CN104473963A - Preparation method of rare earth chemical drug lanthanum carbonatechewable tablets - Google Patents

Preparation method of rare earth chemical drug lanthanum carbonatechewable tablets Download PDF

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CN104473963A
CN104473963A CN 201410815515 CN201410815515A CN104473963A CN 104473963 A CN104473963 A CN 104473963A CN 201410815515 CN201410815515 CN 201410815515 CN 201410815515 A CN201410815515 A CN 201410815515A CN 104473963 A CN104473963 A CN 104473963A
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rare earth
lanthanum
lanthanum carbonate
method
oxide
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CN 201410815515
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CN104473963B (en )
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王锦高
王滢
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厦门科明达科技有限公司
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Abstract

The invention provides a preparation method of rare earth chemical drug lanthanum carbonatechewable tablets, and relates torare earth chemical drugs. The preparation methodcomprises the following steps: a separationproductlanthanum oxideof ion-absorbed rare earth ore purchased from the market is purified, rare earth lanthanum oxideof the separationproductlanthanum oxide of the ion-absorbed rare earth ore accounts for 99.99% of the total amount of rare earth, impurities in rare earth lanthanum oxide are removed, and rare earth lanthanum is separated from other rare earth, wherein the impurities comprise oxides of rare earth elements excluding lanthanum oxide as well as non-rare earth impurity elements; exchange is performed through ion exchange resinabsorption and desorption principle, an organic glass ion exchange column is produced firstly, then the exchange column is filled with ion exchange resin, the ion exchange resin is washed by 2NHCl until the resin doesn't contain iron and then washed by water until the resin is neutral, and resin is soaked for standby application; rare earth lanthanum and non-rare earth impurities are separated; nitrilortiacetic acid is removed through water washing, and the rare earth lanthanum is separated from other rare earth; and obtained pure rare earth lanthanum ions are precipitated by ammonium bicarbonate to obtain a lanthanum carbonate crystal which is sterilized and dried to prepare the rare earth chemical drug lanthanum carbonatechewable tablets.

Description

稀土化学药碳酸镧咀嚼片的制备方法 Preparing rare earth lanthanum carbonate chewable tablet chemical drugs

技术领域 FIELD

[0001] 本发明涉及稀土化学药,尤其是涉及一种稀土化学药碳酸镧咀嚼片的制备方法。 [0001] The present invention relates to a rare earth chemical drugs, particularly to a method for preparing a rare earth chemical agent lanthanum carbonate in chewable tablets.

背景技术 Background technique

[0002] 美国福斯利诺FOSRENOL发现稀土金属镧离子和磷离子的结合产生不溶沉淀,随消化道排出体外,不进入血液循环系统。 [0002] U.S. Fox Illinois FOSRENOL found to bind a rare earth metal lanthanum and phosphorus ions generate insoluble precipitate with gastrointestinal excreted, does not enter the blood circulation system. 大量病受试者并不产生不良副作用,明显好于用碳酸钙,醋酸钙,碳酸铝的疗效。 A large number of adverse side effects are not subject disease, significantly better with calcium carbonate, calcium acetate, aluminum carbonate in efficacy.

[0003] 碳酸镧咀嚼片自发明以来,尤其是近几年已推广全球42个国家,美国90%高磷血症病人得到康复。 [0003] lanthanum carbonate chewable tablets since it was invented, especially in recent years has been extended 42 countries around the world, the United States 90% of hyperphosphatemia patient rehabilitation. 2012年此药进入中国,目前已成为国内治疗高磷血症唯一主推药品。 In 2012 the drug to enter China, it has now become the treatment of hyperphosphatemia, the only main push drugs. 数十万病人在使用,享受到高科技的成果。 Hundreds of thousands of patients in use, to enjoy the high-tech achievements.

