CN102001982A - Method for preparing methionine chelated calcium - Google Patents
Method for preparing methionine chelated calcium Download PDFInfo
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- CN102001982A CN102001982A CN2010105340529A CN201010534052A CN102001982A CN 102001982 A CN102001982 A CN 102001982A CN 2010105340529 A CN2010105340529 A CN 2010105340529A CN 201010534052 A CN201010534052 A CN 201010534052A CN 102001982 A CN102001982 A CN 102001982A
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Abstract
The invention discloses a method for preparing methionine chelated calcium, which comprises the following steps of: in the presence of benzene sulfonic acid serving as a catalyst, adding L-methionine and absolute ethyl alcohol, and taking water out of a reaction system by using a water-carrying agent so as to prepare L-methionine ester; mixing the L-methionine ester and inorganic calcium salt, ultrasonically dispersing, and reacting at the temperature of between 20 and 60 DEG C; and adding the absolute ethyl alcohol for extraction, performing suction filtration and separation under vacuum, and ageing and crystallizing at low temperature so as to prepare the methionine chelated calcium with a hexatomic ring structure which is complexed by nitrogen atoms and sulfur atoms serving as ligands in an L-methionine amino structure with central metal calcium ions. Due to infrared, thermogravimetric and X-ray diffraction (XRD) experiments, the prepared methionine chelated calcium with the hexatomic-ring chelated structure is different from the traditional five-membered ring amino acid metal chelated calcium, has the characteristics that: the technical process is simple, the method is easy to operate, the product structure is stable, the yield and purity are high and the cost is low, and is used for foods, feed additives and health-care medicaments.
Description
Technical field
The present invention relates to a kind of preparation method of methionine chelate calcium, especially a kind of elder generation is prepared into the L-methionine ester with the L-methionine(Met), utilize L-methionine ester and inorganic calcium to be prepared into the preparation method of six-ring methionine chelate calcium again, be used for food, fodder additives and healthcare products medicine.
Background technology
Calcium is one of trace element of needed by human, and replenishing the calcium becomes one of human requisite healthiness condition.
Existing a large amount of goods of replenishing the calcium, majority is a calcium salt, as calcium phosphate, lime carbonate, calglucon, calcium acetate, calcium lactate etc.These calcium additives have between organism absorption difference, the element and have antagonistic action, have certain toxic side effect, can not satisfy the needs of biology growing.Compare with these calcium salts, amino acid whose chelating calcium is easy to absorb safety non-toxic.Become the first-selection of the goods of replenishing the calcium.Openly report is raw material applying high voltage fluid nanometer mill synthesizing amino acid chelating calcium with aspartic acid and calcium oxide, aspartic acid and calcium chloride are feedstock production aspartic acid chelating calcium, it is that raw material application ion exchange method prepares the leucine-calcium goods that inorganic calcium ion is arranged, and these calcium amino acid chelate great majority are N-O five-membered ring structures.
The L-methionine(Met) is the life indispensable amino acid of sulfur-bearing, absorbs the back in the body and forms the S-ademetionine earlier, and the synthetic required methyl of choline is provided.If lack the L-methionine(Met), lack easy hepatitis, liver cirrhosis, the fatty liver diseases of getting of choline in the body easily.Replenish the L-methionine(Met) separately and be subjected to antagonistic action bad stability such as gi tract pH value, mineral ion, proteolytic enzyme.If with the L-methionine(Met) be carrier and nonmetal inorganic calcium complexing be prepared into easily digest and assimilate, anti-interference, L-Methionine calcium salt that toxicity is little, also can replenish the necessary L-methionine(Met) of organism in the time of supplementing calcium element, the present invention is based on this thought, further invented a kind of method for preparing methionine chelate calcium.
Summary of the invention
The invention provides a kind of preparation method of methionine chelate calcium, its objective is with the L-methionine(Met) to be that carrier is transformed into organic a kind of six-ring L-methionine chelate calcium with inorganic calcium, make calcium replenishing and L-methionine(Met) combine together, further improve the needed by human body element structure.
