CN109160931A - A kind of 1/2 water Citicoline sodium compound - Google Patents
A kind of 1/2 water Citicoline sodium compound Download PDFInfo
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- CN109160931A CN109160931A CN201710706599.4A CN201710706599A CN109160931A CN 109160931 A CN109160931 A CN 109160931A CN 201710706599 A CN201710706599 A CN 201710706599A CN 109160931 A CN109160931 A CN 109160931A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The present invention relates to a kind of 1/2 water Citicoline sodium compounds and preparation method thereof, wherein every mole of C14H25N4NaO11P2 contains 1/2 mole of water.Specific preparation method are as follows: C14H25N4NaO11P2 crude product, mosatil, sodium sulfite are added in purified water and acetone mixed solution, stirring and dissolving.Active carbon, stirring and adsorbing, filtering is added.It is adjusted with acid filtrate pH, is stirred evenly.Isopropanol is slowly added dropwise into above-mentioned solution, stands crystallization, filtrate is washed in filtering, and it is dry, obtain 1/2 water Citicoline sodium compound.1/2 water Citicoline sodium compound good fluidity of the invention, impurity content is low, and low in hygroscopicity, solution rate is fast, and stability is good, has broader ground application prospect.
Description
Technical field
The invention belongs to chemical engineering medicine crystallization technique field, be related to a kind of 1/2 water Citicoline sodium compound and its
Preparation method.
Background technique
C14H25N4NaO11P2 (Citicoline Sodium) is the precursor substance of phospholipid phosphatidyl choline, is closed for lecithin
At necessary coenzyme.Its molecular formula is C14H25N4NaO11P2, molecular weight 510.31, No. CAS is 33818-15-4, structural formula
Are as follows:
The method for preparing C14H25N4NaO11P2 at present has: (1) chemical synthesis: being made using CMP (5'-CMP) and phosphocholine
For reactant, p-toluenesulfonyl chloride carries out condensation preparation as condensing agent in the presence of dinethylformamide, with 717
(Cl-) type anion-exchange column and 711 (Cl-) type evaporating column separating liquid alcohol precipitations prepare C14H25N4NaO11P2, the disadvantage is that difficult
It is separated with condensing agent, product is not suitable for medicinal；(2) enzyme' s catalysis: extracting cell liquid cytidine triphosphate (CTP) (CTP) and phosphocholine
Biosynthesis C14H25N4NaO11P2, enzyme and extraction liquid of cell synthesis need substrate CTP, and synthesis price is high；(3) free cell and yeast
Cell-free extract synthesizes C14H25N4NaO11P2, and free yeast synthesis needs a large amount of yeast, and can only be disposable, has very much
Disadvantage.Therefore, it is necessary to find, cost is lower, the preparation method of the simpler C14H25N4NaO11P2 of operating procedure.
Currently, using the C14H25N4NaO11P2 of above method preparation there are poor fluidity, impurity is higher, easy to moisture absorption, stability
The problems such as poor.Because it is to moisture-sensitive, and the product specification is directed to water content, so citicoline must be in spy
It is handled under conditions of different, including low-humidity environment, to provide and maintain relatively low water content.
On the one hand the presence of these problems causes product quality poor and unstable, clinical application is dangerous and can not be with
External imported raw material competition, another aspect such case will cause the serious waste of human and material resources, financial resources.To solve above-mentioned ask
Topic, there is an urgent need to find a kind of more stable, safer, less side effects Citicoline sodium compound for clinical medicine circle.
The prior art is prepared to C14H25N4NaO11P2 and the numerous studies of method for crystallising, provides for its safer and more effective application
Guarantee.And in long-term production and research practice, the present inventor has carried out more in-depth study to C14H25N4NaO11P2, obtains
A kind of novel solvent compound of C14H25N4NaO11P2 is arrived, every mole of Citicoline sodium compound contains 1/2 mole of water.Born of the same parents' phosphorus of the invention
Choline sodium compound has good fluidity, and impurity content is low, and low in hygroscopicity, solution rate is fast, the good feature of stability, has more
Widely application prospect.
