CN1486969A - 枸橼酸氢钾镁复合矿物盐及制备方法 - Google Patents
枸橼酸氢钾镁复合矿物盐及制备方法 Download PDFInfo
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- MNWBULKLOQZRTN-UHFFFAOYSA-K magnesium;potassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Mg+2].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O MNWBULKLOQZRTN-UHFFFAOYSA-K 0.000 title claims abstract description 24
- 239000002131 composite material Substances 0.000 title claims abstract description 12
- 229910052500 inorganic mineral Inorganic materials 0.000 title claims abstract description 9
- 239000011707 mineral Substances 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims 3
- 101100366942 Mus musculus Ston1 gene Proteins 0.000 title 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000011777 magnesium Substances 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 9
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 9
- 150000002681 magnesium compounds Chemical class 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 150000002500 ions Chemical class 0.000 claims abstract description 4
- 150000003112 potassium compounds Chemical class 0.000 claims abstract description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 8
- 239000000395 magnesium oxide Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000000047 product Substances 0.000 claims 2
- 239000012467 final product Substances 0.000 claims 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims 1
- 239000000347 magnesium hydroxide Substances 0.000 claims 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims 1
- 239000011736 potassium bicarbonate Substances 0.000 claims 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims 1
- 210000002700 urine Anatomy 0.000 abstract description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract description 9
- 206010007027 Calculus urinary Diseases 0.000 abstract description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 5
- 239000011575 calcium Substances 0.000 abstract description 5
- 229910052791 calcium Inorganic materials 0.000 abstract description 5
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 abstract description 4
- 208000009911 Urinary Calculi Diseases 0.000 abstract description 4
- -1 citrate radical ion Chemical class 0.000 abstract description 4
- 229910001425 magnesium ion Inorganic materials 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 235000006408 oxalic acid Nutrition 0.000 abstract description 3
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 abstract description 2
