CN113082059B - 一种防治骨质疏松症的组合物及其制备方法和应用 - Google Patents
一种防治骨质疏松症的组合物及其制备方法和应用 Download PDFInfo
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Abstract
本发明提供一种防治骨质疏松症的组合物及其制备方法和应用,具体公开了蜂王浆、维生素k2、异黄酮和钙源在制备防治骨质疏松症组合物及其产品中的应用,组合物能够促进谷氨酸残基羧化,钙在骨骼中的矿物质化,促进钙吸收和增强骨密度,对于制备防治骨质疏松的食品、保健品或药品的开发和应用具有广阔的前景。
Description
技术领域
本发明涉及一种防治骨质疏松症的药品或保健品技术领域,具体地说就是一种补钙组合物及其制备方法。
背景技术
骨组织是一种高度矿化的结缔组织,在骨组织中持续不断地发生骨的吸收和生成,这个过程称之为骨重建。骨的重建受到多种因素影响,包括全身性的激素比如甲状旁腺素、降钙素、雌激素等,还有些局部因子包括含氮氧化物、生长因子、细胞因子等等。骨质疏松就是骨的生成和吸收失衡的一种全身代谢性疾病,以骨量低下、骨微结构破坏、骨脆性增加、易发生骨折为特征,医学上将其称为骨质疏松症(Osteoporosis,OP)。骨质疏松的发生与年龄、雌激素缺乏、营养障碍和某些疾病有关,在病因上可分为原发性和继发性两种。原发性骨质疏松又分为雌激素缺乏性和衰老性,而继发性骨质疏松常由疾病如皮质醇增多症、甲状腺功能亢进症、糖尿病等或某些药物比如皮质类固醇、抗肿瘤药和肝素等引起,其他一些原因如妊娠和哺乳,以及钙、维生素和某些蛋白质的缺乏也会造成骨质疏松。
在防治骨质疏松症方面,国内外都投入了大量的人力和物力,进行了深入的研究。如早在2014年4月,美国骨质疏松基金会(National Osteoporosis Foundation,NOF)发布了新版预防和治疗骨质疏松症临床指南,适用人群为美国绝经后女性及中老年男性(≥50岁)。包括:摄入足够的钙、摄入足够的维生素D、等;抗骨质疏松药物,如美国国家食品药品监督管理局(Food andDrug Administration,FDA)批准的治疗骨质疏松症的药物有双膦酸盐类药物、降钙素、雌激素受体调节剂(雷洛昔芬)、雌激素、组织选择性雌激素复合物(结合雌激素/巴多昔芬)、PTH 1-34(特立帕肽)以及RANKL单抗。在国内,如《原发性骨质疏松症诊疗指南》(中国全科医学杂志,2017.10)中推荐的“碳酸钙、氯化钙、磷酸钙、醋酸钙、乳酸钙、柠檬酸钙、枸橼酸钙、葡萄糖酸钙”等,主要通过充足的钙摄入来获得相对更为理想的骨峰值、减缓骨丢失、改善骨矿化,达到维护骨骼健康的目的。
现有技术也进行了大量的研究,如中国专利ZL.200610057359.8,公开了“一种蜂王浆酸钙及其制备方法”,其在蜂王浆冻干粉中简单加入钙剂(乳酸钙、碳酸钙或葡萄糖酸钙)等组分进行口感的调节和钙质的补充,并且指出不仅可以提高人体免疫力,延缓衰老,对抗人体对高温等,特别是通过王浆酸与钙的有机结合,促进钙在体内的吸收和利用,并在协同作用下可以治疗老年骨质疏松。又如ZL201210063350.3公开了王浆酸钙及与维生素K2制成的抗动脉粥样硬化和骨质疏松症保健品,具体是通过将王浆酸钙和维生素K2按特定比例混合制备了对中老年人群具有良好抗动脉粥样硬化与骨质疏松症双重功能的保健品。虽然,这些技术改进能够在一定程度提升所制备产品的补钙以及治疗骨质疏松症的效果,然而,上述防治骨质疏松症的方式都有着一定的缺陷,一方面主要是内在调节,但钙摄入不足同样是问题,且有一定的副作用,譬如刺激胃粘膜,引起便秘等。另一方面通过维生素D3来促进钙的吸收,吸收过多容易造成钙紊乱、肌肉骨头疼痛等健康问题,且钙的涉入过高,导致钙磷比例失衡,从而导致一系列骨质及肠道吸收问题。因此,研发无副作用、可长期服用、对预防和治疗骨质疏松症有显著疗效的药物和保健品成为了行业内技术人员的研究热点。
