CN106822223A - A kind of astragalus polyose Radix Angelicae Sinensis polysaccharide composition iron supplementary and preparation method and application - Google Patents
A kind of astragalus polyose Radix Angelicae Sinensis polysaccharide composition iron supplementary and preparation method and application Download PDFInfo
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- CN106822223A CN106822223A CN201710097303.3A CN201710097303A CN106822223A CN 106822223 A CN106822223 A CN 106822223A CN 201710097303 A CN201710097303 A CN 201710097303A CN 106822223 A CN106822223 A CN 106822223A
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- iron
- polysaccharide
- angelica
- astragalus
- superparamagnetic
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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Abstract
Description
技术领域:Technical field:
本发明涉及中医中药学和纳米技术领域,具体涉及一种黄芪多糖-当归多糖组合物补铁剂及制备方法和应用。The invention relates to the fields of traditional Chinese medicine and nanotechnology, in particular to an iron supplement composed of astragalus polysaccharide-angelica polysaccharide and its preparation method and application.
背景技术Background technique
目前,缺铁性贫血(iron deficiency anemia,IDA)是指体内铁的储存不能满足正常红细胞生成的需要而发生的贫血,是由于铁摄入量不足、吸收量减少、需要量增加、铁利用障碍或丢失过多所至。缺铁性贫血对身体危害极大,缺铁可显著降低小儿的智力和动作发育,使人的免疫功能、体力、耐力下降;流行性病学调查显示母亲贫血与低体重儿、早产儿和产期婴儿的死亡率相关;铁缺乏对消化道、毛发、指甲、皮肤也有损害。总之,缺铁性贫血是当代世界上最严重的四大营养性疾病之一,严重影响人类的健康。根据世界卫生组织2008年发表的统计数据,全球有20多亿人患有铁缺乏症,缺铁位于严重影响人类健康危险因素中的第九位。发达国家铁缺乏发病率为1%~20%,而发展中国家铁缺乏高达30%~40%,其高危人群为妇女、儿童和婴幼儿。在中国,2005年的营养监测表明,中国有2亿多人患有铁缺乏症,5岁以下儿童贫血的发病率在12.3%~26.7%,育龄妇女贫血的患病率达到35.0%,成年男子贫血的患病率亦在10%左右。更严重的是,近十年来,我国城镇居民贫血发生率每年以10%~1%的速度增长;而那些过度追求减肥瘦身和排毒而导致的饮食不均衡、营养摄入不足、代谢机能紊乱或减弱增加了新的贫血人群。因此,改善铁营养状况,是世界也是我国迫切需要解决的公共卫生问题。At present, iron deficiency anemia (iron deficiency anemia, IDA) refers to the anemia that occurs when the iron storage in the body cannot meet the needs of normal erythropoiesis. Or lose too much. Iron deficiency anemia is extremely harmful to the body. Iron deficiency can significantly reduce children's intelligence and motor development, and reduce people's immune function, physical strength, and endurance; Infant mortality is associated; iron deficiency can also damage the digestive tract, hair, nails, and skin. In short, iron deficiency anemia is one of the four most serious nutritional diseases in the contemporary world, which seriously affects human health. According to statistics published by the World Health Organization in 2008, more than 2 billion people around the world suffer from iron deficiency, and iron deficiency ranks ninth among risk factors that seriously affect human health. The incidence of iron deficiency in developed countries is 1% to 20%, while that in developing countries is as high as 30% to 40%. The high-risk groups are women, children and infants. In China, nutrition monitoring in 2005 showed that more than 200 million people in China suffer from iron deficiency, the incidence of anemia in children under 5 years old ranges from 12.3% to 26.7%, and the prevalence of anemia in women of childbearing age reaches 35.0%. The prevalence of anemia is also around 10%. What's more serious is that in the past ten years, the incidence of anemia among urban residents in my country has been increasing at a rate of 10% to 1% every year; Weakening adds new anemic populations. Therefore, improving the nutritional status of iron is a public health problem that the world and our country urgently need to solve.
缺铁性贫血是世界上最常见的营养缺乏症,也是我国亟需重视的居民健康问题,对于生活在贫困地区的人群更是如此。口服铁剂是缺铁性贫血的首选治疗方案,但其可能导致腹泻等并发症,且疗效得不到保证,因此,选择更加有效且副作用更小的补铁制剂对于铁缺乏或缺铁性贫血患者的治疗和预后都有极大的意义。Iron deficiency anemia is the most common nutritional deficiency in the world, and it is also a health problem that urgently needs attention in my country, especially for people living in poor areas. Oral iron preparation is the first choice for the treatment of iron deficiency anemia, but it may cause complications such as diarrhea, and the curative effect cannot be guaranteed. The treatment and prognosis of patients are of great significance.
而补铁剂是一类治疗缺铁性贫血的主要药物,用铁制剂治疗缺铁性贫血已有多年的历史。目前使用的补血铁剂主要有硫酸亚铁、有机酸亚铁盐类等,但普遍存在人体吸收率低、有异味、副作用强等缺点,补铁效果不太理想。通过食物铁强化来改善缺铁性贫血是全球营养界公认的经济、易行、有效的途径,具有巨大的潜力。食物强化铁有葡萄糖酸亚铁、乙二胺四乙酸铁钠(NaFeEDTA)及生物铁等。蛋白质家族中的乳铁蛋白、卵转铁蛋白、血红蛋白等是天然的优良的补血铁剂,具有生物利用率高、易被消化吸收、不刺激肠胃、性质稳定等特点,但其制备工艺要求高,价格不菲。And iron supplement is a class of main drug for treating iron deficiency anemia, and iron preparations have been used to treat iron deficiency anemia for many years. Currently used blood iron supplements mainly include ferrous sulfate, ferrous organic acid salts, etc., but generally have the disadvantages of low human absorption rate, peculiar smell, strong side effects, etc., and the effect of iron supplementation is not ideal. Improving iron deficiency anemia through food iron fortification is an economical, easy and effective way recognized by the global nutrition community, and has great potential. Food fortified iron includes ferrous gluconate, sodium ferric ethylenediaminetetraacetate (NaFeEDTA) and biological iron. Lactoferrin, ovotransferrin, hemoglobin, etc. in the protein family are natural and excellent blood iron supplements, which have the characteristics of high bioavailability, easy digestion and absorption, no irritating the stomach, and stable properties, but their preparation process requires high , the price is not cheap.