[0004] 众所周知中国是稀土资源大国,拥有丰富的稀土镧资源。 [0004] As we all know China is a big country of rare earth resources, it has abundant resources of rare earth lanthanum. 中国人口众多,患慢性肾病的病人达10. 2%,几乎有1.2亿肾病病人。 China's large population, suffer from chronic kidney disease patients up to 10.2%, almost 120 million kidney patients. 目前我国尿毒症患病人群已超过300万人, 患病人数每年以11 %在增加,约有8成肾病患者死于治疗不当,能接受高科技治疗的人群数有限,不普及,最主要的原因基于两点。 At present, China uremia patient population has more than 3 million people, the number of patients per year with 11% increase, about 80% of kidney patients died from improper treatment, can accept a limited number of high-tech treatment of people, not popular, the most important based on two reasons. 其一是美国福斯利诺碳酸镧咀嚼片的药价十分昂贵,没有进入医保,大多数病人难于承受巨额透析费的压力,更难于接受高价碳酸镧的费用,被迫放弃治疗;其二是科学宣传尚不普及。 One is the United States Fox Lino lanthanum carbonate chewable drug prices are very expensive, there is no access to health insurance, the majority of dialysis patients is difficult to bear the huge cost pressure, more difficult to accept the high costs of lanthanum carbonate, forced to abandon treatment; the other is scientific propaganda is not yet universal. 不但肾衰竭病人惧怕高磷血症引发的心梗, 心脑血管坏死;同样对心脑血管病人、糖尿病人、高血压病人的高磷血症危害,也引发心梗, 对这类病人的除磷教育极需加强。 Not only fear myocardial infarction patients with renal failure caused by hyperphosphatemia, cardiovascular necrosis; the same people for cardiovascular disease, diabetes, high blood pressure patients with hyperphosphatemia harm, but also lead to myocardial infarction, in addition to these patients phosphorus education in dire need of strengthening.

[0005] 北京大学等在中国专利CN102432055A中公开一种用于治疗高磷血症的碳酸镧纳米颗粒的制备方法,包括以下步骤:1)把碳酸氢钠溶液加入氯化镧溶液中,制备八水合碳酸镧,2)然后在常压,40〜120°C条件下脱水制备出稳定的含有1〜4个水的碳酸镧,3)最后通过球磨的方法,把制备的样品从微米颗粒球磨成纳米颗粒。 The method of preparing lanthanum carbonate nanoparticles [0005] Chinese patent CN102432055A Peking discloses a method for treating hyperphosphataemia, comprising the following steps: 1) The sodium bicarbonate solution was added a solution of lanthanum chloride, prepared eight hydrated lanthanum carbonate, 2) then dehydrated stabilized lanthanum carbonate prepared containing ~ 4 months of water at atmospheric pressure, 40~120 ° C conditions, 3) and finally by a process of ball milling, the samples prepared from microparticles ball milled nanoparticles. 该发明还涉及由此制备方法获得的八水合碳酸镧La2 (CO3) 3 • 8H20、含有1〜4个水的碳酸镧La2 (CO3) 3 •XH2O(其中X 为1〜4)以及碳酸镧纳米颗粒,及该碳酸镧纳米颗粒在制备用于治疗高磷血症的药物中的应用。 The invention thus further relates to a method for preparing carbonate octahydrate obtained lanthanum La2 (CO3) 3 • 8H20, ~ 4 containing a carbonate aqueous lanthanum La2 (CO3) 3 • XH2O (wherein X is 1 ~ 4) and lanthanum carbonate nano application of particles, and the lanthanum carbonate nanoparticles of a medicament for the treatment of hyperphosphatemia.

[0006] 英国约翰逊马西有限公司在中国专利CN1184428中公开一种含有选择的碳酸镧水合物的药物组合物,经选择的碳酸镧水合物可以经胃肠道施用,治疗肾衰竭病人的血磷酸盐过多症。 [0006] UK Ltd Johnson Marcy discloses a pharmaceutical composition containing a selected lanthanum carbonate hydrate in Chinese patent CN1184428 can be administered parenterally by lanthanum carbonate hydrate selected blood phosphate treatment of renal failure patients too much salt disease.

发明内容 SUMMARY

[0007] 本发明的目的在于提供一种稀土化学药碳酸镧咀嚼片的制备方法。 [0007] The object of the present invention to provide a method for preparing a rare chemical agent lanthanum carbonate in chewable tablets.

[0008] 本发明包括以下步骤: [0008] The present invention comprises the steps of:

[0009] 1)将从市场采购的离子型稀土矿的分离产物-氧化镧提纯,所述离子型稀土矿的分离产物-氧化镧的稀土氧化镧占稀土总量的99. 99 %,除去稀土氧化镧中的杂质,实现稀土氧化镧与其他稀土分离;所述杂质包括除氧化镧的其他稀土元素的氧化物和非稀土杂质元素; [0009] 1) the isolated product market purchases ionic rare earths from - lanthanum oxide purification, the product was isolated ionic rare earths - rare earth lanthanum oxide lanthanum oxide accounting 99.99% of total rare earth, rare earth removed impurities lanthanum oxide, lanthanum oxide and the other to achieve separation of rare earth; and the non-rare earth oxide impurities comprise impurities of other rare earth elements except lanthanum oxide;

[0010] 在步骤1)中,所述其他稀土元素为铈、镨、钕、铕、钇等,所述非稀土杂质元素为妈、错、猛、铜、铅、锌等,杂质元素的总量小于lOOppm。 [0010] In step 1), the other rare earth element is cerium, praseodymium, neodymium, europium, yttrium, rare earth impurities of the non mother, wrong, manganese, copper, lead and zinc, the total impurity element less than lOOppm.

