醋酸亮丙瑞林注射液的高效液相色谱分析

目的　建立醋酸亮丙瑞林注射液中亮丙瑞林及杂质的测定方法。方法　采用高效液相色谱法。色谱柱 :Kromasil C₁₈-ODS(150mm×4.6mm ,5 μm)不锈钢柱 ;流动相 :水相 (800ml水 +21ml三乙胺 ,磷酸调pH 3.0 ,加水至 1000ml)-有机相 (正丙醇-乙腈 =2∶3)为 84∶16 ;检测波长:220nm ;含量测定采用外标法 ,杂质检查采用自身对照法。结果　在优化的色谱条件下 ,亮丙瑞林及杂质间均能完全分离 ,注射液辅料不干扰测定 ,亮丙瑞林线性范围 9.198～ 82.780 μg·ml^-1,检测限 1.93ng(S/N =3) ,含量测定的回收率 98.74%～100.3% ,RSD<1.5%。结论　该法专属性强,操作方便 ,结果准确 ,重现性好。     

小金胶囊联合注射用醋酸亮丙瑞林微球治疗卵巢巧克力囊肿的临床研究

目的 探讨小金胶囊联合注射用醋酸亮丙瑞林微球治疗卵巢巧克力囊肿的临床效果。方法 选取2015年5月—2017年1月咸阳市第一人民医院收治的116例卵巢巧克力囊肿腹腔镜手术后患者作为研究对象,前瞻性随机分为治疗组及对照组,每组58例。对照组在术后首次月经来潮第1天皮下注射给予注射用醋酸亮丙瑞林微球。治疗组则在对照组的基础上另口服给予小金胶囊,5粒/次,2次/d。两组均连续治疗6个月,并随访1年。观察两组的临床疗效,比较两组性激素指标［雌激素（E2）、卵泡刺激素（FSH）及黄体生成素（LH）］,子宫动脉血流参数［搏动指数（PI）、收缩期峰值流速/舒张末期流速比值（S/D）及阻力指数（RI）］,卵巢巧克力囊肿标记物水平［抗子宫内膜抗体（EMAb）、基质金属蛋白酶-3（MMP-3）,前列腺素F2α（PGF2α）及核因子κB（NF-κB）］,生活质量指标（生理领域、环境领域、社会关系领域及生活领域评分）和1年复发率。结果 治疗后,治疗组总有效率明显高于对照组（P<0.05）。治疗后,两组性激素指标（E2、FSH及LH）,子宫动脉血流参数（PI、S/D及RI）,卵巢巧克力囊肿标记物水平（EMAb、MMP-3,PGF2α及NF-κB）,生活质量指标（生理领域、环境领域、社会关系领域及生活领域评分）均显著得到改善,且治疗组上述指标的改善程度均明显优于对照组（P<0.05）。随访1年,治疗组复发率明显低于对照组（P<0.05）。结论 小金胶囊联合注射用醋酸亮丙瑞林微球治疗卵巢巧克力囊肿具有较好的临床疗效,值得进行深入研究。     