碳水化合物包被的纳米铁颗粒作为一种新型的补铁剂,已经被美国FDA批准,用于缺铁性贫血的临床治疗。[Lu M,Cohen MH,Rieves D,Pazdur R.Fda report:Ferumoxytolfor intravenous iron therapy in adult patients with chronic kidney disease.AmJ Hematol.2010;85:315–319.Spinowitz BS,Kausz AT,Baptista J,Noble SD,Sothinathan R,Bernardo MV,Brenner L,Pereira BJ.Ferumoxytol for treating irondeficiency anemia in ckd.J Am Soc Nephrol.2008;19:1599–1605.]黄芪(Astragalusmembranaceus)和当归(Angelica Sinensis Diels,ASD)是临床上常用的中药补血药,对缺铁性贫血有很好的治疗效果,具有促进铁吸收,调节铁代谢,促进骨髓造血功能等多种效应。已经有研究证实,黄芪多糖和当归多糖是其改善缺铁性贫血的有效成分。因而,将黄芪多糖和当归多糖修饰到磁性纳米颗粒的表面,制备黄芪多糖-当归多糖组合物包被超顺磁性纳米颗粒,将具有补充铁元素、调节铁代谢等多重功效,提高缺铁性贫血的治疗效果。Carbohydrate-coated nano-iron particles, as a new type of iron supplement, have been approved by the US FDA for the clinical treatment of iron deficiency anemia. [Lu M, Cohen MH, Rieves D, Pazdur R. Fda report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease. AmJ Hematol. 2010; 85:315–319. Spinowitz BS, Kausz AT, Baptista J, Noble SD , Sothinathan R, Bernardo MV, Brenner L, Pereira BJ. Ferumoxytol for treating irondeficiency anemia in ckd. J Am Soc Nephrol. 2008; 19:1599–1605.] Astragalus (Astragalus membranaceus) and Angelica (Angelica Sinensis Diels, ASD) are clinical It is a traditional Chinese medicine blood tonic commonly used in the world. It has a good therapeutic effect on iron deficiency anemia, and has various effects such as promoting iron absorption, regulating iron metabolism, and promoting bone marrow hematopoietic function. Studies have confirmed that astragalus polysaccharides and angelica polysaccharides are effective ingredients for improving iron deficiency anemia. Therefore, astragalus polysaccharides and angelica polysaccharides are modified on the surface of magnetic nanoparticles, and the composition of astragalus polysaccharides and angelica polysaccharides is prepared to coat superparamagnetic nanoparticles, which will have multiple functions such as supplementing iron elements and regulating iron metabolism, and can improve iron deficiency anemia. the therapeutic effect.
发明内容Contents of the invention
为了解决上述问题,本发明的目的提供一种生物吸收利用率高,补铁效果比较明显,无毒副作用,且原料来源易得,制备方法科学合理,药理作用及机理明确的黄芪多糖-当归多糖组合物补铁剂及制备方法和用途。In order to solve the above problems, the purpose of the present invention is to provide an astragalus polysaccharide-angelia polysaccharide with high bioabsorption and utilization rate, obvious iron supplementation effect, no toxic and side effects, easy-to-obtain raw material source, scientific and reasonable preparation method, clear pharmacological action and mechanism Composition iron supplement, preparation method and application.
本发明的技术方案是:一种黄芪多糖-当归多糖组合物补铁剂,以水相Fe3O4超顺磁性纳米颗粒为核、以及包覆在所述水相Fe3O4超顺磁性纳米颗粒核表面的黄芪多糖和当归多糖;其中,水相Fe3O4超顺磁性纳米颗粒的质量百分比为25%-58%,黄芪多糖的质量百分比为4%-72%,当归多糖的质量百分比为5%-62%。The technical solution of the present invention is: an astragalus polysaccharide-angelica polysaccharide composition iron supplement, which uses the aqueous phase Fe 3 O 4 superparamagnetic nanoparticles as the core, and is coated on the aqueous phase Fe 3 O 4 superparamagnetic Astragalus polysaccharide and angelica polysaccharide on the surface of the nanoparticle core; wherein, the mass percentage of Fe3O4 superparamagnetic nanoparticles in the aqueous phase is 25%-58%, the mass percentage of astragalus polysaccharide is 4 %-72%, and the mass percentage of angelica polysaccharide The percentage is 5%-62%.
进一步,所述水相Fe3O4超顺磁性纳米颗粒的核粒径为5-30nm。Furthermore, the core diameter of the aqueous phase Fe 3 O 4 superparamagnetic nanoparticles is 5-30 nm.
进一步,所述黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Further, the mass percent of each component of the astragalus polysaccharide-angelica polysaccharide composition iron supplement is:
黄芪多糖46.7%,当归多糖28.3%,水相Fe3O4超顺磁性纳米颗粒25%。Astragalus polysaccharide 46.7%, Angelica polysaccharide 28.3%, water phase Fe 3 O 4 superparamagnetic nanoparticles 25%.
进一步,所述黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Further, the mass percent of each component of the astragalus polysaccharide-angelica polysaccharide composition iron supplement is:
黄芪多糖26.6%,当归多糖48.4%,水相Fe3O4超顺磁性纳米颗粒25%。Astragalus polysaccharide 26.6%, Angelica polysaccharide 48.4%, water phase Fe 3 O 4 superparamagnetic nanoparticles 25%.
进一步,所述黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Further, the mass percent of each component of the astragalus polysaccharide-angelica polysaccharide composition iron supplement is:
黄芪多糖26.3%,当归多糖26.7%,水相Fe3O4超顺磁性纳米颗粒47%。Astragalus polysaccharide 26.3%, Angelica polysaccharide 26.7%, water phase Fe 3 O 4 superparamagnetic nanoparticles 47%.
进一步,所述黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Further, the mass percent of each component of the astragalus polysaccharide-angelica polysaccharide composition iron supplement is:
黄芪多糖15%,当归多糖37%,水相Fe3O4超顺磁性纳米颗粒58%。Astragalus polysaccharide 15%, Angelica polysaccharide 37%, water phase Fe 3 O 4 superparamagnetic nanoparticles 58%.
进一步,所述黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Further, the mass percent of each component of the astragalus polysaccharide-angelica polysaccharide composition iron supplement is:
黄芪多糖50%,当归多糖10%,水相Fe3O4超顺磁性纳米颗粒40%。Astragalus polysaccharide 50%, Angelica polysaccharide 10%, water phase Fe 3 O 4 superparamagnetic nanoparticles 40%.
