CN115536631A - 一种高纯度的右旋硫辛酸镁盐的制备方法 - Google Patents
一种高纯度的右旋硫辛酸镁盐的制备方法 Download PDFInfo
- Publication number
- CN115536631A CN115536631A CN202110736330.7A CN202110736330A CN115536631A CN 115536631 A CN115536631 A CN 115536631A CN 202110736330 A CN202110736330 A CN 202110736330A CN 115536631 A CN115536631 A CN 115536631A
- Authority
- CN
- China
- Prior art keywords
- lipoic acid
- magnesium salt
- dextro
- acid magnesium
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960002663 thioctic acid Drugs 0.000 title claims abstract description 43
- 235000019136 lipoic acid Nutrition 0.000 title claims abstract description 35
- -1 lipoic acid magnesium salt Chemical class 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008213 purified water Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims 4
- 230000001376 precipitating effect Effects 0.000 claims 1
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 15
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 14
- 239000011777 magnesium Substances 0.000 description 14
- 229910052749 magnesium Inorganic materials 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 8
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 159000000003 magnesium salts Chemical class 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 206010063547 Diabetic macroangiopathy Diseases 0.000 description 1
- 206010054044 Diabetic microangiopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000002568 Multienzyme Complexes Human genes 0.000 description 1
- 108010093369 Multienzyme Complexes Proteins 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006362 insulin response pathway Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000009140 magnesium supplementation Methods 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/04—Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
本发明公开了一种高纯度的右旋硫辛酸镁盐的制备方法,用稀碱溶液把右旋硫辛酸充分溶解,然后滴加氯化镁溶液,反应得到右旋硫辛酸镁盐。本发明与现有方法相比,产品易得且纯度高、收率高、成本低、工艺简明安全、绿色环保,特别适合工业化生产。
Description
技术领域
本发明属医药化工领域,特别涉及一种高纯度的右旋硫辛酸镁盐的制备方法。
背景技术
硫辛酸(lipoic acid),化学名为1,2-双硫环戊烷基-3-戊酸,有一个手性中心,两种对映异构体中R型硫辛酸的生理活性远高于S型硫辛酸。硫辛酸能够消除致病的自由基,属于维生素类药物,是唯一兼具脂溶性与水溶性的万能抗氧剂,它在多酶复合体中作为辅酶起作用,并且在三羧酸循环和光合成中表现出关键性作用。临床上,R-硫辛酸越来越多地用于治疗神经性糖尿病,缺血再灌注等疾病;另外,R-硫辛酸对肝病、老年痴呆、白内障、心脏病等多种疾病也具有疗效,并能有效抑制HIV-1在细胞中的扩散。