Summary of the invention
The invention discloses the new solvates of one kind of C14H25N4NaO11P2, are more specifically 1/2 water citicoline sodium
Object is closed, i.e. every mole of Citicoline sodium compound contains 1/2 mole of water, molecular formula C14H25N4NaO11P2·1/2H2O, molecular weight
It is 519.31, structural formula is as follows:
1/2 water Citicoline sodium compound of the present invention, specific preparation process is as follows:
Purified water and acetone are added into reactor, stirs evenly.Weigh C14H25N4NaO11P2 crude product, mosatil, sulfurous acid
Sodium sequentially adds in reactor, at room temperature stirring to dissolution；Active carbon, stirring and adsorbing, filtering are added thereto.It is adjusted with acid filter
Liquid pH, stirs evenly；Isopropanol is slowly added dropwise into above-mentioned solution, is added dropwise to isopropanol, temperature control stands crystallization, filters, and use is different
Propanol rinse filtrate, vacuum drying, obtains 1/2 water Citicoline sodium compound.
Preferably, in above-mentioned preparation method, each step reaction mixing speed is 150~500r/min；It is preferred that 250~
300r/min。
Preferably, in above-mentioned preparation method, the volume ratio of the purified water and acetone is 1:(1~5)；It is preferred that 1:3.
Preferably, in above-mentioned preparation method, the filtrate pH value range that is adjusted with acid is 1~5；It is preferred that 1.5~2.0.
Preferably, in above-mentioned preparation method, the volume ratio of the isopropanol and reaction solution is 1:(1~6)；It is preferred that 1:4.
Preferably, in above-mentioned preparation method, the time that isopropanol is added dropwise is 0.5~3h；It is preferred that the time be 1~
1.5h。
Preferably, in above-mentioned preparation method, the standing crystallization temperature is 0~15 DEG C, and the time is 0.5~3h；It is preferred that analysing
Brilliant temperature is 5~10 DEG C, and the time is 1~1.5h.
Preferably, in above-mentioned preparation method, the vacuum drying temperature is 30~80 DEG C, and drying time is 1~4h；It is preferred that
Temperature is 50~70 DEG C, and drying time is 2~3h.
Karl_Fischer method is one of the most single-minded, accurate method in moisture method in various measurement substances, is had been cited as
The standard method of determination of moisture in many substances, especially to organic compound, as a result accurately and reliably.Born of the same parents' phosphorus gallbladder disclosed by the invention
Alkali sodium compound Karl_Fischer method measures moisture weight content between 1.65~1.80%.Theoretical water content is 1.73%,
The each Citicoline sodium compound of the deducibility present invention contains 1/2 mole of water.
1/2 water Citicoline sodium compound of the present invention, TG analysis is the results show that Citicoline sodium compound
Percentage loss of weight calculated result is it is found that weightlessness about 1.71%, and the theoretical percentage composition of water is 1.73% in citicoline sodium molecule,
Measuring C14H25N4NaO11P2 moisture content referring to expense Xiu Shi method is 1.65~1.80%, and it is 1.71% that experiment, which measures TG weightlessness, with
Theoretical water content is consistent substantially.It can be inferred that C14H25N4NaO11P2 TG weightlessness is and every mole of C14H25N4NaO11P2 caused by removing water
Containing 1/2 mole of water.As shown in Fig. 1.Data are obtained by heat analysis-mass spectrometer (NETZSCH STA 449C) analysis.Point
Analysis condition are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas and protection gas, flow be respectively 40ml/min and
30ml/min, heating rate 10K/min, temperature test range are 25~400 DEG C.Sample decomposition temperature is about 272.0 DEG C.
1/2 water Citicoline sodium compound of the present invention, infrared spectroscopy are 3419.5 ± 2cm in wave number-1,
2665.9±2cm-1, 1654.6 ± 2cm-1, 1611.9 ± 2cm-1, 1487.3 ± 2cm-1, 1380.1 ± 2cm-1, 1234.7 ±
2cm-1, 1135.3 ± 2cm-1, 1071.7 ± 2cm-1, 936.5 ± 2cm-1, 781.7 ± 2cm-1There are characteristic absorption peak, such as attached drawing in place
Shown in 2.Examination of infrared spectrum condition are as follows: Agilent Cary 630, pressing potassium bromide troche.