止痛化癥胶囊联合亮丙瑞林治疗子宫内膜异位症的疗效观察

目的 探究止痛化癥胶囊联合亮丙瑞林治疗子宫内膜异位症的临床疗效。方法 选取2014年1月-2014年7月鄂州市中医医院妇产科收治的子宫内膜异位症患者98例,随机分为对照组和治疗组,每组各49例。对照组皮下注射注射用醋酸亮丙瑞林微球,3.75 mg/次,4周/次,若患者体质量<50 kg,则注射剂量减少50%。治疗组在对照组基础上口服止痛化癥胶囊,4粒/次,2次/d,月经期间停止服用。3个月为1个疗程,连续治疗2个疗程。观察两组的临床疗效,同时比较两组治疗前后促卵泡生成素(FSH)、黄体生成激素(LH)、雌二醇(E₂)、子宫体积、CA₁₂₅、Kupperman评分的变化。比较两组患者绝经症状发生情况。结果 治疗后,对照组和治疗组的总有效率分别为77.55%、91.84%,两组比较差异具有统计学意义(P < 0.05)。治疗后,两组FSH、LH、E₂、子宫体积、CA₁₂₅水平、Kupperman评分均显著降低,同组治疗前后差异具有统计学意义(P < 0.05);且治疗组这些指标的降低程度优于对照组,两组比较差异具有统计学意义(P < 0.05)。治疗组潮热出汗、感觉异常、失眠、情绪波动、抑郁、眩晕、疲乏、骨关节痛、头痛、心悸、皮肤蚊走感、泌尿感染、性生活障碍发生例数均显著低于对照组,两组比较差异具有统计学意义(P < 0.05)。治疗后,两组患者痛经、盆腔痛、性交痛的VAS评分均显著降低,同组治疗前后差异具有统计学意义(P < 0.05);且治疗后,治疗组痛经、盆腔痛的VAS评分低于对照组,两组比较差异具有统计学意义(P < 0.05)。结论 痛化癥胶囊联合亮丙瑞林治疗子宫内膜异位症具有较好的临床疗效,可降低患者FSH、LH、E₂水平和VAS评分,改善患者绝经症状,具有一定的临床推广应用价值。     

Injection systems for two luteinising hormone-releasing hormone agonists: A comparative assessment of administration times and nurses’ perceptions

The aim of this study was to compare the speed of administration (preparation and delivery) and nurses' perceived ease of use and relative safety of two injection systems used to administer luteinising hormone-releasing hormone agonists: a depot system used to administer goserelin acetate ('Zoladex', AstraZeneca) and a vial system used to administer leuprorelin acetate ('Prostap', Wyeth). This was a randomised, crossover study with 82 volunteer nurses (50 pre-registration and 32 post-registration). All nurses were timed in the administration of both systems and all were required to assess the two systems by completing a questionnaire. Results indicate that both pre- and post-registration nurses administered the depot system in less time than the vial system. Overall mean times for administration of the depot system and the vial system were 1.70 and 3.34min, respectively. In questionnaire responses, significantly more nurses thought that the depot system had 'good safety precautions' compared with the vial system (85% versus 40%; P<0.001) and significantly more nurses also expressed a preference for the depot system (58% versus 42%; P=0.036). In conclusion, this study demonstrates that nurses prefer the one-step depot system used to administer goserelin acetate over the vial system used to administer leuprorelin acetate.     

腹腔镜手术前后联合醋酸亮丙瑞林治疗子宫内膜异位症的比较研究

目的探讨腹腔镜手术与促性腺激素释放激素激动剂（GnRH-a）醋酸亮丙瑞林联合治疗子宫内膜异位症（endometriosis,EM）的临床价值。方法回顾性分析2004年1月~2008年11月395例EM的临床资料,A组133例为腹腔镜术前使用醋酸亮丙瑞林,3.75 mg皮下注射,每28天一次,3个月后再手术;B组150例为腹腔镜术后使用醋酸亮丙瑞林3个月;C组（对照组）112例单纯行腹腔镜手术。比较三组术中情况及远期预后。结果 （1）A组手术时间及术中出血量较B组及C组明显减少[手术时间：A组（146.8±42.5）min、B组（254.4±51.2）min、C组（243.5±48.8）min,术中出血量A组（76.4±31.2）ml、B组（110.7±29.9）ml、C组（101.3±35.4）ml,P均=0.000]。（2）较之C组,A组及B组的总有效率均显著升高,复发率均明显下降（总有效率：C组47.1%、A组75.6%、B组77.9%,复发率：C组37.5%、A组13.0%、B组12.2%,P均=0.000）,A组与B组之间比较无统计学差异（P=0.671,0.849）。（3）随访2年,三组妊娠率比较,差异无统计学意义[A组47.6%（20/42）,B组51.8%（29/56）,C组37.5%（15/40）,P=0.377]。结论较之单纯腹腔镜手术治疗,腹腔镜手术联合GnRH-a治疗EM能提高有效率,降低复发率,但不能明显提高妊娠率。腹腔镜手术前或手术后用药疗效相似,但术前用药更有利于手术实施。     