Based on above-mentioned purpose, the preparation method of a kind of methionine chelate calcium of the present invention's preparation is to be raw material with L-methionine(Met) and dehydrated alcohol earlier, Phenylsulfonic acid is a Preparation of Catalyst L-methionine ester, benzene by the ethyl acetate crystallization, obtains the L-methionine ester as the esterification azeotropic agent; This L-methionine ester and inorganic calcium are mixed, ultrasonic dispersing is 20-60 ℃ of reaction 1-2h down in temperature, adds the dehydrated alcohol extraction again, and 0-4 ℃ of ageing 10-24h, vacuum filtration obtain L-methionine chelate calcium.Its described method comprises the steps:
At first, by amount of substance than L-methionine(Met): Phenylsulfonic acid: ethanol: benzene is 1: 1.3: 6: 11 mix;
The second, temperature of reaction is heated to 60-80 ℃, reaction 1-3h is heated to temperature of reaction 77 ℃ again, keeps 2-5h, and cooling obtains product;
Three, in products therefrom, add the 30-50mL ethyl acetate, under 0-10 ℃, leave standstill 10-12h and carry out crystallization, obtain the L-methionine ester;
At last, inorganic calcium and above-mentioned synthetic L-methionine ester are pressed 1-5: 1 amount of substance ratio, after at room temperature ultrasonic wave is disperseed 20min to it, again at 20-60 ℃ of water bath with thermostatic control reaction 1-2h, utilize the dehydrated alcohol crystallization, place 0-4 ℃ of ageing 10-24h, vacuum filtration obtains the L-Methionine calcium salt.
Wherein, add the inorganic calcium amount of substance and be 1-5: 1 with L-methionine ester amount of substance ratio; Described inorganic calcium is a kind of in calcium chloride, calcium phosphate, lime carbonate and the calcium sulfate.
The prepared methionine chelate calcium of aforesaid method of the present invention is different from existing five-ring amino acids metal chelating calcium, and Phenylsulfonic acid is participated in reaction with L-methionine ester form during preparation, the Phenylsulfonic acid that the reaction back produces can be used as the catalyzer of hydrolysis reaction, the acid that need not to add again other is hydrolyzed, and obtain a certain amount of ethanol after the hydrolysis, only need add a spot of crystallizing agent during to the product crystallization again and get final product, Phenylsulfonic acid not only can be used as the catalyzer of esterification but also can be used as the catalyzer of hydrolysis reaction like this; Ethanol not only can be used as the protective material of carboxyl but also can be used as crystallizing agent to product, had reduced experiment and had used reagent, and do not destroyed L-methionine(Met) structure, and synthetic route is simple, easy handling, product structure are stable, productive rate and purity height, cost are low.
Description of drawings
Fig. 1 is methionine chelate calcium P of the present invention
1Shape appearance figure 40 times of microscopically amplifications;
Fig. 2 is a product P of the present invention
2Shape appearance figure 40 times of microscopically amplifications;
Fig. 3 is the different sample infrared spectra of the present invention absorption figure;
Fig. 4 is a product P of the present invention
1Thermogravimetric analysis figure;
Fig. 5 is a product P of the present invention
2Thermogravimetric analysis figure;
Fig. 6 is a product P of the present invention
1XRD analysis figure;
Fig. 7 is a product P of the present invention
2XRD analysis figure.
Embodiment
The method that the present invention prepares a kind of methionine chelate calcium is to be catalyzer with the Phenylsulfonic acid, add L-methionine(Met) and dehydrated alcohol, benzene is taken water and benzene out of reaction system with the form of azeotrope as the esterification azeotropic agent at 60～80 ℃, obtains the L-methionine ester through the ethyl acetate crystallization; L-methionine ester and inorganic calcium are mixed by a certain percentage, ultrasonic dispersing is 20-60 ℃ of reaction 1-2h down in temperature, adds a spot of ethanol to extract again, and low temperature maturation 10-24h obtains L-methionine chelate calcium behind the vacuum filtration.Its described method steps is as follows:
(1) according to the L-methionine(Met): Phenylsulfonic acid: ethanol: benzene is 1: 1.3: 6: the ratio of 11 (amount of substance ratios) is mixed;
(2) temperature of reaction is heated to 60-80 ℃, reaction 1-1.5h continues reacting by heating temperature to 77 ℃, insulation 3-4h, and cooling obtains product;
(3) add the 30-50mL ethyl acetate in product, be placed on 0-10 ℃ of following crystallization 10-12h, obtain the L-methionine ester, productive rate can reach 83.8%.Reaction formula is:
(4) inorganic calcium and above-mentioned synthetic L-methionine ester are pressed 1-5: 1 amount ratio, after at room temperature ultrasonic wave is disperseed 20min to it, at 20-60 ℃ of water bath with thermostatic control reaction 1-2h, add the 30mL dehydrated alcohol again, place 0-4 ℃ of ageing 10-24h, vacuum filtration obtains L-methionine chelate calcium P
1Product (six-ring) productive rate can reach 50-60%.Reaction formula is:
Among the above-mentioned preparation method, select benzene, about 70 ℃, take water and benzene out of reaction system together with the form of azeotrope, obtain purified L-methionine ester through the ethyl acetate crystallization as the esterification azeotropic agent.Reaction does not need anhydrous condition and nitrogen protection,,, forms boiling point and is lower than the alcoholic acid azeotropic liquid with the water azeotropic that produces in the esterification process as azeotropic agent with benzene, takes the water that reaction produces out of system, thereby promotes the esterification forward to move, and improves esterification yield.