目前,有各种各样的硫辛酸衍生物被逐渐发现并合成,可是硫辛酸具有特定的缺点,特别地,天然形态的R-硫辛酸在超过40℃时是不稳定的,它在某些仓库储存环境下会降解。同时,硫辛酸也是吸湿性的。因此,带有一种天然盐类的天然形态的硫辛酸的稳定是需要的。
在众多的R-硫辛酸衍生物中,已知的营养形式之一是镁盐,R-硫辛酸镁盐是一种稳定、不吸湿、淡黄色粉末,这种稳定的盐同时提供镁和R-硫辛酸,镁是人体内第四大最普遍的元素,也是细胞内第二大最丰富的离子,因为镁是300多种酶的辅助因子,充足的镁对于许多生物合成过程都是必不可少的。研究表明镁扮演胰岛素作用的第二信使的角色。相反,胰岛素本身被证明是细胞内镁积累的重要调节因子。有关文献报道了与胰岛素抵抗相关的情况,如高血压或衰老,也与细胞内低镁含量有关。在糖尿病中,细胞内镁水平低已经被报道,可能是由于增加的尿流失和胰岛素抵抗。如此低的细胞内镁含量在多大程度上促进了糖尿病大血管和微血管病变的发展仍有待于确定。据报道,细胞内镁含量减少可导致2型(非胰岛素依赖性)糖尿病患者的胰岛素反应和作用受损。慢性镁补充有助于改善非胰岛素依赖型糖尿病患者的胰岛β细胞反应和胰岛素分泌。
使用R-硫辛酸镁盐生产药物,用于补偿和失代偿胰岛素抵抗及相关疾病和后遗症,或糖尿病及其后遗症、并发症和共病中特别有用,这种成分对男人和女人都有用,且这种盐已被证明是安全且无毒性的。
目前,国内外市场上未见有右旋硫辛酸镁盐的生产及销售,其制备的专利和文献也较为少见,其中专利CN101024641A实例中描绘着右旋硫辛酸镁的制备方法,但使用该方法制备得到的目标物含量很少,大部分为聚合产物,聚合产物在药物应用中是无效的。
发明内容
本发明的目的在于提供一种简便、实用的右旋硫辛酸镁盐的制备方法,该方法产品转化率高、收率高、成本低、绿色环保安全、对设备要求低,是一种非常适合工业化生产的方法。
本发明提供的技术方案如下:
一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于所述方法包括以下步骤:
(1)室温下,在反应瓶内加入右旋硫辛酸(Ⅲ)、溶剂搅拌溶解,在搅拌状态下滴加碳酸氢钠的纯化水溶液,加完后保持室温搅拌1-2小时,过滤得到R-硫辛酸钠盐(Ⅱ)湿品;
(2)将R-硫辛酸钠(Ⅱ)湿品置于一反应瓶中,加入纯化水启动搅拌,搅拌溶解均匀,开始滴加事先配置好的氯化镁水溶液,在0.5-1小时内滴加完毕,滴完后升温保持搅拌反应0.5小时,缓慢降温至2-10℃,析出大量固体,保持此温度下搅拌0.5小时,抽滤,收集固体,真空干燥得到右旋硫辛酸镁盐(Ⅲ)。
所述步骤(1)中原料右旋硫辛酸(Ⅲ)与碳酸氢钠投料摩尔比为:1︰0.8‐1.5,优选1︰1.0‐1.2。
所述步骤(1)中反应溶剂为:甲醇、乙醇、丙醇、丁醇、水,优选甲醇。
所述步骤(1)中反应温度为:10~40℃,优选20~25℃。
所述步骤(2)中右旋硫辛酸钠盐(Ⅱ)与氯化镁投料摩尔比:1︰0.5‐1.5,优选1︰1.0‐1.1。
所述步骤(2)中反应溶剂为:水、甲醇、乙醇、乙酸乙酯、乙酸丁酯、吡啶,优选水。
所述步骤(2)中反应温度为:25~50℃,优选35~40℃。
所述步骤(2)中右旋硫辛酸镁盐(Ⅲ)干燥条件为:真空、时间15~30h、温度60~90℃,优选温度70~80℃、时间20~25h。
本发明的方法相对于现有技术,其主要优点是:利用盐类物质溶解性好的特征进行复分解反应,得到了转化完全的目标产品右旋硫辛酸镁盐,从而克服了用镁类碱性物质直接进行右旋硫辛酸镁盐反应时,易生成聚合物的缺陷。
具体实施方式
实施例1:
称取右旋硫辛酸20.6g(0.1mmol),加入氢氧化钠4.4g(0.11mmol)、甲醇250ml,保温到20℃搅拌反应8小时,过滤,用25ml/次甲醇洗涤产品二次,在60℃真空干燥6小时,得淡黄色右旋硫辛酸钠盐20.8g,纯度99.91%,收率91%。
实施例2:
称取右旋硫辛酸20.6g(0.1mmol),加入氢氧化钠4.8g(0.12mmol)、甲醇225ml,升温到25℃搅拌反应7小时,过滤,用25ml/次甲醇洗涤产品二次,在60℃真空干燥6小时,得淡黄色右旋硫辛酸钠盐20.5g,纯度99.95%,收率90%。
实施例3:
称取右旋硫辛酸钠盐22.8g(0.1mmol),室温下投入到150g水中搅拌溶解,升温至35℃后,把氯化镁10.5g(0.11mmol)用55g水溶解,缓慢滴入到溶液中立刻出现黄色沉淀,滴加时间1h,滴加结束后继续保温3h,过滤,黄色产品用纯水洗涤二次,在70℃真空条件下干燥25h,得米黄色产品右旋硫辛酸镁21.9g,纯度99.96%,收率91%。
实施例4:
称取右旋硫辛酸钠盐22.8g(0.1mmol),室温下投入到150g水中搅拌溶解,升温至40℃后,把氯化镁9.5g(0.1mmol)用50g水溶解,缓慢滴入到溶液中立刻出现黄色沉淀,滴加时间1h,滴加结束后继续保温3h,过滤,黄色产品用纯水洗涤二次,在80℃真空条件下干燥20h,得米黄色产品右旋硫辛酸镁22.2g,纯度99.98%,收率92%。