[0011] 2)采用离子交换树脂吸附和脱附原理进行交换,在有机玻璃离子交换柱中填充60目苯乙烯强酸型离子交换树脂,所述60目苯乙烯强酸型离子交换树脂经2NHC1洗至无铁,用蒸馏水洗至中性,浸泡后备用; [0011] 2) using an ion exchange resin to exchange the adsorption and desorption principle, plexiglass ion exchange column filled with 60 mesh styrenic strongly acidic ion exchange resin, a styrene-60 mesh cation exchange resin was washed to 2NHC1 no iron, washed to neutral with distilled water, soaked in standby;

[0012] 3)将稀土镧与非稀土杂质分离,具体方法如下: [0012] 3) The lanthanum rare earth impurities with a non-separation, specific methods are as follows:

[0013] (1)制样:将稀土样品加入盐酸氢铵,再加入盐酸加热溶解,蒸发至近干,用水稀释后,送往尚子交换柱; [0013] (1) sample preparation: the sample was added ammonium hydrogen rare hydrochloric acid, dissolved by heating and then adding hydrochloric acid, evaporated to near dryness, diluted with water and sent to still-exchange column;

[0014] 在步骤3)第(1)部分中,所述盐酸的加入量与盐酸氢铵的体积比可为1 : 1。 [0014] In step 3) 1) portion (the volume added in an amount of hydrochloric acid and ammonium hydrogen ratio of hydrochloric acid may be 1: 1.

[0015] (2)用氮三乙酸洗涤非镧稀土; [0015] (2) a non-rare earth lanthanum washed with nitrilotriacetic acid;

[0016] 用硫氰酸铵和邻菲啰啉法除铁; [0016] with ammonium thiocyanate and phenanthroline method of eliminating iron;

[0017] 用钙色素和新钙试剂除钙和镁; [0017] In addition to calcium and magnesium with calcium dye reagent and the new calcium;

[0018] 用硫酸钡沉淀法除钡; [0018] Barium sulfate precipitation method in addition to barium;

[0019] 用铬天青S方法除铝; [0019] The method using aluminum removal chromazurol S;

[0020] 用双硫腙-四氯化碳萃取除铜、铅、锌; [0020] dithizone - carbon tetrachloride extracted in addition to copper, lead and zinc;

[0021] 用高锰酸钾氧化法除锰; [0021] oxidation by potassium permanganate and manganese;

[0022] 4)用水洗除去氮三乙酸,实现稀土镧与其它稀土的分离,具体方法如下: [0022] 4) nitrilotriacetic acid was removed by washing with water, and separation to achieve other rare earth lanthanum, the specific method is as follows:

[0023](1)用高氯酸氧化还原法除去氧化铈; [0023] (1) with perchloric acid redox cerium oxide is removed;

[0024] (2)用氯化亚锡氧化法除去氧化镨、钕、钐; [0024] (2) is removed by stannous oxide, praseodymium oxide, neodymium, samarium;

[0025] (3)用硫氰酸铵法除去氧化铕; [0025] (3) removing the europium oxide with ammonium thiocyanate method;

[0026] (4)用高氯酸氧化法除去重稀土钇等; [0026] (4) is removed with perchloric heavy rare yttrium oxide and the like;

[0027](5)用EDTA络合分离富集稀土镧; [0027] (5) complexed with EDTA separation and enrichment of lanthanum;

[0028](6)用乙酰胺洗提稀土镧; [0028] (6) acetamide eluted with lanthanum;

[0029]5)测定稀土镧提纯前后杂质含量变化的ppm值; [0029] 5) ppm measured value change impurity content before and after purification lanthanum;

[0030] 6)将得到的纯稀土镧离子制备碳酸镧晶体,灭菌烘干后制成稀土化学药碳酸镧咀嚼片。 [0030] 6) The crystals obtained in Preparation pure lanthanum carbonate lanthanum ions, drying after sterilization chemical drugs made of rare earth lanthanum carbonate chewable tablet.