Add the inorganic calcium amount of substance in the described method and be 1-5: 1 with L-methionine ester amount of substance ratio.
The inorganic calcium agent is any one in calcium chloride, calcium phosphate, lime carbonate and the calcium sulfate in the described method.
Add a spot of extraction agent after utilizing acid hydrolysis in the described method, product does not have by product residual.
The present invention is that part and calcium metal ion carry out complexing with the nitrogen-atoms and the sulphur atom of methionine(Met) amino, form comparatively stable six-ring chelating calcium, being different from existing amino-acid chelate preparation method and being what to be that complexing ligand and metal ion carry out that chelating forms with N atom on the amino and the O atom on the carboxyl is five-ring, and Phenylsulfonic acid is participated in reaction with the methionine ester form during preparation, the Phenylsulfonic acid that the reaction back produces can be used as hydrolytic reagent, the acid that does not need to add other again is hydrolyzed, and obtain a certain amount of ethanol after the hydrolysis, only need add a spot of crystallizing agent during to the product crystallization again and get final product, Phenylsulfonic acid not only can be used as catalyzer but also can be used as hydrolytic reagent like this; Characteristics such as ethanol not only can be used as the protective material of carboxyl but also can be used as crystallizing agent to product, had reduced experiment and had used reagent, and do not destroyed L-methionine(Met) structure, and synthetic route has fast, cost is low.
The inventive method is low for equipment requirements, process is simple, and used ethanol can reuse, and product need not separate, easy handling.
For the validating experiment result, take by weighing the L-methionine(Met) of quality same as described above, directly add the inorganic calcium of certain mass, according to reacting with above-mentioned experimental procedure (four) condition, adopt organic solvent alcohol extraction resultant, low temperature maturation 10-24h obtains L-Methionine calcium salt P through vacuum filtration
2Product (five-ring).
The product P that the technology of the present invention is obtained
1And product P
2Analyze by polarizing microscope, infrared spectrometer and means such as thermogravimetric analyzer and XRD.Morphology analysis result such as Fig. 1,2; Infrared analysis such as Fig. 3; Thermogravimetric analysis such as Fig. 4,5; XRD analysis is shown in Fig. 6,7.
From Fig. 1,2, can see with the L-methionine ester being the L-Methionine calcium salt (P of the synthetic gained of raw material
1) be the plate crystal body, and its sheet structure is small evenly, is the directly L-Methionine calcium salt product (P of synthetic gained of raw material with the L-methionine(Met)
2) be the needle-like N-type waferN.
Fig. 3 is raw material L-methionine(Met) as can be seen, L-methionine ester 1745cm
-1Near the tangible ester group absorption peak of appearance is simultaneously at 1550cm
-1Near still exist comparatively significantly-NH
2The formation vibration absorption peak.With product P
1Compare and can find with the L-methionine ester, the peculiar absorption peak of the ester group of L-methionine ester is in product P
1In completely dissolve, the substitute is 2112cm
-1Near-NH
2With the formed peculiar absorption peak of metal ion, and product P
2Comparatively significantly complexation characteristic absorption peak is also arranged in this zone.At 3000cm
-1Near this section zone ,-CH
3With-CH
2Stretching vibration wideband characteristic peak obviously exist always.
Product P as can see from Figure 4
1The rate of weight loss maximum temperature be 270.2 ℃, as can be seen from Figure 5 product P
2The rate of weight loss maximum temperature be 273.1 ℃.