发明内容
本发明的目的一方面提供一种防治骨质疏松症的组合物,以解决目前防治骨质疏松症的药物和保健品存在长期服用副作用较大、对预防和治疗骨质疏松症疗效较差的问题。
另一面提供该防治骨质疏松症组合物的制备方法。
再一方面,提供含有该组合物的药品或保健品及其制备方法。
蜂王桨(Royal Jelly)又名蜂皇架,蜂皇乳等,是蜂群中工蜂的舌腺以及上颗腺等腺体分泌的具有复杂化学成分的乳状物质。蜂王架为乳白色或淡黄色半透明乳浆状,味道酸湿并略带辛辣。部分溶于水和乙醇,不溶于氯仿。-18℃下可储存数年,-4℃可保存数月不变质,常温下极易发生变质,长时间暴露在光和空气当中,容易被氧化和水解。通常,蜂王浆的pH值3.5-4.5,酸价3.63-4.60,折光率(20℃)为1.3817-1.3947。蜂王浆含有丰富的营养成分,如王浆蛋白(MRJPs)、10-羟基-2-癸稀酸(10-HDA)(王浆酸)、雌激素以及矿物质、多糖等。且蜂王浆具有多种功能活性,如抗菌消炎、抗肿瘤、免疫调节、抗衰老等。
维生素K2是人体钙和骨代谢的必须物质,是谷氨酸γ-羧化酶的辅酶,没有维生素K2的参与,谷氨酸残基将无法进行羧化,人体钙调节将被中断。并有研究表明,维生素K2对维甲酸致大鼠骨质疏松症的抑制作用。在维生素K2(20)、K2(35)和柠檬酸一苹果酸钙(CCM)对维甲酸致大鼠骨质疏松症的抑制作用对照试验中得到:与模型组比较,维生素K2(20)、(35)和柠檬酸一苹果酸钙(CCM)对维甲酸致大鼠的骨质疏松症有明显抑制作用,且在同等剂量下,维生素K2活性约为CCM的102~104倍,维生素K2(35)尤为显著(参见闰鸿丽、雷泽、沈志强等,中国骨质疏松杂志2009年9月第15卷第9期第664-667页)。在药理学机理上,维生素K2在人体可以合成两种谷氨酸蛋白质γ-羧化骨钙素和基质γ-羧基谷氨酸蛋白,它们均以钙结合蛋白的形式发挥作用,但他们的组织分布和功能不同。骨钙素由成骨细胞产生和分泌,是反映成骨细胞活性特异而敏感的指标。γ-羧化骨钙素对骨骼钙代谢起重要调节作用,与羟磷灰石有特殊亲和性,在细胞外与Ca2+结合,由无规则线团状变成螺旋结构,γ-羧化谷氨酸残基向外,正好与羟基磷灰石钙结合部位的空间结构相吻合。γ-羧化骨钙素促进钙盐沉积,提高骨矿化速率,维持骨的正常钙化和结晶形状,抑制异常羟磷灰石结晶形成及软骨矿化速率,直接反映骨形成和骨重建。而基质γ-羧基谷氨酸蛋白,其大剂量合成依靠软骨细胞和血管中的平滑肌细胞,在这些部位,基质γ-羧基谷氨酸蛋白对软骨和血管钙化具有强烈的抑制作用,从而防止软骨和血管壁的异常钙化。γ-羧化骨钙素和基质γ-羧基谷氨酸蛋白的生物活性依赖于体内维生素K2水平。同时,维生素K2不仅增加肠道对钙的吸收与转运,而且还通过控制肾钙素的γ-羧化显著抑制尿钙的排泄,提高钙的有效利用率,显著促进钙平衡。
异黄酮属于植物雌激素类,主要存在于豆类作物中,细胞培养、动物模型和临床观察研究表明,异黄酮作用复杂,表现为较弱的雌激素样作用,以切除双侧卵巢的哺乳大鼠为模型,添加异黄酮饮料两周哺乳大鼠骨密度明显增高,但所有大鼠的子宫无变化,认为异黄酮对骨质疏松有减缓作用。在体外成骨细胞需添加附加因子促进成骨细胞的矿化能力,钙在矿化中起重要作用。如高培君等人研究发现,采用假手术对照组、手术对照组、大豆异黄酮组、钙组、钙+大豆异黄酮组进行小鼠实验,结果显示与单独补充大豆异黄酮或钙相比,大豆异黄酮与钙的联合应用能够更有效地预防去卵巢大鼠骨质疏松的发生。这表明大豆异黄酮可促进钙在骨骼中的矿物质化(参见高培君,蔡美琴,联合补充大豆异黄酮和钙预防去势大鼠骨质疏松的实验研究,中国骨质疏松杂质,第12卷第5期,2006年10月)。