实施例5:
称取氢氧化钠4.4g(0.11mmol)加入到150g水中,搅拌溶解后,于室温下把右旋硫辛酸20.6g(0.1mmol)添加至溶液中,于25℃搅拌反应8小时,得黄色透明溶液,将溶液升温至35℃,把氯化镁9.5g(0.1mmol)用50g水溶解,缓慢滴入到溶液中立刻出现黄色沉淀,滴加时间1.5h,滴加结束后继续保温3h。过滤,黄色产品用纯水洗涤二次,在80℃真空条件下干燥20h,得米黄色产品右旋硫辛酸镁16.3g,纯度90.7%,收率75%。
通过以上典型实施例对本发明作了进一步技术说明,而不能以此为限制本发明的保护范围,凡采用等同变换或着等效变换而形成的所有技术方案,均在本发明的保护范围之内。
Claims (8)
2.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(1)中原料右旋硫辛酸(Ⅲ)与碳酸氢钠投料摩尔比为:1︰0.8‐1.5。
3.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(1)中反应溶剂为:甲醇、乙醇、丙醇、丁醇、水中的一种或几种组合。
4.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(1)中反应温度为:10~40℃。
5.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(2)中右旋硫辛酸钠盐(Ⅱ)与氯化镁投料摩尔比:1︰0.5‐1.5。
6.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(2)中反应溶剂为:水、甲醇、乙醇、乙酸乙酯、乙酸丁酯、吡啶。
7.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(2)中反应温度为:25~50℃。
8.根据权利要求1所述的一种高纯度的右旋硫辛酸镁盐的制备方法,其特征在于步骤(2)中右旋硫辛酸镁盐(Ⅲ)干燥条件为:真空、时间15~30h、温度60~90℃。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110736330.7A CN115536631B (zh) | 2021-06-30 | 2021-06-30 | 一种高纯度的右旋硫辛酸镁盐的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110736330.7A CN115536631B (zh) | 2021-06-30 | 2021-06-30 | 一种高纯度的右旋硫辛酸镁盐的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115536631A true CN115536631A (zh) | 2022-12-30 |
CN115536631B CN115536631B (zh) | 2024-01-30 |
Family
ID=84717502
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110736330.7A Active CN115536631B (zh) | 2021-06-30 | 2021-06-30 | 一种高纯度的右旋硫辛酸镁盐的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115536631B (zh) |
Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5693664A (en) * | 1993-12-21 | 1997-12-02 | Asta Medica Aktiengesellschaft | Use of R-(+)-α-lipoic acid, R-(-)dihydrolipoic acid and metabolites in the form of the free acid or salts or esters or amides for the preparation of drugs for the treatment of diabetes mellitus as well as of its sequelae |
CN1337228A (zh) * | 2000-07-07 | 2002-02-27 | Basf公司 | 硫辛酸用于改进矿盐的生物可利用率的应用 |
JP2006282609A (ja) * | 2005-04-01 | 2006-10-19 | Japan Natural Laboratory Co Ltd | 安定化αーリポ酸配合化粧料、育毛剤び抗肥満用食品 |
CN1887882A (zh) * | 2006-08-08 | 2007-01-03 | 武汉远大制药集团有限公司 | 右旋硫辛酸氨基酸盐及其制备方法 |
CN1896072A (zh) * | 2005-07-16 | 2007-01-17 | 南京莱尔生物化工有限公司 | R-硫辛酸及其盐的制备方法 |
