CN116491657B - 一种含有维生素d的钙制剂及其制备方法 - Google Patents
一种含有维生素d的钙制剂及其制备方法 Download PDFInfo
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- CN116491657B CN116491657B CN202310262477.6A CN202310262477A CN116491657B CN 116491657 B CN116491657 B CN 116491657B CN 202310262477 A CN202310262477 A CN 202310262477A CN 116491657 B CN116491657 B CN 116491657B
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- whey protein
- calcium
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- protein powder
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Abstract
本发明一种含有维生素D的钙制剂及其制备方法,所述钙制剂包括葡萄糖酸钙60‑80重量份、乳清蛋白粉4‑6重量份,维生素D3 0.25‑0.35重量份;所述乳清蛋白为采用低聚半乳糖进行糖基化修饰的乳清蛋白,所述乳清蛋白在进行糖基化修饰之前先进行超声处理,然后再进行动态高压微射流处理。本发明通过对乳清蛋白粉先进行超声处理,然后再进行动态高压微射流处理,能够有效破坏蛋白质结构,改善其功能性质,为低聚半乳糖进行糖基化反应提供足够的改性位点,最后再进行酶解反应,制得乳清蛋白粉,该乳清蛋白粉与葡萄糖酸钙,维生素D3按一定比例范围进行组合,使得本发明的钙制剂配方更为简单,有助于解决现有钙吸收率低,吸收不完全,补充的钙质流失严重的问题。
Description
技术领域
本发明属于医药食品技术领域,具体涉一种含有维生素D的钙制剂及其制备方法。
背景技术
维生素D是人类必需的一种脂溶性维生素,是钙磷代谢的重要调节因子之一,可促进人体对钙、磷元素的吸收,维持人体正常的血钙和磷水平,参与许多组织细胞的分化和增殖等生命过程。目前已知的维生素D最重要的是维生素D2(麦角骨化醇)和维生素D3(胆钙化醛)。维生素D2是由紫外线照射植物中的麦角固醇产生,但在自然界的存量很少。维生素D3则由人体表皮和真皮内含有的7-脱氢胆固醇经日光中紫外线照射转变而成。维生素D2和维生素D3对人体的作用和作用机制完全相同,哺乳动物和人类对两者的利用亦无区别,常见维生素D有两种,其中维生素D2为骨化醇,维生素D3为胆骨化醇。无论维生素D2还是维生素D3,本身均无活性,需经肝、肾细胞的两次转化生成1,25-二羟基维生素D2后,能促进钙、磷在小肠内的吸收。当维生素D缺乏时,人体吸收钙、磷的能力下降,血中钙、磷水平较低,成骨作用受阻,甚至发生骨盐再溶解——儿童称为佝偻病,成人称为骨软化症。因此人们常常将维生素D与钙相互搭配起来一同服用以保证补钙效果。
目前,预防或治疗维生素D缺乏疾病的主要策略是口服维生素D补充制剂,其中,以服用胆钙化醇(维生素D3)和麦角钙化醇(维生素D2)最为常见,胆钙化醇和麦角钙化醇本身不具备生物活性,需要在体内依次代谢为25-羟基维生素D3和1,25-二羟基维生素D3来发挥作用。然而,由于机体功能衰退或服用药物的拮抗作用,部分特殊人群的维生素D缺乏症的改善不能直接获益于胆钙化醇和麦角钙化醇的补充。对于老年骨质疏松患者,其胃肠道吸收能力弱,肝肾功能减退,使得维生素D3无法通过代谢最终产生足够的25-羟基维生素D3和1,25-二羟基维生素D3。对于脂肪吸收障碍综合征患者,其不能直接吸收脂溶性维生素D。对于肾病综合征患者,其维生素D结合蛋白丢失,血1,25-二羟基维生素D3浓度偏低。对于服用抗惊厥药物的患者,常因维生素D分解代谢增强而导致血25-羟基维生素D3缺乏。
