CN105001256B - The preparation method of Choline Glycerophosphate crystal - Google Patents
The preparation method of Choline Glycerophosphate crystal Download PDFInfo
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- CN105001256B CN105001256B CN201510497093.8A CN201510497093A CN105001256B CN 105001256 B CN105001256 B CN 105001256B CN 201510497093 A CN201510497093 A CN 201510497093A CN 105001256 B CN105001256 B CN 105001256B
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Abstract
The invention discloses a kind of preparation method of Choline Glycerophosphate crystal, which includes：(1) Choline Glycerophosphate and alcohol are mixed to prepare mixture M 1；(2) mixture M 1 and sulfate are mixed, the first filtering is carried out after cooling and filtrate is taken to obtain mixture M 2；(3) mixture M 2 is subjected to the first concentration and mixture M 3 is made；(4) the second concentration is carried out after mixing the mixture M 3 and organic solvent, and mixture M 4 is made；(5) mixture M 4 is dried under reduced pressure to obtain Choline Glycerophosphate crystal.By the way that the water absorption rate of the Choline Glycerophosphate crystal of this method preparation is relatively low, purity is high, has preferable health properties and medical value.
Description
Technical field
The present invention relates to the preparation fields of Choline Glycerophosphate, and in particular, to a kind of preparation side of Choline Glycerophosphate crystal
Method.
Background technology
Choline Glycerophosphate be have 2 aliphatic acid are sloughed by the main phospholipid PC (phosphatidyl choline) for constituting cell membrane after
The water-soluble substances arrived.Choline Glycerophosphate is widely present in vivo, is primarily present in lotion and body fluid.Choline Glycerophosphate
The cognitive ability that brain can be improved has senile dementia fabulous preventive effect, and teenager's body can also be promoted to grow up,
Improve teen-age memory capability, Choline Glycerophosphate can also be effectively protected hepatic tissue from toxic carbon tetrachloride and high in fat
Fatty acid permeation caused by albumen based food, have the function of lipidemia, protection blood vessel, have high health properties and
Medical value, therefore be widely used in terms of medicine, health products and functional food.
Currently, in the prior art, commercially available Choline Glycerophosphate mainly extracted with ethyl alcohol single from the byproduct of soybean and
, the Choline Glycerophosphate that this method obtains is placed in air to be easy to absorb the moisture in air, and water absorption rate is excessively high, to lead
The purity degradation for causing Choline Glycerophosphate, to greatly weaken the health properties and medical value of Choline Glycerophosphate.
Invention content
The object of the present invention is to provide a kind of preparation method of Choline Glycerophosphate crystal, the sweet phosphoric acid prepared by this method
The water absorption rate of choline crystal is relatively low, purity is high, has preferable health properties and medical value.
To achieve the goals above, the present invention provides a kind of preparation method of Choline Glycerophosphate crystal, the preparation methods
Including：
(1) Choline Glycerophosphate and alcohol are mixed to prepare mixture M 1；
(2) mixture M 1 and sulfate mixed, cooled and filtered and filtrate taken to obtain mixture M 2；
(3) mixture M 2 is subjected to the first concentration and mixture M 3 is made；
(4) the second concentration is carried out after mixing the mixture M 3 and organic solvent, and mixture M 4 is made；
(5) mixture M 4 is dried under reduced pressure to obtain Choline Glycerophosphate crystal.
Through the above technical solutions, the present invention provides a kind of preparation method of Choline Glycerophosphate crystal, the preparation method
For Choline Glycerophosphate and alcohol mixed dissolution are obtained mixture M 1 first, mixture M 1 and sulfate hybrid filtering are then taken into filter
Liquid obtains mixture M 2, and after concentration and organic solvent mixes and secondary concentration obtains mixture M 4, finally depressurizes mixture M 4
It is dried to obtain Choline Glycerophosphate crystal, Choline Glycerophosphate crystal habit prepared by this method is different from commercially available sweet phosphoric acid courage
Alkali, water absorption rate is low in air, and to which water content is few, purity is high, there is higher healthcare function and medical value.
Other features and advantages of the present invention will be described in detail in subsequent specific embodiment part.
Specific implementation mode
The specific implementation mode of the present invention is described in detail below.It should be understood that described herein specific
Embodiment is merely to illustrate and explain the present invention, and is not intended to restrict the invention.
