CN114432253B - Citicoline sodium tablet and preparation method thereof - Google Patents

Citicoline sodium tablet and preparation method thereof Download PDF

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CN114432253B
CN114432253B CN202210155937.0A CN202210155937A CN114432253B CN 114432253 B CN114432253 B CN 114432253B CN 202210155937 A CN202210155937 A CN 202210155937A CN 114432253 B CN114432253 B CN 114432253B
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citicoline sodium
monosaccharide
preparation
citicoline
glidant
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CN114432253A (en
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谢荣宇
周再生
赵伟
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No2 People's Hospital Pingdingshan City
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a citicoline sodium tablet and a preparation method thereof. The invention provides a citicoline sodium tablet with high stability, and the formula comprises citicoline sodium, a filling agent, a disintegrating agent, a flow aid and monosaccharide. The monosaccharide is added, so that the stability of the preparation is improved, the direct powder tabletting method is adopted, the preparation process is optimized, the problem of powder flowability is solved, and the problem of degradation caused by moisture absorption is avoided.

Description

Citicoline sodium tablet and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a citicoline sodium tablet and a preparation method thereof.
Background
Citicoline sodium, white crystalline powder. Can gradually recover the functions of four limbs of hemiplegia caused by cerebral apoplexy, can also be used for functional and conscious disturbance caused by acute injury of other central nervous systems, can also be used for ischemic cerebrovascular diseases and vascular dementia, belongs to the application range of neurology, and can promote brain substance metabolism and improve brain circulation by reducing cerebrovascular resistance and increasing cerebral blood flow. Can also enhance the function of the brain stem ascending net activation system, enhance the function of a vertebral body system and improve the motor paralysis, thereby having certain effect on promoting the recovery of brain function and awakening. In addition, citicoline sodium can also be used for treating Parkinson's syndrome, has certain curative effect on senile dementia, and also has improvement effect on delaying senility, improving memory and the like.
The preparation on the market at home is an injection preparation, a common tablet or a capsule.
Chinese patents CN102028664A and CN103191079A disclose citicoline sodium tablets and preparation methods thereof, both of which adopt a traditional wet granulation method, and the method introduces a large amount of aqueous solution, and the drying process requires high temperature conditions, which easily causes citicoline sodium to hydrolyze at high temperature and high humidity during the preparation process to generate degradation impurities, which affects the preparation quality.
Chinese patent CN107496369A adopts a powder direct tabletting method to prepare citicoline sodium tablets, but there is a problem of poor powder flowability in the preparation process, and although this problem is solved to a certain extent by screening auxiliary materials, the uniformity of experimental results such as dissolution rate and stability is not good enough, and quality control is difficult to guarantee.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the citicoline sodium tablet with high stability, the stability of the preparation is improved by adding monosaccharide, the preparation process is optimized by adopting a direct powder tabletting method, the problem of powder flowability is solved, and the problem of degradation caused by moisture absorption is avoided.
Specifically, the technical scheme of the invention is as follows:
the invention provides a citicoline sodium tablet which comprises citicoline sodium, a filling agent, a disintegrating agent, a flow aid and monosaccharide.
Further, the monosaccharide is one of galactose, galactosamine, glucosamine, fucose and mannose.
In particular, the weight ratio of the monosaccharide to the citicoline sodium is 1-4:100.
further, the filler is selected from one or more of dextrin, microcrystalline cellulose, starch, pregelatinized starch, sucrose, lactose, mannitol, calcium bicarbonate, calcium sulfate and calcium carbonate; the disintegrant is selected from one or more of dry starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, croscarmellose sodium and crospovidone; the glidant is selected from one or more of magnesium stearate, aerosil and talcum powder.
In particular, the filler is preferably one or more of microcrystalline cellulose, mannitol and calcium bicarbonate; the disintegrant is preferably one or more of carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose and crospovidone; the glidant is preferably aerosil.
Specifically, the weight ratio of the filler to the citicoline sodium is 1-2:1.
specifically, the weight ratio of the disintegrant to the citicoline sodium is 1-5:10.
specifically, the weight ratio of the glidant to the citicoline sodium is (2-5): 10.
further, the citicoline sodium tablet also comprises pharmaceutically acceptable auxiliary materials.
A second object of the present invention is to provide a process for preparing the citicoline sodium tablet of claim by direct powder compression, comprising the steps of:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant by weight, sieving, mixing, adding the crushed and sieved filler, disintegrant, residual glidant or/and pharmaceutically acceptable auxiliary materials, uniformly mixing, and tabletting.
Compared with the prior art, the invention has the beneficial effects that:
(1) According to the invention, by adding the monosaccharide and preferably selecting the type of the monosaccharide, the proportion of the monosaccharide to the citicoline sodium is further limited, the content of related substances in the preparation is reduced, and the stability of the preparation is improved.