本文拟采用上述三种成分进行组合,制备成一种防治骨质疏松症的组合物,以解决现有技术中难以长期服用以及补钙作用效果不佳的技术问题。
经过前期申请人的研究,在不受任何理论限制的情况,由于采用蜂王浆、异黄酮以及维生素K2进行组合使用,实现了对钙吸收利用的显著提升,所产生的技术效果明显超越了依据现有技术可预期的技术效果,并且也未产生任何的副作用。
一种防治骨质疏松症的组合物,其特征在于,所述的原料包括蜂王浆、异黄酮、维生素K2以及钙源。
进一步优选,所述的原料按重量份计包括蜂王浆30-150份,异黄酮10-15份,维生素K25-10份以及15-30份钙源。
进一步优选,所述的原料按重量份计包括蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。
所述的异黄酮优选大豆异黄酮。
所述的维生素K2优选为K2(20)、K2(35)、K2(45)中的一种或几种。
所述的钙源优选碳酸钙、氯化钙、磷酸钙、醋酸钙、乳酸钙、柠檬酸钙、枸橼酸钙、葡萄糖酸钙中的一种或几种。
本申请还提供上述组合物的制备方法,其具体操作步骤如下:
(1)按产品的配方要求,称取所用各原料的用量;
(2)采用浓度为10%的食用酒精水溶液,与蜂王浆按照10:3比例进行互配,搅拌形成均匀溶液A;
(3)采用pH6.7的磷酸缓冲液进行钙源的溶解,制备成钙溶液B;
(4)将步骤(2)和步骤(3)获得溶液A和B进行混合,并在磁力搅拌器进行混合均匀。0-4℃条件下放置30-90min;
(5)采用10%的食用酒精水溶液对维生素K2进行溶解,制备成溶液C;
(6)步骤(4)放置后的混合溶液与步骤(5)溶液C进行混合,搅拌均匀,并平铺在冷冻盘,放入冷冻干燥机,待物料温度达到-35℃以下,冷阱温度达到-55℃以下时,开启真空泵,当15Pa以下时开始对隔板梯度加热,设置起始温度为-35℃,隔板最终温度为10℃;控制冻干全过程真空压力为5-15Pa,得冻干混合物;
(7)将上述冷冻干燥所得到的固体物质进行粉碎,得到冻干蜂王浆粉末;
(8)将步骤(7)制备得到的蜂王浆冻干粉与异黄酮进行混合,得到所述的防治骨质疏松症的组合物。
所述步骤(3)中磷酸缓冲液与钙源的比例为10:4。
所述步骤(5)中食用酒精水溶液与维生素K2的比例3:1。
进一步优选,所述步骤(4)放置时间为60min。
本发明还提供一种包含上述防治骨质疏松症组合物的药品或保健产品。
所述的药品或保健产品在制备的过程中,可添加药理上可接受辅料,如通常使用的赋形剂、结合剂、润滑剂、崩解剂、表面活性剂、助流剂、添加剂等;赋形剂包括乳糖、果糖、葡萄糖、玉米淀粉、山梨糖醇、结晶纤维素等等;粘合剂包括甲基纤维素、乙基纤维素、阿拉伯树胶、明胶、羟丙基纤维素、聚乙烯基吡咯烷酮等;润滑剂包括滑石粉、硬脂酸镁、聚乙二醇、氢化植物油等;崩解剂包括淀粉、藻酸钠、明胶、碳酸钙、柠檬酸钙、糊精、碳酸镁等;表面活性剂包括十二烷基硫酸钠、大豆软磷脂、蔗糖脂肪酸酯、聚山梨酸酯等等;助流剂包括轻质无水硅酸、干燥氢氧化铝凝胶、合成硅酸铝、硅酸镁等;添加剂包括蜂蜜、糖浆、凡士林、甘油、乙醇、丙二醇、柠檬酸、氯化钠、磷酸钠等;进而制备成颗粒剂、散剂、丸剂、胶囊剂或口服液等中常见的剂型。
所述上述各类常见的剂型可采用本领域常规的方法进行制备,对此没有特别限定。