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 abstract description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 abstract description 2
- 229960003067 cystine Drugs 0.000 abstract description 2
- UHNWOJJPXCYKCG-UHFFFAOYSA-L magnesium oxalate Chemical compound [Mg+2].[O-]C(=O)C([O-])=O UHNWOJJPXCYKCG-UHFFFAOYSA-L 0.000 abstract description 2
- 229940116269 uric acid Drugs 0.000 abstract description 2
- ZUQOBHTUMCEQBG-UHFFFAOYSA-N 4-amino-5-hydroxynaphthalene-1,7-disulfonic acid Chemical compound OS(=O)(=O)C1=CC(O)=C2C(N)=CC=C(S(O)(=O)=O)C2=C1 ZUQOBHTUMCEQBG-UHFFFAOYSA-N 0.000 abstract 1
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 238000002425 crystallisation Methods 0.000 abstract 1
- 230000008025 crystallization Effects 0.000 abstract 1
- QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 abstract 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 7
- 229960003975 potassium Drugs 0.000 description 6
- 239000003826 tablet Substances 0.000 description 5
- 208000008281 urolithiasis Diseases 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000001508 potassium citrate Substances 0.000 description 2
- 229960002635 potassium citrate Drugs 0.000 description 2
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 2
- 235000011082 potassium citrates Nutrition 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010020524 Hydronephrosis Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- BBFQZRXNYIEMAW-UHFFFAOYSA-N aristolochic acid I Chemical compound C1=C([N+]([O-])=O)C2=C(C(O)=O)C=C3OCOC3=C2C2=C1C(OC)=CC=C2 BBFQZRXNYIEMAW-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000003589 nefrotoxic effect Effects 0.000 description 1
- 231100000381 nephrotoxic Toxicity 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种枸橼酸氢钾镁复合矿物盐及制备方法。本发明将枸橼酸和水混合后加入钾化合物、镁化合物，产生反应，控制温度在100℃以下，形成摩尔比镁∶钾∶氢∶枸橼酸＝1∶3∶1∶2。本发明的枸橼酸氢钾镁复合盐治疗尿路结石有显著的效果，枸橼酸根离子和镁离子共同抑制含钙结石的结晶，镁离子通过络合降低尿中成石物质的浓度，与草酸结合形成易溶的草酸镁随尿排出，可提高尿液pH值，直接溶解尿酸结石和胱氨酸结石，人体无不良反应，解决了现有排石冲剂和枸橼酸钾治疗效果不明显和引发高钾血症等的缺陷。本发明工艺简单、成本低。
Description
技术领域
本发明涉及一种复合矿物盐，特别涉及一种枸橼酸氢钾镁复合矿物盐及制备方法。
背景技术
在本发明作出之前，临床上治疗尿石症的药物主要有枸橼酸钾和排石冲剂。患者使用枸橼酸钾后易引发高钾血症，且疗效也不全面；排石冲剂严格来讲并不能溶解结石，而且其中的木通成份含有肾毒性的马兜铃酸，对肾小管有较大危害。而尿石症的人群患病率可达5％，复发率也很高，一年为15％，十年为50％，尿石症的主要后果是肾积水和尿路感染，最终可能导致肾功能损害。因此，临床上缺乏治疗尿结石的有效药物。
发明内容
本发明的目的就在于克服上述缺陷，研制一种能有效治疗尿石症的枸橼酸氢钾镁复合盐及制备方法。
本发明的技术方案是：
枸橼酸氢钾镁复合矿物盐，其主要技术特征在于在一种化合物中含有镁、钾和枸橼酸，其合成反应式为：
其产物结构式为：
其四种离子摩尔比为镁∶钾∶氢∶枸橼酸＝1∶3∶1∶2。
本发明的又一技术方案是：枸橼酸氢钾镁复合矿物盐的制备方法，其特征在于：
(4)将枸橼酸与水混合，搅拌；
(5)加入钾化合物、镁化合物；
(6)在加入镁化合物时，控制反应温度在100℃以下；