The present invention provides a kind of preparation method of Choline Glycerophosphate crystal, which includes：
(1) Choline Glycerophosphate and alcohol are mixed to prepare mixture M 1；
(2) mixture M 1 and sulfate mixed, cooled and filtered and filtrate taken to obtain mixture M 2；
(3) mixture M 2 is subjected to the first concentration and mixture M 3 is made；
(4) the second concentration is carried out after mixing the mixture M 3 and organic solvent, and mixture M 4 is made；
(5) mixture M 4 is dried under reduced pressure to obtain Choline Glycerophosphate crystal.
In the present invention, the dosage of alcohol can select in a wide range, in order to keep Choline Glycerophosphate quickly molten
Solution, it is preferable that relative to the Choline Glycerophosphate of 100 parts by weight, the dosage of alcohol is 450-550 parts by weight.
Certainly, the specific type of alcohol can select in a wide range, can be selected from methanol, ethyl alcohol, propyl alcohol and ethylene glycol
In it is one or more, in order to enable Choline Glycerophosphate more fully to dissolve, it is preferable that alcohol be selected from methanol, ethyl alcohol and third
It is one or more in alcohol.
Similarly, in step (1), mixed temperature and mode can select in a wide range, in order to make sweet phosphorus
Sour choline can quickly dissolve, it is preferable that in step (1), mixed temperature is 35-40 DEG C, and it is mixed to be mixed into stirring
It closes.
Meanwhile the time being stirred also is not particularly limited, it is preferable that mixed mixing time is 20-40min.
In the present invention, in step (2), the specific type of sulfate has diversity, can be sodium sulphate and sulfuric acid
Potassium can also be magnesium sulfate and ammonium sulfate, can also be copper sulphate and zinc sulfate, in order to make Choline Glycerophosphate crystal tool obtained
There is lower water absorption rate, it is preferable that sulfate is one or more in sodium sulphate, potassium sulfate, magnesium sulfate and copper sulphate.
Certainly, the dosage of sulfate can also select in a wide range, in order to make Choline Glycerophosphate crystal obtained exist
Water absorption rate in air is lower, it is preferable that relative to the mixture M 1 of 100 parts by weight, the dosage of sulfate is 30-40 weight
Part.
Meanwhile in step (2), cooling temperature and time can select in a wide range, in order to make crystal more
Fast generation, it is preferable that cooling at least meets the following conditions：Cooling temperature be 25-30 DEG C, cooling time 30-50min.
In the present invention, in step (3), the condition of the first concentration can select in a wide range, in order to make crystalline substance
Body can faster be precipitated, it is preferable that first concentration condition be：Thickening temperature is 30-40 DEG C, and concentration pressure is 40-60KPa,
Concentration time is 1h-3h.
Similarly, in step (4), the dosage of organic solvent can select in a wide range, obtained sweet in order to make
The aerial water absorption rate of phosphocholine crystal is lower, it is preferable that relative to the mixture M 3 of 100 parts by weight, in step
(4) in, the dosage of the organic solvent is 50-70 parts by weight.
Certainly, the type of organic solvent has diversity, can be one kind in ethyl alcohol, acetone and polyvinylpyrrolidone
Or it is a variety of, in order to keep the aerial water absorption rate of Choline Glycerophosphate crystal obtained lower, it is preferable that organic solvent is ethyl alcohol
And/or acetone.
Certainly, in step (4), the temperature and time of the second concentration can select in a wide range, in order to make crystalline substance
Body is precipitated faster, it is preferable that the temperature of the second concentration is less than 40 DEG C, and the time of the second concentration is 1h-2h；
In the present invention, the empty pressure and temperature being dried under reduced pressure can select in a wide range, obtained in order to make
The aerial water absorption rate of Choline Glycerophosphate crystal is lower, it is preferable that the condition being dried under reduced pressure is：Drying pressure is 0.5-
0.8MPa, drying time 1-4h, drying temperature are 35-45 DEG C.
The present invention will be described in detail by way of examples below.In following embodiment, moisture content parameter is by weighing
Method measures, and Choline Glycerophosphate is purchased from Wuhan Merck medication chemistry Co., Ltd.