本发明的另一目的是提供上述黄芪多糖-当归多糖组合物补铁剂的制备方法,该方法具体包括以下步骤:Another object of the present invention is to provide a preparation method of the above-mentioned astragalus polysaccharide-angelica polysaccharide composition iron supplement, which specifically includes the following steps:
步骤(1)制备油相的Fe3O4超顺磁性纳米颗粒;Step (1) preparing the Fe 3 O 4 superparamagnetic nanoparticles of the oil phase;
步骤(2)用含有羧基的极性小分子对步骤(1)制备得到的油相的Fe3O4超顺磁性纳米颗粒表面进行改性,将极性小分子通过羧基与所述纳米颗粒表面的金属离子配位,使Fe3O4超顺磁性纳米颗粒从油相转变为水相,使其能够均匀稳定悬浮于水相溶液中;Step (2) modify the surface of the Fe 3 O 4 superparamagnetic nanoparticles of the oil phase prepared in step (1) with a polar small molecule containing a carboxyl group, and the polar small molecule is connected to the surface of the nanoparticle through the carboxyl group The metal ion coordination of Fe 3 O 4 transforms the superparamagnetic nanoparticles from oil phase to water phase, so that they can be uniformly and stably suspended in the water phase solution;
步骤(3)采用酶-Sevag交联法和乙醇沉淀方法将多糖含量为30%的黄芪多糖和当归多糖进行充分提纯,去除黄芪多糖和当归多糖中的蛋白质、植物色素和其它杂质,使黄芪多糖和当归多糖中的多糖成分的含量高于90%,备用;Step (3) Enzyme-Sevag cross-linking method and ethanol precipitation method are used to fully purify the astragalus polysaccharide and angelica polysaccharide with a polysaccharide content of 30%, remove the protein, plant pigment and other impurities in the astragalus polysaccharide and angelica polysaccharide, and make the astragalus polysaccharide And the content of polysaccharides in Angelica polysaccharides is higher than 90%, and it is reserved;
步骤(4)将经步骤3提纯后的黄芪多糖和当归多糖加入到步骤2制备得到的含有水相Fe3O4超顺磁性纳米颗粒的水相溶液中,超声波处理15-25分钟,然后加热至80-90℃,回流反应时间为1-3小时,即得到黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒,然后加入药学上可接受的輔料或捕助性成分制备而成药学制剂的补铁剂。Step (4) adding the astragalus polysaccharides and angelica polysaccharides purified in step 3 to the aqueous phase solution containing the aqueous phase Fe3O4 superparamagnetic nanoparticles prepared in step 2 , ultrasonic treatment for 15-25 minutes, and then heating to 80-90°C, the reflux reaction time is 1-3 hours, and the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition are obtained, and then the pharmaceutically acceptable auxiliary materials or trapping components are added. Iron supplements for pharmaceutical preparations.
进一步,所述药学制剂包括片剂、胶囊、颗粒剂、丸剂、散剂、口服液和膏剂。Further, the pharmaceutical preparations include tablets, capsules, granules, pills, powders, oral liquids and ointments.
经一步,所述含有羧基的极性小分子为檬酸钠、柠檬酸、琥珀酸、苹果酸、异柠檬酸、a-酮戊二酸、草酰乙酸、丙酮酸、乳酸、延胡索酸、顺乌头酸、甘油、6-磷酸葡萄糖、6-磷酸果糖或2,6-二磷酸果糖。After one step, the polar small molecules containing carboxyl groups are sodium citrate, citric acid, succinic acid, malic acid, isocitric acid, α-ketoglutaric acid, oxaloacetic acid, pyruvic acid, lactic acid, fumaric acid, citric acid, Head acid, glycerol, glucose-6-phosphate, fructose-6-phosphate or fructose-2,6-diphosphate.
进一步,所述的黄芪多糖-当归多糖组合物补铁剂应用于防治缺铁性贫血中。Further, the iron supplement of the astragalus polysaccharide-angelia polysaccharide composition is applied to the prevention and treatment of iron deficiency anemia.
本发明中,用于提取黄芪多糖的原料药黄芪为豆科植物蒙古黄芪Astragalusmembranaceus(Fisch.)Bge.var.mongho-licus(Bge.)Hsiao或膜荚黄芪Astragalusmembranaceus(Fisch.)Bge.的干燥根。本品性温味甘,归肺脾两经,具有补气固表,利尿托毒,排脓敛疮等功效。In the present invention, the raw material Astragalus membranaceus used to extract astragalus polysaccharides is the dry root of leguminous plant Astragalusmembranaceus (Fisch.) Bge.var.mongho-licus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. . This product is warm in taste and sweet in nature, and belongs to the two meridians of the lung and spleen.
本发明所述中药有效部位组合物中,用于提取当归多糖的原料药当归为伞形科植物当归Angelica sinensis(Oliv.)Diels的干燥根。本品性温味辛、甘,归心、肝、肺三经,具有补血,活血,调经止痛,润燥滑肠等功效。In the traditional Chinese medicine effective part composition of the present invention, the raw material Angelica sinensis used for extracting Angelica sinensis polysaccharide is the dried root of Angelica sinensis (Oliv.) Diels of Umbelliferae. This product is warm in taste, pungent and sweet, and has the functions of nourishing blood, promoting blood circulation, regulating menstruation and relieving pain, moistening dryness and smoothing intestines, etc.
黄芪和当归中医经典方剂当归补血汤的成分,常用于血虚诸证的治疗,临床上对缺铁性贫血有很好的治疗效果。对黄芪多糖、当归多糖联合应用治疗缺铁性贫血的研究已有文献报道,涉及的内容为:(1)黄芪、当归原药材联合使用具有抗小鼠、大鼠缺铁性贫血的作用;(2)黄芪和当归混合物的提取物具有改善大鼠、小鼠缺铁性贫血的作用;(3)当归补血汤提取物具有改善大鼠、小鼠缺铁性贫血的作用;(4)黄芪和当归混合提取物与铁或铁纳米颗粒形成复合物具有改善动物缺铁性贫血的作用。但到目前为止,尚未见关于黄芪多糖、当归多糖和超顺磁性纳米铁颗粒不同比例复合物对缺铁性贫血动物模型干预作用的研究报道。Astragalus and Danggui are the components of Danggui Buxue Decoction, a classic traditional Chinese medicine prescription, which are commonly used in the treatment of various syndromes of blood deficiency, and have a good therapeutic effect on iron deficiency anemia clinically. The research on the combined application of astragalus polysaccharides and angelica polysaccharides in the treatment of iron deficiency anemia has been reported in the literature, and the contents involved are: (1) the combined use of astragalus and angelica raw materials has anti-iron deficiency anemia in mice and rats; (2) The extract of the mixture of Astragalus and Angelica has the effect of improving iron deficiency anemia in rats and mice; (3) the extract of Danggui Buxue Decoction has the effect of improving iron deficiency anemia in rats and mice; (4) Astragalus The complex formed by the mixed extract of Angelica sinensis and iron or iron nanoparticles has the effect of improving iron deficiency anemia in animals. But so far, there is no research report on the intervention effect of astragalus polysaccharides, angelica polysaccharides and superparamagnetic nano-iron particles in different proportions on animal models of iron deficiency anemia.