1/2 water Citicoline sodium compound of the present invention, x-ray diffractogram of powder spectrum are 6.07 in 2 θ of the angle of diffraction
± 0.2 °, 6.54 ± 0.2 °, 9.68 ± 0.2 °, 14.60 ± 0.2 °, 15.79 ± 0.2 °, 17.57 ± 0.2 °, 19.40 ± 0.2 °,
There is characteristic diffraction peak at 24.32 ± 0.2 °, 26.49 ± 0.2 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,93.05,
27.66,20.12,15.04,17.31,32.13,27.70,13.58.As shown in Fig. 3.X-ray powder diffraction test condition:
EMPYREAN (sharp shadow) X-ray diffractometer of Dutch Panalytical company, CuK α radiation, light pipe voltage 40kV, heater current
300mA, continuous scanning, 0.02 ° of step-length, 8 °/min of scanning speed, scanning range is 2~50 °.
1/2 water Citicoline sodium compound of the present invention, dsc analysis is the results show that have heat absorption at about 256.5 DEG C
There is endothermic peak at peak at about 273.9 DEG C.As shown in Fig. 4.DSC data is by heat analysis-mass spectrometer (NETZSCH STA
449C) analysis obtains, analysis condition are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas and protection gas, flow
Respectively 40ml/min and 30ml/min.10 DEG C/min of heating rate, 25~400 DEG C of temperature range.
Further purpose of the invention provides a kind of pharmaceutical composition containing 1/2 water Citicoline sodium compound.It is excellent
Selection of land, described pharmaceutical composition include 1/2 water Citicoline sodium compound and the excipient pharmaceutically received.It is highly preferred that medicine
Compositions are selected from pharmaceutically acceptable dosage form.
Detailed description of the invention
The TG analysis chart of 1/2 water Citicoline sodium compound of Fig. 1；
The FTIR spectrum figure of 1/2 water Citicoline sodium compound of Fig. 2；
The X ray diffracting spectrum of 1/2 water Citicoline sodium compound of Fig. 3；
The dsc analysis figure of 1/2 water Citicoline sodium compound of Fig. 4.
Specific embodiment
Below will by specific embodiment, the present invention will be further described, but therefore do not limit the present invention to institute
In the scope of embodiments stated, it should be understood by those skilled in the art that changing to the equivalent replacement that the content of present invention is done, or accordingly
Into still falling within protection scope of the present invention.
The preparation of embodiment 1:1/2 water Citicoline sodium compound
Preparation process:
Purified water 100mL and acetone 300mL is added into reactor, stirs evenly.Weigh C14H25N4NaO11P2 crude product 100.11g,
Mosatil 0.10g, sodium sulfite 0.10g are sequentially added in reactor, at room temperature stirring to dissolution.Activity is added thereto
Charcoal 0.25g, stirring and adsorbing 30min, filtering.Adjust filtrate pH value to 2.0 with the hydrochloric acid solution of 1mol/L, control temperature 15~
20 DEG C, isopropanol 125mL is slowly added dropwise into above-mentioned solution, is added dropwise to isopropanol, controls temperature at 5~10 DEG C, stand
Crystallization 1.5h, filtering wash filtrate with isopropanol 80mL × 2, filtrate are put into the vacuum drying for being equipped with phosphorus pentoxide
Case (- 0.09MPa) for 24 hours after, be warming up to 60 DEG C of dry 2.5h, obtain 1/2 water Citicoline sodium compound 96.21g.
As a result:
Infrared spectroscopy is 3419.5cm in wave number-1, 2665.9cm-1, 1654.6cm-1, 1611.9cm-1, 1487.3cm-1,
1380.1cm-1, 1234.7cm-1, 1135.3cm-1, 1071.7cm-1, 936.5cm-1, 781.7cm-1There is characteristic absorption peak at place.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 6.07 °, 6.54 °, 9.68 °, 14.60 °, 15.79 °, 17.57 °,
There is characteristic diffraction peak at 19.40 °, 24.32 °, 26.49 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,93.05,27.66,
20.12,15.04,17.31,32.13,27.70,13.58.
It is 99.91% that HPLC method, which detects purity,；It is 1.70% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.71%, it is almost the same with the result (theoretical value 1.73%) of 1/2 water contained in this way；Elemental Analysis theory are as follows: C:
32.38%, H:5.04%, Na:4.43%, N:10.79%, O:35.43%, P:11.94%；Measured value are as follows: C:32.35%,
H:5.05%, N:4.40%, Na:10.80%, O:35.47%, S:11.93%.
