CN112870235B - 猴头菌粉在制备预防或治疗高血尿酸相关疾病的产品中的应用 - Google Patents
猴头菌粉在制备预防或治疗高血尿酸相关疾病的产品中的应用 Download PDFInfo
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Abstract
本发明公开了一种猴头菌粉在制备预防或治疗高血尿酸相关疾病的产品中的应用，本发明通过招募痛风疾病患者以及健康人在每日三餐饮食中补充猴头菌粉0.5g/餐的摄入，分析肠道菌群的变化以及血液生化数据来确证猴头菌粉对高血尿酸相关疾病的预防和治疗作用。三餐补充饮食猴头菌粉可显著降低血尿酸水平以及血肌酐水平，且肠道微生物群落结构也发现了显著变化，因此，猴头菌粉可在制备具有预防和/或治疗高血尿酸相关疾病的功能食品或药品中应用。
Description
技术领域
本发明属于医药技术领域，尤其涉及一种猴头菌粉在制备预防或治疗高血尿酸相关疾病的产品中的应用。
背景技术
痛风性肾病，即尿酸性肾病，是血尿酸升高引起肾脏内尿酸盐微结晶沉积，引起间质炎症反应，肾小管阻塞及肾单位丧失的肾脏疾病。痛风性肾病起病隐匿，患者常无自觉症状，肾脏本身却发生了病理改变，随着病情的发展，许多患者确诊时己经进入肾功能衰竭期。长期的高尿酸可以导致肾损害，血肌酐升高，慢性肾衰竭，称痛风性肾病；而各种原因导致的慢性肾衰竭，因为尿酸排泄障碍，也会出现高尿酸血症。痛风和高尿酸血症在全球范围内呈增长趋势。目前治疗痛风性肾病的药物多存在不良反应，且对肾脏保护没有明显效果。因此，开发既能缓解痛风疾病症状又能对此类疾病引起的肾损害有保护作用的药品尤为重要。
猴头菌(Hericium erinaceus)，又称猴头菇，隶属于担子菌门、猴头菌科、猴头菌属，是一种名贵的食用和药用真菌。猴头菌粉含有丰富的蛋白质、多糖、微量元素和膳食纤维，脂肪含量较低。猴头菌粉的生物活性成分在治疗消化道相关疾病领域的应用已经有很多报道，如胃损伤、结肠炎、结肠癌等。但关于猴头菌菇粉和/或猴头菌丝体发酵粉用于预防和/或痛风性肾病没有研究和报道的。
发明内容
为解决上述技术问题，本发明提供一种药食同源的猴头菌粉在制备预防或治疗高血尿酸相关疾病的药品中的应用。
本发明的第一个目的是提供猴头菌粉在制备预防或治疗高血尿酸相关疾病的药品中的应用。
进一步地，所述的高血尿酸相关疾病为高尿酸血症、高血压并发高尿酸血症、糖尿病并发高尿酸血症、代谢综合征并发高尿酸血症、动脉粥样硬化并发高尿酸血症、痛风、痛风性关节炎或痛风性肾病。
进一步地，所述的药品为胶囊剂、片剂或菌粉。
进一步地，所述的猴头菌粉的剂量为0.1～1.0g/餐。
进一步地，所述的猴头菌粉通过猴头菌发酵制备得到。
进一步地，所述的猴头菌发酵包括如下步骤：将猴头菌的孢子在种子培养基中培养5～10天得到种子培养液，将种子培养液接种至发酵培养基中进行发酵培养获得含有菌丝体的发酵液。
进一步地，所述的种子培养基包括葡萄糖15～25g/L、酵母提取物5～15g/L、无水磷酸二氢钾2～4g/L和七水硫酸镁1～2g/L。
进一步地，所述的发酵培养基包括葡萄糖5～15g/L、西瓜汁原浆40～60g/L、酵母提取物4～6g/L、豆粉10～20g/L、无水磷酸二氢钾2～4g/L和七水硫酸镁1～2g/L。
进一步地，含有菌丝体的发酵液在4000～6000g离心条件下离心10～30min，得到所述的菌丝体。
进一步地，所述的菌丝体在40～·60℃条件下干燥，干燥后粉碎得到所述的猴头菌粉。