(2) According to the invention, through the optimized preparation method, the powder direct compression method is adopted, and the glidants are mixed in a grading manner, so that the powder fluidity and the tablet hardness are improved, the friability is reduced, and the quality of the preparation is higher.
Drawings
FIG. 1: accelerated test for the stability Effect of monosaccharides on citicoline sodium tablets
FIG. 2: long-term test of the influence of monosaccharides on the stability of citicoline sodium tablets
FIG. 3: accelerated test of influence of monosaccharide to citicoline sodium ratio on stability of citicoline sodium tablets
FIG. 4: long-term test for influence of monosaccharide to citicoline sodium ratio on stability of citicoline sodium tablets
Detailed Description
In order to make the purpose and technical solution of the present invention more clear, the present invention is further described with reference to the following examples, but the scope of the present invention is not limited to these examples, and the examples are only used for explaining the present invention. It will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true scope of the invention.
Example 1 (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 2
Filler Microcrystalline cellulose 150
Disintegrating agent Low-substituted hydroxypropyl cellulose 20
Glidant Silica gel micropowder 40
The preparation method comprises the following steps:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant by weight, sieving, mixing, adding the crushed and sieved filler, disintegrant and residual glidant, uniformly mixing and tabletting.
Example 2: (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 1
Filler Microcrystalline cellulose 100
Disintegrating agent Low-substituted hydroxypropyl cellulose 10
Glidant Silica gel micropowder 20
The preparation method comprises the following steps: the same as in example 1.
Example 3: (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 4
Filler Microcrystalline cellulose 200
Disintegrating agent Low-substituted hydroxypropyl cellulose 50
Glidants Silica gel micropowder 50
The preparation method comprises the following steps: the same as in example 1.
Example 4: (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 200
Monosaccharides L-fucose 4
Filler Microcrystalline cellulose 200
Disintegrating agent Low-substituted hydroxypropyl cellulose 20
Glidants Silica gel micropowder 40
The preparation method comprises the following steps: the same as in example 1.
Example 5: (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides Galactose 2
Filler Calcium bicarbonate 150
Disintegrating agent Sodium starch glycolate 20
Glidants Magnesium stearate 40
The preparation method comprises the following steps: the same as in example 1.
Example 6: (1000 tablets)
Figure BDA0003512246940000041
The preparation method comprises the following steps: the same as in example 1.
Example 7: (1000 tablets)
Figure BDA0003512246940000042
Figure BDA0003512246940000051
The preparation method comprises the following steps: the same as in example 1.
Example 8: (1000 tablets)
Figure BDA0003512246940000052
The preparation method comprises the following steps: the same as in example 1.
Example 9 (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 2
Filler Microcrystalline cellulose 150
Disintegrating agent Low-substituted hydroxypropyl cellulose 20
Glidants Silica gel micropowder 40
Adhesive agent Methyl cellulose 10
The preparation method comprises the following steps:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant according to the formula, sieving, mixing, adding the crushed and sieved filler, disintegrant, residual glidant and adhesive, uniformly mixing, and tabletting.
COMPARATIVE EXAMPLE 1 (1000 tablets)
Figure BDA0003512246940000053
Figure BDA0003512246940000061
The preparation method comprises the following steps:
respectively crushing citicoline sodium and monosaccharide according to the formula, sieving, mixing, adding the crushed and sieved filler and disintegrant, uniformly mixing, and tabletting.
COMPARATIVE EXAMPLE 2 (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 2
Filler Microcrystalline cellulose 150
Disintegrating agent Low-substituted hydroxypropyl cellulose 20
Glidant Silica gel micropowder 10
The preparation method comprises the following steps:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant by weight, sieving, mixing, adding the crushed and sieved filler, disintegrant and residual glidant, uniformly mixing and tabletting.
COMPARATIVE EXAMPLE 3 (1000 tablets)
Species of Weight (g)
Active ingredient Citicoline sodium salt 100
Monosaccharides L-fucose 2
Filler Microcrystalline cellulose 150
Disintegrating agent Low-substituted hydroxypropyl cellulose 20
Glidants Silica gel micropowder 40
The preparation method comprises the following steps:
the citicoline sodium, the monosaccharide, the filler, the disintegrant and the glidant are respectively crushed, sieved, uniformly mixed and tabletted according to the formula.
COMPARATIVE EXAMPLE 4 (1000 tablets)
Figure BDA0003512246940000062
Figure BDA0003512246940000071
The preparation method comprises the following steps:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant by weight, sieving, mixing, adding the crushed and sieved filler, disintegrant and residual glidant, uniformly mixing and tabletting.
Verification examples
1. Tablet quality control
The angle of repose is also commonly called as the collapse angle, is a relatively common powder flowability model parameter in China, and is obtained by calculating the plane included angle of a conical knot formed when powder vertically flows under the action of gravity, and the requirement on powder flowability in the industrial production process can be met by roughly considering that the angle is less than 40 degrees in general.
TABLE 1 quality control of tablets of examples and comparative examples
Hardness (N) Friability (%) Angle of repose (°) Appearance shape Difference in tablet weight
Example 1 60 0.1 20.3 Complete and smooth Qualified
Example 2 56 0.2 23.1 Complete and smooth Qualified
Example 3 57 0.2 22.8 Complete and smooth Qualified
Example 4 59 0.1 20.7 Complete and smooth Qualified
Example 5 55 0.3 25.6 Complete and smooth Qualified
Example 6 56 0.4 27.1 Complete and smooth Qualified
Example 7 55 0.3 26.4 Complete and smooth Qualified
