CN105131029A - Choline glycerophosphate crystal preparation method - Google Patents
Choline glycerophosphate crystal preparation method Download PDFInfo
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- CN105131029A CN105131029A CN201510493979.5A CN201510493979A CN105131029A CN 105131029 A CN105131029 A CN 105131029A CN 201510493979 A CN201510493979 A CN 201510493979A CN 105131029 A CN105131029 A CN 105131029A
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Abstract
The present invention discloses a choline glycerophosphate crystal preparation method, which comprises: (1) mixing choline glycerophosphate and an alcohol to prepare a mixture M1; (2) carrying out first concentration on the mixture M1 to obtain a mixture M2; (3) mixing the mixture M2 and an organic solvent, and carrying out second concentration to obtain a mixture M3; (4) mixing ethyl acetate and the mixture M3, carrying out crystallization, and then filtering to obtain a crystal M4; and (5) carrying out pressure reducing drying on the crystal M4 to obtain the choline glycerophosphate crystal. The choline glycerophosphate crystal prepared through the method of the present invention has characteristics of low water absorption in air, high purity, high health performance, and high medicinal value.
Description
Technical field
The present invention relates to the preparation field of Choline Glycerophosphate, particularly, relate to a kind of preparation method of Choline Glycerophosphate crystal.
Background technology
Choline Glycerophosphate extensively exists in vivo, is mainly present in emulsion and body fluid, and be a kind of important component of human body, Choline Glycerophosphate can improve the cognitive ability of brain, has fabulous prevention and therapy effect to senile dementia.In addition, it also has the effect of lipidemia, protection blood vessel, also has well prevention and adjuvant treatment effect to hypertension and coronary heart disease.Choline Glycerophosphate can also promote that teenager's health is grown up, and improves teen-age memory capability, has high health properties and pharmaceutical use, is therefore widely used in medicine, healthcare products and functional foodstuff.
At present, in prior art, commercially available Choline Glycerophosphate mainly obtains with the extraction of ethanol single from the byproduct of soybean, the Choline Glycerophosphate that this method obtains has higher moisture absorption, uncovered placement can absorb the moisture in air in atmosphere, there is very high water-intake rate, the purity degradation of Choline Glycerophosphate after water suction, can be caused, thus weaken health properties and the pharmaceutical use of Choline Glycerophosphate greatly.
Summary of the invention
The object of this invention is to provide a kind of preparation method of Choline Glycerophosphate crystal, the Choline Glycerophosphate crystal prepared by the method has very low water-intake rate, higher purity, health properties and pharmaceutical use in atmosphere.
To achieve these goals, the invention provides a kind of preparation method of Choline Glycerophosphate crystal, this preparation method comprises:
(1) by Choline Glycerophosphate and the obtained mixture M 1 of alcohol mixing;
(2) described mixture M 1 is carried out the first concentrated obtained mixture M 2;
(3) the second concentrated obtained mixture M 3 will be carried out after described mixture M 2 and organic solvent mixing;
(4) ethyl acetate and described mixture M 3 are mixed post crystallization, then carry out filtration and obtain crystal M4;
(5) described crystal M4 drying under reduced pressure is obtained Choline Glycerophosphate crystal.
Pass through technique scheme, the invention provides a kind of preparation method of Choline Glycerophosphate crystal, first this preparation method for obtain mixture M 1 by Choline Glycerophosphate and alcohol mixed dissolution, then afterwards concentrated for mixture M 1 and organic solvent are mixed also secondary concentration and obtain mixture M 3, finally mixture M 3 and ethyl acetate mixed crystallization are also filtered and obtain crystal, crystal drying under reduced pressure is obtained Choline Glycerophosphate crystal, Choline Glycerophosphate crystal habit prepared by this method is different from commercially available Choline Glycerophosphate, water-intake rate is very low in atmosphere, thus there is higher purity, health properties and pharmaceutical use.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Embodiment
Below the specific embodiment of the present invention is described in detail.Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
The invention provides a kind of preparation method of Choline Glycerophosphate crystal, this preparation method comprises:
(1) by Choline Glycerophosphate and the obtained mixture M 1 of alcohol mixing;
(2) described mixture M 1 is carried out the first concentrated obtained mixture M 2;
(3) the second concentrated obtained mixture M 3 will be carried out after described mixture M 2 and organic solvent mixing;
(4) ethyl acetate and described mixture M 3 are mixed post crystallization, then carry out filtration and obtain crystal M4;
(5) described crystal M4 drying under reduced pressure is obtained Choline Glycerophosphate crystal.
In above-mentioned preparation method, the consumption of alcohol does not do special restriction, and in order to enable Choline Glycerophosphate fully dissolve, preferably, relative to the Choline Glycerophosphate of 100 weight parts, the consumption of alcohol is 420-520 weight part.
