合适的Cu~(2+)和Zn~(2+)释放速率。因此以这种复合材料制备成的IUD在保证避孕率的同时,还可望降低疼痛、生殖系统感染和异常出血等副作用。
应用振荡烧瓶法进行的抑菌实验结果表明,对于铜含量35%,锌或氧化锌含量15%的纳米和微米复合材料,Cu/ZnO/LDPE复合材料的抗菌能力最强,其次为Cu/LDPE复合材料,Cu/Zn/LDPE复合材料最差。对纳米复合材料和微米复合材料进行对比后发现,由于纳米抗菌剂具有很强的抗菌活性,纳米复合材料的抑菌能力远高于微米复合材料,其中Cu/ZnO/LDPE和Cu/LDPE纳米复合材料,尤其前者在浸泡一个月后仍能保持较好的抗菌活性。
应用血浆复钙化时间实验、溶血率实验和血小板黏附实验对复合材料的血液相容性进行了评估。研究结果表明,在纳米颗粒含量为15%的ZnO/LDPE、Zn/LDPE和Cu/LDPE纳米复合材料中,ZnO/LDPE复合材料的溶血率最低,复钙化时间最长。在纳米铜含量35%的Cu/LDPE纳米复合材料中加入15%的纳米氧化锌后,其溶血率降低,复钙化时间延长。血小板黏附实验结果显示,ZnO/LDPE纳米复合材料表面黏附了少量血小板,而Zn/LDPE纳米复合材料表面黏附了大量血小板,且严重聚集、变形,容易引发血栓的形成。
对Cu/IDM/LDPE三元纳米复合材料的性能研究表明,基材中铜溶解后留下的孔道可为吲哚美辛的溶出提供扩散通道,促进吲哚美辛的释放。当IDM在纳米复合材料表层集中分布时,这种纳米复合材料可提高IDM的利用度、延长药效,并能够减轻Cu~(2+)暴释带来的副作用。
The copper-bearing intrauterine device (Cu-IUD) is the most popularly used IUD at present. However, after Cu-IUDs insertion, some side effects such as pelvic inflammatory disease, pain and bleeding have been observed by some researchers. Concerns about side effects remain stubborn obstacles to a wider use of modern IUDs. In order to decrease the side effects of Cu-IUD, Cu/LDPE nanocomposites were prepared for IUD in our previous study. Further, zinc, zinc oxide and indomethacine were added into Cu/LDPE nanocomposites in this study to decrease the side effects more effectively.
Zinc ion has the function of contraceptive action, antibacterial effects, wound healing and tissue repair of the endometrium. Compared with zinc and zinc oxide bulk, zinc and zinc oxide nanoparticles shew much stronger antibacterial properties. Furthermore, the anticoagulant properties of zinc oxide nanoparticles are excellent. It indicates that nanoparticles of zinc and zinc oxide could decrease the side effects of IUD more effectively. At the same time, indomethacine (IDM) can alleviate menorrhagia that is responsible for the extraction of Cu-IUD. Therefore, by using low-density polyethylene as the carrier , composites of Cu/Zn/LDPE、Cu/ZnO/LDPE and Cu/IDM/LDPE were prepared by method of compressing molding. And the properties of the composites were deeply investigated.
Investigation on Zn~(2+) transformation ratios of zinc and zinc oxide in the simulated uterine solution shows that the Zn~(2+) transformation ratios are affected by human serum albumin in the simulated uterine solution. By the binding of zinc ions with human serum albumin, the dissolutions of zinc and zinc oxide and the transformation ratio of Zn~(2+) can be obviously accelerated in initial stages. But after denaturalization of human serum albumin in later time, Zn~(2+) transformation ratio becomes lower.
It has been found that the release rates of Cu~(2+) and Zn~(2+) of Cu/Zn/LDPE and Cu/ZnO/LDPE nanocomposites can keep stable during the experimentation time after a burst release at beginning. So IUD prepared with this composite should not only have high contraceptive effect but also reduce the side effects like infection, pain and bleeding. With the variation of one kind of nanoparticle content, the ion rate of the other kind of nanoparticles decreases or unchange. The reason is that the copper and zinc nanoparticles (or zinc oxide nanoparticles) can inhibited the dissolution mutually and at the same time provide the pathways for iron release to each other. So the proper release rate of Cu~(2+) and Zn~(2+) in the nanocomposites can be achieved by adjusting the relative contents of copper and zinc.
Shake flask test was employed to evaluate the antibacterial activity of the composites with 35wt% copper particles and 15wt% zinc or zinc oxide particles. The results show that the antibacterial activity of these composites, in descending order of strength, is as follows: Cu/ZnO/LDPE composite, Cu/LDPE composite and Cu/Zn/LDPE composite. The antibacterial activity of all the composites becomes worse if they are immersed in the simulated uterine solution for a month. Furthermore, the antibacterial activity of the nanocomposites is better than that of the microcomposites. Among all the composites, only Cu/ZnO/LDPE and Cu/LDPE nanocomposites, especially the latter, can keep good antibacterial activity even for a month.
The blood compatibility of the nanocomposites with 15% nanoparticles was evaluated in terms of the plasma recalcification time,the hemolysis rate and platelets adhesion. Among ZnO/LDPE、Zn/LDPE and Cu/LDPE nanocomposites, ZnO/LDPE nanocomposite has the lowest hemolysis rate and the longest plasma recalcification time. The results show that a small amount of platelets on the surface of ZnO/LDPE are detected. However, a lot of activated platelets on the surface of Zn/LDPE aggregate and spread out, which may trigger the formation of thrombus. Consequently, compared with zinc nanoparticles, zinc oxide nanoparticles show good antibacterial effect and blood compatibility. The above results indicated that zinc oxide nanoparticles are more suitable for the material of IUD with low side effects.
Cu~(2+) release and IDM release from Cu/IDM/LDPE nanocomposites were studied. IDM in the composites diffuses out through pore channels. Some of the pores created by the dissolution of copper nanoparticles provide diffusion path for IDM release and enhance the release rate of IDM. The preparation process of the nanocomposite was improved in this study by distributing IDM in the surface layer of the nanocomposite. This nanocomposite exhibits much higher release rate of IDM after incubation for 3 months and lower initial burst of Cu~(2+) than the matrix-type nanocomposite, implying that it can enhance the availability ratio of IDM, prolong the service life of IDM, and reduce the burst effect of Cu~(2+).
引文
[1] Kathryn M. Curtis, Camaryn E. Chrisman, Herbert B. Peterson. Contraception for Women in Selected Circumstances. Obstetrics & Gynecology, 2002, 99(6): 1100-1112.
[2]曹小明,张维嘉.宫内节育器的回顾与展望.国外医学计划生育分册, 2001, 20(3): 164-167.
[3] Michel Thiery. Intrauterine contraception: from siliver ring to intrauterine contraceptive implant. European Journal of Obstetrecs & Gynecology and Reproduction Biology, 2000, 90: 145-152.
[4] Zipper ZA, Tatum HJ, Pastene Let al. Metallic copper as an intrauterine contraceptive adjunct to the“T”device. Am J Obstet and Gynecol, 1969, 105: 1274-1278.
[5] D. GuerreiroU, M.A.M. Gigante, L.C. Teles. Sexually transmitted diseases and reproductive tract infections among contraceptive users. International Journal of Gynecology & Obstetrics, 1998, 63(suppl 1): 163-173.
[6] Damrong Reinprayoon, Caroline Gilmore, Gaston Farr, et al. Twelve-Month Comparative Multicenter Study of the Tcu380A and ML 250 Intrauterine Devices in Bangkok, Thailand. Contraception, 1998, 58: 201-206.
[7] Zhou Liying, Xiao Bilian. Emergency contraception with Multiload Cu-375 SL IUD: a multicenter clinical trial. Contraception, 2001, 64: 107-112.
[8] I. Batár, A. Kuukankorpi, I. Rauramo, et al. Two-year clinical experience with Nova-T 380, a novel copper-silver IUD. Advances in Contraception, 1999, 15: 37-48.