Example 8 53 0.3 25.5 Complete and smooth Qualified
Example 9 54 0.5 29.4 Complete and smooth Qualified
Comparative example 1 40 2.3 41.6 Complete and smooth Qualified
Comparative example 2 43 1.6 38.4 Complete and smooth Qualified
Comparative example 3 45 1.8 36.6 Complete and smooth Qualified
As can be seen from Table 1, the tablets prepared in the examples 1 to 9 of the present invention have the advantages of complete and smooth appearance, uniform color, no mottle, no foreign matter, qualified tablet weight difference, hardness of more than 50N, good hardness, friability of less than 0.5%, powder angle of repose of less than 30 degrees, and good powder flowability. The powder flowability is poor, the angle of repose is more than 40 degrees and the hardness and friability of the prepared tablet are not as good as those of the tablet in the example 1, while the amount of the glidant added in the comparative example 2 is not within the protection range of the invention, the powder flowability is poor, the angle of repose is 38.4 degrees and the hardness and friability of the tablet are not as good as those of the tablet in the example, and the preparation method of the comparative example 3 is different from the method of the invention and has influence on the powder flowability, the hardness and friability of the tablet.
TABLE 2 results of limit detection of microorganisms in examples
Figure BDA0003512246940000081
Figure BDA0003512246940000091
Note that: item A: the number of bacteria; item B: the number of mold and yeast; item C: escherichia coli and live mite
2. Stability test
1. Stability Effect of monosaccharides on citicoline sodium tablets
Group 1: the tablets were prepared according to reference example 1;
group 2: the preparation process is the same as that of example 1 except that monosaccharide and other auxiliary materials are not added.
Accelerated tests and long-term tests were performed separately.
2. Stability Effect of monosaccharide types on citicoline sodium tablets
Group 1: galactose
Group 2: galactosamine
Group 3: glucosamine
Group 4: fucose sugar
Group 5: mannose
Group 6: fucose + galactose (1
Group 7: mannose + glucosamine (1
The other auxiliary materials and the preparation process are the same as example 1, and an accelerated test and a long-term test are respectively carried out.
Table 3 Long term test results for groups 1-7
Figure BDA0003512246940000092
TABLE 4 results of accelerated tests for groups 1-7
Figure BDA0003512246940000101
3. Test of Effect of monosaccharide to citicoline sodium ratio on stability of citicoline sodium tablets
Group 1: monosaccharide: citicoline sodium =1
Group 2: monosaccharide: citicoline sodium =1
Group 3: monosaccharide: citicoline sodium =1
Group 4: monosaccharide: citicoline sodium =1
Group 5: monosaccharide: citicoline sodium =1
The above are all in parts by weight.
The other auxiliary materials and the preparation process are the same as example 1, and an accelerated test and a long-term test are respectively carried out.
In fig. 3, the long-term test curves of the groups 1 to 3 are overlapped, the content of the related substances in the groups 1 to 3 is only 0.01% in the 0 th month, the 3 rd month, the 6 th month, the 9 th month, the 12 th month, the 24 th month and the 36 th month, the stability is high after the long-term test, and the content of the related substances is basically kept unchanged.
In FIG. 4, the accelerated test curves of groups 1-3 overlap, and the content of related substances in groups 1-3 is only 0.01% at the end of 1 month, 2 months, 3 months and 6 months.
It should be noted that the curves of the long-term test and the accelerated test of the groups 1 to 3 in fig. 3 and 4 are overlapped, so that the experimental result is not influenced, and the understanding of the technical effect of the invention is not influenced.
The test method comprises the following steps:
and (3) accelerated test: the test sample is placed for 6 months under the conditions of commercial package temperature of 40 +/-2 ℃ and relative humidity of 75% +/-5%, and is respectively sampled at the end of 1 month, 2 months, 3 months and 6 months during the test period to measure the content of related substances.
And (3) long-term test: according to the commercial package, the sample is placed under the conditions that the temperature is 25 +/-2 ℃ and the relative humidity is 60% +/-10%, and the samples are respectively taken at 0 month, 3 months, 6 months, 9 months, 12 months, 24 months and 36 months during the test period, and the content of the related substances is detected.
The related substances were measured by high performance liquid chromatography (general rule 0512).
Test solution: taking a proper amount of fine powder under the content measurement item, precisely weighing, adding water to dissolve and quantitatively diluting to prepare a solution containing about 2.5mg of citicoline sodium in each 1ml, filtering, and taking a subsequent filtrate.
Control solution: precisely measuring 1ml of the test solution, placing the test solution into a 500ml measuring flask, diluting the test solution to the scale with water, and shaking up.
5' -cytidylic acid reference substance solution, citicoline sodium reference substance solution, system applicability solution, chromatographic conditions, system applicability requirements and determination method, see China pharmacopoeia 2020 edition citicoline sodium related substance item.
Limitation: if an impurity peak exists in a chromatogram of a test solution, the chromatogram contains 5' -cytidylic acid which is 0.3 percent of the labeled amount of citicoline sodium which cannot be obtained by calculating the peak area according to an external standard method; the peak area of other single impurities should not be larger than the main peak area of the control solution (0.2%), and the sum of the peak areas of other impurities should not be larger than 3.5 times (0.7%) of the main peak area of the control solution.
The tablets of examples 1 to 9 were subjected to accelerated tests and long-term tests, and the stability of the formulations was examined, which revealed that the total impurity content of the relevant substances was kept at 0.01%, and the stability was high.

