CN104208058A - 樱黄素-3′-磺酸钠在制备治疗男性不育症的药物中的应用 - Google Patents
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Abstract
本发明公开了樱黄素-3′-磺酸钠在制备治疗男性不育症的药物中的应用。由于樱黄素-3′-磺酸钠可以提高生精障碍模型大鼠的精子密度和精子活率，降低其精子畸形率，因此本发明将其用于制备增强雄性动物或人类生精功能的药物或保健品，为治疗男性不育症提供了新的候选药物，具有较好的经济意义。
Description
技术领域
本发明属于医药技术领域，具体而言，涉及樱黄素-3′-磺酸钠在制备治疗男性不育症的药物中的应用。
背景技术
近50年来，男性的精液质量不断下降，导致暂时或永久性的不育，或者胎儿质量下降，给个人造成巨大的精神压力，给家庭带来极大的痛苦，甚至酿成生活悲剧，成为必须重视的社会问题。
1998年国家计科所曾在对1981-1996年16年间公开发表的，来源于北京、上海、天津等39个市县、256份文献共11726人的数据进行分析后发现，精液质量正以每年1％的速度下降，而且下降速度越来越快。2002年成都计划生育技术指导所李刚等人在完成对成都地区12所高校295名在校大学生调查后，在《现代预防医学》杂志上发表《成都地区大学生精子质量及抗精子抗体的调查》的论文，揭示精子质量异常者99人占33.56％；扩大范围至14所高校549名在校大学生调查后，在2003年12月的《中华男科学》上发表了《成都地区549例大学生精子质量调查》的论文，揭示精子质量异常者204人占37.16％，并惊呼“将来不育症的发生率可能高于目前文献报道的12％-16％，甚至可超1/3”。 精子质量下降而导致的男性不育症，必须得到有效的防治，否则影响人类自身繁殖的正常延续。
CN101020684A公开了樱黄素-3′-磺酸钠及其制备方法，其工艺包括：在溶剂中加入反应物樱黄素，再加入磺化剂，反应物与磺化剂进行化学反应，得到本发明化合物。另外，该专利还公开了樱黄素-3′-磺酸钠在制备治疗高脂血症和脂肪肝症的药物中的应用。CN101904836A公开了芒柄花素-3′-磺酸钠在制备治疗或预防心血管疾病的药物中的应用，具体涉及芒柄花素-3′-磺酸钠在制备治疗或预防冠心病、心绞痛或心肌梗塞的药物中的应用。
通过检索国内外现有技术，目前尚没有文献报道樱黄素-3′-磺酸钠具有增强雄性动物或人类生精功能的生物活性。
发明内容
少精或弱精等精子质量异常是男性不育的主要原因。本发明人在试验中意外的发现，樱黄素-3′-磺酸钠具有对环磷酰胺所致生精障碍的保护作用，进而通过深入研究后提供了该药物的制药用途，实现了本发明的目的。
具体地，本发明提供了如下制药用途：
樱黄素-3′-磺酸钠在制备治疗男性不育症的药物中的应用，所述的男性不育症是少精或弱精引起的男性不育症。
樱黄素-3′-磺酸钠在制备治疗无精症或少精症的药物中的应用。
樱黄素-3′-磺酸钠在制备治疗弱精症的药物中的应用。
樱黄素-3′-磺酸钠在制备增强雄性动物或人类生精功能的药物或保健品中的应用。
基于樱黄素-3′-磺酸钠可以提高生精障碍模型大鼠的精子密度和精子活率，降低其精子畸形率，因此本发明首次提出将樱黄素-3′-磺酸钠用于制备增强雄性动物或人类生精功能的药物或保健品，为治疗男性不育症提供了新的候选药物，具有较好的经济意义。
发明内容
环磷酰胺是一种烷化剂类药物，是常用的抗肿瘤药物和免疫抑制剂，对男性生殖系统的损伤和对后代的潜在致畸危险已经引起医患双方的高度关注。临床研究显示，儿童期因白血病、肿瘤、自身免疫性疾病接受环磷酰胺治疗的男性患儿，成年后80.2％～92．6％为无精症或少精症，目前已广泛采用环磷酰胺制备生精障碍模型。本发明通过环磷酰胺所致生精障碍模型，进一步研究了樱黄素-3′-磺酸钠的生物活性，从而为该药物治疗男性不育方面提供试验依据。具体的试验过程如下：
SPF级健康Bal b/c雄性小鼠48只，体重(20±2)g，适应性喂养后，随即分为如下四组：正常对照组、模型对照组、药物高剂量组、药物低剂量组，每组12只。除正常对照组外，其余各组小鼠腹腔注射环磷酰胺75mg/kg/d，连续5d，制备生精障碍动物模型。模型制备后，药物高剂量组、低剂量组分别给予樱黄素-3′-磺酸钠200mg/kg、100mg/kg灌胃，正常对照组和模型对照组灌胃给予等体积生理盐水，每天1次，共计灌胃4周。
将盛有10 mL精子BWW培养液（陈德宇，抗精液抗体对精子线粒体功能的影响，汕头大学医学院学报，2008年第1期）的试管置于恒温水浴箱中预热至37℃，取单侧附睾去除结缔组织和脂肪，眼科剪剪碎组织并放入试管中，37℃静止l0min，待精子充分游离后，取1滴滴于血细胞计数板上，计算精子密度、精子活率、精子畸形率。
通过表1的试验结果可以看出，模型对照组小鼠精子密度、精子活率显著低于正常对照组(P＜0.01)，精子畸形率显著高于正常对照组(P＜0.01)。樱黄素-3′-磺酸钠各剂量组与模型对照组相比均显著提高精子密度(P＜0.01)，精子活率显著提高(P＜0.01)，精子畸形率降低(P＜0.01)。