The preparation of embodiment 2:1/2 water Citicoline sodium compound
Preparation process:
Purified water 100mL and acetone 400mL is added into reactor, stirs evenly.Weigh C14H25N4NaO11P2 crude product 100.05g,
Mosatil 0.12g, sodium sulfite 0.12g are sequentially added in reactor, at room temperature stirring to dissolution.Activity is added thereto
Charcoal 0.31g, stirring and adsorbing 30min, filtering.Adjust filtrate pH value to 1.5 with the hydrochloric acid solution of 1mol/L, control temperature 15~
20 DEG C, isopropanol 160mL is slowly added dropwise into above-mentioned solution, is added dropwise to isopropanol, temperature is controlled at 0~5 DEG C, is stood
Crystallization 1h, filtering wash filtrate with isopropanol 80mL × 2, filtrate are put into the vacuum oven for being equipped with phosphorus pentoxide
(- 0.09MPa) for 24 hours after, be warming up to 70 DEG C of dry 2h, obtain 1/2 water Citicoline sodium compound 95.79g.
As a result:
Infrared spectroscopy is 3419.4cm in wave number-1, 2665.7cm-1, 1654.3cm-1, 1611.5cm-1, 1487.2cm-1,
1380.4cm-1, 1234.5cm-1, 1135.6cm-1, 1071.5cm-1, 936.3cm-1, 781.4cm-1There is characteristic absorption peak at place.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 6.02 °, 6.55 °, 9.69 °, 14.62 °, 15.77 °, 17.58 °,
There is characteristic diffraction peak at 19.42 °, 24.34 °, 26.50 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,92.32,26.58,
22.35,14.70,18.29,34.15,28.45,12.17.
It is 99.92% that HPLC method, which detects purity,；It is 1.65% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.70%, it is almost the same with the result (theoretical value 1.73%) of 1/2 water contained in this way；Elemental Analysis theory are as follows: C:
32.38%, H:5.04%, Na:4.43%, N:10.79%, O:35.43%, P:11.94%；Measured value are as follows: C:32.39%,
H:5.03%, N:4.42%, Na:10.81%, O:35.45%, S:11.90%.
Embodiment 3: the preparation of citicoline sodium freeze-dried preparation
1/2 water Citicoline sodium compound prepared by Example 2 prepares C14H25N4NaO11P2 freeze-drying system using this raw material
Agent, specification 0.25g.
Prescription:
Preparation process:
1, match liquid
(1) water for injection of recipe quantity 80% is added into Agitation Tank；
(2) 1/2 water Citicoline sodium compound of recipe quantity is added, stirring and dissolving is complete, and benefit adds to the full amount of water for injection；
(3) 0.05% medical charcoal (injection), stirring and adsorbing 15min will be added in medical fluid；
(4) with 0.45 μm of membrane filtration decarburization；
(5) with 0.22 μm of membrane filtration decarburization.
2, filling: filling in middle Pyrex tubulose injection bottle according to theoretical loading amount, pressure half is filled in；
3, it is freeze-dried；
4, it rolls lid, examine.
It is 1.70% with Karl_Fischer method measurement Citicoline sodium compound freeze-dried powder water content result, born of the same parents' phosphorus gallbladder before being lyophilized
Alkali sodium compound determination of moisture result is 1.65%, almost the same with the result (theoretical value 1.73%) of 1/2 mole of water contained；
The result shows that Citicoline sodium compound moisture is not lost after freeze-drying, inferring that every mole compound institute is aqueous should be 1/2 mole of knot
Brilliant water.
Comparative example 1: the preparation of 1 hydrate of C14H25N4NaO11P2
1 hydrate of C14H25N4NaO11P2 is prepared according to the method for embodiment in existing technical literature CN1284880A
Commercially available citicoline sodium raw materials are taken, are directly exposed to 40 DEG C, 4 hours under conditions of 75%RH.
The content that Karl_Fischer method detects water in C14H25N4NaO11P2 is 3.45%, and 1 hydrate theoretical water of C14H25N4NaO11P2
Content be 3.41%, it is almost the same, can determine in the Citicoline sodium compound containing 1 mole of water.