Embodiment 1
(1) at 38 DEG C, by Choline Glycerophosphate and methanol (weight ratio 100：500) 30min is mixed and mixing is made
Object M1；
(2) by mixture M 1 and sodium sulphate (weight ratio 100：35) mixing, the cooling 40min at 28 DEG C, then carry out
First filters and filtrate is taken to obtain mixture M 2；
(3) under conditions of 35 DEG C and 50KPa, mixture M 2 is subjected to the first concentration 2h, mixture M 3 is made；
(4) by mixture M 3 and ethyl alcohol (weight ratio 100：60) it mixes and carries out the second concentration 1.5h at 35 DEG C and be made
Mixture M 4；
(5) at 40 DEG C, by mixture M 4, dry 3h obtains Choline Glycerophosphate crystal A1 at 0.7MPa.
Embodiment 2
(1) at 35 DEG C, by Choline Glycerophosphate and ethyl alcohol (weight ratio 100：450) 40min is mixed and mixing is made
Object M1；
(2) by mixture M 1 and potassium sulfate (weight ratio 100：35) mixing, the cooling 30min at 25 DEG C, then carry out
First filters and filtrate is taken to obtain mixture M 2；
(3) under conditions of 30 DEG C and 40KPa, mixture M 2 is subjected to the first concentration 1h, mixture M 3 is made；
(4) by mixture M 3 and acetone (weight ratio 100：50) it mixes and carries out the second concentration 1h at 30 DEG C and be made mixed
Close object M4；
(5) at 35 DEG C, by mixture M 4, dry 1h obtains Choline Glycerophosphate crystal A2 at 0.5MPa.
Embodiment 3
(1) at 40 DEG C, by Choline Glycerophosphate and propyl alcohol (weight ratio 100：550) 20min is mixed and mixing is made
Object M1；
(2) by mixture M 1 and magnesium sulfate (weight ratio 100：40) mixing, the cooling 50min at 30 DEG C, then carry out
First filters and filtrate is taken to obtain mixture M 2；
(3) under conditions of 40 DEG C and 60KPa, mixture M 2 is subjected to the first concentration 3h, mixture M 3 is made；
(4) by mixture M 3 and acetone (weight ratio 100：70) it mixes and carries out the second concentration 2h at 38 DEG C and be made mixed
Close object M4；
(5) at 45 DEG C, by mixture M 4, dry 4h obtains Choline Glycerophosphate crystal A3 at 0.8MPa.
Embodiment 4
Choline Glycerophosphate crystal A4 is prepared Following the procedure of Example 1, unlike, in step (2), sodium sulphate is changed
For copper sulphate.
Comparative example 1
Choline Glycerophosphate crystal B1 is prepared Following the procedure of Example 1, unlike, the process of step (3) is not carried out.
Comparative example 2
Choline Glycerophosphate crystal B2 is prepared Following the procedure of Example 1, unlike, the process of step (4) is not carried out.
Detect example 1
Sweet phosphoric acid prepared by commercially available Choline Glycerophosphate S (being purchased from Wuhan Merck medication chemistry Co., Ltd) and the present invention
Choline crystal A1-A3, B1-B2 weigh to obtain initial weight m1, are then placed within 2h in the air that air humidity is 30%, weigh
Weight m2 after being absorbed water, water absorption rate (w/%)=[(m2-m1)/m1] × 100%.
Table 1
| Number | Water absorption rate (w/%) |
| A1 | 1.9 |
| A2 | 1.8 |
| A3 | 1.8 |
| A4 | 1.9 |
| B1 | 12.2 |
| B2 | 13.4 |
| S | 16.6 |
As shown in Table 1, water absorption rate is very low after Choline Glycerophosphate crystal provided by the invention places 2h in air, relative to
The water absorption rate of A1-A4, S significantly increase, and illustrate the aerial water absorption rate of Choline Glycerophosphate crystal prepared by this method
Smaller, to purity higher, drug effect is stronger；Relative to A1-A4, the water absorption rate of B1-B2 is also increased, and illustrates that the present invention carries
It is acted synergistically between the preparation process (3) of confession and (4), tribute is made that the water absorption rate for reducing Choline Glycerophosphate crystal
It offers.