本发明人采用缺铁饮食诱导的小鼠缺铁性贫血模型,系统研究了本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒治疗缺铁性贫血的作用及其机理。结果显示,本发明中药有效部位组合物能显著提高缺铁性贫血小鼠外周血红细胞数量和血红蛋白含量。这表明,本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒具有显著的治疗缺铁性贫血的作用,可以用于缺铁性贫血的治疗。该实验结果还提示,本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒的治疗缺铁性贫血的作用可能与其调节铁代谢有关。The present inventors used the iron-deficiency anemia model in mice induced by an iron-deficiency diet to systematically study the effect and mechanism of the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention in treating iron-deficiency anemia. The results show that the traditional Chinese medicine effective part composition of the present invention can significantly increase the number of red blood cells and the content of hemoglobin in the peripheral blood of mice with iron deficiency anemia. This shows that the superparamagnetic nano-iron particle coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention has a significant effect on treating iron deficiency anemia and can be used for the treatment of iron deficiency anemia. The experimental results also suggest that the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention may be related to the regulation of iron metabolism in the treatment of iron deficiency anemia.
本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒原料来源易得,制备方法科学合理,药理作用及机理明确,对缺铁性贫血能起到标本兼治的良好效果,使用本发明的补铁剂日补铁量1mg/kg体重的剂量下(低于2mg/kg体重)即有很好的补铁效果,能够减轻机体的铁负载,防止铁中毒的发生,具有广阔的应用前景。The source of the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention is easy to obtain, the preparation method is scientific and reasonable, the pharmacological action and mechanism are clear, and it can have a good effect on treating both symptoms and root causes of iron deficiency anemia. The invented iron supplement has a good iron supplement effect at a dose of 1mg/kg body weight per day (less than 2mg/kg body weight), can reduce the iron load of the body, and prevent the occurrence of iron poisoning, and has a wide range of applications prospect.
具体实施方式detailed description
下面结合实施例对本发明作进一步的说明,但不以任何方式对本发明加以限制,基于本发明教导所作的任何变换或替换,均属于本发明的保护范围。The present invention will be further described below in conjunction with the examples, but the present invention is not limited in any way, and any transformation or replacement based on the teaching of the present invention belongs to the protection scope of the present invention.
本发明一种黄芪多糖-当归多糖组合物补铁剂,以水相Fe3O4超顺磁性纳米颗粒为核、以及包覆在所述水相Fe3O4超顺磁性纳米颗粒核表面的黄芪多糖和当归多糖;其中,水相Fe3O4超顺磁性纳米颗粒的质量百分比为25%-58%,黄芪多糖的质量百分比为4%-72%,当归多糖的质量百分比为5%-62%,所述水相Fe3O4超顺磁性纳米颗粒的核粒径为5-30nm。The present invention is an astragalus polysaccharide-angelica polysaccharide composition iron supplement, which uses the aqueous phase Fe3O4 superparamagnetic nanoparticle as the core and is coated on the surface of the aqueous phase Fe3O4 superparamagnetic nanoparticle core Astragalus polysaccharide and angelica polysaccharide; wherein, the mass percentage of Fe3O4 superparamagnetic nanoparticles in water phase is 25%-58%, the mass percentage of astragalus polysaccharide is 4 %-72%, and the mass percentage of angelica polysaccharide is 5%- 62%, the core diameter of the Fe 3 O 4 superparamagnetic nanoparticles in the water phase is 5-30nm.
实施例1:Example 1:
该补铁剂的各个组分的质量百分比为:The mass percent of each component of this iron supplement is:
黄芪多糖46.7%,当归多糖28.3%,水相Fe3O4超顺磁性纳米颗粒25%。Astragalus polysaccharide 46.7%, Angelica polysaccharide 28.3%, water phase Fe 3 O 4 superparamagnetic nanoparticles 25%.
步骤(1)制备油相的Fe3O4超顺磁性纳米颗粒;Step (1) preparing the Fe 3 O 4 superparamagnetic nanoparticles of the oil phase;
步骤(2)用含有羧基的极性小分子对油相的Fe3O4超顺磁性纳米颗粒表面进行改性,将极性小分子通过羧基与纳米颗粒表面的金属离子配位,使Fe3O4纳米颗粒从油相转变为水相,使其能够均匀稳定悬浮于水相溶液中;Step (2) modify the surface of the Fe 3 O 4 superparamagnetic nanoparticles in the oil phase with a small polar molecule containing a carboxyl group, coordinate the small polar molecule with the metal ion on the surface of the nanoparticle through the carboxyl group, and make the Fe 3 O 4 nanoparticles change from the oil phase to the water phase, so that they can be uniformly and stably suspended in the water phase solution;
步骤(3)采用酶-Sevag交联法和乙醇沉淀方法将多糖含量为30%的黄芪多糖和当归多糖充分提纯,去除蛋白质、植物色素和其它杂质,使黄芪多糖和当归多糖中的多糖成分的含量高于90%,备用;Step (3) using enzyme-Sevag cross-linking method and ethanol precipitation method to fully purify the astragalus polysaccharide and angelica polysaccharide with polysaccharide content of 30%, remove protein, plant pigment and other impurities, and make the polysaccharide composition in astragalus polysaccharide and angelica polysaccharide Content higher than 90%, reserve;
步骤(4)将经步骤3提纯后的黄芪多糖和当归多糖加入到步骤2制备得到的含有水相Fe3O4超顺磁性纳米颗粒的水相溶液中,超声波处理15分钟,然后加热至80℃,回流反应时间为1小时,即得到黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒,然后加入药学上可接受的輔料或捕助性成分制备而成药学制剂的补铁剂。Step (4) Add the astragalus polysaccharides and angelica polysaccharides purified in step 3 to the aqueous phase solution containing the aqueous phase Fe 3 O 4 superparamagnetic nanoparticles prepared in step 2, ultrasonically treat for 15 minutes, and then heat to 80 ℃, the reflux reaction time is 1 hour, and the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelia polysaccharide composition are obtained, and then the iron supplement of the pharmaceutical preparation is prepared by adding pharmaceutically acceptable auxiliary materials or trapping components .
实施例2:该补铁剂的各个组分的质量百分比为:Embodiment 2: the mass percent of each component of this iron supplement is:
黄芪多糖26.6%,当归多糖48.4%,水相Fe3O4超顺磁性纳米颗粒25%。Astragalus polysaccharide 26.6%, Angelica polysaccharide 48.4%, water phase Fe 3 O 4 superparamagnetic nanoparticles 25%.