JP2007070303A (ja) * | 2005-09-08 | 2007-03-22 | Tateyama Kasei Kk | α−リポ酸アルカリ塩の製法 |
CN101024641A (zh) * | 2006-02-20 | 2007-08-29 | 南京莱尔生物化工有限公司 | R-(+)-硫辛酸及其盐的制备方法 |
WO2009021991A1 (de) * | 2007-08-16 | 2009-02-19 | Encrypta Gmbh | Verwendung von r(+)-alpha-liponsäure bei kryptogener neuropathie |
US20100317873A1 (en) * | 2009-06-12 | 2010-12-16 | Ampac Fine Chemicals LLC, a California Limited Liability Company | Preparation of polymer-free r-(+)-alpha-lipoic acid |
WO2010147957A2 (en) * | 2009-06-15 | 2010-12-23 | Encore Health, Llc | Dithiol compounds, derivatives, and uses therefor |
US20110213021A1 (en) * | 2008-03-04 | 2011-09-01 | Indigene Pharmaceuticals, Inc. | Compositions and methods for treating nos-associated diseases |
US20110213022A1 (en) * | 2008-10-24 | 2011-09-01 | Biolink Life Sciences, Inc. | Stable, water-insoluble r-(+)-alpha-lipoic acid salt useful for the treatment of diabetes mellitus and its co-morbidities |
WO2012014746A1 (ja) * | 2010-07-30 | 2012-02-02 | 株式会社シクロケム | αリポ酸複合体 |
CN103880816A (zh) * | 2014-03-27 | 2014-06-25 | 张家港威胜生物医药有限公司 | 一种α-硫辛酸锌的合成方法 |
CN111100113A (zh) * | 2018-10-26 | 2020-05-05 | 江苏同禾药业有限公司 | 一种右旋硫辛酸钠盐的制备方法 |
-
2021
- 2021-06-30 CN CN202110736330.7A patent/CN115536631B/zh active Active
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5693664A (en) * | 1993-12-21 | 1997-12-02 | Asta Medica Aktiengesellschaft | Use of R-(+)-α-lipoic acid, R-(-)dihydrolipoic acid and metabolites in the form of the free acid or salts or esters or amides for the preparation of drugs for the treatment of diabetes mellitus as well as of its sequelae |
CN1337228A (zh) * | 2000-07-07 | 2002-02-27 | Basf公司 | 硫辛酸用于改进矿盐的生物可利用率的应用 |
JP2006282609A (ja) * | 2005-04-01 | 2006-10-19 | Japan Natural Laboratory Co Ltd | 安定化αーリポ酸配合化粧料、育毛剤び抗肥満用食品 |
CN1896072A (zh) * | 2005-07-16 | 2007-01-17 | 南京莱尔生物化工有限公司 | R-硫辛酸及其盐的制备方法 |
JP2007070303A (ja) * | 2005-09-08 | 2007-03-22 | Tateyama Kasei Kk | α−リポ酸アルカリ塩の製法 |
CN101024641A (zh) * | 2006-02-20 | 2007-08-29 | 南京莱尔生物化工有限公司 | R-(+)-硫辛酸及其盐的制备方法 |
CN1887882A (zh) * | 2006-08-08 | 2007-01-03 | 武汉远大制药集团有限公司 | 右旋硫辛酸氨基酸盐及其制备方法 |