针对上述技术问题,中国授权专利CN107281218B公开了一种高吸收复合补钙制剂及其制备方法,该补钙制剂各组分按重量份数计含碳酸钙40~60重量份、酪蛋白磷酸肽8~12重量份,山楂粉1~4重量份、麦芽粉0.1~0.25重量份、桃胶0.45~0.65重量份、玉米淀粉0.5~0.7重量份、白砂糖7~10重量份、维生素D3 0.08~0.25重量份、硬脂酸镁0.35~1.5重量份、低取代羟丙纤维素1~3重量份。具体的制备方法为将各原辅料过筛、之后按配方称量,经制粒、干燥、批混和压片的步骤可得。该补钙制剂中维生素D和酪蛋白磷酸肽具有促进钙吸收的作用、而山楂粉和麦芽粉可促进胃液分泌,也能在一定程度上促进钙吸收,尤其对于胃酸较少的老年人效果更为显著,山楂粉、麦芽粉同酪蛋白磷酸肽的协同作用大大地增加了钙吸收效率。
再例如,中国授权专利CN112386601B公开了一种维生素D补充制剂及其应用。本发明所提供的维生素D补充制剂,其活性成分包括:骨化二醇和齐墩果酸。骨化二醇和齐墩果酸协同作用,可有效促进骨髓干细胞和成骨细胞表达CYP27B1,提高1,25-二羟基维生素D3的合成,可快速补充人体尤其是特殊人群所需的维生素D3,调节钙磷代谢,促进骨矿物质沉积,可应用于制备预防或治疗由维生素D缺乏引起的骨性疾病。
现有技术中虽然报道了一些能够促进维生素D吸收或者促进1,25-二羟基维生素D3的合成的制剂,但对于如何提高钙质的吸收,本领域仍然存在需求。
发明内容
基于上述背景技术,本发明所要解决的技术问题在于提供一种含有维生素D的钙制剂及其制备方法,以提高钙质的消化吸收。为了实现本发明的发明目的,拟采用如下技术方案:
本发明一方面涉及一种含有维生素D的钙制剂,其包括葡萄糖酸钙 60-80重量份、乳清蛋白粉 4-6重量份,维生素D3 0.25-0.35重量份;所述乳清蛋白为采用低聚半乳糖进行糖基化修饰的乳清蛋白,所述乳清蛋白在进行糖基化修饰之前先进行超声处理,然后再进行动态高压微射流处理。
在本发明的一个优选实施方式中,所述糖基化修饰的乳清蛋白还进一步通过碱性蛋白酶进行酶解。
在本发明的一个优选实施方式中,所述钙制剂还包括玉米淀粉1-1.5重量份、白砂糖6-10重量份、硬脂酸镁1.2-1.5重量份、羟丙基甲基纤维素4-6重量份。
在本发明的一个优选实施方式中,所述钙制剂为片剂。
在本发明的一个优选实施方式中,所述乳清蛋白是通过如下制备方法制备得到,所述制备方法包括如下步骤:
(1)超声波和动态高压微射流预处理:用超纯水配制乳清蛋白溶液,充分搅拌,先采用超声波细胞破碎仪对其进行处理,再采用动态高压微射流均质机进行处理,超声处理功率为100-300W,时间5-30min,动态高压微射流均质机处理压力为30-70MPa,处理1-5次;
(2)糖基化修饰:将超声波和动态高压微射流预处理的以乳清蛋白计的乳清蛋白溶液与低聚半乳糖混合均匀,置于恒温箱中在40-60℃下反应1-3h;
(3)酶解:将糖基化修饰的乳清蛋白溶液调节pH值至10-11,加入0.1-0.3%重量的碱性蛋白酶进行酶解0.8-1.5h,酶解温度为45-55℃,酶解反应后调节pH至6.5-7.5;
(4)过滤:将酶解液在陶瓷膜中过滤,收集过滤液;
(5)喷雾干燥:将滤液进行喷雾干燥获得乳清蛋白。
在本发明的一个优选实施方式中,所述步骤(1)中,超声处理功率为150-300W,时间10-20min,动态高压微射流均质机处理压力为40-60MPa,处理1-2次。
在本发明的一个优选实施方式中,所述步骤(2)中乳清蛋白粉与低聚半乳糖质量比1:0.5-1。