It is 99.46% that HPLC method, which detects purity,；Elemental Analysis theory are as follows: C:31.83%, H:5.15%, Na:
4.35%, N:10.61%, O:36.34%, P:11.73%；Measured value are as follows: C:31.85%, H:5.14%, Na:4.37%, N:
10.60%, O:36.32%, P:11.74%.
Comparative example 2: Citicoline sodium compound is prepared according to existing technical literature CN 103509073A
Using the identical method of patent document embodiment 2
Preparation process:
1, the 300mL mixed solvent that methanol and isopropanol (volume ratio 1:4) are prepared is added in C14H25N4NaO11P2 crude product 45.1g
In, 30 DEG C are heated to, is stirred, filtering obtains crude product solution, spare.
2, by acetone and chloroform by volume 1:3 ratio prepare recrystallisation solvent, the recrystallisation solvent volume be 400mL,
It is spare.
3, under stirring, the recrystallisation solvent of step 2 is added into the crude product solution of step 1, there is solid precipitation；It is added dropwise
Afterwards, continue that chloroform is added dropwise under stiring, the volume of dropwise addition is 5 times of C14H25N4NaO11P2 crude product weight, and process control is entirely added dropwise
Solution temperature is 30 DEG C；Drop finishes, and is cooled to 5 DEG C of standing 1h, filters, and washing, 50 DEG C of vacuum drying 3h obtain C14H25N4NaO11P2 chemical combination
Object 41.2g.
It is 99.48% that HPLC method, which detects purity,；It is 0.95% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.98%；Elemental Analysis theory are as follows: C:32.95%, H:4.94%, Na:4.51%, N:10.98%, O:34.49%, P:
12.14%；Measured value are as follows: C:32.98%, H:4.93%, Na:4.50%, N:10.96%, O:34.48%, P:12.16%.
1 mobility of test example is investigated
The mobility of Citicoline sodium compound prepared by embodiment 1, comparative example 1 and comparative example 2 is studied.Stop
Angle detection method is to be placed in particle in fixed funnel, drops down onto its freely on horizontal plane, forms the circle that a bottom radius is r
Dish type accumulation body, the height for measuring accumulation body is H, is calculated according to formula tan θ=H/r.
Test results in the following table:
As a result: the mobility of 1/2 water Citicoline sodium compound prepared by the embodiment of the present invention 1 is significantly better than the prior art
Citicoline sodium compound prepared by comparative example 1, comparative example 2 can satisfy a variety of preparation sides in the preparation process of preparation
The needs of formula.
2 purity detecting of test example
To Citicoline sodium compound prepared by the embodiment of the present invention 1, comparative example 1 and comparative example 2 carried out purity and
Related substance detection.
Test results in the following table:
As a result: 1/2 water Citicoline sodium compound purity prepared by the embodiment of the present invention 1 is higher than comparative example 1 and comparative example 2
The Citicoline sodium compound of preparation, related substance is lower than Citicoline sodium compound prepared by comparative example 1, comparative example 2, this hair
Bright product quality is preferable.
Test example 3 draws moist investigation
Moist carry out is drawn to Citicoline sodium compound prepared by the embodiment of the present invention 1, comparative example 1 and comparative example 2
Research.Investigation condition is relative humidity 75% (RH) and relative humidity 92.5% (RH), and temperature is 40 DEG C, and inspection target is born of the same parents' phosphorus
Water content in choline sodium.
Test results in the following table:
As a result: 1/2 water Citicoline sodium compound prepared by the embodiment of the present invention 1 is drawn moist significantly lower than the prior art pair
Citicoline sodium compound prepared by ratio 1, comparative example 2.Illustrate that 1/2 water Citicoline sodium compound of the present invention is stablized
Property it is good, be suitble to pharmaceutical preparation manufacture and long term storage.
4 solution rate of test example is investigated
Citicoline sodium compound prepared by embodiment 1, comparative example 1 and comparative example 2 is distinguished to soluble in water, shaking,
Compare the speed of solution rate by dissolution time.