[0031] 在步骤6)中,所述将得到的纯稀土镧离子制备碳酸镧晶体可先采用碳酸氢铵沉淀制备含1〜4个结晶水的碳酸镧晶体,再采用溶胶-凝胶法制备粒度为40〜60nm的细结晶碳酸镧纳米颗粒; [0031] In step 6), the preparation of lanthanum carbonate obtained pure crystals of lanthanide ions on ammonium bicarbonate may be employed to precipitate crystal water containing ~ 4 Preparation of lanthanum carbonate crystals, and then using the sol - gel method 40~60nm particle size of the fine-crystalline nanoparticles of lanthanum carbonate;

[0032] 所述碳酸氢铵可采用食用级碳酸氢铵;所述采用碳酸氢铵沉淀制备含1〜4个结晶水的碳酸镧晶体时,pH可控制在5. 5〜6. 0,温度可为55〜65°C; [0032] The food grade ammonium bicarbonate may be employed; when using the lanthanum carbonate crystals contained ~ 4 crystal water prepared by precipitation of ammonium bicarbonate, pH 5. 5 to 6 0 can be controlled, temperature. may 55~65 ° C;

[0033] 所述采用溶胶-凝胶法制备粒度为40〜60nm的细结晶碳酸镧纳米颗粒的具体方法如下:在得到的含1〜4个结晶水的碳酸镧晶体中加入柠檬酸,按质量比,碳酸镧:柠檬酸=1 : 2,再加入聚乙二醇至均相,然后将混合溶液形成溶胶,用冰冻法使溶胶转为凝胶, 温度为-KTC,再将凝胶于110〜120°C烘干,用机械法磨碎凝胶,即获得粒度为40〜60nm, 含1〜4个结晶水碳酸镧晶体La2 (CO3)3,不含碱性碳酸镧La(OH) (CO3)的细结晶碳酸镧纳米颗粒; [0033] The use of sol - gel method 40~60nm particle size of fine-crystalline lanthanum carbonate nanoparticles specific method is as follows: the addition of citric acid containing ~ 4 lanthanum carbonate crystals obtained by crystallization in water, by mass ratio, lanthanum carbonate: citric acid = 1: 2, then polyethylene glycol is added until homogeneous, and then the mixed solution was a sol, the sol into gel by freezing method, the temperature is -KTC, then the gel was 110 ~120 ° C dried, mechanically triturated with a gel, i.e., to obtain a particle size of 40~60nm, crystal water containing ~ 4 crystal of lanthanum carbonate La2 (CO3) 3, free of basic lanthanum carbonate La (OH) ( CO3) fine crystalline nanoparticles of lanthanum carbonate;

[0034] 所述灭菌烘干的条件可在20°C灭菌真空干燥箱烘干48h;所述稀土化学药碳酸镧咀嚼片可制成25mg/片,可按每20片(500mg)或40片(IOOOmg)规格包装。 [0034] The drying conditions may be sterilized dried 20 ° C and a vacuum oven for 48h sterilization; the rare chemical agent lanthanum carbonate chewable tablet can be prepared 25mg / tablets, can be every 20 (500mg), or 40 (IOOOmg) specification packaging.

[0035] 由于现有市售稀土氧化镧的纯度只有99. 99%,即仍然有0.01 %杂质,相当于lOOppm。 [0035] Since the conventional purity of commercially available lanthanum oxide only 99.99%, 0.01% impurities, i.e., there is still equivalent to lOOppm. 这些IOOppm的杂质包括其他稀土元素的氧化物和非稀土杂质元素,这些杂质都不容许进入人体内,本发明将现有市售稀土氧化镧中的杂质含量降至最低,甚至接近0,以确保药物的三大功能,即有确切疗效、安全无副作用、价格低廉。 These impurities include IOOppm non-rare earth oxides and rare earth element other impurities, these impurities are not allowed to enter the human body, the conventional commercially available rare earth impurity content of lanthanum oxide in the present invention is to minimize, or even close to zero, to ensure drugs three functions, ie, the exact effect, safe and without side effects, low prices. 另外,本发明制得的碳酸镧咀嚼片中的碳酸镧达纳米级,其晶体粒径为40〜60nm。 Further, the present invention is prepared in lanthanum carbonate lanthanum carbonate chewable tablet NM grade, the crystal grain size of 40~60nm.