本发明另一方面还涉及上述钙制剂的制备方法,所述制备方法包括如下步骤:
(1)粘合剂的制备:
将纯化水放入冲浆罐中加热煮沸后,加入羟丙基甲基纤维素,加热溶解,得2-10%的羟丙基甲基纤维素浆,备用;将纯化水放入冲浆罐中加热煮沸后,加入砂糖,并打开搅拌桨至全溶,制成50-70%糖浆,备用;将羟丙基甲基纤维素浆和糖浆投入冲浆罐内启动搅拌桨搅拌均匀,过120目筛,放入不锈钢桶中,贴上物料标识,放冷45-50℃备用,得到粘合剂;
(2)干混及制软材:
将已称量好的葡萄糖酸钙、乳清蛋白粉、玉米淀粉、维生素D3按先后顺序投入高效湿法制粒机内,干混15分钟,停机后加入45-50℃的粘合剂,开启搅拌桨和制粒刀,先低速后高速,湿混5-8秒,搅拌均匀后,在出料口准备装料容器,打开出料口,待物料全部接出后,关闭接料口;
(3)制颗粒、干燥及整粒:
在摇摆制粒机上用12目不锈钢筛网制成湿颗粒,将制好的湿颗粒移至沸腾干燥机中,干燥30-40分钟,温度控制在60-75℃,取出,将干燥后的颗粒用摇摆制粒机整粒,用12目筛网进行整粒;
(4)批混:
将制得的颗粒和称量好的硬脂酸镁投入到三维运动混合机或二维运动混合机中,转速调至10-14rpm,开机混合15分钟,停机下料;
(5)压片:
将总混物料置压片机的料斗中,开机试压,调节好填充量、压力,使片重、硬度、脆碎度符合要求,之后开机正式压片,得到钙制剂。
有益效果
本发明通过对乳清蛋白粉先进行超声处理,然后再进行动态高压微射流处理,能够有效破坏蛋白质结构,改善其功能性质,为低聚半乳糖进行糖基化反应提供足够的改性位点,最后再进行酶解反应,制得乳清蛋白粉,该乳清蛋白粉与葡萄糖酸钙,维生素D3按一定比例范围进行组合,使得本发明的钙制剂配方更为简单,有助于解决现有钙吸收率低,吸收不完全,补充的钙质流失严重的问题。
具体实施方式
为了进一步理解本发明,下面将结合本发明实施例,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
如无特殊说明,本发明实施例中所涉及的试剂均为市售产品,均可以通过商业渠道购买获得。
实施例1:
(1)超声波和动态高压微射流预处理:用超纯水配制20mg/mL的乳清蛋白溶液,充分搅拌,先采用超声波细胞破碎仪对其进行处理,再采用动态高压微射流均质机进行处理,超声处理功率为200W,时间10min,动态高压微射流均质机处理压力为50MPa,处理1次。
(2)糖基化修饰:将超声波和动态高压微射流预处理的以乳清蛋白计的乳清蛋白溶液先与低聚半乳糖(质量比1:0.5)混合均匀,置于恒温箱中在50℃下反应2h。
(3)酶解:将糖基化修饰的乳清蛋白溶液调节pH值至10.5,加入0.2%重量的碱性蛋白酶进行酶解1h,酶解温度为50℃,酶解反应后调节pH至7.0。
(4)过滤:将酶解液在孔径为0.8nm的陶瓷膜中过滤,收集过滤液。
(5)喷雾干燥:将滤液进行喷雾干燥至水含量低于5重量%,获得乳清蛋白粉。
实施例2:
(1)超声波和动态高压微射流预处理:用超纯水配制20mg/mL的乳清蛋白溶液,充分搅拌,先采用超声波细胞破碎仪对其进行处理,再采用动态高压微射流均质机进行处理,超声处理功率为200W,时间20min,动态高压微射流均质机处理压力为50MPa,处理2次。
(2)糖基化修饰:将超声波和动态高压微射流预处理的以乳清蛋白计的乳清蛋白溶液先与低聚半乳糖(质量比1:0.5)混合均匀,置于恒温箱中在50℃下反应2h。
(3)酶解:将糖基化修饰的乳清蛋白溶液调节pH值至10.5,加入0.2%重量的碱性蛋白酶进行酶解1h,酶解温度为50℃,酶解反应后调节pH至7.0。
(4)过滤:将酶解液在孔径为0.8nm的陶瓷膜中过滤,收集过滤液。
(5)喷雾干燥:将滤液进行喷雾干燥至水含量低于5重量%,获得乳清蛋白粉。
实施例3:
(1)超声波和动态高压微射流预处理:用超纯水配制20mg/mL的乳清蛋白溶液,充分搅拌,先采用超声波细胞破碎仪对其进行处理,再采用动态高压微射流均质机进行处理,超声处理功率为200W,时间20min,动态高压微射流均质机处理压力为50MPa,处理2次。
(2)糖基化修饰:将超声波和动态高压微射流预处理的以乳清蛋白计的乳清蛋白溶液先与低聚半乳糖(质量比1:0.8)混合均匀,置于恒温箱中在50℃下反应2h。
(3)酶解:将糖基化修饰的乳清蛋白溶液调节pH值至10.5,加入0.2%重量的碱性蛋白酶进行酶解1h,酶解温度为50℃,酶解反应后调节pH至7.0。
(4)过滤:将酶解液在孔径为0.8nm的陶瓷膜中过滤,收集过滤液。
(5)喷雾干燥:将滤液进行喷雾干燥至水含量低于5重量%,获得乳清蛋白粉。
比较例1:
与实施例1相同,区别在于采用同等重量的葡萄糖代替低聚半乳糖。
比较例2:
与实施例1相同,区域在于步骤(3)为将糖基化修饰的乳清蛋白溶液加入0.2%重量的地衣芽胞杆菌蛋白酶和胰蛋白酶(质量比1:1)进去酶解,酶解温度为45℃,酶解1h,酶解反应后,将酶解液用沸水浴灭酶10min,冷却。
实施例4:钙质吸收率对比实验
本实施例的原料配方是由如下重量份数的各组份组成:葡萄糖酸钙60、乳清蛋白粉4,玉米淀粉1、白砂糖6、维生素D3 0.25、硬脂酸镁1.2、羟丙基甲基纤维素4。其中,A-E分别采用实施例1-3、比较例1-2所制备的乳清蛋白粉,F组中的乳清蛋白粉为未经处理的乳清蛋白粉。
(1)粘合剂的制备:
将纯化水放入冲浆罐中加热煮沸后,加入羟丙基甲基纤维素,加热溶解,得2-10%的羟丙基甲基纤维素浆,备用;将纯化水放入冲浆罐中加热煮沸后,加入砂糖,并打开搅拌桨至全溶,制成50-70%糖浆,备用;将羟丙基甲基纤维素浆和糖浆投入冲浆罐内启动搅拌桨搅拌均匀,过120目筛,放入不锈钢桶中,贴上物料标识,放冷45-50℃备用,得到粘合剂;
(2)干混及制软材:
将已称量好的葡萄糖酸钙、乳清蛋白粉、玉米淀粉、维生素D3按先后顺序投入高效湿法制粒机内,干混15分钟,停机后加入45-50℃的粘合剂,开启搅拌桨和制粒刀,先低速后高速,湿混5-8秒,搅拌均匀后,在出料口准备装料容器,打开出料口,待物料全部接出后,关闭接料口;
(3)制颗粒、干燥及整粒:
在摇摆制粒机上用12目不锈钢筛网制成湿颗粒,将制好的湿颗粒移至沸腾干燥机中,干燥30-40分钟,温度控制在60-75℃,取出,将干燥后的颗粒用摇摆制粒机整粒,用12目筛网进行整粒;
(4)批混:
将制得的颗粒和称量好的硬脂酸镁投入到三维运动混合机或二维运动混合机中,转速调至10-14rpm,开机混合15分钟,停机下料;
(5)压片:
将总混物料置压片机的料斗中,开机试压,调节好填充量、压力,使片重、硬度、脆碎度符合要求,之后开机正式压片,得到钙制剂。
60只大鼠按性别随机分成A-F 6组,每组10只,雌雄各半。各组单笼喂养,自由进食,每组基础饲料中加入2%重量的钙制剂,饮用去离子水,每周称其体重、身长至三个月,将全部大鼠处死,取出左侧股骨,烘干称量长度重和量。
表1钙制剂对大鼠的影响
组别 | 例数 | 体重(g) | 股骨长度(cm) | 股骨干重(mg) |
A | 10 | 203.2±15.8 | 4.20±0.12 | 527.4±23.1 |
B | 10 | 204.8±14.9 | 4.01±0.09 | 513.5±22.8 |
C | 10 | 201.3±16.2 | 4.12±0.07 | 524.9±21.9 |
D | 10 | 207.4±13.9 | 3.53±0.10 | 481.3±20.7 |
E | 10 | 205.9±15.7 | 3.42±0.11 | 472.6±21.5 |
F | 10 | 211.5±16.4 | 3.21±0.12 | 456.3±22.4 |