WO2009021991A1 (de) * | 2007-08-16 | 2009-02-19 | Encrypta Gmbh | Verwendung von r(+)-alpha-liponsäure bei kryptogener neuropathie |
US20110213021A1 (en) * | 2008-03-04 | 2011-09-01 | Indigene Pharmaceuticals, Inc. | Compositions and methods for treating nos-associated diseases |
US20110213022A1 (en) * | 2008-10-24 | 2011-09-01 | Biolink Life Sciences, Inc. | Stable, water-insoluble r-(+)-alpha-lipoic acid salt useful for the treatment of diabetes mellitus and its co-morbidities |
US20100317873A1 (en) * | 2009-06-12 | 2010-12-16 | Ampac Fine Chemicals LLC, a California Limited Liability Company | Preparation of polymer-free r-(+)-alpha-lipoic acid |
WO2010147957A2 (en) * | 2009-06-15 | 2010-12-23 | Encore Health, Llc | Dithiol compounds, derivatives, and uses therefor |
WO2012014746A1 (ja) * | 2010-07-30 | 2012-02-02 | 株式会社シクロケム | αリポ酸複合体 |
CN103880816A (zh) * | 2014-03-27 | 2014-06-25 | 张家港威胜生物医药有限公司 | 一种α-硫辛酸锌的合成方法 |
CN111100113A (zh) * | 2018-10-26 | 2020-05-05 | 江苏同禾药业有限公司 | 一种右旋硫辛酸钠盐的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN115536631B (zh) | 2024-01-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1834092B (zh) | 盐酸普拉克索的制备方法 | |
CN108558721A (zh) | 一种n,n-二乙酰-l-胱氨酸的制备方法 | |
CN101139280B (zh) | 无水醋酸钠的制备方法 | |
CN108569975B (zh) | 一种溴芬酸钠倍半水合物的制备方法 | |
KR101899015B1 (ko) | L-카르니틴 타르트레이트의 제조방법 | |
CN107400069B (zh) | 一种月桂酰精氨酸乙酯盐酸盐的制备方法 | |
CN115536631A (zh) | 一种高纯度的右旋硫辛酸镁盐的制备方法 | |
CN114031488A (zh) | 一种四氢姜黄素的合成方法 | |
CN106518962B (zh) | 一种从酵母细胞中制备还原型谷胱甘肽的方法 | |
CN108017561B (zh) | 一种精制卡谷氨酸的方法 | |
CN101781264A (zh) | 1-甲基-5-巯基-1,2,3,4-四氮唑的生产方法 | |
CN102827044A (zh) | 一种半胱胺螯合锌的制备方法 | |
CN103965058B (zh) | 一种盐酸美金刚的生产工艺 | |
CN112552231B (zh) | 一种2-(3-氯-5-(三氟甲基)吡啶-2-基)乙胺的合成方法 | |
CN104178540B (zh) | 一种生物催化法合成腺苷蛋氨酸的方法 | |
CN114685300A (zh) | 一种邻氯苯甘氨酸的制备方法 | |
CN110903247B (zh) | 一种大幅降低奥芬达唑杂质b的制备方法 | |
CN111233683A (zh) | 一种dl-炔丙基甘氨酸中间体及其制备方法、基于该中间体的炔丙基甘氨酸的制备方法 | |
CN101492388A (zh) | 一种合成米曲肼药物原料的方法 | |
CN102010325A (zh) | 一种对羟基苯乙酸的合成方法 | |
CN101186277A (zh) | 以氯化钙为原料制备过氧化钙的方法 | |
CN103467331A (zh) | 一种甘氨酸螯合铁的结晶成长方法 | |
CN111377840A (zh) | 一种r-(+)-二氢硫辛酸的制备方法 | |
CN111100113A (zh) | 一种右旋硫辛酸钠盐的制备方法 | |
JP2008156282A (ja) | α−リポ酸L−オルニチン塩およびその製造法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |