CN112972386A - 一种nmn脂质体纳米粒子及其制备方法 - Google Patents
一种nmn脂质体纳米粒子及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种NMN脂质体纳米粒子及其制备方法。其包括以下重量份的组分:NMN 120~200份、胆固醇1~10份、大豆卵磷脂40~60份、巯基壳聚糖5~10份、十二烷基硫酸钠1~5份、稳定剂1~5份,以及有益菌粉5~10份。本发明制备得到的纳米粒子不仅利于肠道吸收,同时还具有高的包封率。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种NMN脂质体纳米粒子及其制备方法。
背景技术
β-烟酰胺单核苷酸,英文名称:Beta-Nicotinamide Mononucleotide;简称:NMN;分子式:C11H15N2O8P;分子量:334.22。NMN是人体内本来就存在的物质,对人体细胞具有重要的生理功能,是NAD+(辅酶I)补救合成途径中合成NAD+的前体;其可来源于多种食物,包括西兰花、卷心菜、黄瓜、毛豆、鳄梨等,但含量都很低,达不到有效外源补充的目的。
NAD全称烟酰胺腺嘌呤二核苷酸,在细胞中不仅作为辅酶,也作为多种信号反应的底物,参与上千种生化反应。2016年,经哈佛大学实验证实,服用NMN烟酰胺单核甘酸一周后22个月大的小鼠(相当于人类60岁)回到了6个月(相当于人类20岁)的状态,并延长了30的寿命。后续还发现NMN有助于维持端粒长度、激活干细孢、激活DNA修护酶、修护受损DNA等多方面起到延缓衰老方面的效果,相关轮文也被发表在《Science》、《Cell》、《Nature》等世界顶级学术期刊上。
NMN作为一种新型的营养补充剂,针对营养吸收能力较弱、身体机能下降,NMN合成水平较低的中老年人,能够在增强肌体活力、改善睡眠,抗衰老、促进身体健康等各方面发挥着越来越大的积极作用。但随着相关产品不断推向市场,已有研究发现,NMN服用一段时间后,使用者吸收NMN的效率会明显下降,可能与相关载体蛋白相关。而NMN主要是以肠道吸收的方式进入细胞,因此有必要研究开发能保护肠道微生态以及维持激活NMN吸收相关的载体蛋白活性的组合物来保证NMN的吸收效果。
发明内容
针对现有技术中的上述不足,本发明提供一种NMN脂质体纳米粒子及其制备方法,可有效解决现有NMN制剂肠道吸收利用率低,且制备得到的NMN制剂包封率低的问题。
为实现上述目的,本发明解决其技术问题所采用的技术方案是:
一种NMN脂质体纳米粒子,包括以下重量份的组分:
NMN 120~200份、胆固醇1~10份、大豆卵磷脂40~60份、巯基壳聚糖5~10份、十二烷基硫酸钠1~5份、稳定剂1~5份,以及有益菌粉5~10份。
进一步地,包括以下重量份的组分:
NMN 180份、胆固醇10份、大豆卵磷脂60份、巯基壳聚糖10份、十二烷基硫酸钠5份、稳定剂2份,以及有益菌粉5份。
进一步地,稳定剂为维生素C、维生素E及其衍生物或亚硫酸氢钠。
进一步地,有益菌粉为枯草杆菌和双歧杆菌目可食用双歧杆菌中的至少一种。
上述NMN脂质体纳米粒子的制备方法,包括以下步骤:
(1)将NMN、稳定剂以及有益菌粉混合,加水搅拌溶解;
(2)将司盘-80溶解于有机溶剂中,然后加入步骤(1)所得产物,搅拌均匀,形成油包水微乳液;
(3)将胆固醇和大豆卵磷脂加入步骤(2)所得产物中,室温搅拌2~5h;
(4)将巯基壳聚糖加入步骤(3)所得产物中,于35~55℃搅拌1~3h后,减压浓缩,再于1500~2000r/min离心,收集液相,即得巯基壳聚糖修饰的NMN脂质体纳米粒子。
进一步地,有机溶剂为不与水互溶的有机溶剂。
进一步地,有机溶剂为二氯甲烷、三氯甲烷或正己烷。
进一步地,司盘-80溶于有机溶剂后的质量浓度为2~5%。