本发明的优点和效果在于：在尿路结石中约近90％是含钙结石，其主要成份是草酸钙和磷酸钙结晶，而枸橼酸根离子和镁离子是含钙结石结晶的抑制因子；枸橼酸氢钾镁在人体尿液中可解离出枸橼酸根离子和镁离子，不仅可直接抑制含钙结石结晶的形成，而且也可通过络合，可降低尿中成石物质的浓度，从而间接抑制结石的形成；具体地讲就是枸橼酸根离子可与尿中钙络合物合成可溶性枸橼酸钙，降低尿中钙离子的浓度，镁离子可与尿中草酸结合，形成易溶的草酸镁随尿排出，降低尿中草酸的浓度；另外，枸橼酸氢钾镁是一种碱性物质，可提高尿液的pH值，直接溶解尿酸结石和胱氨酸结石，这类结石约占尿路结石的5％；枸橼酸氢钾镁在人体尿液解离形成各种离子均属人体生理性物质，在常规剂量下无不良反应。
具体实施方式
实施例1：
将120g枸橼酸和30g水在一罐中混和，快速搅拌，加入12.6g氧化镁，在通入CO2的情况下，将64.8g碳酸钾分四等份加入，最后加10g水完成反应；反应温度控制在100℃以下，超过120℃，产物易发生退化现象，最适宜温度控制在80℃；干燥后，测得密度大于1.1g/mm3，可制得片剂。每片含有1.75mmol镁、5.25mmol钾和3.5mmol枸橼酸。
实施例2：
将48.03kg枸橼酸和12kg水在7加仑的带状混合容器中混合约2分钟，再将5.04kgMgO分三等份(每份连续搅拌3分钟)加入，温度控制则同实施例1；再将51.8kgK2CO3分成三份(每份连续搅拌5分钟)加入；最后加入4kg水，混合2～5分钟，将产物过滤，在60℃温度下干燥3小时，得到产物(颗粒)的密度大于1.1g/mm3。粉碎至医药级，供制药用。
将干燥的枸橼酸氢钾镁与1％(重量比)的硬脂酸镁混合，并经多次压片制成片剂；每片含42mg镁、205.5mg钾和662mg枸橼酸。
实施例3：
用MgCO3代替MgO，制成密度大于1.0g/mm3的枸橼酸氢钾镁。
实施例4：
用Mg(OH)2代替MgO，制成密度大于1.0/mm3的枸橼酸氢钾镁。
枸橼酸氢钾镁有良好的摩尔比，可制成肠溶片。
无腊片密度为1.6g/mm3，有腊片密度为1.4g/mm3。
可用蔗糖、聚维酮、碳酸钙等包衣。
枸橼酸氢钾镁片剂理想的重量比为：
镁∶钾∶氢∶枸橼酸＝4.8∶23∶0.2∶72。
含水混合物的含水量控制在10％～20％。若含水量低于10％，反应进行不够完全；含水量高于20％，则会产生膏状物，使反应时间延长。
本发明中，每3.5mmol(893mg)枸橼酸氢钾镁中含有1.75mmol镁、5.25mmol钾、1.751mmol氢和3.5mmol枸橼酸。
Claims (7)
1.枸橼酸氢钾镁复合矿物盐，其特征在于含有钾、镁和枸橼酸，其合成反应式为：
其四种离子摩尔比为镁∶钾∶氢∶枸橼酸＝1∶3∶1∶2。
2.枸橼酸氢钾镁复合矿物盐的制备方法，其特征在于：
(1)将枸橼酸与水混合，搅拌；
(2)加入钾化合物、镁化合物；
(3)在加入镁化合物时，控制反应温度在100℃以下。
3.根据权利要求2所述的枸橼酸氢钾镁的制备方法，其特征在于步骤(3)的反应温度控制在80℃。
4.据权利要求2所述的枸橼酸氢钾镁的制备方法，其特征在于最后生成物的含水量控制在10％～20％。
5.根据权利要求2所述的枸橼酸氢钾镁的制备方法，其特征在于钾化合物选用KHCO3、K2CO3。
6.根据权利要求2所述的枸橼酸氢钾镁的制备方法，其特征在于镁化合物选用MgCO3、MgO、Mg(OH)2。
7.根据权利要求2所述的枸橼酸氢钾镁的制备方法，其特征在于将得到的生成物放入带式混合器中搅拌，形成颗粒，干燥后得到枸橼酸氢钾镁颗粒，再粉碎至医药级，供制药用。
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1722772A4 (en) * | 2004-03-08 | 2008-03-19 | Mission Pharma Co | FOOD SUPPLEMENT WITH STOCHIOMETRIC SPECIFIC CALIUM MAGNESIUM CITRATE |
| CN102557921A (zh) * | 2011-12-28 | 2012-07-11 | 合肥科尚医药科技有限公司 | 一种枸橼酸氢钾钠复盐水合物的制备方法 |
| CN109529107A (zh) * | 2018-12-07 | 2019-03-29 | 中鼎凯瑞科技成都有限公司 | 多微量元素有机化合物与无机化合物通过水合桥化形成的有机-无机自凝固复合骨移植物 |
| CN116924902A (zh) * | 2023-07-21 | 2023-10-24 | 石家庄杏林锐步医药科技股份有限公司 | 一种枸橼酸氢钾钠颗粒的制备方法 |
-
2003
- 2003-08-13 CN CNA031323057A patent/CN1486969A/zh active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1722772A4 (en) * | 2004-03-08 | 2008-03-19 | Mission Pharma Co | FOOD SUPPLEMENT WITH STOCHIOMETRIC SPECIFIC CALIUM MAGNESIUM CITRATE |
| CN102557921A (zh) * | 2011-12-28 | 2012-07-11 | 合肥科尚医药科技有限公司 | 一种枸橼酸氢钾钠复盐水合物的制备方法 |
| CN109529107A (zh) * | 2018-12-07 | 2019-03-29 | 中鼎凯瑞科技成都有限公司 | 多微量元素有机化合物与无机化合物通过水合桥化形成的有机-无机自凝固复合骨移植物 |
| CN116924902A (zh) * | 2023-07-21 | 2023-10-24 | 石家庄杏林锐步医药科技股份有限公司 | 一种枸橼酸氢钾钠颗粒的制备方法 |
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