所述防治骨质疏松症的药品或保健品,该药品或保健品单独服用可以起到骨质疏松显著的治疗效果,但也不排斥与其他营养补充剂联合使用;其营养补充剂为维生素D和/或其它治疗骨质疏松症的药物等。
本发明首次将蜂王浆、维生素K2、异黄酮以及钙源进行组合,由于所用的蜂王浆、维生素K2以及异黄酮三者之间存在一定的互补协同作用,可以有效的提高钙源在体内的代谢吸收,降低的钙源的添加量,起到节约成本的作用效果。将其应用于制成防治骨质疏松症的药品或保健品具有成本低、防治效果好、用量少、长期服用无毒副作用等优势,在防治骨质疏松症医药和保健等领域具有广阔的应用前景。
本发明提供的防治骨质疏松症的药品或保健品,其建议使用有效剂量为:成人每日每千克体重服用的有效剂量为60-1200mg/kg,优选推荐的剂量是120-600mg/kg,最优选推荐的剂量是360mg/kg。
本发明具有以下有益效果:
(1)首次实现将蜂王浆、维生素K2、异黄酮和钙源进行组合,制备具有防治骨质疏松症的组合物。在所制备的组合物中,并不仅限于现有技术的原理,但可以依据现有技术中已经知晓的部分原理来解释,蜂王浆中所含有的王浆酸与维生素K2可能实现的协同的作用,促进了钙源在体内的代谢以及在骨头中沉积;另一方面,蜂王浆中所含有的雌激素可能与异黄酮发生了增效的作用,有利的调节了身体的内部代谢技能,促进了对钙源的消化吸收,并且抑制了骨吸收率。此外,蜂王浆中的所含有的王浆蛋白也在一定程度提升了对钙源的利用率。综上已知晓的技术原理,实现了上述成分综合利用,以获得本申请所述的技术效果。
(2)克服了现有技术中较为复杂的制备方法以及单独成分的组合来提升对钙源的充分利用,如ZL201210063350.3,其仅是利用了蜂王浆中的王浆酸,难以实现对蜂王浆中的其它成分的有效利用,如雌激素以及王浆蛋白。
(3)在组合物的制备过程,降蜂王浆与钙源先进行混合,并放置了一段时间,有利于钙源与蜂王浆中的王浆酸等脂肪酸的结合,并且将脂溶性的维生素K2也前期与蜂王浆与钙源进行混合,提升了三者的作用效果。特别是对于放置的时间筛选,实现了作用效果的最大化。
(4)通过上述组合物的制备方法,所得到的产品,比单纯的直接简单混合,具有更佳的产品稳定性。
具体实施方式:
下面实施例用于进一步详细说明本发明,但不以任何形式限制本发明。
实施例1
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆30份,异黄酮10份,维生素K25份以及20份钙源。
其具体操作步骤如下:
(1)按产品的配方要求,称取所用各原料的用量;
(2)采用浓度为10%的食用酒精水溶液,与蜂王浆按照10:3比例进行互配,搅拌形成均匀溶液A;
(3)采用pH6.7的磷酸缓冲液进行钙源的溶解,制备成钙溶液B;
(4)将步骤(2)和步骤(3)获得溶液A和B进行混合,并在磁力搅拌器进行混合均匀。0-4℃条件下放置30min;
(5)采用10%的食用酒精水溶液对维生素K2进行溶解,制备成溶液C;
(6)步骤(4)放置后的混合溶液与步骤(5)溶液C进行混合,搅拌均匀,并平铺在冷冻盘,放入冷冻干燥机,待物料温度达到-35℃以下,冷阱温度达到-55℃以下时,开启真空泵,当15Pa以下时开始对隔板梯度加热,设置起始温度为-35℃,隔板最终温度为10℃;控制冻干全过程真空压力为5-15Pa,得冻干混合物;
(7)将上述冷冻干燥所得到的固体物质进行粉碎,得到冻干蜂王浆粉末;
(8)将步骤(7)制备得到的蜂王浆冻干粉与异黄酮进行混合,得到所述的防治骨质疏松症的组合物。
实施例2