本发明中获得的猴头菌粉中，果糖含量以无水葡萄糖计，含量为5.0％～10.0％，含肽量不得少于5.0％，菌粉置于4℃干燥密封保存备用。
借由上述方案，本发明至少具有以下优点：
本发明通过招募痛风疾病患者以及健康人在每日三餐饮食中补充猴头菌粉0.5g/餐的摄入，分析肠道菌群的变化以及血液生化数据来确证猴头菌粉对高血尿酸相关疾病的预防和治疗作用。三餐补充饮食猴头菌粉可显著降低血尿酸水平以及血肌酐水平，且肠道微生物群落结构也发现了显著变化，因此，猴头菌粉可在制备具有预防和/或治疗高血尿酸相关疾病的药品中应用。
上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合详细说明如后。
附图说明
图1为饮食中补充猴头菌粉摄入对肠道微生物群落结构多样性的影响。
图2为饮食中补充猴头菌粉摄入对血液肾功能生化指标的影响。
具体实施方式
实施例1：
猴头菌丝体发酵菌粉的制备方法，包括以下步骤；
第一步：将猴头菌的孢子放在下述培养物中培养7天(g/L):葡萄糖，20；酵母提取物，10；无水磷酸二氢钾，3；七水硫酸镁，1.5；培养基pH为5；
第二步：7天后将培养液以10％的体积比接种到100L的发酵罐中，发酵体系为(g/L)：葡萄糖，10；西瓜汁原浆，50；酵母提取物，5；豆粉，15；无水磷酸二氢钾，3；七水硫酸镁，1.5；发酵体系原pH为5；
第三步：经过放大体系至1000L发酵后，在5000g离心条件下离心20分钟将猴头菌的菌丝体产物收集，然后进行热风50℃干燥，干燥后将干粉研磨后过100目筛；
第四步：检测所得猴头菌丝体发酵菌粉中，果糖含量以无水葡萄糖计，含量为5.0％～10.0％，含肽量不得少于5.0％，菌粉置于4℃干燥密封保存备用。
实施例2：
猴头菌粉对人肠道微生物的影响
(1)实验对象：40名刚确诊为无症状高尿酸血症痛风患者尚未进行任何药物干预的志愿者；34名健康人。
(2)干预方式：所有人于每日三餐饮食中添加猴头菌粉，剂量为0.5g/餐，食用周期持续7天。分别在食用前和食用第7天时收集所有志愿者的粪便并进行16S rRNA基因高通量测序以研究食用猴头菌粉对肠道微生物的影响。
(3)观察指标：健康人和痛风患者食用猴头菌粉前后肠道微生物在属水平的群落多样性，结果如图1所示。由图可知痛风患者和健康人的肠道菌群在属水平的群落结构差异较大(p<0.001),食用猴头菌粉后，痛风患者与健康人的肠道菌群在属水平的群落结构比较无显著性差异(p>0.05)。三餐饮食猴头菌粉可调节肠道微生物群落结构，恢复痛风患者肠道微生物群落的稳态。
实施例3：
猴头菌粉对高血尿酸患者的治疗作用。
(1)实验对象：招募了32例无症状高尿酸血症痛风患者且为初确诊未进行相关药物干预，所有患者初始血清尿酸水平为517±27μmol/L。
(2)治疗方式：16名患者根据临床指南食进行药物治疗，另外16名进行猴头菌粉食用治疗，剂量为0.8/餐，每日三餐随餐服用。
(3)检测指标：控制血尿酸可以延缓肾损害，根据纳入标准血清尿酸水平的变化来反应猴头菌粉对高血尿酸患者的治疗作用，采用尿酸酶—过氧化物酶偶联法检测，结果如表1所示，食用猴头菌粉可显著降低痛风患者血清尿酸水平。
表1两种治疗方式对痛风患者血清尿酸水平的影响
注：****p＜0.0001值
实施例4：
猴头菌粉预防痛风性肾病的作用
(1)实验对象：招募13名健康志愿者进行为期1个月的食用猴头菌粉。