Effects of fadrozole and leuprorelin acetate on aromatase activity and cell proliferation in a human breast cancer cell line (SK-BR-3)

Background. In recent years, aromatase inhibitors have been used to treat hormone-dependent breast cancer in postmenopausal women. Although gonadotropin-releasing hormone (GnRH) agonists inhibit the growth of breast cancers by estrogen deprivation, it is not known whether GnRH agonists have a direct effect on breast cancer cells. In the present study, we examined the direct effect of a GnRH agonist (leuprorelin acetate) on aromatase activity in a human breast cancer cell line, SK-BR-3. We also studied the synergistic effect of fadrozole (an aromatase inhibitor) and leuprorelin acetate on aromatase activity and cell proliferation in SK-BR-3 cells. Methods. Aromatase activity was determined by measuring [³H] water released upon the conversion of [1β-³H] androstenedione to estrone. Cell proliferation was estimated by determining the incorporation of 5-bromo-2′-deoxyuridine in cellular DNA (cell proliferation assay system). Results. Aromatase activity in SK-BR-3 was inhibited by fadrozole. In addition, SK-BR-3 aromatase activity was inhibited by leuprorelin acetate. Stimulation of cell proliferation by estradiol (10 nM) and testosterone (20 nM) was almost completely inhibited by the addition of an estrogen receptor antagonist, ICI 182780 (10 nM), and fadrozole (1 nM). When both these compounds were added, the most potent inhibition of aromatase activity (fadrozole, 0.1 nM; leuprorelin acetate, 1 nM) and cell proliferation (fadrozole, 10 nM; leuprorelin acetate, 100 nM) was observed. Conclusions. These results lead us to the conclusion that combination therapy with an aromatase inhibitor and a GnRH agonist may provide a new treatment for both pre- and postmenopausal patients with hormone-dependent breast cancer. Received: October 26, 1999 / Accepted: January 26, 2000     

HPLC梯度洗脱法测定醋酸亮丙瑞林中醋酸的含量

目的 测定醋酸亮丙瑞林中醋酸的含量。方法采用HPLC梯度洗脱法,检测波长210nm,流动相为甲醇和磷酸盐缓冲液。结果平均加样回收率为99．36％,RSD=0．75％。结论此方法可行。     

知母皂苷元对性早熟大鼠下丘脑Kiss-1和GPR54mRNA表达的影响

目的 探讨知母皂苷元对性早熟大鼠的治疗作用及可能的作用机制.方法 将24只SD大鼠分为正常组、模型组、亮丙瑞林组和知母皂苷元组,每组6只.5日龄大鼠皮下注射达那唑300μg,建立性早熟模型,造模10d后进行药物干预.采用苏木精-伊红(HE)染色观察子宫和卵巢发育情况;酶联免疫吸附试验(ELISA)法测定血清黄体生成素(...     

Sex Hormone Dependency of Diethylnitrosamine-induced Liver Tumors in Mice and Chemoprevention by Leuprorelin

The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3FJ mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 μg/g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E₂ pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm ( P <0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and/or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors.     

三维腹腔镜手术联合醋酸亮丙瑞林治疗盆腔深部浸润型子宫内膜异位症疗效观察

目的 探讨三维(3D)腹腔镜手术联合促性腺激素释放激素激动剂(GnRH-a)治疗盆腔深部浸润型子宫内膜异位症(DIE)的疗效.方法 选取医院2015年7月至2018年7月收治的行3D腹腔镜手术患者110例,分为观察组和对照组,各55例.观察组予皮下注射醋酸亮丙瑞林微球治疗,对照组予孕三烯酮治疗,均持续治疗6个月.结果 ...