Certainly, the concrete kind of alcohol can be selected in wide scope, can being selected from one or more in ethanol, methyl alcohol, propyl alcohol and ethylene glycol, dissolving sooner to enable Choline Glycerophosphate, preferably, alcohol is selected from one or more in ethanol, propyl alcohol and ethylene glycol.
Similarly, in step (1), the temperature of mixing and method all can be selected in wide scope, in order to enable Choline Glycerophosphate dissolve quickly, preferably, in step (1), the temperature of mixing is 37-40 DEG C, and is mixed into and is uniformly mixed.
Certainly, the time be uniformly mixed also can be selected in wide scope, and preferably, the churning time be uniformly mixed is 1h-2h.
In above-mentioned preparation method, in step (2), the first condition concentrated all can be selected in wide scope, in order to make crystal separate out sooner, preferably, the first condition concentrated is: concentrated pressure is 50-80KPa, thickening temperature is 45-55 DEG C, and concentration time is 30-60min.
Similarly, in step (3), the kind of organic solvent has diversity, can be one or more in ethanol, acetone and polyvinylpyrrolidone, in order to make the aerial water-intake rate of Choline Glycerophosphate crystal that obtains less, preferably, organic solvent is ethanol and/or acetone.
Certainly, the consumption of organic solvent can be selected in wide scope, and in order to make the aerial water-intake rate of Choline Glycerophosphate crystal that obtains less, preferably, relative to the described mixture M 2 of 100 weight parts, the consumption of organic solvent is 50-70 weight part.
Meanwhile, in step (3), the second temperature and time concentrated all can be selected in wide scope, and in order to make crystal separate out faster, preferably, the second temperature concentrated is lower than 45 DEG C, and the second time concentrated was 1h-3h.
Similarly, in step (4), the consumption of ethyl acetate also can be selected in wide scope, and in order to make crystal separate out faster, preferably, relative to the mixture M 3 of 100 weight parts, the consumption of ethyl acetate is 40-60 weight part.
In above-mentioned preparation method, in step (4), the temperature and time of mixing all has diversity, separate out faster to make crystal and make the aerial water-intake rate of Choline Glycerophosphate crystal that obtains less, preferably, mixing at least meets the following conditions: mixing temperature is 45-50 DEG C, and blend pressure is 60-80KPa.
Certainly, in step (5), the pressure and temperature of drying under reduced pressure all can be selected in wide scope, in order to make the aerial water-intake rate of Choline Glycerophosphate crystal that obtains less, preferably, drying pressure is 0.6-0.8MPa, time of drying is 1-3h, and drying temperature is 35-45 DEG C.
Below will be described the present invention by embodiment.In following examples, water ratio parameter is recorded by weighting method, and Choline Glycerophosphate is purchased from Wuhan Merck medication chemistry company limited.
Embodiment 1
(1) at 38 DEG C, Choline Glycerophosphate and ethanol (weight ratio is 100:470) mix and blend 1.5h are obtained mixture M 1;
(2) under 50 DEG C of conditions with 65KPa, mixture M 2 is carried out the first concentrated 45min and obtain mixture M 2;
(3) by mixed to mixture M 2 and ethanol (weight ratio is 100:60) be incorporated in 35 DEG C at carry out the second concentrated 2h and obtain mixture M 3;
(4) at 48 DEG C, ethyl acetate and mixture M 3 (weight ratio is 50:100) are mixed post crystallization and carry out the second filtration under 70KPa condition obtain crystal M4;
(5) at 40 DEG C, described crystal M4 dry 2h under 0.7MPa is obtained Choline Glycerophosphate crystal A1.
Embodiment 2
(1) at 37 DEG C, Choline Glycerophosphate and propyl alcohol (weight ratio is 100:420) mix and blend 1h are obtained mixture M 1;
(2) under 45 DEG C of conditions with 50KPa, mixture M 2 is carried out the first concentrated 60min and obtain mixture M 2;
(3) by mixed to mixture M 2 and acetone (weight ratio is 100:50) be incorporated in 30 DEG C at carry out the second concentrated 1h and obtain mixture M 3;
(4) at 45 DEG C, ethyl acetate and mixture M 3 (weight ratio is 40:100) are mixed post crystallization and carry out the second filtration under 60KPa condition obtain crystal M4;
(5) at 35 DEG C, described crystal M4 dry 1h under 0.6MPa is obtained Choline Glycerophosphate crystal A2.
Embodiment 3
(1) at 40 DEG C, Choline Glycerophosphate and propyl alcohol (weight ratio is 100:520) mix and blend 2h are obtained mixture M 1;
(2) under 55 DEG C of conditions with 80KPa, mixture M 2 is carried out the first concentrated 30min and obtain mixture M 2;
(3) by mixed to mixture M 2 and acetone (weight ratio is 100:70) be incorporated in 40 DEG C at carry out the second concentrated 3h and obtain mixture M 3;
(4) at 50 DEG C, ethyl acetate and mixture M 3 (weight ratio is 60:100) are mixed post crystallization and carry out the second filtration under 80KPa condition obtain crystal M4;
(5) at 45 DEG C, described crystal M4 dry 3h under 0.8MPa is obtained Choline Glycerophosphate crystal A3.