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆150份,异黄酮15份,维生素K210份以及15份钙源。除步骤(4)中放置的时间按照90min,其它的操作均按照实施例1制备方法进行制备。
实施例3
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。除步骤(4)中放置的时间按照60min,其它的操作均按照实施例1制备方法进行制备。
对比例1:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。其制备方法为:将蜂王浆直接进行冻干制备成蜂王浆冻干粉,所采用的冻干条件为实施例1制备方法所限定的;直接将维生素K2以及钙源和异黄酮进行混合,而未采用实施例1的制备方法进行处理。
对比例2:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。除了将步骤(4)中的放置时间修改为0(即不进行放置处理)外,其它的操作均按照实施例1的方法进行操作。
对比例3:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。除了将步骤(4)中的放置时间修改为100min外,其它的操作均按照实施例1的方法进行操作。
对比例4:
按照ZL201210063350.3公开的技术内容重复实验制备王浆酸钙与维生素K2的混合物,其质量比为250:1。
对比例5:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份,异黄酮12份以及20份钙源。除步骤(4)中放置的时间按照60min,其它的操作均按照实施例1制备方法进行制备。
对比例6:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括蜂王浆45份、维生素K27份以及20份钙源。除步骤(4)中放置的时间按照60min,其它的操作均按照实施例1制备方法进行制备。
对比例7:
一种防治骨质疏松症的组合物,所述的原料按重量份计包括异黄酮12份、维生素K27份以及20份钙源。除步骤(4)中放置的时间按照60min,其它的操作均按照实施例1制备方法进行制备。
当上述对比例中省略组分后采用相对应组分用量的水作为替代剂。
试验例1:
选取体重190-240g的6月龄雌性Wistar大鼠130只,SPF级,饲养标准控制在室温18-22℃、湿度45%-65%。随机分为13组:假手术组、实施例1-3以及对比例1-7的实验组、阳性对照组、模型组,每组10只;给药剂量为100mg/kg。质量比浓度0.25%戊巴比妥钠25mg/kg腹腔注射麻醉动物,采用背侧切口,无菌条件下切开皮肤、皮下组织,实验组、阳性对照组、模型组切除卵巢;假手术组只切除卵巢周围少量脂肪组织,逐层缝合;术后连续3d肌注青霉素注射液,均给普通饲料,自由饮食。
手术后1周给药,10个实验组给药剂量为均为100mg/kg进且采用罐胃方式进行给药。阳性对照组采用6.6μg/kg的降钙素皮下注射,模型组采用生理盐水灌胃,连续给药12周,假手术组无特殊处理。于手术后1周、12周重复测量大鼠左侧股骨骨密度。骨密度扫描的部位包括全股骨和胫骨上端,扫描前水合氯醛腹腔注射,麻醉后使大鼠处于俯卧位,后肢维持在外旋位,股骨与胫骨呈45°角。扫描重复3次,每次重置大鼠,扫描结果如表1所示,其结果为三次扫描的平均值。
表1实施例1-3以及对比例1-7对去势骨质疏松大鼠骨密度的影响(mg/cm2)
组别(n=10) | 1周末 | 12周末 |
假手术组 | 137.6±0.634 | 136.4±0.731 |