[0036] 碳酸镧咀嚼片是一种稀土化学口服药,以稀土为原料。 [0036] Lanthanum Carbonate Chewable oral chemical is a rare earth, rare earth-based raw materials. 这种内服药是利用稀土镧离子与病人体内多余的磷离子相结合生成不溶于水的磷酸镧沉淀,随消化道排出体外,不进入人的血液系统,却把消化道多余的磷离子浓度降低至适度。 This is the use of medication in a patient with lanthanum ions excess phosphorus ions combine to form insoluble lanthanum phosphate precipitation, excreted with the digestive tract, do not enter the human blood system, yet reduced gastrointestinal excess phosphorus ion concentration to moderate. 利用镧离子和磷酸盐的高亲和性,当镧离子在人体胃内酸性环境中从碳酸释放出来,与食物中磷酸盐相结合,形成不溶性的磷酸镧,因而降低了胃肠道对磷的吸收。 Lanthanum and phosphate ions using a high affinity, lanthanum ions when released in the body from the stomach acidic environment out of carbonate, phosphate combined with food, form insoluble lanthanum phosphate, thereby reducing the gastrointestinal tract of phosphorus absorb.

具体实施方式 detailed description

[0037] 以下实施例将对本发明作进一步的说明。 [0037] The following embodiments of the present invention will be further described.

[0038] 本发明实施例包括以下步骤: [0038] Example embodiments of the present invention comprises the steps of:

[0039] 1)将从市场采购的离子型稀土矿的分离产物-氧化镧提纯,所述离子型稀土矿的分离产物-氧化镧的稀土氧化镧占稀土总量的99. 99%,除去稀土氧化镧中的杂质,实现稀土镧与其他稀土分离;所述杂质包括除氧化镧的其他稀土元素的氧化物和非稀土杂质元素;所述其他稀土元素为铈、镨、钕、铕、钇等,所述非稀土杂质元素为钙、铝、锰、铜、铅、锌等,杂质元素的总量小于lOOppm。 [0039] 1) the isolated product market purchases ionic rare earths from - lanthanum oxide purification, the product was isolated ionic rare earths - rare earth lanthanum oxide lanthanum oxide accounting 99.99% of total rare earth, rare earth removed impurities lanthanum oxide, lanthanum with other rare earth to realize separation; the impurities comprise a non-rare earth oxide and the rare earth element impurities other inter lanthanum oxide; the other rare earth element is cerium, praseodymium, neodymium, europium and yttrium the non-rare earth elements as an impurity, calcium, aluminum, manganese, copper, lead and zinc, the total amount of impurities is less than lOOppm.

[0040] 2)采用离子交换树脂吸附和脱附原理进行交换,先制作有机玻璃离子交换柱,有机玻璃离子交换柱填充60目苯乙烯强酸型离子交换树脂,所述60目苯乙烯强酸型离子交换树脂经2NHC1洗至无铁,用蒸馏水洗至中性,浸泡(防止树脂层干涸)后备用; [0040] 2) using an ion exchange resin to exchange the adsorption and desorption principle, first ion exchange column made of plexiglass, glass ion exchange column filled with 60 mesh styrenic strongly acidic ion exchange resin, a strong acid ion styrene 60 mesh exchange resin was washed until no iron 2NHC1, washed to neutral with distilled water, soaked (to prevent dry resin layer) backup;

[0041] 3)将稀土镧与非稀土杂质分离,具体方法如下: [0041] 3) The lanthanum rare earth impurities with a non-separation, specific methods are as follows:

[0042] (1)制样:将稀土样品加入盐酸氢铵,再加入盐酸加热溶解,蒸发至近干,用水稀释,送往离子交换柱;所述盐酸的加入量与稀土样品和盐酸氢铵的体积比可为1 : 1。 [0042] (1) sample preparation: the sample was added rare hydrochloric acid, ammonium hydroxide, hydrochloric acid was added and then dissolved by heating, and evaporated to near dryness, diluted with water and sent to an ion exchange column; the amount of hydrochloric acid and hydrogen with rare samples ammonium hydrochloride volume ratio may be 1: 1.

[0043] (2)用氮三乙酸洗绦,控制流速,洗非镧稀土; [0043] (2) with a nitrogen acid triethyl sash, controlling the flow rate, wash non-rare earth lanthanum;

[0044] 用硫氰酸铵和邻菲啰啉法除铁; [0044] with ammonium thiocyanate and phenanthroline method of eliminating iron;

[0045] 用钙色素和新钙试剂除钙和镁; [0045] In addition to calcium and magnesium with calcium dye reagent and the new calcium;

[0046] 用硫酸钡沉淀法除钡; [0046] Barium sulfate precipitation method in addition to barium;

[0047] 用铬天青S方法除铝; [0047] The method using aluminum removal chromazurol S;

[0048] 用双硫腙-四氯化碳萃取除铜、铅、锌; [0048] dithizone - carbon tetrachloride extracted in addition to copper, lead and zinc;