步骤(1)制备油相的Fe3O4超顺磁性纳米颗粒;Step (1) preparing the Fe 3 O 4 superparamagnetic nanoparticles of the oil phase;
步骤(2)用含有羧基的极性小分子对油相的Fe3O4超顺磁性纳米颗粒表面进行改性,将极性小分子通过羧基与纳米颗粒表面的金属离子配位,使Fe3O4纳米颗粒从油相转变为水相,使其能够均匀稳定悬浮于水相溶液中;Step (2) modify the surface of the Fe 3 O 4 superparamagnetic nanoparticles in the oil phase with a small polar molecule containing a carboxyl group, coordinate the small polar molecule with the metal ion on the surface of the nanoparticle through the carboxyl group, and make the Fe 3 O 4 nanoparticles change from the oil phase to the water phase, so that they can be uniformly and stably suspended in the water phase solution;
步骤(3)采用酶-Sevag交联法和乙醇沉淀方法将多糖含量为30%的黄芪多糖和当归多糖充分提纯,去除蛋白质、植物色素和其它杂质,使黄芪多糖和当归多糖中的多糖成分的含量高于90%,备用;Step (3) using enzyme-Sevag cross-linking method and ethanol precipitation method to fully purify the astragalus polysaccharide and angelica polysaccharide with polysaccharide content of 30%, remove protein, plant pigment and other impurities, and make the polysaccharide composition in astragalus polysaccharide and angelica polysaccharide Content higher than 90%, reserve;
步骤(4)将经步骤3提纯后的黄芪多糖和当归多糖加入到步骤2制备得到的含有水相Fe3O4超顺磁性纳米颗粒的水相溶液中,超声波处理25分钟,然后加热至90℃,回流反应时间为3小时,即得到黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒,然后加入药学上可接受的輔料或捕助性成分制备而成药学制剂的补铁剂。Step (4) Add the astragalus polysaccharides and angelica polysaccharides purified in step 3 to the aqueous phase solution containing the aqueous phase Fe 3 O 4 superparamagnetic nanoparticles prepared in step 2, ultrasonically treat for 25 minutes, and then heat to 90 ℃, the reflux reaction time is 3 hours, and the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition are obtained, and then the iron supplement of the pharmaceutical preparation is prepared by adding pharmaceutically acceptable auxiliary materials or trapping components .
实施例3:该补铁剂的各个组分的质量百分比为:Embodiment 3: the mass percent of each component of this iron supplement is:
黄芪多糖26.3%,当归多糖26.7%,水相Fe3O4超顺磁性纳米颗粒47%。Astragalus polysaccharide 26.3%, Angelica polysaccharide 26.7%, water phase Fe 3 O 4 superparamagnetic nanoparticles 47%.
步骤(1)制备油相的Fe3O4超顺磁性纳米颗粒;Step (1) preparing the Fe 3 O 4 superparamagnetic nanoparticles of the oil phase;
步骤(2)用含有羧基的极性小分子对油相的Fe3O4超顺磁性纳米颗粒表面进行改性,将极性小分子通过羧基与纳米颗粒表面的金属离子配位,使Fe3O4纳米颗粒从油相转变为水相,使其能够均匀稳定悬浮于水相溶液中;Step (2) modify the surface of the Fe 3 O 4 superparamagnetic nanoparticles in the oil phase with a small polar molecule containing a carboxyl group, coordinate the small polar molecule with the metal ion on the surface of the nanoparticle through the carboxyl group, and make the Fe 3 O 4 nanoparticles change from the oil phase to the water phase, so that they can be uniformly and stably suspended in the water phase solution;
步骤(3)采用酶-Sevag交联法和乙醇沉淀方法将多糖含量为30%的黄芪多糖和当归多糖充分提纯,去除蛋白质、植物色素和其它杂质,使黄芪多糖和当归多糖中的多糖成分的含量高于90%,备用;Step (3) using enzyme-Sevag cross-linking method and ethanol precipitation method to fully purify the astragalus polysaccharide and angelica polysaccharide with polysaccharide content of 30%, remove protein, plant pigment and other impurities, and make the polysaccharide composition in astragalus polysaccharide and angelica polysaccharide Content higher than 90%, reserve;
步骤(4)将经步骤3提纯后的黄芪多糖和当归多糖加入到步骤2制备得到的含有水相Fe3O4超顺磁性纳米颗粒的水相溶液中,超声波处理20分钟,然后加热至85℃,回流反应时间为1.5小时,即得到黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒,然后加入药学上可接受的輔料或捕助性成分制备而成药学制剂的补铁剂。Step (4) Add the astragalus polysaccharides and angelica polysaccharides purified in step 3 to the aqueous phase solution containing the aqueous phase Fe 3 O 4 superparamagnetic nanoparticles prepared in step 2, ultrasonically treat for 20 minutes, and then heat to 85 ℃, the reflux reaction time is 1.5 hours, and the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition are obtained, and then the iron supplement of the pharmaceutical preparation is prepared by adding pharmaceutically acceptable auxiliary materials or trapping components .
实施例4:黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Example 4: Astragalus polysaccharide-Angelica polysaccharide composition The mass percentage of each component of the iron supplement is:
黄芪多糖26.3%,当归多糖26.7%,水相Fe3O4超顺磁性纳米颗粒47%。Astragalus polysaccharide 26.3%, Angelica polysaccharide 26.7%, water phase Fe 3 O 4 superparamagnetic nanoparticles 47%.
实施例5:黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Example 5: Astragalus polysaccharide-angelica polysaccharide composition The mass percentage of each component of the iron supplement is:
黄芪多糖15%,当归多糖37%,水相Fe3O4超顺磁性纳米颗粒58%。Astragalus polysaccharide 15%, Angelica polysaccharide 37%, water phase Fe 3 O 4 superparamagnetic nanoparticles 58%.
实施例6:黄芪多糖-当归多糖组合物补铁剂的各个组分的质量百分比为:Example 6: Astragalus Polysaccharide-Angelica Polysaccharide Composition The mass percentage of each component of the iron supplement is:
黄芪多糖50%,当归多糖10%,水相Fe3O4超顺磁性纳米颗粒40%。Astragalus polysaccharide 50%, Angelica polysaccharide 10%, water phase Fe 3 O 4 superparamagnetic nanoparticles 40%.
采用本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对小鼠缺铁性贫血的治疗作用。Therapeutic effect of the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention on iron deficiency anemia in mice.
1.供试样品1. Test sample
本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒1:简称“颗粒1”,按本发明实施例2制备;Superparamagnetic nano-iron particles 1 coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention: referred to as "particle 1", prepared according to Example 2 of the present invention;
本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒2:简称“颗粒2”,按本发明实施例2制备;The superparamagnetic iron nanoparticle 2 coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention: referred to as "particle 2", prepared according to Example 2 of the present invention;
本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒3:简称“颗粒3”,按本发明实施例2制备;The superparamagnetic iron nanoparticle 3 coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention: referred to as "particle 3", prepared according to Example 2 of the present invention;
对照药物硫酸亚铁片:上海黄海制药有限公司提供,批准文号:国药准字H31021752。The control drug, ferrous sulfate tablets: provided by Shanghai Huanghai Pharmaceutical Co., Ltd., approval number: Guoyao Zhunzi H31021752.