进一步地,步骤(4)中温度为35℃。
本发明的有益效果为:
1、本发明采用脂质体作为NMN的载体,由于NMN为水溶性成分,因此,NMN负载于制备得到的脂质体纳米粒子的脂质体内囊中,能够在体内随着脂质体的降解而缓慢的释放出来,有效的保证了NMN在体内的吸收率。
2、本申请在制备得到脂质体纳米粒子后,通过巯基壳聚糖对其进行修饰,巯基壳聚糖带有正电荷,而大豆卵磷脂和胆固醇制备得到的脂质体表面带有负电荷,两者能够通过静电结合的方式相结合,从而制备得到巯基壳聚糖修饰的纳米粒子。而巯基修饰的壳聚糖能够能够有效的提升肠道的吸收率,从而进一步的提升了肠道对于NMN药物的吸收率。同时,配方中添加的十二烷基硫酸钠也能促进肠道对药物的吸收率,可辅助提升肠道对NMN的吸收效率。
3、本申请选用大豆卵磷脂作为原料制备脂质体,大豆卵磷脂为两亲性成分,而NMN为易溶于水的亲水性成分,因此,使用大豆卵磷脂能够有效的提升NMN在脂质体纳米粒子中的包封率。
4、本申请中脂质体与NMN的结合是在油包水微乳液体系中进行的,在微乳液体系中能够有效的提升NMN的扩散效果,提升制备得到的纳米粒子的包封率,再与呈两亲性的大豆卵磷脂、胆固醇以及NMN等成分用量相配合,进一步的提升制备得到的脂质体纳米粒子的包封率。
具体实施方式
下面对本发明的具体实施方式进行描述,以便于本技术领域的技术人员理解本发明,但应该清楚,本发明不限于具体实施方式的范围,对本技术领域的普通技术人员来讲,只要各种变化在所附的权利要求限定和确定的本发明的精神和范围内,这些变化是显而易见的,一切利用本发明构思的发明创造均在保护之列。
实施例1
一种NMN脂质体纳米粒子,包括以下重量份的组分:
NMN 180份、胆固醇10份、大豆卵磷脂60份、巯基壳聚糖10份、十二烷基硫酸钠5份、维生素E 2份,以及枯草杆菌5份。
上述NMN脂质体纳米粒子的制备方法为:
(1)将NMN、维生素E以及枯草杆菌混合,加水搅拌溶解;
(2)将司盘-80溶解于有机溶剂中,然后加入步骤(1)所得产物,搅拌均匀,形成油包水微乳液;
(3)将胆固醇和大豆卵磷脂加入步骤(2)所得产物中,室温搅拌2h;
(4)将巯基壳聚糖加入步骤(3)所得产物中,于35℃搅拌1h后,减压浓缩,再于1800r/min离心,收集液相,即得巯基壳聚糖修饰的NMN脂质体纳米粒子分散液。
实施例2
一种NMN脂质体纳米粒子,包括以下重量份的组分:
NMN 120份、胆固醇10份、大豆卵磷脂40份、巯基壳聚糖5份、十二烷基硫酸钠5份、维生素E1份,以及枯草杆菌10份。
上述NMN脂质体纳米粒子的制备方法为:
(1)将NMN、维生素E以及枯草杆菌混合,加水搅拌溶解;
(2)将司盘-80溶解于有机溶剂中,然后加入步骤(1)所得产物,搅拌均匀,形成油包水微乳液;
(3)将胆固醇和大豆卵磷脂加入步骤(2)所得产物中,室温搅拌3h;
(4)将巯基壳聚糖加入步骤(3)所得产物中,于55℃搅拌2h后,减压浓缩,再于1500r/min离心,收集液相,即得巯基壳聚糖修饰的NMN脂质体纳米粒子分散液。
实施例3
一种NMN脂质体纳米粒子,包括以下重量份的组分:
NMN 200份、胆固醇5份、大豆卵磷脂50份、巯基壳聚糖8份、十二烷基硫酸钠1份、维生素E 2份,以及枯草杆菌6份。
上述NMN脂质体纳米粒子的制备方法为:
(1)将NMN、维生素E以及枯草杆菌混合,加水搅拌溶解;
(2)将司盘-80溶解于有机溶剂中,然后加入步骤(1)所得产物,搅拌均匀,形成油包水微乳液;
(3)将胆固醇和大豆卵磷脂加入步骤(2)所得产物中,室温搅拌2~5h;
(4)将巯基壳聚糖加入步骤(3)所得产物中,于40℃搅拌1h后,减压浓缩,再于2000r/min离心,收集液相,即得巯基壳聚糖修饰的NMN脂质体纳米粒子分散液。
实施例4
将实施例1中的巯基壳聚糖替换为壳聚糖,其余均与实施例1相同。