[9] I. Batár, A. Kuukankorpi, M. Siljanderet al. Five-year clinical experiences with NOVAT 380 copper IUD. Contraception, 2002, 66: 309-314.
[10]梁成浩,陈邦义.宫内节育器及其耐蚀性研究进展.腐蚀科学与防护技术, 2003, 15: 94-96.
[11] Scommegna A, Pandya GN, Christ Met al. Intrauterine administration f progesterone by a slow releasing device. Fertil Steril, 1970, 21: 201-205.
[12] Nilsson CG, Luukkainen T, Arko H. Endometrial morphology of women using a d-norgestrel-releasing intrauterine device. Fertil Steril, 1978, 29: 397-401.
[13]张娜,彭毅仁.新型铜药复合IUD的体外药物释放研究.中国计划生育学杂志, 1998, 2: 59-60.
[14]陈飒英,张梅芳,许天丽.宫内节育器的发展及临床应用.中国实用妇科与产科杂志, 1999, 15(5): 309-310.
[15] Li Wei, Cao Lumin, Chen Zaojao. Study on the effects of FCu-IUD and FICu-IUD on matrix metalloproteinases in human uterine flushing and endometrium. Journal of HuazhongUniversity of Science and Technology - Medical Science, 2002, 22: 9-11.
[16] Liu Changguan, Li Shuxiang, Liu Xiaoai et al. Morphological observation of endometrium in rats and rabbits after insertion of indomethacin-Cu-IUD. Journal of reproductive medicine, 1999, S1: 59-62.
[17]王益夫.消炎痛缓释系统的释放特与子宫相容性的初步研究.生殖与避孕, l989, 9(1): 25―27.
[18]杨邦元,庄留琪.含不同剂量消炎痛T型IUD比较性研究.生殖与避孕, 1995, 15(4): 300-305.
[19]刘晓瑷等.刘昌官,李恕香.吲哚美辛宫内节育器的药效学研究.生殖与避孕, 2000, 20(3): 165-171.
[20] Yang BY, Zhuang LQ, Yuan HL. Comparative study of Y--IUDs with different doses of indomethacin. Journal of reproduction and contraception, 1995, 15: 300--304 .
[21]李亮,李瑛.宫内节育器副作用和并发症的研究进展.国外医学计划生育分册,2003, 22(2): 72-74.
[22] M. Toppozada. Treatment of increased menstrual blood loss in iud users. Contraception, 1987, 36: 145-157.
[23] Miguel J. Beltran-Garcia, Adriana Espinosa et al. Formation of Copper Oxychloride and Reactive Oxygen Species as Causes of Uterine Injury During Copper Oxidation of Cu-IUD. Contraception, 2000, 61(2): 99-103.
[24]高清,李瑛,刘建平等.活性元宫型药铜365宫内节育器体外释放吲哚美辛的研究.生殖与避孕, 2006, 26(10): 602-606.
[25]林建华,潘家骧,严隽鸿.置释铜IUD妇女经血纤溶活性与宫颈粘液铜离子浓度相关性研究.生殖与避孕, 1992, 12(1): 24-28.
[26] Ka′lma′n Patai, La′szlo′De′ve′nyi, Roma′na Zelko′. Comparison of surface morphology and composition of intrauterine devices in relation to patient complaints. Contraception, 2004, 70(2): 149-152.
[27] M. E. Tuttle, R. W. Baker, L. E. Laufe. Slow release aprotinin delivery for control of intrauterine-device-induced hemorrhage. Journal of Membrane Science, 1980, 7: 351-358.
[28]周玉玲.宫内节育器影响子宫出血机理的研究现状.中国计划生育学杂志, 1999, 7(8): 379-381.
[29] David Hubacher. Copper intrauterine device use by nulliparous women: review of side effects. Contraception, 2007, 75: S8-S11.
[30] Bruno Dahlberg, Stig Kullander, Jan Ursing. Bacterial infection in relation to pain and irregular bleeding in women using IUD. Contraception, 1979, 20: 71-75.
[31] Kaufman DW, Watson J, Rosenberg L et al. The effect of different types of intrauterine deviceson the risk of pelvic inflrdashgqdgammatory disease. J Am Med Assoc., 1983, 250: 759-762.
[32] Vessey MP, Yeats D, Flavel R, et al. Pelvic inflammatory disease and the intrauterine device: finding a large cohort study. Br Med J., 1981, 288: 855-857.
[33] Lee WC, Rubin GL, Ory HW, et al. Type of intrauterine device and the risk of pelvic in￡ammatory disease. Obstet Gynecol, 1983, 62: 1-6.
[34] Jean Bouyeret. Risk factors for extrauterine pregnancy in women using an intrauterine device. fertility and sterilityt, 2000, 74(5): 899-908.
[35] Xu Xiong, Pierre Buekens, Elisabeth Wollast. IUD use and the risk of ectopic pregnancy: A meta-analysis of case-control studies. Contraception, 1995, 52(1): 23-24.
[36] Phupong V, Sueblingvong T, Pmksananonda Ket a1. Uterine perforation with Lippes Loop intrauterine devices associated actinomycosis. Contraception, 2000, 61(5): 347―350.
[37] Raul Mederos, Lynda Humaran, Donald Minervini. Surgical removal of an intrauterine device perforating the sigmoid colon: A case report. International Journal of Surgery, 2007, In Press: Corrected Proof.
[38] N. D. Goldstuck. Insertion forces with intrauterine devices: implications for uterine perforation. European Journal of Obstetrics & Gynecology and Reproductive Biology, 1987, 25: 315-323.
[39] Mario Medel, Carmen Espinoza, Jaime Zipper. Reversibility of the contraceptive action of copper and zinc in the rat and rabbit. Contraception, 1972, 6(3): 241-247.
[40] M. S. Fahim and M. Wang. Zinc acetate and lyophilized aloe barbadensis as vaginal contraceptive. Contraception, 1996, 53(4): 231-236.
[41] William L. Williams. New antifertility agents active in the rabbit vaginal contraception (RVC) method. Contraception, 1980, 22: 689-672.
[42] Anteby. S O, Bassat. H A, Yarkoni. S et al. The effect of intrauterine devices containing zinc and copper on their levels in serum. Fertility And Sterility, 1978, 29: 30-34.
[43] Erika C.S. Oliveira, Maria Raquel Moura, Valdemiro A. Silva Jr et al. Intratesticular injection of a zinc-based solution as a contraceptive for dogs. Theriogenology, 2007, 68(2): 137-145.
[44] P. Blanc, H. Wong, M.S. Bernstein. An experimental human model of metal fume fever. Ann Intern Med, 1991, 114(11): 930-936.
[45]朱文华,陶梅.锌离子对离体人精子的制动作用.生殖与避孕, 1991, 11(3): 73-74.
[46] Oster G.K. Chemical reactions of the copper intruterine device. Fertll Steril, 1972, 23: 18-23.
[47] Holland M.K, White I.G. Heavy. metal and spermatozoaI. lnhibition of the motility and metabolism of spermatozoa by metals related to copper. Fertil sterile, 1980, 34(5): 483.
[48]尤昭玲,王若光.宫内节育器引起异常子宫出血中医治疗评述.湖南中医药导报,1998, 4(3): 10-11.
[49]彭新君,雷磊,徐丽霞等.锌-金属硫蛋白防治带铜宫内节育器出血副反应的机理探讨.湖南中医学院学报, 2001, 21(4): 33-34.
[50]许莹.无机抗菌剂和抗菌功能材料的现状和发展.河北理工学院学报,2001, 23(4): 77-79.
[51]黄鑫泉,陈运法.抗菌剂与银系列无机抗菌材料.精细与专用化学品, 2001, 9(18): 26-28.
[52]周宜,张祖欣.宫内节育器引起子宫出血的机理与中西医治疗.重庆教育学院学报, 2002, 15(3): 67-69 .