2.实验仪器与试剂:2. Experimental instruments and reagents:
全自动血液分析仪(美国贝克曼库尔特公司);B204-N型电子天平(瑞士Mettler公司)。Automatic blood analyzer (Beckman Coulter, USA); B204-N electronic balance (Mettler, Switzerland).
小鼠低铁饲料,北京科澳协力饲料有限公司提供;血清铁测定试剂盒,南京建成生物工程研究所提供;血清铁调素ELISA试剂盒,武汉华美生物工程有限公司提供。Low-iron feed for mice was provided by Beijing Keao Xieli Feed Co., Ltd.; serum iron assay kit was provided by Nanjing Jiancheng Bioengineering Research Institute; serum hepcidin ELISA kit was provided by Wuhan Huamei Bioengineering Co., Ltd.
3.实验动物3. Experimental animals
ICR小鼠,雄性,体重18-20g,斯贝福(北京)生物技术有限公司提供。ICR mice, male, weighing 18-20 g, were provided by Sibeifu (Beijing) Biotechnology Co., Ltd.
4.实验方法4. Experimental method
4.1、造模及给药4.1. Modeling and administration
SD大鼠60只,随机分为6组,即正常对照组、模型组、颗粒1组(8mg/kg)、颗粒2组(8mg/kg)、颗粒3组(8mg/kg)和阳性对照药硫酸亚铁组(5.43mg/kg),每组10只。模型组与各治疗组小鼠采用低铁饲料复制小鼠缺铁性贫血模型,具体操作步骤如下:在实验环境下适应3d后,饲予低铁饲料及去离子水,实验过程中严格避免铁污染。第4周对所有实验大鼠采尾血测定血红蛋白(Hb)含量,选择血红蛋白低于100g/L的大鼠进行贫血恢复实验。血红蛋白低于100g/L的大鼠根据体重和血红蛋白水平随机分为5组,包括模型组、硫酸亚铁组、颗粒1组、颗粒2组、颗粒3组、每组10只。各组在恢复贫血实验期间继续给予低铁饲料和去离子水。贫血模型对照组每天灌胃给予去离子水溶液,硫酸亚铁对照组每天给予5.43/(kg·d)硫酸亚铁溶液,颗粒1组每天给予颗粒1悬浊液8mg/(kg·d),颗粒2组每天给予颗粒2悬浊液8mg/(kg·d),颗粒3组每天给予颗粒3悬浊液8mg/(kg·d)。30天后取材,测定以下指标:60 SD rats were randomly divided into 6 groups, namely normal control group, model group, granule 1 group (8 mg/kg), granule 2 group (8 mg/kg), granule 3 group (8 mg/kg) and positive control drug Ferrous sulfate group (5.43mg/kg), 10 rats in each group. The mice in the model group and each treatment group were fed with low-iron feed to reproduce the iron-deficiency anemia model of mice. The specific operation steps were as follows: after adapting to the experimental environment for 3 days, they were fed with low-iron feed and deionized water, and iron was strictly avoided during the experiment. pollute. In the 4th week, tail blood was collected from all experimental rats to measure hemoglobin (Hb) content, and rats with hemoglobin lower than 100 g/L were selected for anemia recovery experiment. Rats with hemoglobin lower than 100g/L were randomly divided into 5 groups according to body weight and hemoglobin level, including model group, ferrous sulfate group, granule 1 group, granule 2 group, and granule 3 group, with 10 rats in each group. Each group continued to receive low-iron diet and deionized water during recovery from anemia experiment. The anemia model control group was given deionized water solution by intragastric administration every day, the ferrous sulfate control group was given 5.43/(kg d) ferrous sulfate solution every day, and the granule 1 group was given 1 granule suspension 8 mg/(kg d) every day, and the granule Group 2 was given 8 mg/(kg·d) of granule 2 suspension every day, and group 3 was given 8 mg/(kg·d) of granule 3 suspension every day. After 30 days, the materials were taken, and the following indicators were measured:
4.2取末梢血,用全自动血液分析仪测定红细胞数量和血红蛋白含量。4.2 Take the peripheral blood, and measure the number of red blood cells and hemoglobin content with an automatic blood analyzer.
4.3腹主动脉取血,室温静置4h,4℃300转/分钟×5分钟离心分离血清,按试剂盒说明书操作检测血清铁含量。4.3 Blood was collected from the abdominal aorta, left at room temperature for 4 hours, and the serum was centrifuged at 300 rpm at 4°C for 5 minutes, and the serum iron content was detected according to the kit instructions.
4.4腹主动脉取血,室温静置4h,4℃300转/分钟×5分钟离心分离血清,按试剂盒说明书操作检测血清铁调素含量。4.4 Blood was collected from the abdominal aorta, left at room temperature for 4 hours, and the serum was centrifuged at 300 rpm at 4°C for 5 minutes, and the serum hepcidin content was detected according to the instructions of the kit.
5实验结果5 Experimental results
5.1本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对外周血红细胞数量和血红蛋白含量的影响5.1 The influence of the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention on the number of peripheral red blood cells and the content of hemoglobin
外周血红细胞数量和血红蛋白含量是缺铁性贫血的诊断指标,也是评价治疗效果的重要指标。The number of red blood cells and hemoglobin content in peripheral blood are diagnostic indicators for iron deficiency anemia, and are also important indicators for evaluating the therapeutic effect.
模型组大鼠外周血红细胞数量显著低于正常对照组,且血红蛋白含量小于100g/L,表明造模成功。颗粒1组、颗粒2组、颗粒3组和硫酸亚铁组大鼠的外周血红细胞数和血红蛋白含量均升高,表明颗粒1、颗粒2、颗粒3和硫酸亚铁这4种药物对缺铁性贫血均有治疗效果,其中以颗粒2组的效果最好。结果见表1。The number of peripheral red blood cells in the model group was significantly lower than that in the normal control group, and the hemoglobin content was less than 100g/L, indicating that the model was successfully established. The number of peripheral blood red blood cells and hemoglobin content of the rats in the granule 1 group, granule 2 group, granule 3 group and ferrous sulfate group were all increased, indicating that the four drugs of granule 1, granule 2, granule 3 and ferrous sulfate were effective for iron deficiency. All of them have curative effect on chronic anemia, among which the granule 2 group has the best effect. The results are shown in Table 1.
表1黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对外周血红细胞数量和血红蛋白含量的影响Table 1 Effect of astragalus polysaccharide-angelica polysaccharide composition coated superparamagnetic iron nanoparticles on the number of peripheral red blood cells and hemoglobin content
由上述实验数据可见,本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒能明显改善缺铁性贫血模型大鼠的贫血状况。From the above experimental data, it can be seen that the superparamagnetic nano-iron particles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention can significantly improve the anemia of iron deficiency anemia model rats.