模型组 | 138.2±0.362 | 116.2±0.392& |
实施例1 | 137.9±0.163 | 126.6±0.436&* |
实施例2 | 137.8±0.562 | 127.9±0.185&* |
实施例3 | 138.2±0.501 | 133.8±0.715&* |
对比例1 | 138.2±0.469 | 122.3±0.883&* |
对比例2 | 137.8±0.865 | 123.1±0.193&* |
对比例3 | 137.9±0.662 | 125.9±0.018&* |
对比例4 | 137.6±0.984 | 120.5±0.098&* |
对比例5 | 138.2±0.062 | 119.9±0.233& |
对比例6 | 138.2±0.123 | 120.8±0.967&* |
对比例7 | 138.2±0.147 | 118.9±0.163& |
阳性对照组 | 137.6±0.895 | 129.3±0.203&* |
表1中:与假手术组比较,&P<0.05,与模型组比较,*P<0.05.
从以上结果可以看出实验鼠在用药之前各组骨密度基线总体无差异,用药12周后检测各组实验鼠的差异比较显著,其中模型组的骨密度低于假手术组,表明造模成功。而实施例1-3以及对比例1-7均能够减缓模型组大鼠骨密度指标下降,成显著性,说明本申请所制备的组合物具有促进骨形成、抑制骨吸收以及降低骨代谢率的作用。同时,实施例1-3的比对结果可以看出,实施例3的结果相对较优,但相比对比例4来说,实施例1-3的结果偏好。且由对比例1-3以及对比例5-7的结果也可以显示出采用本申请的制备方法有利于提升所制备组合物的作用效果,以及本申请所采用的组分之间存在一定的互配关系。
试验例2:
选用SPF级健康雌性Wistar大鼠140只,随机分为13组,分别是:正常对照组10只、假手术组10只、阳性对照组10只、给药实验组110只。所有大鼠适应性喂养1周后,将给药实验组和假手术组的大鼠以45mg/kg剂量的戊巴比妥钠腹腔注射麻醉,腹位固定,将给药实验组进行卵巢切除术,假手术组只是切除小块脂肪组织,但不摘除卵巢。手术后10周,将卵巢切除后的给药实验组大鼠随机分为11小组,分别是实施例1-3(每组10只),对比例1-7(每组10只),己烯雌酚组(10只)。随后,己烯雌酚组分别给予大鼠罐服己烯雌酚2mg/kg,实施例1-3以及对比例1-7分别灌服同等剂量的对应组合物,各给药组每日1次,连续6天,休息1天,再连续给药6,每周称重1次。正常对照组、假手术组以及阳性对照组按同法灌服等体积的蒸馏水。给药12周结束,处死。处死前16天和前3天分别腹腔注射盐酸四环素30mg/kg体质量,以对骨进行荧光标记。给药结束后,取大鼠右侧胫骨近端1/3,制作不脱钙骨切片,进行骨组织形态计量学指标的检测。
用Leica Qwin图像分析系统进行计量分析:1.骨量的检测:用骨小梁体积百分比(percentage of trabecular bone volume,TBV%),即骨小梁体积占被测骨髓腔总体积的百分比进行表示,它是衡量骨量水平的主要标志;2.骨小梁矿化率(mineralization rateoftrabecular bone,MAR):骨小梁表面荧光双标记带的平均距离除以2次标记相隔的天数;3.骨皮质矿化率(mineralization rate of cortical bone,mAR):皮质内表面荧光双标记带的平均距离除以2次标记相隔的天数。其检测结果如表2所示。(上述试验例1-2所采用的实验方法参考ZL.201810013556.2)。
表2实施例1-3以及对比例1-7对去势骨质疏松大鼠骨形态学影响
