CN1052402C - 新型低聚寡糖类抗精神病药物 - Google Patents
新型低聚寡糖类抗精神病药物 Download PDFInfo
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Abstract
本发明研制了一种新型、安全、高效的精神病防治药物。
本发明首次发现具有下式(式Ⅰ)的低聚寡糖的中枢神经系统药理作用，并用其作为主要成分制成一类新型抗精神病药物。
Description
本发明涉及低聚寡糖用于抗精神病作用的用途及用低聚寡糖作为主要成分制成的一类新型抗精神病药物。
现有的抗精神病药物，特别是用于治疗抑郁症的药物有三环类药物如阿米替林、丙咪嗪等，四环类药物如麦普替林等以及苯乙肼等单胺氧化酶抑制剂。这些药物均为合成的含氮化合物，各有较明显的毒副作用(陈新谦等《新编药物学》，人民卫生出版社，北京，1990年，256页)。
低聚寡糖是一类安全无毒的天然化合物，30年代以来，国外已将其作为食品、化妆品添加剂使用(日本公开特许公报JP 03 266，937[91 266，937]，PCT Int.Appl.WO 93 00,067)，还有文献报道低聚寡糖的药理学作用，如利尿作用(日本公开特许公报JP 59,110621[84,110,621])，抗衰老作用(Ger.Offen.DE 3,632,791)等。但迄今未见到低聚寡糖对于神经中枢作用的报道。
本发明的目的是研制一种结构类型新、安全、高效的精神病防治药物。
本发明首次发现具有下式(式I)的低聚寡糖有中枢神经系统药理作用，并用其作为主要成分制成一类新型抗精神病药物。
这些低聚寡糖类单体成分分别由1个α-葡萄吡喃糖残基和若干个β-果呋喃糖残基组成，优选的是具有1-8个β-果呋喃糖残基，即式I中n＝1-8。
这种药物可以是各种剂型的，包括口服、注射等，可用低聚寡糖活性物质能接受的载体作为赋形剂。低聚寡糖的用量范围是0.03-200mg/千克体重/日。较好的用量为0.03-50mg/千克体重/日，优选用量为0.05-25mg/千克体重/日。抗抑郁活性试验：
用小白鼠或大白鼠等整体动物模型，采用腹腔注射或经口给药途径测定。动物使用体重20-24克的雌性KM小鼠或体重为180-200克的Wistar大白鼠，雌雄各取半。抗抑郁活性采用小鼠悬尾法、小鼠强迫游泳法及大鼠强迫游泳法等筛选抗抑郁药物的经典方法来测定。被试药物首先测试对动物活动性的影响，再据此选择对活动性没有影响的剂量来测试抗抑郁活性。阳性对照药使用地昔帕明(又名去甲基丙咪嗪，以下简称DMI)。为了解药物的作用机理，采用5-羟色胺酸诱导小鼠甩头法(观察药物对于5-羟色胺神经系统的作用)、小鼠育亨宾致死法(观察药物对去甲肾上腺素神经系统的作用)、去扑吗啡诱导小鼠刻板行为法(观察药物对于多巴胺神经系统的作用)等常规方法，探讨了药物作用机理。
生物活性测得的所有数据均用Dunnett′s方法统计处理。
生物活性测试结果表明，具有式I的各寡糖均有明显的抗抑郁活性，最小有效量为0.0313-25mg/千克体重/日。药物作用机制研究表明。大多寡糖类同时作用于5-羟色胺、多巴胺及去甲肾上腺素神经系统。
实施例：低聚寡糖注射液配方注射液 式I化合物 NaCl 蒸馏水加至1 n＝2 25mg 65mg 10.0ml2 n＝3 25mg 65mg 10.0ml3 n＝4 25mg 65mg 10.0ml4 n＝5 25mg 65mg 10.0ml抗抑郁活性结果(小鼠悬尾实验)：注射液 最小有效剂量(mg/kg) 不动时间减少百分率(％)*1 0.0625 35.92 0.125 58.23 0.0625 44.44 0.0625 39.5DMI(阳性对照) 10.0 63.1*p＜0.05 样本数：10药理作用结果：
小鼠甩头实验 小鼠刻板行为实验 小鼠育亨宾实验
剂量 增加率 剂量 增加率 剂量(死亡数/存活数)
(μg/kg ％) (μg/kg ％) (μg/kg)注射液1 31.3 104.5* 31.3 51.0** 31.3 9/10*注射液2 31.3 124.1* 62.5 301.6* 62.5 5/10*注射液3 31.3 190.9** 无效 无效注射液4 31.3 212.1** 31.3 162.2** 31.3 10/10*DMI 无显著差异 无显著差异 10,000.0 8/10**
*p＜0.05 **p＜0.01 样本数：8-10
Claims (2)
1.式I低聚寡糖在制备抗抑郁的药物中的用途，
其中，n＝1-8。
2.根据权利要求1所述的用途，其中所述药物可是口服或注射剂型。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94103415A CN1052402C (zh) | 1994-04-07 | 1994-04-07 | 新型低聚寡糖类抗精神病药物 |
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| CN94103415A CN1052402C (zh) | 1994-04-07 | 1994-04-07 | 新型低聚寡糖类抗精神病药物 |
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| Publication Number | Publication Date |
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| CN1110143A CN1110143A (zh) | 1995-10-18 |
| CN1052402C true CN1052402C (zh) | 2000-05-17 |
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| CN94103415A Expired - Lifetime CN1052402C (zh) | 1994-04-07 | 1994-04-07 | 新型低聚寡糖类抗精神病药物 |
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| CN115089596A (zh) * | 2022-06-20 | 2022-09-23 | 自然资源部第三海洋研究所 | 新琼寡糖用于制备治疗抑郁症产品的新用途 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59110621A (ja) * | 1982-12-17 | 1984-06-26 | Meiji Seika Kaisha Ltd | 利尿剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59110621A (ja) * | 1982-12-17 | 1984-06-26 | Meiji Seika Kaisha Ltd | 利尿剤 |
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