CN105712895A - Preparation method for magnesium aspartate hydrochloride trihydrate - Google Patents
Preparation method for magnesium aspartate hydrochloride trihydrate Download PDFInfo
- Publication number
- CN105712895A CN105712895A CN201410723144.XA CN201410723144A CN105712895A CN 105712895 A CN105712895 A CN 105712895A CN 201410723144 A CN201410723144 A CN 201410723144A CN 105712895 A CN105712895 A CN 105712895A
- Authority
- CN
- China
- Prior art keywords
- magnesium
- preparation
- hydrochloride trihydrate
- aspartate hydrochloride
- magnesium aspartate
- 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.)
- Pending
Links
Abstract
The invention provides a preparation method for magnesium aspartate hydrochloride trihydrate. The preparation method comprises the following steps: dissolving an L-aspartate compound with a structure as shown in a formula (1) that is described in the specification in hot water weighing 3 to 10 times of the L-aspartate compound; then adding magnesium oxide and magnesium oxide; adding at least one organic solvent selected from a group consisting of methanol, ethanol, acetonitrile and methanamide and controlling the acid-base value of the obtained mixed solution to be 4.0 to 5.5 properly; carrying out stirring at room temperature so as to allow a crystal to be precipitated; then carrying out cooling at -5 to -15 DEG C; and carrying out filtering and vacuum drying at 30 to 80 DEG C. The method is simple and easily practicable; and the prepared magnesium aspartate hydrochloride trihydrate has good crystal stability and is suitable for industrial production and storage.
Description
Technical field
The present invention relates to a kind of crystal preparation method of compound.
Background technology
The chemical molecular formula of Magnesium aspartate hydrochloride trihydrate is: (C4H6ClNO4)Mg·3H2O, as the formula (1), chemical name is structure: the trihydrate of L-2-aminosuccinic acid list magnesium salt hydrochlorate.
Magnesium aspartate hydrochloride trihydrate is the trihydrate of a kind of diacid list magnesium salt hydrochlorate replaced with 2 upper amino, for white or off-white color crystallization or crystalline powder；Have draw moist.
Magnesium aspartate hydrochloride is to be developed at first by VERLA-PHARM company of Germany, is mainly used in treating constitutional and Secondary cases magnesium deficiency, it is especially useful in heart disease, musculation that prevention and treatment magnesium deficiency and anxiety cause are obstructed.The rising of diet food, cholesterol levels, arteriosclerosis, liver cirrhosis, pancreatitis, anemia of pregnant woman, age of sucking, oral contraceptive etc. all can cause magnesium deficiency.And prevent the formation etc. of calcium oxalate (renal calculus).Magnesium aspartate hydrochloride trihydrate is medicinal compound, it is possible to make intravenous injection or oral drug preparation for, extensive use clinically.
Patent documentation DE1283810 reports, takes a certain amount of two water Magnesium Aminosuccinates and is dissolved in water, and rapidly joins equimolar hydrochloric acid, produces precipitation, filters to obtain solution, concentration, crystallization, recrystallization and get final product.
Summary of the invention
The preparation method that the invention provides a kind of Magnesium aspartate hydrochloride trihydrate, the crystal thing prepared by the method has good stability and suitable bulk density, it is easy to large-scale industry manufacture and using as drug regimen.
The preparation method of Magnesium aspartate hydrochloride trihydrate of the present invention, it is characterized in that being dissolved in the hot water of 3～10 times by the L-ASPARTIC ACID compound of formula (1) structure, add magnesium oxide, magnesium oxide, add methanol, ethanol, acetonitrile, Methanamide at least one organic solvent therein, control suitable acid-base value 4.0～5.5, after stirring precipitates out crystal under room temperature, in-5～-15 DEG C of coolings, filter, 30～80 DEG C of vacuum dryings.
The above-mentioned described organic solvent for making Magnesium aspartate hydrochloride trihydrate precipitate out, generally can select such as methanol, ethanol, acetonitrile, Methanamide at least one organic solvent therein.
Magnesium aspartate hydrochloride three hydration that the present invention prepares has stable composition and suitable bulk density, it is simple to produces, transport and storage, and manufacture method is simple and easy to do, the performance needed for having large-scale industry manufacture and being configured to pharmaceutical preparation.
Following example provide the detailed description of the invention of foregoing invention, but they are not limited to the gamut of the present invention.
Detailed description of the invention
Embodiment 1
Aspartic Acid 26.6g adds 80ml purified water, and heating, to 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.5, under stirring at normal temperature state, dropping methanol 150ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, methanol washs, 40～50 DEG C of vacuum dryings 4 hours, obtains
Magnesium aspartate hydrochloride trihydrate white solid 25g.