注:与假手术组相比,**P<0.01;#P<0.01。
从表2可以看出,己烯雌酚组、实施例1-3以及对比例1-7的大鼠胫骨TBV%均显著高于阳性对照,但低于假手术组,而实施例1-3的结果明显要好于对比例1-7,且从对比例1-3的结果也可以显示出,本申请组合物的制备方法对组合物作用效果有着一定的影响,但同样也显示出本申请的制备方法并非是本申请的关键之处,其仅是在于提升作用的效果。综上,采用本申请的组合物以及相应制备方法制备得到的组合物,对骨质疏松症有着较强的防治作用效果。
实施例4
在洁净环境中,取实施例3所制备的组合物36g加入容器中,充分混合后,再加入964g大豆油、玉米油、橄榄油、食用调和油、核桃油中的一种或几种的混合物,在剧烈搅拌下将其灌装成软胶囊,每粒装量0.5g,其中每粒含组合物180mg。检验,分装,包装即得。
实施例5
在洁净环境中,取实施例3所制备的组合物36g加入容器中,充分混合后,再加入964g淀粉或微晶纤维素,或它们的混合物后,将其压制片或硬胶囊,每粒或每片装0.5g,其中每粒/片含组合物180mg。检验,分装,包装即得。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受所述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (8)
1.一种防治骨质疏松症的组合物,其特征在于,所述组合物的原料由以下组分组成:蜂王浆、异黄酮、维生素K2以及钙源;
所述的原料按重量份计:蜂王浆30-150份,异黄酮10-15份,维生素K25-10份以及15-30份钙源;
其制备方法为:
(1)按产品的配方要求,称取所用各原料的用量;
(2)采用浓度为10%的食用酒精水溶液,与蜂王浆按照10:3比例进行互配,搅拌形成均匀溶液A;
(3)采用pH6.7的磷酸缓冲液进行钙源的溶解,制备成钙溶液B;
(4)将步骤(2)和步骤(3)获得溶液A和B进行混合,并在磁力搅拌器进行混合均匀;0-4℃条件下放置30-90min;
(5)采用10%的食用酒精水溶液对维生素K2进行溶解,制备成溶液C;
(6)步骤(4)放置后的混合溶液与步骤(5)溶液C进行混合,搅拌均匀,并平铺在冷冻盘,放入冷冻干燥机,待物料温度达到-35℃以下,冷阱温度达到-55℃以下时,开启真空泵,当15Pa以下时开始对隔板梯度加热,设置起始温度为-35℃,隔板最终温度为10℃;控制冻干全过程真空压力为5-15Pa,得冻干混合物;
(7)将上述冷冻干燥所得到的固体物质进行粉碎,得到冻干蜂王浆粉末;
(8)将步骤(7)制备得到的蜂王浆冻干粉与异黄酮进行混合,得到所述的防治骨质疏松症的组合物。
2.根据权利要求1所述的组合物,其特征在于,所述的原料按重量份计为蜂王浆45份,异黄酮12份,维生素K27份以及20份钙源。
3.根据权利要求1所述的组合物,其特征在于,所述的异黄酮为大豆异黄酮。
4.根据权利要求1所述的组合物,其特征在于,所述的维生素K2为K2(20)、K2(35)、K2(45)中的一种或几种。
5.根据权利要求1所述的组合物,其特征在于,所述的钙源为碳酸钙、氯化钙、磷酸钙、醋酸钙、乳酸钙、柠檬酸钙、枸橼酸钙、葡萄糖酸钙中的一种或几种。
6.一种包含权利要求1所述防治骨质疏松症组合物的药品。
7.根据权利要求6所述的药品,其特征在于,所述的药品在制备的过程中,添加药品可接受辅料。
8.一种权利要求1所述防治骨质疏松症组合物在制备防治骨质疏松或增加骨密度产品中的应用。
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