5.2本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对血清铁的影响5.2 The influence of the superparamagnetic iron nanoparticles coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention on serum iron
铁在体内多以结合铁的形式存在,且主要存在于血红蛋白和铁蛋白中,并广泛参与机体的代谢过程。各治疗组均能提高缺铁性贫血模型大鼠血清铁含量,而且颗粒1组、颗粒2组和颗粒3组的血清铁含量均高于硫酸亚铁组。但颗粒2组和颗粒3组大鼠的铁摄入量是1mg/kg,仅为硫酸亚铁组的1/2,这表明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒中的铁更容易被吸收。结果见表2。Iron exists mostly in the form of bound iron in the body, mainly in hemoglobin and ferritin, and widely participates in the metabolic process of the body. Each treatment group can increase the serum iron content of iron deficiency anemia model rats, and the serum iron content of granule 1 group, granule 2 group and granule 3 group are all higher than those of ferrous sulfate group. However, the iron intake of rats in the granule 2 group and the granule 3 group was 1 mg/kg, which was only 1/2 of the ferrous sulfate group. iron is more easily absorbed. The results are shown in Table 2.
表2黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对外周血红细胞数量和血红蛋白含量的影响Table 2 Effect of astragalus polysaccharide-angelica polysaccharide composition coated superparamagnetic iron nanoparticles on the number of peripheral red blood cells and hemoglobin content
5.3本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对血清铁调素含量的影响5.3 The effect of the superparamagnetic iron nanoparticles coated with the Astragalus polysaccharide-Angelica polysaccharide composition of the present invention on the content of serum hepcidin
健康人体中参与代谢的铁每天仅有12mg通过膳食摄入,而约20mg是通过肝、脾及骨髓中的网状内皮系统对衰老的红细胞的吞噬作用循环利用。体内铁的营养状况会直接影响肝细胞合成和分泌铁调素,铁调素可以在十二指肠上皮细胞、肝细胞等细胞中直接结合膜铁转运蛋白。当体内铁含量下降时,铁调素合成分泌受到抑制,铁调素与膜铁转运蛋白结合减少,膜铁转运蛋白降解吸收被抑制,从而促进铁从细胞释放到血浆促进铁的重复利用;当体内铁含量增加时则反之。铁调素蛋白水平可以直接反映体内铁的营养状况,而且其异常表达会导致铁代谢和吸收紊乱。实验结果表明,与正常对照组相比,模型组血清铁调素含量下降。提示贫血状态下机体通过减少铁调素分泌来促进铁的吸收。与模型组相比,各治疗组血清铁调素均有不同程度的上升,提示表明其除了通过提高体内铁含量补铁外,也可能通过加速衰老的红细胞中铁的循环利用,起到更好的补铁效果。Only 12 mg of iron involved in metabolism in a healthy human body is taken in through diet every day, while about 20 mg is recycled through the phagocytosis of aging red blood cells by the reticuloendothelial system in the liver, spleen and bone marrow. The nutritional status of iron in the body will directly affect the synthesis and secretion of hepcidin in liver cells. Hepcidin can directly bind to ferroportin in duodenal epithelial cells, liver cells and other cells. When the iron content in the body decreases, the synthesis and secretion of hepcidin is inhibited, the binding of hepcidin and ferroportin is reduced, and the degradation and absorption of ferroportin is inhibited, thereby promoting the release of iron from cells to plasma to promote iron reuse; when The opposite is true when the iron content in the body increases. The level of hepcidin protein can directly reflect the nutritional status of iron in the body, and its abnormal expression can lead to disorders of iron metabolism and absorption. The experimental results showed that, compared with the normal control group, the serum hepcidin content of the model group decreased. It is suggested that the body promotes iron absorption by reducing the secretion of hepcidin in the state of anemia. Compared with the model group, serum hepcidin in each treatment group increased to varying degrees, suggesting that in addition to increasing the iron content in the body, it may also accelerate the recycling of iron in aging red blood cells to play a better role. Iron effect.
表3黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对血清铁调素含量的影响Table 3 Effect of astragalus polysaccharide-angelica polysaccharide composition coated superparamagnetic iron nanoparticles on serum hepcidin content
6、结论6 Conclusion
血液学结果表明,黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒改善缺铁性贫血可能的作用机制是有效增加体内结合铁的水平,促进红细胞的生成,而不仅仅是提高体内游离铁的水平。黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒上调铁调素的表达,则表明其除了通过提高体内铁含量补铁外,也可能通过加速衰老的红细胞中铁的循环利用,起到更好的补铁效果。The results of hematology showed that the possible mechanism of action of the superparamagnetic nano-iron particles coated with astragalus polysaccharide-angelica polysaccharide composition to improve iron deficiency anemia is to effectively increase the level of bound iron in the body and promote the production of red blood cells, not just to improve the Levels of free iron. The superparamagnetic nano-iron particles coated with astragalus polysaccharide-angelica polysaccharide composition up-regulate the expression of hepcidin, indicating that it not only supplements iron by increasing the iron content in the body, but also may play a role in accelerating the recycling of iron in aging red blood cells. Better iron supplementation effect.
黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒对缺铁性贫血患者的治疗作用Therapeutic effect of superparamagnetic nano-iron particles coated with Astragalus polysaccharide-Angelica polysaccharide composition on patients with iron deficiency anemia
1病例资料病例来源于门诊患者,共94例,随机分为治疗组和对照组。治疗组48例中,男19例,女29例,年龄17-72岁,平均43岁,病程4个月-25年,平均13.5年,其中轻度贫血27例,中度贫血21例;对照组46例,其中男16例,女30例,年龄16-73岁,平均42.4岁,病程5个月-23年,平均12.7年,其中轻度贫血24例,中度贫血22例.每1例服药前后填写预先设计的观察表格,两组患者年龄、性别、病因、病程、贫血程度等经统计学处理,无显著性差异(P>0.05)。具有可比性。1 Case data Cases come from outpatients, a total of 94 cases were randomly divided into treatment group and control group. Among the 48 cases in the treatment group, there were 19 males and 29 females, aged 17-72 years, with an average of 43 years, and the course of disease was 4 months to 25 years, with an average of 13.5 years, including 27 cases of mild anemia and 21 cases of moderate anemia; 46 cases in the group, including 16 males and 30 females, aged 16-73 years, with an average of 42.4 years, with a course of disease ranging from 5 months to 23 years, with an average of 12.7 years, including 24 cases of mild anemia and 22 cases of moderate anemia. Every 1 Cases filled out the pre-designed observation form before and after taking the medicine, and the age, sex, etiology, course of disease, and anemia degree of the two groups were statistically processed, and there was no significant difference (P>0.05). comparable.