Embodiment 2
Aspartic Acid 26.6g adds 100ml purified water, and heating, to 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.6, under stirring at normal temperature state, dropping methanol 200ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, methanol washs, 40～50 DEG C of vacuum dryings 4 hours, obtains
Magnesium aspartate hydrochloride trihydrate white solid 24g.
Embodiment 3
Aspartic Acid 26.6g adds 80ml purified water, and heating, to more than 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.4, under stirring at normal temperature state, dropping ethanol 150ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, washing with alcohol, 40～50 DEG C of vacuum dryings 4 hours, obtain
Magnesium aspartate hydrochloride trihydrate white solid 26g.
Embodiment 4
Aspartic Acid 26.6g adds 80ml purified water, and heating, to more than 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.5, under stirring at normal temperature state, dropping Methanamide 150ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, washing with alcohol, 40～50 DEG C of vacuum dryings 4 hours, obtain Magnesium aspartate hydrochloride trihydrate white solid 22g.
Embodiment 4
Aspartic Acid 26.6g adds 80ml purified water, and heating, to more than 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, adjusts PH4.0～5.5, under stirring at normal temperature state, dropping acetonitrile 200ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, washing with alcohol, 40～50 DEG C of vacuum dryings 4 hours, obtain Magnesium aspartate hydrochloride trihydrate white solid 23g.
Embodiment 5
Aspartic Acid 26.6g adds 100ml purified water, and heating, to 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.6, under stirring at normal temperature state, dropping ethanol 150ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, washing with alcohol, 40～50 DEG C of vacuum dryings 4 hours, obtain
Magnesium aspartate hydrochloride trihydrate white solid 25g.
Embodiment 6
Aspartic Acid 26.6g adds 80ml purified water, and heating, to 60 DEG C, adds magnesium oxide 4.0g, magnesium chloride 20.3g, surveying PH is 4.6, under stirring at normal temperature state, dropping methanol/ethanol (1:1 mixed solution) 200ml, precipitate out white solid, after being added dropwise to complete, continue stirring 1～2 hour, be cooled to-5 DEG C stirred below 30 minutes, sucking filtration, washing with alcohol, 40～50 DEG C of vacuum dryings 4 hours, obtain Magnesium aspartate hydrochloride trihydrate white solid 26g.
Claims (4)
1. the preparation method of Magnesium aspartate hydrochloride trihydrate, the L-ASPARTIC ACID compound of formula (1) structure is dissolved in the hot water of 3～10 times, add magnesium oxide, magnesium oxide, add methanol, ethanol, acetonitrile, Methanamide at least one organic solvent therein, control suitable acid-base value 4.0～5.5, after stirring precipitates out crystal under room temperature, in-5～-15 DEG C of coolings, filter, 30～80 DEG C of vacuum dryings.
2. the preparation method of Magnesium aspartate hydrochloride trihydrate according to claim 1, is characterized in that described L-ASPARTIC ACID compound is dissolved in the hot water of 3～10 times.
3. the preparation method of Magnesium aspartate hydrochloride trihydrate according to claim 1, is characterized in that described adding methanol, ethanol, acetonitrile, Methanamide at least one organic solvent therein.
4. the preparation method of Magnesium aspartate hydrochloride trihydrate according to claim 1, is characterized in that the acid-base value 4.0～5.5 that described control is suitable.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723144.XA CN105712895A (en) | 2014-12-04 | 2014-12-04 | Preparation method for magnesium aspartate hydrochloride trihydrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723144.XA CN105712895A (en) | 2014-12-04 | 2014-12-04 | Preparation method for magnesium aspartate hydrochloride trihydrate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105712895A true CN105712895A (en) | 2016-06-29 |
Family
ID=56146582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410723144.XA Pending CN105712895A (en) | 2014-12-04 | 2014-12-04 | Preparation method for magnesium aspartate hydrochloride trihydrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105712895A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1809119A1 (en) * | 1968-11-15 | 1970-06-11 | Verla Pharm | Magnesium aspartate prepn for the treatment - of infarction conditions |
| EP0108937A2 (en) * | 1982-10-14 | 1984-05-23 | Verla-Pharm Arzneimittelfabrik Apotheker H.J. von Ehrlich GmbH & Co. KG | Process for the production of amino-dicarboxylic acid-bivalent metal-halogen complexes and novel such complexes |
| CN101239925A (en) * | 2008-03-10 | 2008-08-13 | 北京京卫信康医药科技发展有限公司 | Method for preparing magnesium aspartate |