[53]季君晖,史维明.抗菌材料.化学工业出版社, 2003, 45-46.
[54]李群,陈水林,李艳春等.纳米氧化锌整理剂的研制.印染, 2003, 29(8): 1-4.
[55] Osamu Yamamoto, Kyoko Nakakoshi, Tadashi Sasamoto et al. Adsorption and growth inhibition of bacteria on carbon materials containing zinc oxide. Carbon, 2001, 39(11): 1643-1651.
[56] J. Sawai. Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay. Journal of Microbiological Methods, 2003, 54(2): 177- 182.
[57] Osamu Yamamoto. Influence of particle size on the antibacterial activity of zinc oxide. International Journal of Inorganic Materials, 2001, 3(7): 643-646.
[58]楚珑晟,周柞万,段晓飞. ZnOw/纳米复合抗菌剂的研制.材料导报, 2003, 17(6): 84-85.
[59] Bruck S D. Biomedical Application of Polymeric Materials and Their Interactions with Blood Components: A Critical Review of Current Developments. Inter J Artif Organs, 1990, 13: 469-471.
[60]赵国梁,鲁险锋,王晓春.聚醋纤维抗凝血性能研究进展.北京服装学院学报, 2004, 24(2): 56-61.
[61]李潮,胡国栋,何艳花. ZnO纳米材料抗凝血性能的初步评价.过程工程学报, 2003, 3(1): 34-36.
[62] Liu Xiaoai, Yao Meiying, Zheng Yubo et al. The Multi-Center Comparative Clinical Trial of the Second Generation of Indomethacin VCu and TCu380A. Journal of reproduction and contraception, 2002, 13: 28-36.
[63]屈秦红,任景芳,刘宗梅等.消炎止血胶囊治疗宫内节育器致子宫异常出血的机制研究.中国药物与临床, 2006, 6(2): 102-104.
[64]周玉玲,曹路敏,刘子龙等.释放吲哚美辛的固定式铜宫内节育器减少子宫出血机制的研究.同济医科大学学报, 2000, 29(1): 49-52.
[65] Lu Xin, Wu Jinmei, Xu Sheng et al. Effect of IUD with Indomethacin on Rabbits Endometrium by Enzyme Histochemistry. Journal of reproduction and contraception, 1996, 7(2): 97-102.
[66]尤昭玲,谈珍瑜,梁欣韫等.活血化瘀法对置Cu―IUD家兔子宫内膜超微结构的影响.湖南中医学院学报, 2005, 25(2): 4-6.
[67]谷诏,李民石,朱蓬第等.置入含消炎痛铜珠宫内节育器的子宫内膜形态计量学观察.生殖与避孕. 1998, 18(1):49-52.
[68]吴尚纯,王翠萍,南秀牌等.释放吲哚美辛的吉妮宫内节育器对改善出血副反应的临床研究.中华妇产科杂志, 2004, 39(12): 842-843.
[69] Liu Xiao-Ai, ZhuYan-Ping, Jin Yu-Cui. The effect of indomethacin on prostaglandin e2 uptake by human endometrial cells. Journal of reproduction and contraception, 1989, 1: 61-61.
[70]吴昌杰,曹路教,陈莉等.消炎痛硅橡胶缓释系统体内、外释放率相关性研究.同济医科大学学报, 2001, 30(4): 324-326.
[71]杨中文.释放吲哚美辛的固定式宫内节育器―药物缓释制剂研制.海生物医学工程, 2004, 25(3): 23-28.
[72] Mihai Rusu, Nicoleta Sofian and Daniela Rusu. Mechanical and thermal properties of zinc powder filled high density polyethylene composites. Polymer Testing, 2001, 20(4): 409-417.
[73]徐铜文,何炳林.扩散型膜控制释放技术的进展.世界科技研究与发展, 2000, 22(1): 20-25.
[74] Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci., 1961, 50: 874-875.
[75] Xu Tongwen, He Binglin. Mechanism of sustained drug release in diffusion-controlled polymer matrix-application of percolation theory. International journal of pharmaceutics, 1998, 170(2): 139-149.
[76] T. J. Rose man, I-liguchi W I. Release of medxoxypxogestexone acetate from a silicone polymer. J. Pharm Sci., 1970, 59(3): 353-357.
[77] Paul W. Jones, David M. Taylor, David R. Williams. Analysis and chemical speciation of copper and zinc in wound fluid. Journal of Inorganic Biochemistry, 2000, 81(1-2): 1-10.
[78] E.Carden Yeiser, Anna A. Lerant, R.Michael Casto et al. Free zinc increases at the site of injury after cortical stab wounds in mature but not immature rat brain. Neuroscience Letters, 1999, 277: 75-78.
[79] Yong Hyun, Seung Ju Lee, Ji Youl Lee et al. Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis. International Journal of Antimicrobial Agents, 2002, 19(6): 576-582.
[80] Hagenfeldt MDK. Intrauterine contraception with the copper-T device: 1. Effect on trace elements in the endometrium. Cervical mucus and plasma, Contraception, 1972, 6(1): 37-54.
[81] Daunter B, Chantler EM, Elstein M. Trace metals(Cu,Mn,Zn,Fe), sulphydryl and bisulphide groups of cervical mucus. Contraception, 1977, 15(5): 543-552.
[82] N. Mora, E. Cano, E. M. Mora, et al. Influence of pH and oxygen on copper corrosion in simulated uterine fluid. Biomaterials, 2002, 23(3): 667-671.
[83] Ahti Kosonen, Michel Thiery. Corrosion of filamentous intra-uterine copper. The MLCu250 and the MLCu375. Contraception, 1983, 27(1): 85-93.
[84] C.Zhang, N.Xu, B.Yang. the corrosion behaviour of copper in simulated uterine fluid. Corrosion Science, 1996, 38(4): 635-641.
[85]周本省.工业水处理技术(第一版).北京:北京化学工业出版社,1997. 406-407.
[86] Shuizhou Cai, Xianping Xia, Changsheng Xie. Research on Cu2+ transformations of Cu and its oxides particles with different sizes in the simulated uterine solution. Corrosion Science, 2005, 47(4): 1039-1047.
[87] Mohammed A. Amin. Passivity and passivity breakdown of a zinc electrode in aerated neutral sodium nitrate solutions. Electrochimica Acta, 2005, 50(6): 1265-1274.
[88] Motoi Kitano, Toshio Okabe, Makoto Shiojiro. morphology and growth mechanism of ZnO particles electro-crystallized on Zn in aqueous solution. Journal of crystal growth, 1996, 166(1-4): 1116-1120.
[89] Hamdy H Hassan. corrosion behaviour of zinc in sodium perchlorate solutions. Applied Surface Science, 2001, 174(3-4): 201-209.
[90] A. Vinogradov, T. Mimaki, S. Hashimoto et al. On the corrosion behaviour of ultra-fine grain copper. Scripta Materialia, 1999, 41(3): 319-326.
[91]朱建军,徐乃欣,张承典等.血清白蛋白对模拟宫腔液中铜腐蚀的影响.中国腐蚀与防护学报, 2000, 20(2): 81-87.
[92]朱建军,葛红花,徐乃欣等.人血清白蛋白对模拟宫腔液中铜的光电响应特性的影响.腐蚀与防护, 2002, 23(4): 144-147.
[93] Jianjun Zhu, Naixin Xu, Chengdian Zhang. Characteristics of copper corrosion in simulated uterine fluid in the presence of protein. Advances in Contraception, 1999, 15: 179-190.
[94] John C. Wataha, Steven K. Nelson, Petra E. Lockwood. Elemental release from dental casting alloys into biological media with and without protein. Dental Materials, 2001, 17(5): 409-414.
[95] Emiko ohyoshi, Yoshito Hamada, Kana Nakata et al. the interaction between human and bovine serum albumin and zinc studied by competivive spectropHometry. Journal of inorganic biochemistry, 1999, 75(3): 213-218.