2参照《血液病诊断及疗效标准》(张之南.血液病诊断疗效标准[M].天津:天津科学出版社,1999.9-14)中的缺铁性贫血的诊断标准拟定。贫血分级标准:以血红蛋白多少为标准,轻度:H b男91-120g/L,女81-105g/L;中度:Hb男61-90g/L,女61-81g/L。2 The diagnostic criteria for iron deficiency anemia in "Diagnostic and Curative Criteria for Blood Diseases" (Zhang Zhinan. Diagnostic and Curative Criteria for Blood Diseases [M]. Tianjin: Tianjin Science Press, 1999.9-14) were drawn up. Anemia grading standard: based on the amount of hemoglobin, mild: Hb 91-120g/L for men and 81-105g/L for women; moderate: Hb 61-90g/L for men and 61-81g/L for women.
3排除标准:重度贫血患者:Hb男31-60g/L,女41-60g/L;患者有贫血症状而无铁缺乏者;合并心血管、脑血管、肝、肾、及造血系统其他严重原发性疾病、精神病患者;原发病尚未控制,持续出血所致贫血;两周内接受过输血治疗或1个月内接受铁剂治疗者。3 Exclusion criteria: patients with severe anemia: male Hb 31-60g/L, female 41-60g/L; patients with symptoms of anemia but no iron deficiency; patients with cardiovascular, cerebrovascular, liver, kidney, and other serious causes of hematopoietic system Patients with epidemiological diseases and mental illness; the primary disease has not been controlled, and anemia caused by continuous bleeding; those who have received blood transfusion within two weeks or received iron therapy within one month.
4治疗方法:治疗组给予本发明黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒2(简称“颗粒2”,按本发明实施例2制备)0.16g,每天3次(相当于Fe 0.16g/日),饭后服。对照组口服硫酸亚铁(广西桂林南药股份有限公司),每次0.3g,每天3次(相当于Fe0.33/日),饭后服。治疗期间停用其他补血药物。两组均以1个月为1疗程。4. Therapeutic method: the treatment group is given 0.16 g of superparamagnetic nano-iron particles 2 (abbreviated as "particle 2", prepared according to Example 2 of the present invention) coated with the astragalus polysaccharide-angelica polysaccharide composition of the present invention, 3 times a day (equivalent to Fe 0.16g/day), after meals. The control group took ferrous sulfate (Guangxi Guilin Pharmaceutical Co., Ltd.) orally, 0.3g each time, 3 times a day (equivalent to Fe0.33/day), after meals. During the treatment, other blood enriching drugs were stopped. Both groups took 1 month as a course of treatment.
5疗效观察及指标及检测方法:两组均于治疗前后检测血红蛋白(H b),红细胞数(RBC)、平均红细胞体积(MCV)、平均血红蛋白(MCH)、红细胞平均血红蛋白浓度(MCHC)。5 Curative effect observation, indicators and detection methods: Both groups were tested before and after treatment for hemoglobin (Hb), red blood cell count (RBC), mean corpuscular volume (MCV), mean hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).
疗效评定标准参照《血液病诊断及疗效标准》分为治愈、显效、有效和无效4级。临床治愈:Hb男>120g/L,女>105g/L,临床症状消失,血清铁,总铁结合力等恢复正常;显效:临床症状明显好转,贫血严重分级转为轻度,改善2级以上;有效:临床症状好转,贫血严重度改善1级;无效:临床症状及贫血严重度分级无改善。The curative effect evaluation standard is divided into 4 grades: cured, markedly effective, effective and ineffective according to the "Criteria for Diagnosis and Curative Effect of Blood Diseases". Clinical cure: Hb male>120g/L, female>105g/L, clinical symptoms disappear, serum iron, total iron binding capacity, etc. return to normal; markedly effective: clinical symptoms are significantly improved, the severity of anemia is reduced to mild, and the improvement is above 2 grades ; Effective: the clinical symptoms improved, and the severity of anemia improved by 1 grade; Ineffective: the clinical symptoms and anemia severity grades did not improve.
6统计方法计数资料采用χ2检验,计量资料用t检验,等级资料用Ridit分析。6 Statistical methods The χ 2 test was used for the count data, the t test was used for the measurement data, and the Ridit analysis was used for the rank data.
7结果7 results
7.1临床疗效比较治疗组疗效优于对照组(P<0.05)。见表4。7.1 Clinical curative effect comparison The curative effect of the treatment group was better than that of the control group (P<0.05). See Table 4.
表4两组疗效比较Table 4 Comparison of curative effects between the two groups
注:两组总有效率比较,P<0.05。Note: The comparison of the total effective rate between the two groups, P<0.05.
7.2两组治疗前后Hb MCV MCH MCHC等指标比较,见表5。7.2 Comparison of Hb MCV MCH MCHC and other indicators before and after treatment between the two groups, see Table 5.
表5两组治疗前后观察指标变化比较(x±s)Table 5 Comparison of changes in observation indicators before and after treatment in the two groups (x±s)
7.3不良反应7.3 Adverse reactions
治疗组未见不良反应,对照组14例出现不同程度胃肠反应,作对症处理后,症状缓解。There was no adverse reaction in the treatment group, and 14 cases in the control group had different degrees of gastrointestinal reactions. After symptomatic treatment, the symptoms were relieved.
8结论8 Conclusion
黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒治疗缺铁性贫血的效果优于硫酸亚铁,在改善各项血液指标方面均优于硫酸亚铁,日补铁量仅为常规补铁量的50%即可达到很好的治疗效果。且未见任何不良反应,值得临床推广使用。Astragalus polysaccharide-angelica polysaccharide-coated superparamagnetic nano-iron particles are more effective than ferrous sulfate in treating iron deficiency anemia, and are better than ferrous sulfate in improving various blood indicators, and the daily iron supplementation is only conventional A good therapeutic effect can be achieved with 50% of iron supplementation. And no adverse reactions have been seen, and it is worthy of clinical promotion and use.
实施例6:胶囊剂Embodiment 6: Capsules
黄芪多糖-当归多糖组合物包被的超顺磁性纳米铁颗粒 32%Astragalus Polysaccharide-Angelica Polysaccharide Composition Coated Superparamagnetic Nano Iron Particles 32%
淀粉 68%Starch 68%
将上述本发明中药组合物与淀粉混合后,填充入硬明胶胶囊中,即得。The above-mentioned traditional Chinese medicine composition of the present invention is mixed with starch, filled into hard gelatin capsules, and obtained.
实施例7:口服液Embodiment 7: oral liquid
将上述本发明中药组合物、柠檬酸、蔗糖和蒸馏水搅拌混匀,装入口服液瓶中,即得。Stir and mix the above-mentioned traditional Chinese medicine composition of the present invention, citric acid, sucrose and distilled water, put it into an oral liquid bottle, and obtain the product.
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