表1中可见饲养三个月时,各组大鼠体重的对应数值,可见各组大鼠的体重并没有显著差异,说明本发明的钙制剂对于大鼠体重并没有特别明显的影响。而通过对比股骨长度以及干重,则可明显看出各组大鼠之间的差别,A-C组大鼠的股骨长度以及干重明显高于D-F组(P<0.05),这说明本发明的钙制剂通过加入特定的乳清蛋白粉具有增加大鼠对钙制剂中钙质吸收率的作用,而未经处理的乳清蛋白粉对于增加大鼠对钙制剂中钙质的吸收率增加作用有限。
以上描述了本发明优选实施方式,然其并非用以限定本发明。本领域技术人员对在此公开的实施方案可进行并不偏离本发明范畴和精神的改进和变化。
Claims (5)
1. 一种含有维生素D的钙制剂,其特征在于,所述钙制剂由以下组分构成:葡萄糖酸钙60-80重量份、乳清蛋白粉 4-6重量份和维生素D3 0.25-0.35重量份、玉米淀粉1-1.5重量份、白砂糖6-10重量份、硬脂酸镁1.2-1.5重量份、羟丙基甲基纤维素4-6重量份;所述乳清蛋白粉为采用低聚半乳糖进行糖基化修饰的乳清蛋白粉;
所述乳清蛋白粉是通过如下制备方法制备得到,所述制备方法包括如下步骤:
(1)超声波和动态高压微射流预处理:用超纯水配制乳清蛋白溶液,充分搅拌,先采用超声波细胞破碎仪对其进行处理,再采用动态高压微射流均质机进行处理,超声处理功率为100-300W,时间5-30min,动态高压微射流均质机处理压力为30-70MPa,处理1-5次;
(2)糖基化修饰:将超声波和动态高压微射流预处理的乳清蛋白溶液与低聚半乳糖混合均匀,置于恒温箱中在40-60℃下反应1-3h;
(3)酶解:将糖基化修饰的乳清蛋白溶液调节pH值至10-11,加入0.1-0.3%重量的碱性蛋白酶进行酶解0.8-1.5h,酶解温度为45-55℃,酶解反应后调节pH至6.5-7.5;
(4)过滤:将酶解液在陶瓷膜中过滤,收集过滤液;
(5)喷雾干燥:将滤液进行喷雾干燥获得乳清蛋白粉。
2.根据权利要求1所述的钙制剂,所述钙制剂为片剂。
3.根据权利要求1所述的钙制剂,所述步骤(1)中,超声处理功率为150-300W,时间10-20min,动态高压微射流均质机处理压力为40-60MPa,处理1-2次。
4.根据权利要求1所述的钙制剂,所述步骤(2)中乳清蛋白溶液中的乳清蛋白与低聚半乳糖质量比1:0.5-1。
5.权利要求1-4任意一项所述钙制剂的制备方法,所述制备方法包括如下步骤:
(1)粘合剂的制备:
将纯化水放入冲浆罐中加热煮沸后,加入羟丙基甲基纤维素,加热溶解,得2-10%的羟丙基甲基纤维素浆,备用;将纯化水放入冲浆罐中加热煮沸后,加入白砂糖,并打开搅拌桨搅拌至全溶,制成50-70%糖浆,备用;将羟丙基甲基纤维素浆和糖浆投入冲浆罐内启动搅拌桨搅拌均匀,过120目筛,放入不锈钢桶中,贴上物料标识,放冷45-50℃备用,得到粘合剂;
(2)干混及制软材:
将已称量好的葡萄糖酸钙、乳清蛋白粉、玉米淀粉、维生素D3按先后顺序投入高效湿法制粒机内,干混15分钟,停机后加入45-50℃的粘合剂,开启搅拌桨和制粒刀,湿混5-8秒,搅拌均匀后,在出料口准备装料容器,打开出料口,待物料全部接出后,关闭接料口;
(3)制颗粒、干燥及整粒:
在摇摆制粒机上用12目不锈钢筛网制成湿颗粒,将制好的湿颗粒移至沸腾干燥机中,干燥30-40分钟,温度控制在60-75℃,取出,将干燥后的颗粒用摇摆制粒机整粒,用12目筛网进行整粒;
(4)批混:
将制得的颗粒和称量好的硬脂酸镁投入到三维运动混合机或二维运动混合机中,转速调至10-14rpm,开机混合15分钟,停机下料;
(5)压片:
将总混物料置压片机的料斗中,开机试压,调节好填充量、压力,使片重、硬度、脆碎度符合要求之后,开机正式压片,得到钙制剂。
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