CN111588729A - β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用 - Google Patents
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Abstract
本发明公开了β‑烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,涉及预防脱发或促进毛发生长产品技术领域,本发明的研究结果显示,整个试验周期内对照组与试验组小鼠的体重没有显著差异,小鼠生长状况良好,说明NMN无毒副作用;与空白组和模型组相比,经高剂量灌胃8周后,小鼠毛发生长更为致密,高剂量组的脱毛区真皮层毛囊数目轻度减少,残存毛囊结构基本完整,皮脂腺略有减少,而低剂量组对此改善不明显,提示NMN可促进脱毛小鼠毛发生长的作用。
Description
技术领域
本发明涉及预防脱发或促进毛发生长产品技术领域,特别涉及β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用。
背景技术
β-烟酰胺单核苷酸(NMN)全名nicotinamide mononucleotide,即烟酰胺单核苷酸,是一种自然存在的生物活性核苷酸,NMN有2种不规则存在形式,α和β;β异构体是NMN的活性形式,分子量为334.221g/mol。在日常食物中分布较广,蔬菜如花椰菜(0.25–1.12mgNMN/100gm)和大白菜(0.0–0.90mg NMN/100gm),水果如鳄梨(0.36–1.60mg NMN/100gm)、西红柿(0.26–0.30mg NMN/100gm),肉类如生牛肉(0.06–0.42mg NMN/100gm)都含有丰富的NMN。
NMN是NAD+的前体,其功能也主要通过NAD+体现,NAD+具体参与的生理反应主要有以下几种:生长、DNA修复(PARPs介导)、SIRTs蛋白、NADP(H)合成。在衰老过程中NAD+的下降被认为是导致疾病和残疾的主要原因,如听力和视力丧失,认知和运动功能障碍,免疫缺陷,自身免疫炎症反应失调导致的关节炎、代谢障碍和心血管疾病。因此,补充NMN提高了体内NAD+含量,从而延缓、改善、防止衰老相关的多种表型,或年龄诱导的代谢紊乱、老年疾病等。
目前,毛发脱落和脱发是人们的常见问题。超过40%的男性和接近15%的女性会发生一定程度的毛发脱落或脱发。脱发有多方面的诱因,在男性脱发人群中,雄激素性秃发,占所有毛发脱落的95%以上,睾酮和二氢睾酮水平扮演了重要角色。简单地说,个体的雄激素水平越高则越容易脱发。
遗传的男性型脱发是最常见的脱发形式:其表现是头发数量减少,甚至秃发。急剧的脱发可能与化学疗法、压力、严重的营养不良、缺铁、内分泌紊乱、艾滋病或强烈的辐射有关。簇状脱发似乎由自身免疫(细胞调节机制)引起,其特征是在身体一个或多个地方形成大小不同的“斑”。秃头属于一种簇状脱发扩展至整个头皮的形式,而全秃属于簇状脱发扩展至整个身体的形式。从机理上看,在所有的脱发形式中,毛发脱落直接与能力减弱相关,毛囊进入毛发生长初期减慢或不能进入毛发生长初期,或不能使毛囊维持在毛发生长初期,因此毛干的形成减少、减慢或者完全停止。毛发可能在生长初期阶段还没达到充分生长时便进入毛发生长中期阶段,因此形成持久的毛发短且稀的状态(即:毛发变少)由于目前还不能再生新的毛囊,治疗方法集中于保存它们。
目前常见的治疗方法包括局部治疗、药物治疗和毛发修复手术。采用米诺地尔或非那雄胺等药物局部和口服治疗能有效治疗某些个体的雄激素性秃发,但不是对所有个体有效。尽管有效,但这两种药物有显著缺点。米诺地尔除了对于大多数人来说是昂贵的,它还是血管扩张药,如果其多余量被通过皮肤吸收还可造成心率或血压改变和胸痛。在男性中,非那雄胺生发剂可造成性功能障碍、乳腺压痛,并有可能造成前列腺肥大。尽管毛发修复手术可能是有效的,但它及其痛苦且花费巨大。因此需要能有效刺激毛发生长、费用经济且几乎没有不良副作用的新物质。
发明内容
本发明提供了β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,解决现有的毛发脱落和脱发治疗效果不佳且具有副作用的问题。
为了解决上述技术问题,本发明的技术方案为:
β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用。
优选的,所述β-烟酰胺单核苷酸的使用剂量为1.0~10.0mg/kg/d。
优选的,所述预防脱发或促进毛发生长产品为预防脱发或促进毛发生长药物、预防脱发或促进毛发生长保健品或预防脱发或促进毛发生长营养食品。
优选的,所述预防脱发或促进毛发生长药物为口服制剂、静脉注射剂、吸入剂或鼻吹剂。
优选的,所述预防脱发或促进毛发生长药物为固体制剂或液体制剂。
优选的,所述预防脱发或促进毛发生长药物为片剂、胶囊剂、丸剂或口服液。
优选的,所述预防脱发或促进毛发生长药物为立即释放剂型或缓慢释放剂型。
采用上述技术方案,本发明的研究结果显示,整个试验周期内对照组与试验组小鼠的体重没有显著差异,小鼠生长状况良好,说明NMN无毒副作用;与空白组和模型组相比,经高剂量灌胃8周后,小鼠毛发生长更为致密,高剂量组的脱毛区真皮层毛囊数目轻度减少,残存毛囊结构基本完整,皮脂腺略有减少,而低剂量组对此改善不明显,提示NMN可促进脱毛小鼠毛发生长的作用。
附图说明
图1为脱毛小鼠脱毛区皮肤组织病理形态学的变化图。
具体实施方式