| CN101301311A (en) * | 2007-05-10 | 2008-11-12 | 深圳北大高科五洲医药有限公司 | Potassium magnessium aspartape sterilized powder injection and preparation thereof |
| CN101659624A (en) * | 2009-09-23 | 2010-03-03 | 河北精信化工集团有限公司 | Method for preparing N-alkyl aspartic acid alkaline earth metal salt |
| GR1007225B (en) * | 2009-12-07 | 2011-03-30 | Uni-Pharma Κλεων Τσετης Φαρμακευτικα Εργαστηρια Αβεε Με Δ.Τ. Uni-Pharma Abee, | Pharmaceutical composition of intestine-soluble tablets of trihydrate magnesium aspartate hydrochloride |
-
2014
- 2014-12-04 CN CN201410723144.XA patent/CN105712895A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1809119A1 (en) * | 1968-11-15 | 1970-06-11 | Verla Pharm | Magnesium aspartate prepn for the treatment - of infarction conditions |
| EP0108937A2 (en) * | 1982-10-14 | 1984-05-23 | Verla-Pharm Arzneimittelfabrik Apotheker H.J. von Ehrlich GmbH & Co. KG | Process for the production of amino-dicarboxylic acid-bivalent metal-halogen complexes and novel such complexes |
| CN101301311A (en) * | 2007-05-10 | 2008-11-12 | 深圳北大高科五洲医药有限公司 | Potassium magnessium aspartape sterilized powder injection and preparation thereof |
| CN101239925A (en) * | 2008-03-10 | 2008-08-13 | 北京京卫信康医药科技发展有限公司 | Method for preparing magnesium aspartate |
| CN101659624A (en) * | 2009-09-23 | 2010-03-03 | 河北精信化工集团有限公司 | Method for preparing N-alkyl aspartic acid alkaline earth metal salt |
| GR1007225B (en) * | 2009-12-07 | 2011-03-30 | Uni-Pharma Κλεων Τσετης Φαρμακευτικα Εργαστηρια Αβεε Με Δ.Τ. Uni-Pharma Abee, | Pharmaceutical composition of intestine-soluble tablets of trihydrate magnesium aspartate hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| HUBERT SCHMIDBAUR等: ""Elucidation of the Structure of Pharmacologically Active Magnesium L-Aspartate Complexes", 《ANGEW. CHEM. INT. ED.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chadha et al. | Cocrystals of telmisartan: characterization, structure elucidation, in vivo and toxicity studies | |
| CN107787323A (en) | For suppressing the compound and composition of SHP2 activity | |
| JP2017526699A (en) | Composition of (6S) -5-methyltetrahydrofolic acid or its salt and its preparation and application | |
| CN103059030B (en) | Pyrimidine compound with effect of adhesion kinase inhibition and preparation method and application thereof | |
| CN102471273A (en) | 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-n-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide benzene- sulfonate, crystals of same, polymorphs thereof, and processes for production thereof | |
| CN105418641B (en) | It is a kind of former to develop quality Ceftriaxone Sodium and its pharmaceutical preparation | |
| US7608641B2 (en) | Creatine oral supplementation using creatine hydrochloride salt | |
| CN104203965B (en) | Complexes of germanium with amino acids and carboxylic acids and method for preparing same | |
| CN102260244B (en) | Stable rabeprazole sodium compound | |
| CN102234265B (en) | Lansoprazole compound | |
| CN105712895A (en) | Preparation method for magnesium aspartate hydrochloride trihydrate | |
| CN104744464B (en) | Istradefylline crystal formation | |
| KR20140113740A (en) | Crystal form of (6s)-5-methyltetrahydrofolate salt and method for preparing same | |
| ES2811325T3 (en) | Sodium salt of uric acid transporter inhibitor and its crystalline form | |
| ES2746016T3 (en) | Procedure for the preparation of fingolimod hydrochloride crystals | |
| CN104140384B (en) | The method of alkylthio/alkenyl cysteine sulfoxide is prepared in a kind of fractional crystallization | |
| CN102964335B (en) | Esomeprazole sodium compound and preparation method and applications thereof | |
| CN105175470A (en) | Arsenic sugar compound with anti-tumor activity and preparation method therefor and application thereof | |
| CN102372679A (en) | Febuxostat water-soluble derivative and preparation method thereof | |
| CN104725431A (en) | Cobalt (II) complex of quinolinone derivative, and synthesis method and application thereof | |
| CN104736152A (en) | Pharmaceutical formulations containing 3-(4-cinnamyl-1-piperazinyl) amino derivatives of 3-formylrifamycin SV and 3-formylrifamycin S and a process of their preparation | |
| CN104245682A (en) | Manufacturing method of irsogladine maleate | |
| CN105085421B (en) | Bit piperazine fumarate difficult to understand, hydrate, crystal formation and preparation method thereof | |
| BR112020000856B1 (en) | METHOD FOR PREPARING A METHIONINE-METAL CHELLATE AND METHOD FOR PREPARING CALCIUM NITRATE | |
| BR112020000854A2 (en) | methionine-metal chelate and its preparation method, feed or food additive, method for preparing calcium chloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160629 |