Comparative example 1
Choline Glycerophosphate crystal B1 is obtained according to the method for embodiment 1, unlike, do not carry out the process of step (2).
Comparative example 2
Choline Glycerophosphate crystal B2 is obtained according to the method for embodiment 1, unlike, do not carry out the process of step (3).
Test example 1
By Choline Glycerophosphate crystal A1-A3 prepared by commercially available Choline Glycerophosphate S (purchased from Wuhan Merck medication chemistry company limited) and the present invention, B1-B2 weighs and obtains initial weight m1, then being placed on atmospheric moisture is 2h in the air of 30%, weigh weight m2 after obtaining absorbing water, water-intake rate (w/%)=[(m2-m1)/m1] × 100%.
Table 1
| Numbering | Water-intake rate (w/%) |
| A1 | 1.8 |
| A2 | 1.9 |
| A3 | 1.8 |
| B1 | 11.2 |
| B2 | 12.2 |
| S | 16.6 |
As shown in Table 1, after Choline Glycerophosphate crystal provided by the invention places 2h in atmosphere, water-intake rate is very low, relative to A1-A3, the water-intake rate of S obviously increases, describe the aerial water-intake rate of Choline Glycerophosphate crystal prepared by present method less, thus purity is higher, drug effect is stronger; Also increase to some extent relative to the water-intake rate of A1-A3, B1-B2, describe between preparation process provided by the invention (2) and (3) and there occurs synergy, all contribution has been made to the water-intake rate reducing Choline Glycerophosphate crystal.
More than describe the preferred embodiment of the present invention in detail; but the present invention is not limited to the detail in above-mentioned embodiment, within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.
It should be noted that in addition, each concrete technical characteristic described in above-mentioned embodiment, in reconcilable situation, can be combined by any suitable mode, in order to avoid unnecessary repetition, the present invention illustrates no longer separately to various possible array mode.
In addition, also can carry out arbitrary combination between various different embodiment of the present invention, as long as it is without prejudice to thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (10)
1. a preparation method for Choline Glycerophosphate crystal, is characterized in that, described preparation method comprises:
(1) by Choline Glycerophosphate and the obtained mixture M 1 of alcohol mixing;
(2) described mixture M 1 is carried out the first concentrated obtained mixture M 2;
(3) the second concentrated obtained mixture M 3 will be carried out after described mixture M 2 and organic solvent mixing;
(4) ethyl acetate and described mixture M 3 are mixed post crystallization, then carry out filtration and obtain crystal M4;
(5) described crystal M4 drying under reduced pressure is obtained Choline Glycerophosphate crystal.
2. preparation method according to claim 1, wherein, in step (1), relative to the described Choline Glycerophosphate of 100 weight parts, the consumption of described alcohol is 420-520 weight part;
Preferably, described alcohol is selected from one or more in ethanol, propyl alcohol and ethylene glycol.
3. preparation method according to claim 2, wherein, in step (1), the temperature of described mixing is 37-40 DEG C, and described in be mixed into and be uniformly mixed.
4. preparation method according to claim 3, wherein, described in the churning time that is uniformly mixed be 1h-2h.
5., according to the preparation method in claim 1-3 described in any one, wherein, in step (2), the described first condition concentrated is: concentrated pressure is 50-80KPa, and thickening temperature is 45-55 DEG C, and concentration time is 30-60min.
6. preparation method according to claim 5, wherein, in step (3), described organic solvent is ethanol and/or acetone.
7. preparation method according to claim 6, wherein, in step (3), relative to the described mixture M 2 of 100 weight parts, the consumption of described organic solvent is 50-70 weight part.
8. the preparation method according to claim 6 or 7, wherein, in step (3), the described second temperature concentrated is lower than 45 DEG C, and the second time concentrated was 1h-3h.
9. preparation method according to claim 8, wherein, in step (4), relative to the described mixture M 3 of 100 weight parts, the consumption of described ethyl acetate is 40-60 weight part.
10. preparation method according to claim 8, wherein, in step (4), mixing at least meets the following conditions: mixing temperature is 45-50 DEG C, and blend pressure is 60-80KPa;
Preferably, in step (5), the condition of described drying under reduced pressure is: drying pressure is 0.6-0.8MPa, and time of drying is 1-3h, and drying temperature is 35-45 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105920609A (en) * | 2016-06-08 | 2016-09-07 | 芜湖福民生物药业有限公司 | Choline alfoscerate-containing medicine and preparation method thereof |
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Address after: No. 3 plant of star fire Industrial Park, Yijiang District, Wuhu, Anhui Patentee after: Wuhu Fumin pharmaceutical Limited by Share Ltd Address before: 241000 Wuhu City, Anhui high tech Development Zone star fire Industrial Park No. 3 plant Patentee before: WUHU FOMAN BIOPHARMA CO., LTD. |