[96] Ming Guo, Hanfa Zou, Hailin Wang et al. Binding of metal ions with protein studied by a combined technique of microdialysis with liquid chromatography. Analytica Chimica Acta, 2001, 443(1): 91-99.
[97] Huai Qing, He Yanlin, Sheng Fenlin et al. Effects of pH and metal ions on the conformation of bovine serum albumin in aqueous solution- An Attenuated Total Reflection (ATR) FTIR spectroscopic study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1996, 52(13): 1795-1800.
[98] E.E. Foad El Sherbini, S.S. Abd El Rehim. Pitting corrosion of zinc in Na2SO4 solutions and the e.ect of some inorganic inhibitors. Corrosion Science, 2000, 42(5): 785-798.
[99] F.H. Assafa, S.S. Abd El-Rehiem, A.M. Zaky. Pitting corrosion of zinc in neutral halide solutions. Materials Chemistry and Physics, 1999, 58(1): 58-63.
[100] P.Quintana, L.Veleva, W.Cauich, et al. Study of the composition and morphology of initial stages of corrosion products formed on Zn plates exposed to the atmosphere of southeast Mexico. Applied Surface Science, 1996, 99(4): 325-334.
[101] Qing Qu, Chuanwei Yan, Ye Wan et al. Effects of NaCl and SO2 on the initial atmospheric corrosion of zinc. Corrosion Science, 2002, 44(12): 2789-2803.
[102] Yan Li. Formation of nano-crystalline corrosion products on Zn-Al alloy coating exposed to seawater. Corrosion science, 2001, 43(9): 1793-1800.
[103] P. Spathis, I. Pooulios. The corrosion and photocorrosion of zinc and zinc oxide coatings. Corrosion Science, 1995, 37(5): 673-680.
[104] Cai SZ,Xia XP, Xie CS. Corrosion behavior of copper/LDPE nanocomposites in simulated uterine solution. Biomaterials, 2005, 26(15): 2671-2676.
[105] T. Xu, H. Lei, S. Z. Cai, et al. The release of cupric ion in simulated uterine: New material nano-Cu/low-density polyethylene used for intrauterine devices. contraception, 2004, 70(2): 153-157.
[106] Doelker E Gumy R, Peppas NA. Modeling of sustained release of water-soluble drugs from porous, hydrophobic polymers. Biomaterials, 1982, 3(1): 27-32.
[107] Caraballo I, Fernández-Arévalo M, Holgado MA, et al. Percolation theory: Application to the study of the release behaviour from inert matrix systems. Int. J. Pharm, 1993, 96(1-3): 175-181.
[108] Caraballo I, Millán M, Rabasco AM, et al. Zero-order release periods in inert matrices. Influence of the distance to the percolation threshold. Pharmaceutics Acta Helvetiae, 1996, 71(5): 335-339.
[109] Young CR, Koleng JJ, McGinity JW. Production of spherical pellets by a hot-melt extrusion and spheronization process. Int. J. Pharm, 2002, 242(1-2): 87-92.
[110] Crowley MM, Schroeder B, Fredersdorf A, et al. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int. J. Pharm., 2004, 269(2): 509-522.
[111] Millán M, Caraballo I. Effect of drug particle size in ultrasound compacted tablets Continuum percolation model approach. Int. J. Pharm., 2006, 310(1-2): 168-174.
[112] Higuchi T. Mechanism of sustained-action medication-theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52: 1145-1149.
[113] Bastidas JM, Cano E, Mora N. Copper corrosion-simulated uterine solutions. Contraception, 2000, 61(6): 395-399.
[114] Patai K, De′ve′nyi L, Zelko′R. Comparison of surface morphology and composition of intrauterine devices in relation to patient complaints. Contraception, 2004, 70(2): 149-152.
[115] Rizk M, Shaban N, Medhat I, et al. Electron microscopic and chemical study of the deposits formed on the copper and inert IUCDs. Contraception, 1990, 42(6): 643-653.
[116] Patai K, Bere′nyi M, Sipos M, et al. Characterization of Calcified Deposits on Contraceptive Intrauterine Devices. Contraception, 1998, 58(5): 305-308.
[117] F. Zielske, U. J. Koch, R. Badura et al. studies on copper release from copper-T device(T-Cu200) and its influence on sperm migration in vitro. Contraception, 1974, 10(6): 651-666.
[118] Elchalal U, Abramov Y. Uterine biology and the intrauterine device. Adv Drug Delivery Rev 1995, 17:151–164.
[119] Lee NC. Type of intrauterine device and the risk of pelvic inflammatory disease. Obstet. Gynecol, 1983, 62:1–6.
[120] PhD Saeed R. Khan, MD Edward J. Wilkinson. Scanning electron microscopy, X-ray diffraction, and electron microprobe analysis of calcific deposits on intrauterine contraceptive devices. Human Pathology, 1985,16(7):732-738.
[121] Patai K, Bere′nyi M. Incrustation of intrauterine devices (in German). Zentralbl Gynakol, 1982,104:1385–1387.
[122]周红.酸性条件下锌试剂测定铜.贵州化工, 2003, 28(3): 33-34.
[123]吴丽香,赵崇峰,于大勇等.锌试剂-OP显色体系测定原油中的铜.石油化工, 2001, 30(12): 935-937.
[124] J.M. Bastidas, E. Cano, N. Mora. Copper Corrosion-Simulated Uterine Solutions. Contraception, 2000, 61: 395-399.
[125]王莉.宫内节育器作用机制的研究现状.甘肃中医, 2003, 16(1): 6-9.
[126] Petta CA, Amatya R, Farr G. Clinical evaluation of the TCu 380A IUD at six Latin American centers. Contraception, 1994, 50(1): 17-25.
[127] Luukkainen T, Allonen H, Nielsen NCet al. Five years experience of intrauterine contraception with Nova T and the Copper T-200. Am J Obstet Gynecol, 1983, 147: 885-892.
[128]杨文平译.海水中锌腐蚀产物的研究.国外舰船工程, 2005,(4): 19-22
[129]李焰,魏绪钧,冯法伦.热浸镀层的海水全浸腐蚀行为研究.材料保护, 2001, 34(5): 11-12.
[130] A.G.KHOMASSURIDZE, G.I.TSERTSVADZE, T.G.TSERETELI. Intrauterine device and pelvic inflammatory disease. Advance in Contraception, 1997, 13: 71-78.
[131] M.R Joesoef, A.Karundeng. High rate of bacterial vaginosis among woman with intrauterine device in Manado,Indonesia. Contraception, 2001, 64(3): 169-172.
[132] James D Shelton. Risk of clinical pelvic inflammatory disease attributable to an intrauterine device. The lancet, 2001, 357(9254): 443.
[133] Belanger MC, Marois Y, Roy R et al. Selection of a polyurethane membrance for the manufacture of ventricles for a totally implantable artificical heart:blood compatibility and biocompatibility studies. Artifical Organs, 2000, 24(11): 879-888.
[134] Hong J, Larsson A, Ekadahl K.N. et al. Contact between a polymer and whole blood:sequence of events leading to thrombin generation. The Journal of Laboratory and clinical medicine, 2001, 138(2): 139-145.
[135]刘欣,史弘道.医用生物材料血液相容性评价研究概况.透析与人工器官, 2003, 14(1): 40-44.
[136]鲁险锋,赵国梁,高扬等.纳米ZnO改性聚酯抗凝血性能研究.合成纤维工业2005, 2005, 28(3): 13-15.
[137]许海军,赵国梁,王晓春等.纳米ZnO/聚乙二醇改性聚酯的抗凝血性能.聚酯工业, 2006, 19(1): 21-23.
[138] Grasel T G Goodman S L, Cooper S L et al. Platelet shape change and cytoskeletal reorganization on polyurethaneureas. J. Biomed. Mater. Res., 1989, 23: 105-123.
[139] Lelah M D Goodman S L, Lambrecht L K, Cooper S L et al. In vitro versus ex vivo platelet deposition on polymer surfaces. Scan. Electron. Microsc, 1984, 1: 379-390.