下面结合附图对本发明的具体实施方式作进一步说明。在此需要说明的是,对于这些实施方式的说明用于帮助理解本发明,但并不构成对本发明的限定。此外,下面所描述的本发明各个实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互组合。
实施例
一、材料:
1、动物:SPF级雄性小鼠,体重18-20g
2、样品:NMN(β-烟酰胺单核苷酸)
3、仪器:奥林巴斯显微镜,电镜,单反相机
二、试验方法:
1、模型制备:在小鼠脱毛区单次皮下注射环磷酰胺150mg·kg-1,建立小鼠脱毛模型。
2、分组给药:根据随机数字表将小鼠分为4组:模型组、空白组和低、高2个剂量组,每组8只。模型组,造模后不做任何处理,任其自然生长;空白组,给予生理盐水灌胃;低、高2个剂量组灌胃给予NMN水溶液灌胃,62和310mg/kg/d,连续8周。
3、分别在给药前1天和给药后1,2,8周,通过肉眼观察各组小鼠的脱毛区毛发生长情况,用佳能单反相机图像采集、保存备用。
4、HE染色观察毛囊形态学及数目变化,分别在给药后1,2,8周,每组随机选取小鼠各2只,立即处死,取其脱毛区域皮肤组织。经10%福尔马林固定,常规石蜡包埋,切片,切片厚4-5um,零下80℃下保存备用。用氏HE染色方法,对脱毛区域皮肤组织进行染色,梯度乙醇脱水,中性树胶封片,在各个时间点,随机选取5个高倍视野(*400)进行毛囊计数,取其平均值。
5、结果用x±s表示,用SPSS17.0统计软件分析数据,组间比较应用单因素方差分析。
三、试验结果:
1、体重变化和毛发生长情况
给药前,各组小鼠脱毛区已有毛发自然生长,呈灰色。诱导脱毛至实验结束,各组小鼠体重无明显变化(P>0.05)。给药1周后,各组小鼠脱毛程度最为严重,背部毛发基本脱尽,皮肤呈粉色。给药2周后,小鼠脱毛区局部皮肤由粉色逐渐转变成灰黑色,与模型组和空白组相比,高剂量组的小鼠脱毛区皮肤灰黑色区域明显增大;而低剂量组的灰黑色区域变化无明显区别。给药8周后,各组小鼠脱毛区呈黑色,且已有较多毛发逐渐长出、伸长。与模型组和空白组比较,高剂量组的毛发生长更为致密;而低剂量组致密程度不明显。
由下表可以看出,整个试验周期内对照组与试验组小鼠的体重没有显著差异,小鼠生长状况良好,说明NMN无毒副作用。
2、NMN对脱毛小鼠脱毛区毛囊数目变化的影响
结果如下表所示,脱毛后,各组小鼠毛囊数目逐渐减少。在各时间点,与模型组与空白组相比,高剂量组的毛囊数目明显增加,差异有统计学意义(P<0.05);而低剂量组,虽略有增加,但差异无统计学意义(P>0.05)。
与模型组比较,*P<0.05;与空白组比较,#P<0.05
3、NMN对脱毛小鼠脱毛区皮肤组织病理形态学变化的影响
结果如图1所示,给药2周后,模型组和空白组,脱毛区真皮层毛囊结构基本完整,但毛囊管变得膨大,呈退行性中期改变。毛囊数目、毛囊细胞黑素形成程度,与模型组和空白组比较,高剂量组明显增多,而低剂量组无明显差异。给药8周后,模型组和空白组,脱毛区真皮层毛囊数目重度减少,分布稀疏,毛囊细小,皮脂腺明显减少。与模型组和空白组相比,高剂量组的脱毛区真皮层毛囊数目轻度减少,残存毛囊结构基本完整,皮脂腺略有减少;而低剂量组无明显改善。
本研究结果显示,整个试验周期内对照组与试验组小鼠的体重没有显著差异,小鼠生长状况良好,说明NMN无毒副作用;与空白组和模型组相比,经高剂量灌胃8周后,小鼠毛发生长更为致密,高剂量组的脱毛区真皮层毛囊数目轻度减少,残存毛囊结构基本完整,皮脂腺略有减少,而低剂量组对此改善不明显,提示NMN可促进脱毛小鼠毛发生长的作用。
以上结合附图对本发明的实施方式作了详细说明,但本发明不限于所描述的实施方式。对于本领域的技术人员而言,在不脱离本发明原理和精神的情况下,对这些实施方式进行多种变化、修改、替换和变型,仍落入本发明的保护范围内。
Claims (7)
1.β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用。
2.根据权利要求1所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:所述β-烟酰胺单核苷酸的使用剂量为1.0~10.0mg/kg/d。
3.根据权利要求1所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:所述预防脱发或促进毛发生长产品为预防脱发或促进毛发生长药物、预防脱发或促进毛发生长保健品或预防脱发或促进毛发生长营养食品。
4.根据权利要求3所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:所述预防脱发或促进毛发生长药物为口服制剂、静脉注射剂、吸入剂或鼻吹剂。
5.根据权利要求3所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:所述预防脱发或促进毛发生长药物为固体制剂或液体制剂。
6.根据权利要求3所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:其特征在于:所述预防脱发或促进毛发生长药物为片剂、胶囊剂、丸剂或口服液。
7.根据权利要求3所述的β-烟酰胺单核苷酸在预防脱发或促进毛发生长产品中的应用,其特征在于:所述预防脱发或促进毛发生长药物为立即释放剂型或缓慢释放剂型。
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