[0049] 用高锰酸钾氧化法除锰; [0049] oxidation by potassium permanganate and manganese;

[0050] Sd.Hg-般很少存在,Si在盐酸中大部溶出,用硅钼蓝测定; [0050] Sd.Hg- like rarely present, Si dissolution of most of the hydrochloric acid, measured by silicon molybdenum blue;

[0051] 4)再用水洗除去氮三乙酸,实现稀土镧与其它稀土的分离,具体方法如下: [0051] 4) nitrilotriacetic acid was removed and then washed, separated from the other to achieve lanthanum rare earth, as follows:

[0052] (1)用高氯酸氧化还原法除去氧化铈; [0052] (1) with perchloric acid redox cerium oxide is removed;

[0053] (2)用氯化亚锡氧化法除去氧化镨、钕、钐; [0053] (2) is removed by stannous oxide, praseodymium oxide, neodymium, samarium;

[0054] (3)用硫氰酸铵法除去氧化铕; [0054] (3) removing the europium oxide with ammonium thiocyanate method;

[0055] (4)用高氯酸氧化法除去重稀土钇等; [0055] (4) is removed with perchloric heavy rare yttrium oxide and the like;

[0056] (5)用EDTA络合分离富集稀土镧; [0056] (5) complexed with EDTA separation and enrichment of lanthanum;

[0057] (6)用乙酰胺洗提稀土镧; [0057] (6) acetamide eluted with lanthanum;

[0058] (7)测定稀土镧提纯前后杂质含量变化ppm值; [0058] (7) Measurement of change in impurity content before and after ppm lanthanum purification;

[0059] 5)将得到的纯稀土镧离子用碳酸氢铵沉淀获得碳酸镧晶体,灭菌烘干后制成稀土化学药碳酸镧咀嚼片。 [0059] 5) The obtained pure lanthanum carbonate lanthanum ions obtained by ammonium bicarbonate precipitation of crystals, the chemical agent is made of rare earth lanthanum carbonate chewable tablet after sterilization and drying. 所述碳酸氢铵可采用食用级碳酸氢铵;所述用碳酸氢铵沉淀获得碳酸镧晶体时,pH可控制在5. 5〜6. 0,温度可为55〜65°C;获得的碳酸镧晶体为含1〜4 个结晶水,粒度为40〜60nm的细结晶碳酸镧纳米颗粒;所述灭菌烘干的条件可在20°C真空干燥箱烘干48h;所述稀土化学药碳酸镧咀嚼片可制成25mg/片,可按每20片(500mg)或40片(IOOOmg)规格包装。 The food grade ammonium bicarbonate may be employed; when obtaining the lanthanum carbonate crystals precipitated ammonium bicarbonate, pH 5. 5 to 6 may be controlled to 0, the temperature may be 55~65 ° C;. Carbonate obtained ~ 4 containing lanthanum crystals crystal water, particle size of the fine-crystalline 40~60nm lanthanum carbonate nanoparticles; drying of the sterilization conditions may 48h 20 ° C and the drying vacuum oven; the rare chemical drugs carbonate chewable tablets can be made of lanthanum 25mg / tablets, can be every 20 (500mg) or 40 (IOOOmg) packaging specifications.

[0060] 本发明制备的稀土化学药碳酸镧咀嚼片是一种稀土化学口服药,以稀土为原料。 Rare earth lanthanum carbonate chewable tablet prepared chemical drugs of the present invention [0060] This is a rare chemical oral, rare earth-based raw materials. 这种内服药是利用稀土镧离子与病人体内多余的磷离子相结合生成不溶于水的磷酸镧沉淀,随消化道排出体外,不进入人的血液系统,却把消化道多余的磷离子浓度降低至适度。 This is the use of medication in a patient with lanthanum ions excess phosphorus ions combine to form insoluble lanthanum phosphate precipitation, excreted with the digestive tract, do not enter the human blood system, yet reduced gastrointestinal excess phosphorus ion concentration to moderate. 利用镧离子和磷酸盐的高亲和性,当镧离子在人体胃内酸性环境中从碳酸释放出来,与食物中磷酸盐相结合,形成不溶性的磷酸镧,因而降低了胃肠道对磷的吸收。 Lanthanum and phosphate ions using a high affinity, lanthanum ions when released in the body from the stomach acidic environment out of carbonate, phosphate combined with food, form insoluble lanthanum phosphate, thereby reducing the gastrointestinal tract of phosphorus absorb.