Claims (1)

1. The citicoline sodium tablet is characterized by comprising citicoline sodium, a filling agent, a disintegrating agent, a flow aid and monosaccharide;
the filler is microcrystalline cellulose; the disintegrating agent is low-substituted hydroxypropyl cellulose; the glidant is micro-powder silica gel; the monosaccharide is one of galactose, galactosamine, glucosamine, fucose and mannose;
the weight ratio of the monosaccharide to the citicoline sodium is 1-4:100, respectively;
the weight ratio of the filler to the citicoline sodium is 1-2:1;
the weight ratio of the disintegrant to the citicoline sodium is 1-5:10;
the weight ratio of the glidant to the citicoline sodium is (2-5): 10;
the preparation method of the citicoline sodium tablet adopts a powder direct compression method, and comprises the following steps:
respectively crushing citicoline sodium, monosaccharide and 1/2 of glidant by weight, sieving, mixing, adding the crushed and sieved filler, disintegrant and residual glidant, uniformly mixing, and tabletting.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6057301A (en) * 1997-12-24 2000-05-02 Interneuron Pharmaceuticals, Inc. Hyperhydrated citicoline, process and use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102028664B (en) * 2010-12-22 2013-09-25 四川梓橦宫药业有限公司 Citicoline sodium tablets and preparation method thereof
CN107496369B (en) * 2017-09-15 2020-06-26 福建省闽东力捷迅药业有限公司 Citicoline sodium tablet and direct powder tabletting preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6057301A (en) * 1997-12-24 2000-05-02 Interneuron Pharmaceuticals, Inc. Hyperhydrated citicoline, process and use

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