实施例5
与实施例1相比,缺少油包水微乳液体系,巯基壳聚糖替换为PEG,其余均与实施例1相同。
实施例6
与实施例1相比,缺少微乳液体系以及巯基壳聚糖,其余均与实施例1相同。
实验例
1、检测实施例1~6制备得到的纳米粒子的包封率,其结果见表1。
实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 | |
包封率(%) | 95.4±1.4 | 92.3±1.2 | 92.6±1.5 | 93.2±1.6 | 80.6±2.4 | 78.2±1.8 |
2、取禁食16h(只有饮水)的SD雄性大鼠,采用异氟烷吸入入麻醉,仰卧位固定于手术台上,沿腹部中线剪开,小心分离出十二指肠、空肠、回肠和结肠。其中十二指肠、空肠、结肠长度约为10cm,回肠约4cm。于肠段两端切口,插管后结扎,手术中应该小心操作,避免损伤肠系膜上的血管。
实验开始先用已经预热至37℃的0.9%氯化钠溶液冲洗干净肠道内的内容物。然后采用实施例1~6制备得到的产品制备质量浓度为3.0g/L的灌流液10mL,并将其预热至37℃,以1.0mL·min-1的灌流速度冲洗10min,再将流速调整为0.2mL·min-1,预平衡30min。
正式实验开始时,先在进口端用装有供试溶液已知质量的小瓶以相0.2mL·min-1流速进行灌流,出口端放置已称重的收集小瓶,每10min收集得到一份灌流液,称重记录下此时供试液小瓶与收集小瓶的质量。灌流实验结束后,剪下供试肠段,测量其长度和内径,并按以下公式计算肠道对NMN的吸收速率Ka,其结果见表2。
其中,Vin与Vout分别为实验中流入和流出的供试液体积,Cin和Cout分别为流入和流出灌流液的质量浓度,r与l为供试肠段内径与长度(单位为cm),Q为灌流速度(单位为mL·s-1)。
表2 NMN吸收速率
实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 | |
Ka×10<sup>-3</sup>/s<sup>-1</sup> | 76.2±0.23 | 74.3±0.34 | 74.8±0.22 | 52.8±0.15 | 40.4±0.16 | 15.8±0.28 |
根据表1和表2数据可知,本申请实施例1~3的包封率明显优于实施例5和实施例6,其中,由于实施例1~3中配方用量不同,使得实施例1具有最优的包封率和吸收速率,实施例4中将巯基壳聚糖替换为了壳聚糖,使得肠道对于纳米粒子的吸收率有所下降,但并不会对包封率带来显著影响,因此,其包封率明显优于实施例5和实施例6。实施例5和实施例6并未在微乳液环境中进行制备,其包封率显著降低。
同时,实施例5缺少微乳液环境,且巯基壳聚糖替换为PEG,在包封率降低的同时,也明显影响了肠道的吸收速率;实施例6由于直接缺少了实施例1配方中的微乳液体系以及巯基壳聚糖,使得吸收速率大幅度的降低,包封率也显著低于实施例1~5。综上,只有在本申请记载的配方用量和制备方法的配合下,才能制备得到的利于肠道吸收,且包封率高的纳米粒子。
Claims (8)
1.一种NMN脂质体纳米粒子,其特征在于,包括以下重量份的组分:
NMN 120~200份、胆固醇1~10份、大豆卵磷脂40~60份、巯基壳聚糖5~10份、十二烷基硫酸钠1~5份、稳定剂1~5份,以及有益菌粉5~10份。
2.根据权利要求1所述的NMN脂质体纳米粒子,其特征在于,包括以下重量份的组分:
NMN 180份、胆固醇10份、大豆卵磷脂60份、巯基壳聚糖10份、十二烷基硫酸钠5份、稳定剂2份,以及有益菌粉5份。
3.根据权利要求1所述的NMN脂质体纳米粒子,其特征在于,所述稳定剂为维生素C、维生素E及其衍生物或亚硫酸氢钠。
4.根据权利要求1所述的NMN脂质体纳米粒子,其特征在于,所述有益菌粉为枯草杆菌和双歧杆菌目可食用双歧杆菌中的至少一种。