[0061]表1 [0061] TABLE 1

[0062] [0062]

Figure CN104473963AD00071

Figure CN104473963AD00081

Claims (10)

  1. 1. 稀土化学药碳酸镧咀嚼片的制备方法,其特征在于包括以下步骤: 1) 将从市场采购的离子型稀土矿的分离产物-氧化镧提纯,所述离子型稀土矿的分离产物-氧化镧的稀土氧化镧占稀土总量的99. 99 %,除去稀土氧化镧中的杂质,实现稀土氧化镧与其他稀土分离;所述杂质包括除氧化镧的其他稀土元素的氧化物和非稀土杂质元素; 2) 采用离子交换树脂吸附和脱附原理进行交换,在有机玻璃离子交换柱中填充60目苯乙烯强酸型离子交换树脂,所述60目苯乙烯强酸型离子交换树脂经2NHC1洗至无铁,用蒸馏水洗至中性,浸泡后备用; 3) 将稀土镧与非稀土杂质分离,具体方法如下: (1) 制样:将稀土样品加入盐酸氢铵,再加入盐酸加热溶解,蒸发至近干,用水稀释后, 送往离子交换柱; (2) 用氮三乙酸洗涤非镧稀土; 用硫氰酸铵和邻菲啰啉法除铁; 用钙色素 A process for producing a rare earth chemical drugs lanthanum carbonate chewable tablet, comprising the steps of: 1) isolating the product market purchases ionic rare earths from - lanthanum oxide purification, the product was isolated ionic rare earths - Oxidation lanthanum rare earth lanthanum oxide accounted for 99.99% of total rare earth, rare earth oxide, lanthanum removal of impurities, to achieve lanthanum oxide with other rare earth separation; the other rare earth element impurities comprise oxides of lanthanum oxide and other non-rare earth impurities element; 2) ion-exchange resin to exchange the adsorption and desorption principle, plexiglass ion exchange column filled with 60 mesh styrenic strongly acidic ion exchange resin, a styrene-60 mesh cation exchange resin was washed until no 2NHC1 iron, washed with distilled water to neutral, soaked standby; 3) rare earth lanthanum non-rare earth impurities separation, as follows: (1) sample preparation: rare earth sample was added ammonium hydrogen hydrochloric acid, adding hydrochloric acid dissolved by heating, and evaporated to near dryness, diluted with water and sent to the ion exchange column; (2) nitrilotriacetic acid washed non-rare earth lanthanum; with ammonium thiocyanate and phenanthroline method of eliminating iron; calcium dye 新钙试剂除钙和镁; 用硫酸钡沉淀法除钡; 用铬天青S方法除铝; 用双硫腙-四氯化碳萃取除铜、铅、锌; 用高锰酸钾氧化法除锰; 4) 用水洗除去氮三乙酸,实现稀土镧与其它稀土的分离,具体方法如下: (1) 用高氯酸氧化还原法除去氧化铈; (2) 用氯化亚锡氧化法除去氧化镨、钕、钐; (3) 用硫氰酸铵法除去氧化铕; (4) 用高氯酸氧化法除去重稀土钇等; (5) 用EDTA络合分离富集稀土镧; (6) 用乙酰胺洗提稀土镧; 5) 测定稀土镧提纯前后杂质含量变化的ppm值; 6) 将得到的纯稀土镧离子制备碳酸镧晶体,灭菌烘干后制成稀土化学药碳酸镧咀嚼片。 New reagent of calcium and magnesium in addition to calcium; except for using barium sulfate precipitation barium; aluminum removal method with chromazurol S; dithizone - carbon tetrachloride extracted in addition to copper, lead and zinc; other oxidation by potassium permanganate manganese; 4) nitrilotriacetic acid was removed by washing with water, and separation to achieve other rare earth lanthanum, and specifically as follows: (1) with perchloric acid to remove redox cerium oxide; (2) removing the oxide by oxidation of stannous chloride praseodymium, neodymium, samarium; (3) with ammonium thiocyanate europium oxide is removed; (4) was removed with perchloric acid oxidation heavy rare yttrium and the like; (5) separation and enrichment with lanthanum of EDTA; (6) acetamide eluted with lanthanum; 5) ppm measured value change of impurity content before and after purification lanthanum; 6) the preparation of lanthanum carbonate crystals obtained pure lanthanum ions, drying after sterilization chemical drugs made of rare earth lanthanum carbonate chewable tablet .
  2. 2. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤1)中, 所述其他稀土元素为铈、镨、钕、铕、钇。 2. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs claim, wherein in step 1), the other rare earth element is cerium, praseodymium, neodymium, europium, yttrium.
  3. 3. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤1)中, 所述非稀土杂质元素为1¾、错、猛、铜、铅、锌,杂质元素的总量小于lOOppm。 3. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs claim, wherein in step 1), the non-rare earth elements as an impurity 1¾, wrong, manganese, copper, lead, zinc, impurity elements the total is less than lOOppm.