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail can carry out a variety of simple variants to technical scheme of the present invention within the scope of the technical concept of the present invention, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the present invention to it is various can
The combination of energy no longer separately illustrates.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally
The thought of invention, it should also be regarded as the disclosure of the present invention.
Claims (8)
1. a kind of preparation method of Choline Glycerophosphate crystal, which is characterized in that the preparation method includes：
(1) Choline Glycerophosphate and alcohol are mixed to prepare mixture M 1；
(2) mixture M 1 and sulfate mixed, cooled and filtered and filtrate taken to obtain mixture M 2；
(3) mixture M 2 is subjected to the first concentration and mixture M 3 is made；It is described first concentration condition be：Thickening temperature is
30-40 DEG C, concentration pressure is 40-60KPa, concentration time 1h-3h；
(4) the second concentration is carried out after mixing the mixture M 3 and organic solvent, and mixture M 4 is made；Second concentration
Temperature is less than 40 DEG C, and the time of the second concentration is 1h-2h；
(5) mixture M 4 is dried under reduced pressure to obtain Choline Glycerophosphate crystal；The condition being dried under reduced pressure is：Drying pressure
For 0.5-0.8MPa, drying time 1-4h, drying temperature is 35-45 DEG C.
2. preparation method according to claim 1, wherein in step (1), the sweet phosphorus relative to 100 parts by weight
The dosage of sour choline, the alcohol is 450-550 parts by weight；
The alcohol is one or more in methanol, ethyl alcohol and propyl alcohol.
3. preparation method according to claim 2, wherein in step (1), the temperature of the mixing is 35-40 DEG C, and
And described be mixed into is stirred.
4. preparation method according to claim 3, wherein the mixing time being stirred is 20-40min.
5. according to the preparation method described in any one of claim 1-4, wherein in step (2), the sulfate is selected from
It is one or more in sodium sulphate, potassium sulfate, magnesium sulfate and copper sulphate.
6. preparation method according to claim 5, wherein in step (2), the mixing relative to 100 parts by weight
The dosage of object M1, the sulfate are 30-40 parts by weight.
7. preparation method according to claim 5, wherein in step (2), the cooling at least meets the following conditions：
Cooling temperature be 25-30 DEG C, cooling time 30-50min.
8. preparation method according to claim 7, wherein in step (4), the mixing relative to 100 parts by weight
The dosage of object M3, the organic solvent are 50-70 parts by weight；
The organic solvent is ethyl alcohol and/or acetone.
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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 |
| CN115536710B (en) * | 2022-10-18 | 2024-04-16 | 南京工业大学 | Preparation method of high-quality cytidine sulfate crystal |
Citations (3)
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|---|---|---|---|---|
| US5523450A (en) * | 1992-01-22 | 1996-06-04 | Genzyme Limited | Crystallization process for preparing glycerophosphocholine |
| CN1560057A (en) * | 2004-03-10 | 2005-01-05 | 山东师范大学 | Preparationj process of high pureness phosphatidyl inositol |
| CN103429603A (en) * | 2011-03-14 | 2013-12-04 | 株式会社韩西克慕 | I- and II-type crystals of L-a-glyceryl phosphoryl choline, and method for preparing same |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103172659A (en) * | 2013-03-29 | 2013-06-26 | 山东罗欣药业股份有限公司 | L-alpha-glyceryl phosphoryl choline crystal form compound |
| CN103304594B (en) * | 2013-06-18 | 2015-07-08 | 上海科利生物医药有限公司 | Preparation method of L-alpha-glycerophosphoryl choline |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5523450A (en) * | 1992-01-22 | 1996-06-04 | Genzyme Limited | Crystallization process for preparing glycerophosphocholine |
| CN1560057A (en) * | 2004-03-10 | 2005-01-05 | 山东师范大学 | Preparationj process of high pureness phosphatidyl inositol |
| CN103429603A (en) * | 2011-03-14 | 2013-12-04 | 株式会社韩西克慕 | I- and II-type crystals of L-a-glyceryl phosphoryl choline, and method for preparing same |
Non-Patent Citations (1)
| Title |
|---|
| 甘油磷酸胆碱的结晶_结构解析及年产100吨原料药工艺设计;赵成磊;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20140815;B016-457 第12-13、54-55页 * |
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