[140]蒋书文.钛合金基类金刚石梯度薄膜材料制备及其生物摩擦学性能和血液相容性的研究.博士论文, 2002.
[141]喻凯,陈治清.白蛋白被人体硬组织替代材料吸附后构象的改变.华西口腔医学杂志, 1996, 14(3): 174-176.
[142] Yuh-Lang Lee, Chi-Yun Chen. Surface wettability and platelet adhesion studies on Langmuir Blodgett films. Applied Surface Science, 2003, 207(1-4): 51-62.
[143]王春仁,杨子彬.生物材料表面血浆蛋白的吸附.国外医学:生物医学工程分册, 1995, 18(6): 334-339.
[144]陈宝林,王东安,封麟先等.生物医用高分子材料的血液相容性研究―抗凝血材料的设计.绥化学院学报, 2007, 27(1): 186-188.
[145]张守松,周长忍,邹翰.甲壳糖-聚硅氧烷复合材料研究.高分子材料科学与工程, 1999, 15(3): 163-165.
[146] Shan-Hui Hsu, Cheng-Ming Tang, C.C.Chu-Chieh Lin. Biocompatibility of poly(-caprolactone)/poly(ethylene glycol) diblock copolymers with nanophase separation. Biomaterials, 2004, 25(25): 5593-5601.
[147] Kazunori Kataoka, Teruo Okano, Yasuhisa Sakurai et al. Effect of microphase separated structure of polystyrene/polyamine graft copolymer on adhering rat platelets in vitro. Biomaterials, 1982, 3(4): 237-240.
[148] P. Yang, S. C. H. Kwok, R. K. Y. Fu et al. Structure and properties of annealed amorphous hydrogenated carbon (a-C:H) films for biomedical applications. Surface and Coatings Technology, 2004, 177-178: 747-751.
[149] Nan Huang, Ping Yang, Xuan Cheng et al. Blood compatibility of amorphous titanium oxide films synthesized by ion beam enhanced deposition. Biomaterials, 1998, 19(7-9): 771-776.
[150]霍丹群.肝素化高分子液晶/聚醚氨酯生物材料的研究.博士论文,重庆大学,2004.
[151]高洁,李瑛,刘建平等.活性元宫型365宫内节育器体外释放吲哚美辛的研究.生殖与避孕, 2006, 26(10): 602-605.
[152] Hiroo Maeda, Toshihiko Sugie. Study on accelerated evaluation system for release profiles of covered-rod type silicone formulation using indomethacin as a model drug. Journal of Controlled Release, 2004, 94 (2-3): 337-349.
[153] Xue Huashi, Xu Naixin, Zhang Chendian. Corrosion behavior of copper in a copper bearing intrauterine device in the presence of indomethacin. Contraception, 1998, 57(1): 49-53.
[154]吴昌杰,陈莉.消炎痛硅橡胶缓释系统体外释放率的初步研究.实用医学杂志, 1997, 10(3): 6-8.
[155]毕淑云,宋大千,魏士刚等.用荧光猝灭法研究人血清白蛋白与吲哚美辛的结合反应.吉林大学学报(理学版), 2006, 44(3): 493-496.
[156]徐铜文,何炳林.扩散控制型高分子药膜缓释体系的渗透现象.中国科学(B辑), 1998, 28(2): 178-185.
[2]曹小明,张维嘉.宫内节育器的回顾与展望.国外医学计划生育分册, 2001, 20(3): 164-167.
[3] Michel Thiery. Intrauterine contraception: from siliver ring to intrauterine contraceptive implant. European Journal of Obstetrecs & Gynecology and Reproduction Biology, 2000, 90: 145-152.
[4] Zipper ZA, Tatum HJ, Pastene Let al. Metallic copper as an intrauterine contraceptive adjunct to the“T”device. Am J Obstet and Gynecol, 1969, 105: 1274-1278.
[5] D. GuerreiroU, M.A.M. Gigante, L.C. Teles. Sexually transmitted diseases and reproductive tract infections among contraceptive users. International Journal of Gynecology & Obstetrics, 1998, 63(suppl 1): 163-173.
[6] Damrong Reinprayoon, Caroline Gilmore, Gaston Farr, et al. Twelve-Month Comparative Multicenter Study of the Tcu380A and ML 250 Intrauterine Devices in Bangkok, Thailand. Contraception, 1998, 58: 201-206.
[7] Zhou Liying, Xiao Bilian. Emergency contraception with Multiload Cu-375 SL IUD: a multicenter clinical trial. Contraception, 2001, 64: 107-112.
[8] I. Batár, A. Kuukankorpi, I. Rauramo, et al. Two-year clinical experience with Nova-T 380, a novel copper-silver IUD. Advances in Contraception, 1999, 15: 37-48.
[9] I. Batár, A. Kuukankorpi, M. Siljanderet al. Five-year clinical experiences with NOVAT 380 copper IUD. Contraception, 2002, 66: 309-314.
[10]梁成浩,陈邦义.宫内节育器及其耐蚀性研究进展.腐蚀科学与防护技术, 2003, 15: 94-96.
[11] Scommegna A, Pandya GN, Christ Met al. Intrauterine administration f progesterone by a slow releasing device. Fertil Steril, 1970, 21: 201-205.
[12] Nilsson CG, Luukkainen T, Arko H. Endometrial morphology of women using a d-norgestrel-releasing intrauterine device. Fertil Steril, 1978, 29: 397-401.
[13]张娜,彭毅仁.新型铜药复合IUD的体外药物释放研究.中国计划生育学杂志, 1998, 2: 59-60.
[14]陈飒英,张梅芳,许天丽.宫内节育器的发展及临床应用.中国实用妇科与产科杂志, 1999, 15(5): 309-310.
[15] Li Wei, Cao Lumin, Chen Zaojao. Study on the effects of FCu-IUD and FICu-IUD on matrix metalloproteinases in human uterine flushing and endometrium. Journal of HuazhongUniversity of Science and Technology - Medical Science, 2002, 22: 9-11.
[16] Liu Changguan, Li Shuxiang, Liu Xiaoai et al. Morphological observation of endometrium in rats and rabbits after insertion of indomethacin-Cu-IUD. Journal of reproductive medicine, 1999, S1: 59-62.
[17]王益夫.消炎痛缓释系统的释放特与子宫相容性的初步研究.生殖与避孕, l989, 9(1): 25―27.
[18]杨邦元,庄留琪.含不同剂量消炎痛T型IUD比较性研究.生殖与避孕, 1995, 15(4): 300-305.
[19]刘晓瑷等.刘昌官,李恕香.吲哚美辛宫内节育器的药效学研究.生殖与避孕, 2000, 20(3): 165-171.
[20] Yang BY, Zhuang LQ, Yuan HL. Comparative study of Y--IUDs with different doses of indomethacin. Journal of reproduction and contraception, 1995, 15: 300--304 .
[21]李亮,李瑛.宫内节育器副作用和并发症的研究进展.国外医学计划生育分册,2003, 22(2): 72-74.
[22] M. Toppozada. Treatment of increased menstrual blood loss in iud users. Contraception, 1987, 36: 145-157.
[23] Miguel J. Beltran-Garcia, Adriana Espinosa et al. Formation of Copper Oxychloride and Reactive Oxygen Species as Causes of Uterine Injury During Copper Oxidation of Cu-IUD. Contraception, 2000, 61(2): 99-103.
[24]高清,李瑛,刘建平等.活性元宫型药铜365宫内节育器体外释放吲哚美辛的研究.生殖与避孕, 2006, 26(10): 602-606.
[25]林建华,潘家骧,严隽鸿.置释铜IUD妇女经血纤溶活性与宫颈粘液铜离子浓度相关性研究.生殖与避孕, 1992, 12(1): 24-28.
[26] Ka′lma′n Patai, La′szlo′De′ve′nyi, Roma′na Zelko′. Comparison of surface morphology and composition of intrauterine devices in relation to patient complaints. Contraception, 2004, 70(2): 149-152.