Can see by the XRD figure spectrum: product P
1At the tangible absorption peak of existence of 5.78,23.32,29.28,35.34 four angles, calculating: θ=5.9252, I=6352, B=0.1172. gets λ=0.15406nm, then Dc=0.89 λ/BCos θ=1.1762; Product P
2The tangible absorption peak of existence 5.84,23.28,29.24,35.28 four angles, calculate: θ=5.9108, I=4291, B=0.1290. gets λ=0.15406nm, then θ, B, the I difference of Dc=0.89 λ/BCos θ=1.0686, two kind of L-Methionine calcium salt.
Further the specific embodiment of the present invention is made detailed description with embodiment below:
2.4gL-methionine(Met) and 5mL dehydrated alcohol are mixed, add 3.1g Phenylsulfonic acid solid then, fully shake up it is dissolved fully.Then 33mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 67 ℃, reaction 1.5h, continue reacting by heating temperature to 77 ℃, under this temperature, keep 3h, again after cooling add the 30mL ethyl acetate in the product, with its under 4 ℃, leave standstill, crystallization 10h, obtain the L-methionine ester, productive rate is 80.8%.
With of the 2.10gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.1, add 1.33g calcium chloride ultrasonic wave (40Hz) dispersion at room temperature 20min, in 50 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, adding 30mL dehydrated alcohol low temperature is placed 24h down precipitated crystal.Decompress filter obtains 1.11g white plates L-methionine chelate calcium then.
Embodiment 2
3.2gL-methionine(Met) and 7mL dehydrated alcohol are mixed, add 4.05g Phenylsulfonic acid solid then, fully shake up it is dissolved fully.Then 42mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 68 ℃, reaction 1h, continue reacting by heating temperature to 77 ℃, under this temperature, keep 3h, again after cooling add the 40mL ethyl acetate in the product, with its under 10 ℃, leave standstill, crystallization 12h, obtain the L-methionine ester, productive rate is 83.1%.。
With of the 2.6gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.2, add 2.25g lime carbonate and mix the 20min of ultrasonic wave (40Hz) dispersion at room temperature, in 40 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, the ethanol low temperature of adding 30mL is placed 10h down precipitated crystal.Decompress filter obtains 1.31g white plates L-methionine chelate calcium then.
Embodiment 3
5.1gL-methionine(Met) and 10mL dehydrated alcohol are mixed, add 6.5g Phenylsulfonic acid solid then, fully shake up it is dissolved fully.Then 68mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 75 ℃, reaction 1.5h, continue reacting by heating temperature to 77 ℃, under this temperature, keep 4h, again after cooling add the 50mL ethyl acetate in the product, with its under 0 ℃, leave standstill, crystallization 11h, obtain the L-methionine ester, productive rate is 83.4%.
With of the 3.98gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.0, adding 8.07g nitrocalcite mixes, ultrasonic wave under the room temperature (40Hz) is disperseed 20min, in 60 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, adding 30mL dehydrated alcohol low temperature is placed 10h down precipitated crystal, and decompress filter obtains white tablets 2.03g shape L-methionine chelate calcium then.
Embodiment 4
1.6gL-methionine(Met) and 5mL dehydrated alcohol are mixed, add 2.02g Phenylsulfonic acid solid then, fully shake up it is dissolved fully.Then 21mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 68 ℃, reaction 1.5h, continue reacting by heating temperature to 747 ℃, under this temperature, keep 3h, again after cooling add the 30mL ethyl acetate in the product, with its under 4 ℃, leave standstill, crystallization 10h, obtain the L-methionine ester, productive rate is 82.5%.
With of the 1.3gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.3, adding 1.15g calcium phosphate and 1.3gL-methionine ester mixes, ultrasonic wave under the room temperature (40Hz) is disperseed 20min, in 30 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, add the 30mL dehydrated alcohol, low temperature is placed 24h down precipitated crystal.Decompress filter obtains 0.78g white plates L-methionine chelate calcium then.
7.45gL-methionine(Met) and 14.6mL dehydrated alcohol are mixed, add 8.4g Phenylsulfonic acid solid then, fully shake up, it is dissolved fully.Then 100mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 70 ℃, reaction 1.5h, continue reacting by heating temperature to 77 ℃, under this temperature, keep 2h, after cooling, get adding 30mL ethyl acetate in the product again, be placed on 4 ℃ of following crystallization 10h, obtain the L-methionine ester, productive rate is 83.2%.