(2)预防措施：所有人于每日三餐饮食中添加猴头菌粉，剂量为0.5g/餐，食用周期持续30天。分别在食用前和食用第30天时进行静脉采血。
(3)观察指标：血液生化检测了反映肾功能的指标(尿素氮、肌酐、尿酸)，肌酐是我们人体肌肉新陈代谢的物质，而血尿酸是嘌呤代谢的产物，结果如图2所示；血常规检测了血细胞组成，结果如表2所示。健康人食用猴头菌粉30天后不会对血常规指标造成影响，且能一定程度降低体内血尿酸和血肌酐水平。
表2猴头菌粉对血常规指标的影响
| 血常规 | 饮食前(n＝13) | 饮食后(n＝13) | p值 |
| 红细胞(10<sup>9</sup>/L) | 4.848±0.311 | 4.802±0.316 | 0.077 |
| 白细胞(10<sup>9</sup>/L) | 6.522±0.923 | 6.495±1.106 | 0.883 |
| 血红蛋白(g/L) | 144.333±11.448 | 143.250±11.959 | 0.286 |
| 血小板(10<sup>9</sup>/L) | 247.308±35.569 | 251.231±54.104 | 0.564 |
| 淋巴细胞(10<sup>9</sup>/L) | 2.465±0.576 | 2.244±0.417 | 0.052 |
| 单核细胞(10<sup>9</sup>/L) | 0.382±0.061 | 0.389±0.061 | 0.615 |
| 中性粒细胞(10<sup>9</sup>/L) | 3.508±0.613 | 3.705±0.892 | 0.106 |
| 嗜酸性粒细胞(10<sup>9</sup>/L) | 0.150±0.114 | 0.143±0.096 | 0.590 |
以上仅是本发明的优选实施方式，并不用于限制本发明，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和变型，这些改进和变型也应视为本发明的保护范围。
Claims (4)
1.猴头菌粉在制备预防或治疗高血尿酸相关疾病的药品中的应用，其特征在于，所述的猴头菌粉通过猴头菌发酵制备得到；
所述的猴头菌发酵包括如下步骤：将猴头菌的孢子在种子培养基中培养5~10天得到种子培养液，将种子培养液接种至发酵培养基中进行发酵培养获得含有菌丝体的发酵液，将含有菌丝体的发酵液在4000~6000g离心条件下离心10~30min，得到所述的菌丝体，将所述菌丝体在40~60℃条件下干燥，干燥后粉碎得到所述的猴头菌粉；
所述的种子培养基包括葡萄糖15~25 g/L、酵母提取物5~15 g/L、无水磷酸二氢钾2~4g/L和七水硫酸镁1~2 g/L；所述的发酵培养基包括葡萄糖5~15 g/L、西瓜汁原浆40~60 g/L、酵母提取物4~6 g/L、豆粉10~20 g/L、无水磷酸二氢钾2~4 g/L和七水硫酸镁1~2 g/L。
2.根据权利要求1所述的应用，其特征在于，所述的高血尿酸相关疾病为高尿酸血症、高血压并发高尿酸血症、糖尿病并发高尿酸血症、代谢综合征并发高尿酸血症、动脉粥样硬化并发高尿酸血症、痛风、痛风性关节炎或痛风性肾病。
3.根据权利要求1所述的应用，其特征在于，所述的药品为胶囊剂、片剂或菌粉。
4.根据权利要求1所述的应用，其特征在于，所述的猴头菌粉的剂量为0.1~1.0g/餐。
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