[27] M. E. Tuttle, R. W. Baker, L. E. Laufe. Slow release aprotinin delivery for control of intrauterine-device-induced hemorrhage. Journal of Membrane Science, 1980, 7: 351-358.
[28]周玉玲.宫内节育器影响子宫出血机理的研究现状.中国计划生育学杂志, 1999, 7(8): 379-381.
[29] David Hubacher. Copper intrauterine device use by nulliparous women: review of side effects. Contraception, 2007, 75: S8-S11.
[30] Bruno Dahlberg, Stig Kullander, Jan Ursing. Bacterial infection in relation to pain and irregular bleeding in women using IUD. Contraception, 1979, 20: 71-75.
[31] Kaufman DW, Watson J, Rosenberg L et al. The effect of different types of intrauterine deviceson the risk of pelvic inflrdashgqdgammatory disease. J Am Med Assoc., 1983, 250: 759-762.
[32] Vessey MP, Yeats D, Flavel R, et al. Pelvic inflammatory disease and the intrauterine device: finding a large cohort study. Br Med J., 1981, 288: 855-857.
[33] Lee WC, Rubin GL, Ory HW, et al. Type of intrauterine device and the risk of pelvic in￡ammatory disease. Obstet Gynecol, 1983, 62: 1-6.
[34] Jean Bouyeret. Risk factors for extrauterine pregnancy in women using an intrauterine device. fertility and sterilityt, 2000, 74(5): 899-908.
[35] Xu Xiong, Pierre Buekens, Elisabeth Wollast. IUD use and the risk of ectopic pregnancy: A meta-analysis of case-control studies. Contraception, 1995, 52(1): 23-24.
[36] Phupong V, Sueblingvong T, Pmksananonda Ket a1. Uterine perforation with Lippes Loop intrauterine devices associated actinomycosis. Contraception, 2000, 61(5): 347―350.
[37] Raul Mederos, Lynda Humaran, Donald Minervini. Surgical removal of an intrauterine device perforating the sigmoid colon: A case report. International Journal of Surgery, 2007, In Press: Corrected Proof.
[38] N. D. Goldstuck. Insertion forces with intrauterine devices: implications for uterine perforation. European Journal of Obstetrics & Gynecology and Reproductive Biology, 1987, 25: 315-323.
[39] Mario Medel, Carmen Espinoza, Jaime Zipper. Reversibility of the contraceptive action of copper and zinc in the rat and rabbit. Contraception, 1972, 6(3): 241-247.
[40] M. S. Fahim and M. Wang. Zinc acetate and lyophilized aloe barbadensis as vaginal contraceptive. Contraception, 1996, 53(4): 231-236.
[41] William L. Williams. New antifertility agents active in the rabbit vaginal contraception (RVC) method. Contraception, 1980, 22: 689-672.
[42] Anteby. S O, Bassat. H A, Yarkoni. S et al. The effect of intrauterine devices containing zinc and copper on their levels in serum. Fertility And Sterility, 1978, 29: 30-34.
[43] Erika C.S. Oliveira, Maria Raquel Moura, Valdemiro A. Silva Jr et al. Intratesticular injection of a zinc-based solution as a contraceptive for dogs. Theriogenology, 2007, 68(2): 137-145.
[44] P. Blanc, H. Wong, M.S. Bernstein. An experimental human model of metal fume fever. Ann Intern Med, 1991, 114(11): 930-936.
[45]朱文华,陶梅.锌离子对离体人精子的制动作用.生殖与避孕, 1991, 11(3): 73-74.
[46] Oster G.K. Chemical reactions of the copper intruterine device. Fertll Steril, 1972, 23: 18-23.
[47] Holland M.K, White I.G. Heavy. metal and spermatozoaI. lnhibition of the motility and metabolism of spermatozoa by metals related to copper. Fertil sterile, 1980, 34(5): 483.
[48]尤昭玲,王若光.宫内节育器引起异常子宫出血中医治疗评述.湖南中医药导报,1998, 4(3): 10-11.
[49]彭新君,雷磊,徐丽霞等.锌-金属硫蛋白防治带铜宫内节育器出血副反应的机理探讨.湖南中医学院学报, 2001, 21(4): 33-34.
[50]许莹.无机抗菌剂和抗菌功能材料的现状和发展.河北理工学院学报,2001, 23(4): 77-79.
[51]黄鑫泉,陈运法.抗菌剂与银系列无机抗菌材料.精细与专用化学品, 2001, 9(18): 26-28.
[52]周宜,张祖欣.宫内节育器引起子宫出血的机理与中西医治疗.重庆教育学院学报, 2002, 15(3): 67-69 .
[53]季君晖,史维明.抗菌材料.化学工业出版社, 2003, 45-46.
[54]李群,陈水林,李艳春等.纳米氧化锌整理剂的研制.印染, 2003, 29(8): 1-4.
[55] Osamu Yamamoto, Kyoko Nakakoshi, Tadashi Sasamoto et al. Adsorption and growth inhibition of bacteria on carbon materials containing zinc oxide. Carbon, 2001, 39(11): 1643-1651.
[56] J. Sawai. Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay. Journal of Microbiological Methods, 2003, 54(2): 177- 182.
[57] Osamu Yamamoto. Influence of particle size on the antibacterial activity of zinc oxide. International Journal of Inorganic Materials, 2001, 3(7): 643-646.
[58]楚珑晟,周柞万,段晓飞. ZnOw/纳米复合抗菌剂的研制.材料导报, 2003, 17(6): 84-85.
[59] Bruck S D. Biomedical Application of Polymeric Materials and Their Interactions with Blood Components: A Critical Review of Current Developments. Inter J Artif Organs, 1990, 13: 469-471.
[60]赵国梁,鲁险锋,王晓春.聚醋纤维抗凝血性能研究进展.北京服装学院学报, 2004, 24(2): 56-61.
[61]李潮,胡国栋,何艳花. ZnO纳米材料抗凝血性能的初步评价.过程工程学报, 2003, 3(1): 34-36.
[62] Liu Xiaoai, Yao Meiying, Zheng Yubo et al. The Multi-Center Comparative Clinical Trial of the Second Generation of Indomethacin VCu and TCu380A. Journal of reproduction and contraception, 2002, 13: 28-36.
[63]屈秦红,任景芳,刘宗梅等.消炎止血胶囊治疗宫内节育器致子宫异常出血的机制研究.中国药物与临床, 2006, 6(2): 102-104.
[64]周玉玲,曹路敏,刘子龙等.释放吲哚美辛的固定式铜宫内节育器减少子宫出血机制的研究.同济医科大学学报, 2000, 29(1): 49-52.
[65] Lu Xin, Wu Jinmei, Xu Sheng et al. Effect of IUD with Indomethacin on Rabbits Endometrium by Enzyme Histochemistry. Journal of reproduction and contraception, 1996, 7(2): 97-102.
[66]尤昭玲,谈珍瑜,梁欣韫等.活血化瘀法对置Cu―IUD家兔子宫内膜超微结构的影响.湖南中医学院学报, 2005, 25(2): 4-6.
[67]谷诏,李民石,朱蓬第等.置入含消炎痛铜珠宫内节育器的子宫内膜形态计量学观察.生殖与避孕. 1998, 18(1):49-52.
[68]吴尚纯,王翠萍,南秀牌等.释放吲哚美辛的吉妮宫内节育器对改善出血副反应的临床研究.中华妇产科杂志, 2004, 39(12): 842-843.
[69] Liu Xiao-Ai, ZhuYan-Ping, Jin Yu-Cui. The effect of indomethacin on prostaglandin e2 uptake by human endometrial cells. Journal of reproduction and contraception, 1989, 1: 61-61.
[70]吴昌杰,曹路教,陈莉等.消炎痛硅橡胶缓释系统体内、外释放率相关性研究.同济医科大学学报, 2001, 30(4): 324-326.