Test results in the following table:
| Test example | Embodiment 1 | Comparative example 1 | Comparative example 2 |
| Sample weighting amount (g) | 2.5 | 2.5 | 2.5 |
| Amount of water (mL) | 50 | 50 | 50 |
| Dissolution time (min) | 1.0±0.3 | 3.7±0.8 | 4.5±0.6 |
As a result: the solution rate of 1/2 water Citicoline sodium compound prepared by the embodiment of the present invention 1 is significantly better than comparative example
1 and comparative example 2 Citicoline sodium compound.
5 stability study of test example
1, high-temperature stability is evaluated
Citicoline sodium compound prepared by Example 1 and comparative example 1, comparative example 2 places 10 under the conditions of setting 60 DEG C
It, sampled in the 10th day.Inspection target is character, moisture, related substance and the content of sample.
Test results in the following table:
As a result: can be seen that by above-mentioned hot test, the moisture of the embodiment of the present invention 1 does not change substantially, 1 He of comparative example
The moisture of comparative example 2 is substantially reduced, and infers that sample contained humidity prepared by the present embodiment 1 is the crystallization water, comparative example 1 and comparative example
The sample contained humidity of 2 preparations is absorption water.It can be seen that from the above, other items of sample prepared by the embodiment of the present invention 1
The sample that Testing index is substantially better than comparative example 1, prepared by comparative example 2, shows that 1/2 water Citicoline sodium compound of the invention is steady
It is qualitative good.
2, accelerated stability is evaluated
Citicoline sodium compound prepared by Example 1, comparative example 1 and comparative example 2, condition of investigating are 40 DEG C of temperature
±2℃.It places 6 months, is sampled respectively at 0,1,2,3,6 the end of month.Inspection target is character, the clarity of solution and color, water
Divide, related substance and content.
Test results in the following table:
As a result: can be seen that by accelerated test result, significant change, comparative example 1 do not occur for the moisture of the embodiment of the present invention 1
It is substantially reduced with the moisture of comparative example 2, can further infer that sample contained humidity prepared by the present embodiment 1 is the crystallization water, comparison
Sample contained humidity prepared by example 1 and comparative example 2 is absorption water；Other every Testing index of the embodiment of the present invention 1 are also obvious
Better than comparative example 1 and comparative example 2, absolutely prove that 1/2 water Citicoline sodium compound stability prepared by the present invention is more preferable, matter
Amount is better than similar product.
Citicoline sodium compound of the invention proves that its every mole compound contains 1/2 mole of crystallization water through multiple tests；
It is examined through many index and stability test investigation shows that its stability is good, quality is far superior to the product of the prior art, this hair
It is bright that there is unexpected technical effect, reliable in quality.
Claims (4)
1. a kind of 1/2 water Citicoline sodium compound, which is characterized in that every mole of C14H25N4NaO11P2 contains 1/2 mole of water, molecular formula
For C14H25N4NaO11P2·1/2H2O, molecular weight 519.31, structural formula is as follows:
2. a kind of pharmaceutical composition, it is characterised in that include 1/2 water Citicoline sodium compound described in claim 1.
3. a kind of pharmaceutical composition, it is characterised in that include 1/2 water Citicoline sodium compound described in claim 1 and pharmacy
The excipient of upper receiving.
4. pharmaceutical composition according to claim 3, it is characterised in that described pharmaceutical composition is selected from pharmaceutically acceptable
Dosage form.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109160932A (en) * | 2017-08-18 | 2019-01-08 | 刘兆娟 | One kind 11/2Water Citicoline sodium compound and its drug combination preparation |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1284880A (en) * | 1997-12-24 | 2001-02-21 | 英特纳龙制药公司 | Hyperhydrated citicoline, process and use |
| CN103509073A (en) * | 2013-08-29 | 2014-01-15 | 洪军 | Citicoline sodium compound |
| WO2015048558A1 (en) * | 2013-09-30 | 2015-04-02 | Geron Corporation | Phosphorodiamidate backbone linkage for oligonucleotides |
| CN106146590A (en) * | 2016-06-29 | 2016-11-23 | 陈建峰 | A kind of preparation method of C14H25N4NaO11P2 |
-
2017
- 2017-08-17 CN CN201710706599.4A patent/CN109160931A/en active Pending
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| CN109160932A (en) * | 2017-08-18 | 2019-01-08 | 刘兆娟 | One kind 11/2Water Citicoline sodium compound and its drug combination preparation |
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Application publication date: 20190108 |