  4. 4. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤3)第(1)部分中,所述盐酸的加入量与盐酸氢铵的体积比为1 : 1。 4. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs claim, wherein in step 3) (1) section, an amount of hydrochloric acid and ammonium hydrogen volume ratio of the hydrochloric acid in 1: 1 .
  5. 5. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤6)中, 所述将得到的纯稀土镧离子制备碳酸镧晶体是先采用碳酸氢铵沉淀制备含1〜4个结晶水的碳酸镧晶体,再采用溶胶-凝胶法制备粒度为40〜60nm的细结晶碳酸镧纳米颗粒。 5. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs as claimed in claim 6 characterized in that step), the obtained pure crystalline preparation of lanthanum carbonate lanthanum ions is first prepared containing precipitated using ammonium bicarbonate ~ 4 crystal water lanthanum carbonate crystals, and then using the sol - gel method 40~60nm particle size of fine-crystalline lanthanum carbonate nanoparticles.
  6. 6. 如权利要求5所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于所述碳酸氢铵采用食用级碳酸氢铵。 The method of preparing the rare earth chemical agent 5 lanthanum carbonate chewable tablet as claimed in claim 6, wherein said food grade ammonium bicarbonate employed.
  7. 7. 如权利要求5所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于所述采用碳酸氢铵沉淀制备含1〜4个结晶水的碳酸镧晶体时,pH控制在5. 5〜6. 0,温度为55〜65°C。 7. The method of preparing the rare earth chemical agent lanthanum carbonate chewable tablet as claimed in claim, wherein said lanthanum carbonate using ammonium bicarbonate precipitate crystals prepared containing ~ 4 crystal water, pH controlled at -5 to 5. 6.0, a temperature of 55~65 ° C.
  8. 8. 如权利要求5所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于所述采用溶胶-凝胶法制备粒度为40〜60nm的细结晶碳酸镧纳米颗粒的具体方法为:在得到的含1〜 4个结晶水的碳酸镧晶体中加入柠檬酸,按质量比,碳酸镧:柠檬酸=1 : 2,再加入聚乙二醇至均相,然后将混合溶液形成溶胶,用冰冻法使溶胶转为凝胶,温度为-l〇°C,再将凝胶于110〜120°C烘干,用机械法磨碎凝胶,即获得粒度为40〜60nm,含1〜4个结晶水碳酸镧晶体La2 (C03) 3,不含碱性碳酸镧La (OH) (C03)的细结晶碳酸镧纳米颗粒。 8. The method of preparing the rare earth chemical agent lanthanum carbonate chewable tablet as claimed in claim, wherein said using the sol - specific methods 40~60nm fine crystalline nanoparticles of lanthanum carbonate prepared gel method is size: in to give lanthanum carbonate 1 ~ 4 crystals containing water of crystallization of citric acid was added, the mass ratio, lanthanum carbonate: citric acid = 1: 2, then polyethylene glycol is added until homogeneous, and then the sol solution was mixed with ice into the sol-gel method, a temperature of -l〇 ° C, and then drying the gel at 110~120 ° C, the gel was mechanically pulverized, i.e., to obtain a particle size of 40~60nm, containing ~ 4 months water of crystallization crystals of lanthanum carbonate La2 (C03) 3, free of basic lanthanum carbonate La (OH) (C03) of the fine-crystalline lanthanum carbonate nanoparticles.
  9. 9. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤6)中, 所述灭菌烘干的条件是在20°C灭菌真空干燥箱烘干48h。 9. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs claim, characterized in that in step 6), the sterilizing and drying conditions are 20 ° C and vacuum oven drying sterilization 48h.
  10. 10. 如权利要求1所述稀土化学药碳酸镧咀嚼片的制备方法,其特征在于在步骤6)中, 所述稀土化学药碳酸镧阻嚼片为制成25mg/片,按每20片(500mg)或40片(lOOOmg)规格包装。 10. The method of preparing a rare earth lanthanum carbonate chewable tablet chemical drugs as claimed in claim 6 characterized in that step), the rare earth chemical barrier agent lanthanum carbonate chewable tablets was prepared 25mg / tablets per 20 ( 500 mg of) or 40 (lOOOmg) packaging specifications.
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