[71]杨中文.释放吲哚美辛的固定式宫内节育器―药物缓释制剂研制.海生物医学工程, 2004, 25(3): 23-28.
[72] Mihai Rusu, Nicoleta Sofian and Daniela Rusu. Mechanical and thermal properties of zinc powder filled high density polyethylene composites. Polymer Testing, 2001, 20(4): 409-417.
[73]徐铜文,何炳林.扩散型膜控制释放技术的进展.世界科技研究与发展, 2000, 22(1): 20-25.
[74] Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci., 1961, 50: 874-875.
[75] Xu Tongwen, He Binglin. Mechanism of sustained drug release in diffusion-controlled polymer matrix-application of percolation theory. International journal of pharmaceutics, 1998, 170(2): 139-149.
[76] T. J. Rose man, I-liguchi W I. Release of medxoxypxogestexone acetate from a silicone polymer. J. Pharm Sci., 1970, 59(3): 353-357.
[77] Paul W. Jones, David M. Taylor, David R. Williams. Analysis and chemical speciation of copper and zinc in wound fluid. Journal of Inorganic Biochemistry, 2000, 81(1-2): 1-10.
[78] E.Carden Yeiser, Anna A. Lerant, R.Michael Casto et al. Free zinc increases at the site of injury after cortical stab wounds in mature but not immature rat brain. Neuroscience Letters, 1999, 277: 75-78.
[79] Yong Hyun, Seung Ju Lee, Ji Youl Lee et al. Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis. International Journal of Antimicrobial Agents, 2002, 19(6): 576-582.
[80] Hagenfeldt MDK. Intrauterine contraception with the copper-T device: 1. Effect on trace elements in the endometrium. Cervical mucus and plasma, Contraception, 1972, 6(1): 37-54.
[81] Daunter B, Chantler EM, Elstein M. Trace metals(Cu,Mn,Zn,Fe), sulphydryl and bisulphide groups of cervical mucus. Contraception, 1977, 15(5): 543-552.
[82] N. Mora, E. Cano, E. M. Mora, et al. Influence of pH and oxygen on copper corrosion in simulated uterine fluid. Biomaterials, 2002, 23(3): 667-671.
[83] Ahti Kosonen, Michel Thiery. Corrosion of filamentous intra-uterine copper. The MLCu250 and the MLCu375. Contraception, 1983, 27(1): 85-93.
[84] C.Zhang, N.Xu, B.Yang. the corrosion behaviour of copper in simulated uterine fluid. Corrosion Science, 1996, 38(4): 635-641.
[85]周本省.工业水处理技术(第一版).北京:北京化学工业出版社,1997. 406-407.
[86] Shuizhou Cai, Xianping Xia, Changsheng Xie. Research on Cu2+ transformations of Cu and its oxides particles with different sizes in the simulated uterine solution. Corrosion Science, 2005, 47(4): 1039-1047.
[87] Mohammed A. Amin. Passivity and passivity breakdown of a zinc electrode in aerated neutral sodium nitrate solutions. Electrochimica Acta, 2005, 50(6): 1265-1274.
[88] Motoi Kitano, Toshio Okabe, Makoto Shiojiro. morphology and growth mechanism of ZnO particles electro-crystallized on Zn in aqueous solution. Journal of crystal growth, 1996, 166(1-4): 1116-1120.
[89] Hamdy H Hassan. corrosion behaviour of zinc in sodium perchlorate solutions. Applied Surface Science, 2001, 174(3-4): 201-209.
[90] A. Vinogradov, T. Mimaki, S. Hashimoto et al. On the corrosion behaviour of ultra-fine grain copper. Scripta Materialia, 1999, 41(3): 319-326.
[91]朱建军,徐乃欣,张承典等.血清白蛋白对模拟宫腔液中铜腐蚀的影响.中国腐蚀与防护学报, 2000, 20(2): 81-87.
[92]朱建军,葛红花,徐乃欣等.人血清白蛋白对模拟宫腔液中铜的光电响应特性的影响.腐蚀与防护, 2002, 23(4): 144-147.
[93] Jianjun Zhu, Naixin Xu, Chengdian Zhang. Characteristics of copper corrosion in simulated uterine fluid in the presence of protein. Advances in Contraception, 1999, 15: 179-190.
[94] John C. Wataha, Steven K. Nelson, Petra E. Lockwood. Elemental release from dental casting alloys into biological media with and without protein. Dental Materials, 2001, 17(5): 409-414.
[95] Emiko ohyoshi, Yoshito Hamada, Kana Nakata et al. the interaction between human and bovine serum albumin and zinc studied by competivive spectropHometry. Journal of inorganic biochemistry, 1999, 75(3): 213-218.
[96] Ming Guo, Hanfa Zou, Hailin Wang et al. Binding of metal ions with protein studied by a combined technique of microdialysis with liquid chromatography. Analytica Chimica Acta, 2001, 443(1): 91-99.
[97] Huai Qing, He Yanlin, Sheng Fenlin et al. Effects of pH and metal ions on the conformation of bovine serum albumin in aqueous solution- An Attenuated Total Reflection (ATR) FTIR spectroscopic study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 1996, 52(13): 1795-1800.
[98] E.E. Foad El Sherbini, S.S. Abd El Rehim. Pitting corrosion of zinc in Na2SO4 solutions and the e.ect of some inorganic inhibitors. Corrosion Science, 2000, 42(5): 785-798.
[99] F.H. Assafa, S.S. Abd El-Rehiem, A.M. Zaky. Pitting corrosion of zinc in neutral halide solutions. Materials Chemistry and Physics, 1999, 58(1): 58-63.
[100] P.Quintana, L.Veleva, W.Cauich, et al. Study of the composition and morphology of initial stages of corrosion products formed on Zn plates exposed to the atmosphere of southeast Mexico. Applied Surface Science, 1996, 99(4): 325-334.
[101] Qing Qu, Chuanwei Yan, Ye Wan et al. Effects of NaCl and SO2 on the initial atmospheric corrosion of zinc. Corrosion Science, 2002, 44(12): 2789-2803.
[102] Yan Li. Formation of nano-crystalline corrosion products on Zn-Al alloy coating exposed to seawater. Corrosion science, 2001, 43(9): 1793-1800.
[103] P. Spathis, I. Pooulios. The corrosion and photocorrosion of zinc and zinc oxide coatings. Corrosion Science, 1995, 37(5): 673-680.
[104] Cai SZ,Xia XP, Xie CS. Corrosion behavior of copper/LDPE nanocomposites in simulated uterine solution. Biomaterials, 2005, 26(15): 2671-2676.
[105] T. Xu, H. Lei, S. Z. Cai, et al. The release of cupric ion in simulated uterine: New material nano-Cu/low-density polyethylene used for intrauterine devices. contraception, 2004, 70(2): 153-157.
[106] Doelker E Gumy R, Peppas NA. Modeling of sustained release of water-soluble drugs from porous, hydrophobic polymers. Biomaterials, 1982, 3(1): 27-32.
[107] Caraballo I, Fernández-Arévalo M, Holgado MA, et al. Percolation theory: Application to the study of the release behaviour from inert matrix systems. Int. J. Pharm, 1993, 96(1-3): 175-181.
[108] Caraballo I, Millán M, Rabasco AM, et al. Zero-order release periods in inert matrices. Influence of the distance to the percolation threshold. Pharmaceutics Acta Helvetiae, 1996, 71(5): 335-339.
[109] Young CR, Koleng JJ, McGinity JW. Production of spherical pellets by a hot-melt extrusion and spheronization process. Int. J. Pharm, 2002, 242(1-2): 87-92.
[110] Crowley MM, Schroeder B, Fredersdorf A, et al. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int. J. Pharm., 2004, 269(2): 509-522.
[111] Millán M, Caraballo I. Effect of drug particle size in ultrasound compacted tablets Continuum percolation model approach. Int. J. Pharm., 2006, 310(1-2): 168-174.
[112] Higuchi T. Mechanism of sustained-action medication-theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52: 1145-1149.