5.权利要求1~4任一项所述的NMN脂质体纳米粒子的制备方法,其特征在于,包括以下步骤:
(1)将NMN、稳定剂以及有益菌粉混合,加水搅拌溶解;
(2)将司盘-80溶解于有机溶剂中,然后加入步骤(1)所得产物,搅拌均匀,形成油包水微乳液;
(3)将胆固醇和大豆卵磷脂加入步骤(2)所得产物中,室温搅拌2~5h;
(4)将巯基壳聚糖加入步骤(3)所得产物中,于35~55℃搅拌1~3h后,减压浓缩,再于1500~2000r/min离心,收集液相,即得巯基壳聚糖修饰的NMN脂质体纳米粒子。
6.根据权利要求5所述的制备方法,其特征在于,所述有机溶剂为不与水互溶的有机溶剂。
7.根据权利要求5所述的制备方法,其特征在于,所述司盘-80溶于有机溶剂后的质量浓度为2~5%。
8.根据权利要求5所述的制备方法,其特征在于,所述步骤(4)中温度为35℃。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107595778A (zh) * | 2017-11-03 | 2018-01-19 | 宁夏医科大学 | 一种紫杉醇口服功能化脂质体及其制备方法 |
CN109432496A (zh) * | 2018-12-06 | 2019-03-08 | 暨南大学 | 一种可原位注射成型的巯基化多糖基水凝胶及其药物载体的制备方法和应用 |
CN109700671A (zh) * | 2018-02-13 | 2019-05-03 | 深圳高尚科美生物科技有限公司 | 包含活性小分子物质的柔性脂质体化妆品及其制备方法 |
CN111557910A (zh) * | 2020-04-08 | 2020-08-21 | 厦门诺康得生物科技有限公司 | 一种靶向肝脏的nmn脂质体纳米粒子及其制备方法和应用 |
CN112089775A (zh) * | 2020-10-30 | 2020-12-18 | 成都及禾生物科技有限公司 | 一种nmn有益菌健康组合物及其制备方法和应用 |
-
2021
- 2021-02-23 CN CN202110200756.0A patent/CN112972386A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107595778A (zh) * | 2017-11-03 | 2018-01-19 | 宁夏医科大学 | 一种紫杉醇口服功能化脂质体及其制备方法 |
CN109700671A (zh) * | 2018-02-13 | 2019-05-03 | 深圳高尚科美生物科技有限公司 | 包含活性小分子物质的柔性脂质体化妆品及其制备方法 |
CN109432496A (zh) * | 2018-12-06 | 2019-03-08 | 暨南大学 | 一种可原位注射成型的巯基化多糖基水凝胶及其药物载体的制备方法和应用 |
CN111557910A (zh) * | 2020-04-08 | 2020-08-21 | 厦门诺康得生物科技有限公司 | 一种靶向肝脏的nmn脂质体纳米粒子及其制备方法和应用 |
CN112089775A (zh) * | 2020-10-30 | 2020-12-18 | 成都及禾生物科技有限公司 | 一种nmn有益菌健康组合物及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
GRADAUER K等: "Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats", 《J CONTROL RELEASE》 * |
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