表l 樱黄素-3′-磺酸钠对精子密度、活率及畸形率的影响
| 组别 | n | 精子密度（×1000000/mL） | 精子活率（%） | 精子畸形率（%） |
| 正常对照组 | 12 | 73.85±12.03 | 82.49±4.71 | 5.54±0.81 |
| 模型对照组 | 12 | 25.41±5.42■■ | 33.62±6.43■■ | 14.42±1.60■■ |
| 药物低剂量组 | 12 | 45.28±9.26★★ | 62.24±9.36★★ | 8.17±1.46★★ |
| 药物高剂量组 | 12 | 59.42±11.81★★ | 67.17±10.11★★ | 5.89±1.25★★ |
与正常对照组比较，■ P＜0.05；■■ P＜0.01
与模型对照组比较，★ P＜0.05；★★ P＜0.01。
Claims (4)
1.樱黄素-3′-磺酸钠在制备治疗男性不育症的药物中的应用，所述的男性不育症是少精或弱精引起的男性不育症。
2.樱黄素-3′-磺酸钠在制备治疗无精症或少精症的药物中的应用。
3.樱黄素-3′-磺酸钠在制备治疗弱精症的药物中的应用。
4.樱黄素-3′-磺酸钠在制备增强雄性动物或人类生精功能的药物或保健品中的应用。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101020684A (zh) * | 2007-01-31 | 2007-08-22 | 陕西师范大学 | 芒柄花素－3′－磺酸钠、樱黄素－3′－磺酸钠及其制备方法和药物用途 |
| CN101669935A (zh) * | 2005-10-25 | 2010-03-17 | 上海医药工业研究院 | 一种含樱黄素的药物组合物及其在医药上的应用 |
| CN102250049A (zh) * | 2011-06-07 | 2011-11-23 | 南京泽朗农业发展有限公司 | 一种高纯度樱黄素的制备方法 |
| WO2014017741A1 (ko) * | 2012-07-25 | 2014-01-30 | 상지대학교 산학협력단 | 프루네틴을 유효성분으로 함유하는 비만 또는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669935A (zh) * | 2005-10-25 | 2010-03-17 | 上海医药工业研究院 | 一种含樱黄素的药物组合物及其在医药上的应用 |
| CN101020684A (zh) * | 2007-01-31 | 2007-08-22 | 陕西师范大学 | 芒柄花素－3′－磺酸钠、樱黄素－3′－磺酸钠及其制备方法和药物用途 |
| CN102250049A (zh) * | 2011-06-07 | 2011-11-23 | 南京泽朗农业发展有限公司 | 一种高纯度樱黄素的制备方法 |
| WO2014017741A1 (ko) * | 2012-07-25 | 2014-01-30 | 상지대학교 산학협력단 | 프루네틴을 유효성분으로 함유하는 비만 또는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
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Effective date of registration: 20160909 Address after: Jinghu District of Anhui city of Wuhu province Jiuhua Road 241000 No. 263 Wuhu Second People's Hospital Patentee after: Wuhu No.2 Peoples Hospital Address before: Jinghu District of Anhui city of Wuhu province Jiuhua Road 241000 No. 263 Wuhu Second People's Hospital Patentee before: Li Jian |
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Effective date of registration: 20190904 Address after: Room 1115, 1187 Aksu Road, Jiading District, Shanghai, 201801 Patentee after: Zhaoyuan Pharmaceutical Co., Ltd. Address before: 241000 Wuhu Second People's Hospital, 263 Jiuhua Middle Road, Jinghu District, Wuhu City, Anhui Province Patentee before: Wuhu No.2 Peoples Hospital |