[113] Bastidas JM, Cano E, Mora N. Copper corrosion-simulated uterine solutions. Contraception, 2000, 61(6): 395-399.
[114] Patai K, De′ve′nyi L, Zelko′R. Comparison of surface morphology and composition of intrauterine devices in relation to patient complaints. Contraception, 2004, 70(2): 149-152.
[115] Rizk M, Shaban N, Medhat I, et al. Electron microscopic and chemical study of the deposits formed on the copper and inert IUCDs. Contraception, 1990, 42(6): 643-653.
[116] Patai K, Bere′nyi M, Sipos M, et al. Characterization of Calcified Deposits on Contraceptive Intrauterine Devices. Contraception, 1998, 58(5): 305-308.
[117] F. Zielske, U. J. Koch, R. Badura et al. studies on copper release from copper-T device(T-Cu200) and its influence on sperm migration in vitro. Contraception, 1974, 10(6): 651-666.
[118] Elchalal U, Abramov Y. Uterine biology and the intrauterine device. Adv Drug Delivery Rev 1995, 17:151–164.
[119] Lee NC. Type of intrauterine device and the risk of pelvic inflammatory disease. Obstet. Gynecol, 1983, 62:1–6.
[120] PhD Saeed R. Khan, MD Edward J. Wilkinson. Scanning electron microscopy, X-ray diffraction, and electron microprobe analysis of calcific deposits on intrauterine contraceptive devices. Human Pathology, 1985,16(7):732-738.
[121] Patai K, Bere′nyi M. Incrustation of intrauterine devices (in German). Zentralbl Gynakol, 1982,104:1385–1387.
[122]周红.酸性条件下锌试剂测定铜.贵州化工, 2003, 28(3): 33-34.
[123]吴丽香,赵崇峰,于大勇等.锌试剂-OP显色体系测定原油中的铜.石油化工, 2001, 30(12): 935-937.
[124] J.M. Bastidas, E. Cano, N. Mora. Copper Corrosion-Simulated Uterine Solutions. Contraception, 2000, 61: 395-399.
[125]王莉.宫内节育器作用机制的研究现状.甘肃中医, 2003, 16(1): 6-9.
[126] Petta CA, Amatya R, Farr G. Clinical evaluation of the TCu 380A IUD at six Latin American centers. Contraception, 1994, 50(1): 17-25.
[127] Luukkainen T, Allonen H, Nielsen NCet al. Five years experience of intrauterine contraception with Nova T and the Copper T-200. Am J Obstet Gynecol, 1983, 147: 885-892.
[128]杨文平译.海水中锌腐蚀产物的研究.国外舰船工程, 2005,(4): 19-22
[129]李焰,魏绪钧,冯法伦.热浸镀层的海水全浸腐蚀行为研究.材料保护, 2001, 34(5): 11-12.
[130] A.G.KHOMASSURIDZE, G.I.TSERTSVADZE, T.G.TSERETELI. Intrauterine device and pelvic inflammatory disease. Advance in Contraception, 1997, 13: 71-78.
[131] M.R Joesoef, A.Karundeng. High rate of bacterial vaginosis among woman with intrauterine device in Manado,Indonesia. Contraception, 2001, 64(3): 169-172.
[132] James D Shelton. Risk of clinical pelvic inflammatory disease attributable to an intrauterine device. The lancet, 2001, 357(9254): 443.
[133] Belanger MC, Marois Y, Roy R et al. Selection of a polyurethane membrance for the manufacture of ventricles for a totally implantable artificical heart:blood compatibility and biocompatibility studies. Artifical Organs, 2000, 24(11): 879-888.
[134] Hong J, Larsson A, Ekadahl K.N. et al. Contact between a polymer and whole blood:sequence of events leading to thrombin generation. The Journal of Laboratory and clinical medicine, 2001, 138(2): 139-145.
[135]刘欣,史弘道.医用生物材料血液相容性评价研究概况.透析与人工器官, 2003, 14(1): 40-44.
[136]鲁险锋,赵国梁,高扬等.纳米ZnO改性聚酯抗凝血性能研究.合成纤维工业2005, 2005, 28(3): 13-15.
[137]许海军,赵国梁,王晓春等.纳米ZnO/聚乙二醇改性聚酯的抗凝血性能.聚酯工业, 2006, 19(1): 21-23.
[138] Grasel T G Goodman S L, Cooper S L et al. Platelet shape change and cytoskeletal reorganization on polyurethaneureas. J. Biomed. Mater. Res., 1989, 23: 105-123.
[139] Lelah M D Goodman S L, Lambrecht L K, Cooper S L et al. In vitro versus ex vivo platelet deposition on polymer surfaces. Scan. Electron. Microsc, 1984, 1: 379-390.
[140]蒋书文.钛合金基类金刚石梯度薄膜材料制备及其生物摩擦学性能和血液相容性的研究.博士论文, 2002.
[141]喻凯,陈治清.白蛋白被人体硬组织替代材料吸附后构象的改变.华西口腔医学杂志, 1996, 14(3): 174-176.
[142] Yuh-Lang Lee, Chi-Yun Chen. Surface wettability and platelet adhesion studies on Langmuir Blodgett films. Applied Surface Science, 2003, 207(1-4): 51-62.
[143]王春仁,杨子彬.生物材料表面血浆蛋白的吸附.国外医学:生物医学工程分册, 1995, 18(6): 334-339.
[144]陈宝林,王东安,封麟先等.生物医用高分子材料的血液相容性研究―抗凝血材料的设计.绥化学院学报, 2007, 27(1): 186-188.
[145]张守松,周长忍,邹翰.甲壳糖-聚硅氧烷复合材料研究.高分子材料科学与工程, 1999, 15(3): 163-165.
[146] Shan-Hui Hsu, Cheng-Ming Tang, C.C.Chu-Chieh Lin. Biocompatibility of poly(-caprolactone)/poly(ethylene glycol) diblock copolymers with nanophase separation. Biomaterials, 2004, 25(25): 5593-5601.
[147] Kazunori Kataoka, Teruo Okano, Yasuhisa Sakurai et al. Effect of microphase separated structure of polystyrene/polyamine graft copolymer on adhering rat platelets in vitro. Biomaterials, 1982, 3(4): 237-240.
[148] P. Yang, S. C. H. Kwok, R. K. Y. Fu et al. Structure and properties of annealed amorphous hydrogenated carbon (a-C:H) films for biomedical applications. Surface and Coatings Technology, 2004, 177-178: 747-751.
[149] Nan Huang, Ping Yang, Xuan Cheng et al. Blood compatibility of amorphous titanium oxide films synthesized by ion beam enhanced deposition. Biomaterials, 1998, 19(7-9): 771-776.
[150]霍丹群.肝素化高分子液晶/聚醚氨酯生物材料的研究.博士论文,重庆大学,2004.
[151]高洁,李瑛,刘建平等.活性元宫型365宫内节育器体外释放吲哚美辛的研究.生殖与避孕, 2006, 26(10): 602-605.
[152] Hiroo Maeda, Toshihiko Sugie. Study on accelerated evaluation system for release profiles of covered-rod type silicone formulation using indomethacin as a model drug. Journal of Controlled Release, 2004, 94 (2-3): 337-349.
[153] Xue Huashi, Xu Naixin, Zhang Chendian. Corrosion behavior of copper in a copper bearing intrauterine device in the presence of indomethacin. Contraception, 1998, 57(1): 49-53.
[154]吴昌杰,陈莉.消炎痛硅橡胶缓释系统体外释放率的初步研究.实用医学杂志, 1997, 10(3): 6-8.
[155]毕淑云,宋大千,魏士刚等.用荧光猝灭法研究人血清白蛋白与吲哚美辛的结合反应.吉林大学学报(理学版), 2006, 44(3): 493-496.
[156]徐铜文,何炳林.扩散控制型高分子药膜缓释体系的渗透现象.中国科学(B辑), 1998, 28(2): 178-185.