阅读说明：本技术 加波沙朵在制备用于治疗阿尔茨海默氏病的药物中的应用以及药物组合物 (Use of gaboxadol for the treatment of alzheimer's disease and pharmaceutical compositions ) 是由 王建枝 郑杰 于 2019-11-19 设计创作，主要内容包括：本发明涉及药物化学领域,具体涉及加波沙朵在制备用于治疗阿尔茨海默氏病的药物中的应用以及药物组合物。该药物组合物含有加波沙朵以及药学上可接受的辅料。按照本发明,加波沙朵可以促进AD小鼠的海马神经元新生,降低tau蛋白的过度磷酸化及异常聚集,改善认知功能。(The present invention relates to the field of medicinal chemistry, in particular to the use of gaboxadol for the preparation of a medicament for the treatment of alzheimer's disease and a pharmaceutical composition. The pharmaceutical composition contains gaboxadol and pharmaceutically acceptable excipients. According to the invention, gaboxadol can promote the regeneration of hippocampal neurons of AD mice, reduce hyperphosphorylation and abnormal aggregation of tau protein, and improve cognitive function.)

1. Use of gaboxadol for the preparation of a medicament for the treatment of alzheimer's disease.

2. A pharmaceutical composition for treating alzheimer's disease comprising gaboxadol and a pharmaceutically acceptable excipient.

3. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition is in the form of a tablet, a pill, a granule, a powder, a capsule, a syrup, an emulsion, an injection or a suspension.

Technical Field

The present invention relates to the field of medicinal chemistry, in particular to the use of gaboxadol for the preparation of a medicament for the treatment of alzheimer's disease and a pharmaceutical composition.

Background

Alzheimer Disease (AD) is a degenerative disease of the central nervous system with progressive cognitive dysfunction as the major clinical manifestation, the most common type of dementia. The anti-AD medicaments which are approved and widely used clinically belong to symptomatic treatment, and can not change the disease process of progressive AD, so that the research and development of new anti-AD medicaments have great scientific and social significance.

4,5,6, 7-tetrahydroisooxazolo- [5,4-c ] pyridin-3-ol, also known as gaboxadol, is the first anti-insomnia drug designed by taking GABA-A receptors outside brain synapses as targets, has higher affinity with GABA A receptors containing delta subunits, and is a specific agonist thereof. The structural formula of gaboxadol is shown as formula I, which has different action mode with traditional benzodiazepine medicine. Gaboxadol is commonly used in the study of analgesics, anesthetics, anticonvulsants, and food suppressants, however, there is no report in the literature on the use of gaboxadol in alzheimer's disease.

Disclosure of Invention

The following describes in detail specific embodiments of the present invention. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.

The invention aims to provide a novel medical application of gaboxadol, in particular to application of gaboxadol in preparing medicines for treating Alzheimer's disease and a pharmaceutical composition.

In a first aspect, the invention provides the use of gaboxadol for preparing a medicament for treating alzheimer's disease.

In a second aspect, the invention provides a pharmaceutical composition for the treatment of alzheimer's disease comprising gaboxadol and a pharmaceutically acceptable excipient.

In the present invention, the pharmaceutically acceptable adjuvant may be an adjuvant conventionally used in the art.

In the present invention, the dosage form of the pharmaceutical composition may be a solid dosage form and a liquid dosage form conventionally used in the art. In specific embodiments, the pharmaceutical composition may be in the form of tablets, pills, granules, powders, capsules, syrups, emulsions, injections or suspensions. Various dosage forms of the pharmaceutical composition may be prepared by methods known in the art.

The inventor discovers through animal experiments in the research process that gaboxadol can effectively prevent the reduction of hippocampal neuron neogenesis of AD mice, and hardly influences the hippocampal neuron neogenesis of normal mice; can effectively reduce hyperphosphorylation and abnormal aggregation of tau protein in hippocampal dentate gyrus region of AD mice, and hardly influences the phosphorylation level of tau protein of normal mice; can effectively improve the learning and memory functions of AD mice, and can not influence the cognitive function of normal mice.

Drawings

FIG. 1 shows the observation of mouse brain sections;

FIG. 2 shows the results of the measurement of the dendritic length and the number of DCX-positive cells in mice;

FIG. 3 shows the results of the detection of phosphorylated tau protein and total tau protein in mice;

FIG. 4 shows the results of the detection of abnormal aggregation and phosphorylation of mouse tau protein;

FIG. 5 shows a schematic representation of the mouse object-location identification assay process;

FIG. 6 shows a heat map of the exploration trajectory of a mouse during an object-location identification trial;

figure 7 shows the preference scores of mice for object B during the object-location identification test.

Detailed Description