With of the 5.8gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.1, adding 3.32g calcium chloride mixes, ultrasonic wave under the room temperature (40Hz) is disperseed 20min, in 30 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, add the 30mL dehydrated alcohol, low temperature is placed 20h down precipitated crystal.Decompress filter obtains 3.13g white plates L-methionine chelate calcium then.
Embodiment 6
9.1gL-methionine(Met) and 20mL dehydrated alcohol are mixed, add 10.04g Phenylsulfonic acid solid then, fully shake up it is dissolved fully.Then 120mL benzene is added in the above-mentioned solution, temperature of reaction is heated to 65 ℃, reaction 3h, continue reacting by heating temperature to 77 ℃, under this temperature, keep 3h, again after cooling add the 50mL ethyl acetate in the product, with its under 4 ℃, leave standstill, crystallization 11h, obtain the L-methionine ester, productive rate is 83.8%.。
With of the 5.4gL-methionine ester dissolving of 25mL distilled water with above-mentioned preparation, regulating pH is 5.2, add 10.6g lime carbonate and mix the 20min of ultrasonic wave (40Hz) dispersion at room temperature, in 60 ℃ of water-baths, heat, stir 2h, reduce to room temperature after the reaction, the ethanol low temperature of adding 30mL is placed 15h down precipitated crystal.Decompress filter obtains 2.97g white plates L-methionine chelate calcium then.
Claims (3)
1. the preparation method of a methionine chelate calcium, this method is to be raw material with L-methionine(Met) and dehydrated alcohol, and Phenylsulfonic acid is a Preparation of Catalyst L-methionine ester, adds azeotropic agent benzene again, take water out of reaction system, obtain the L-methionine ester through the ethyl acetate crystallization; Then L-methionine ester and inorganic calcium are mixed, ultrasonic dispersing 20-60 ℃ of reaction down, adds the dehydrated alcohol extraction again, and low temperature maturation, vacuum filtration obtain L-methionine chelate calcium.
2. the method for claim 1, its described method comprises the steps:
(1) by amount of substance than L-methionine(Met): Phenylsulfonic acid: ethanol: benzene is 1: 1.3: 6: 11 mix;
(2) temperature of reaction is heated to 60-80 ℃, reaction 1-3h is heated to temperature of reaction 77 ℃ again, keeps 2-5h, and cooling obtains product;
(3) in product, add the 30-50mL ethyl acetate, under 0-10 ℃, leave standstill 10-12h and carry out crystallization, obtain the L-methionine ester;
(4) inorganic calcium and above-mentioned synthetic L-methionine ester are pressed 1-5: 1 amount of substance ratio, at room temperature behind the ultrasonic dispersing 20min, at 20-60 ℃ of water bath with thermostatic control reaction 1-2h, the dehydrated alcohol crystallization, place 0-4 ℃ of ageing 10-24h, vacuum filtration obtains L-methionine chelate calcium.
3. method as claimed in claim 1 or 2, described inorganic calcium are a kind of in calcium chloride, calcium phosphate, lime carbonate and the calcium sulfate.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919136A (en) * | 2014-04-29 | 2014-07-16 | 吉林大学 | Methionine chelating calcium tablets and processing method thereof |
| CN111825584A (en) * | 2020-07-30 | 2020-10-27 | 北京福元医药股份有限公司沧州分公司 | Preparation method of racemic hydroxy methionine calcium |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1218058A (en) * | 1997-11-26 | 1999-06-02 | 中国林业科学研究院林产化学工业研究所 | Method for drying heparin by atomization |
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| 安广杰等: "蛋氨酸烷基酯的合成", 《食品添加剂》, vol. 25, no. 12, 31 December 2004 (2004-12-31) * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919136A (en) * | 2014-04-29 | 2014-07-16 | 吉林大学 | Methionine chelating calcium tablets and processing method thereof |
| CN103919136B (en) * | 2014-04-29 | 2016-07-06 | 吉林大学 | A kind of methionine sequestration calcium tablet and processing method |
| CN111825584A (en) * | 2020-07-30 | 2020-10-27 | 北京福元医药股份有限公司沧州分公司 | Preparation method of racemic hydroxy methionine calcium |
| CN111825584B (en) * | 2020-07-30 | 2022-04-12 | 北京福元医药股份有限公司沧州分公司 | Preparation method of racemic hydroxy methionine calcium |
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