CN104027304B - Citicoline sodium glucose injection - Google Patents
Citicoline sodium glucose injection Download PDFInfo
- Publication number
- CN104027304B CN104027304B CN201410244261.8A CN201410244261A CN104027304B CN 104027304 B CN104027304 B CN 104027304B CN 201410244261 A CN201410244261 A CN 201410244261A CN 104027304 B CN104027304 B CN 104027304B
- Authority
- CN
- China
- Prior art keywords
- glucose
- injection
- citicoline sodium
- glycine
- citric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to citicoline sodium glucose injection, belonging to the field of pharmaceutical preparations. The citicoline sodium glucose injection provided by the invention is composed of 3 g of citicoline sodium, 40 g of glucose, 1.8 g of glycine, and 1.3 g of citric acid; the pH value is adjusted to 5.5-5.6 by using sodium hydroxide; and water for injection is added till the citicoline sodium glucose injection is 1000 ml.
Description
Technical field
The present invention relates to a kind of citicoline sodium glucose injection, belong to field of pharmaceutical preparations.
Background technology
The chemical name of C14H25N4NaO11P2 is single sodium salt of choline cytidine diphosphate ester, and its chemical structural formula is:
Molecular formula is C14H25N4NaO11P2, and molecular weight is 510.31.
C14H25N4NaO11P2 is nucleoside derivate, has the effect strengthening the up network structure activating system of brain stem and the activity of pyramidal system, level of strengthening the awareness and motion function; Also have and reduce cerebral blood vessel resistance, increase cerebral blood flow, especially increase the blood flow in brain stem portion, thus improve cerebral circulation, promotion brain function is recovered and revive have certain effect.Be mainly used in Acute Brain Injury and brain Post operation disturbance of consciousness.
C14H25N4NaO11P2 is white crystals or crystalline powder; Odorless.Easily molten in water, insoluble in ethanol, acetone, chloroform.But the problem of poor heat stability is being produced and existed in storage process to the citicoline sodium glucose injection sold, and its related substances is higher, can not meet the demand of producing and using.A kind of new citicoline sodium glucose injection of present urgent need invention, to overcome the deficiency that existing citicoline sodium glucose injection exists.
Summary of the invention
Present inventor is by groping and test of many times, find to add one of glycine, citric acid or the compositions of the two in the aqueous solution of C14H25N4NaO11P2 and glucose, and use the main ingredient of specified quantitative, significantly can strengthen the stability of obtained citicoline sodium glucose injection, significantly reduce the generation of related substance.
Technical solution of the present invention comprises:
1. a citicoline sodium glucose injection, comprising C14H25N4NaO11P2, glucose.
2. a citicoline sodium glucose injection, comprising C14H25N4NaO11P2, glucose, glycine.
3. a citicoline sodium glucose injection, comprising C14H25N4NaO11P2, glucose, citric acid.
4. a citicoline sodium glucose injection, comprising C14H25N4NaO11P2, glucose, glycine, citric acid.
5. a citicoline sodium glucose injection, it is made up of C14H25N4NaO11P2, glucose, glycine, citric acid, its
Middle C14H25N4NaO11P2 is 3g, and glucose is 40g, and glycine is 1.8g, and citric acid is 1.3g, uses sodium hydroxide to regulate
PH value is 5.5-5.6, injects water to 1000ml.
Citicoline sodium glucose injection tool of the present invention has the following advantages:
(1) glycine added in injection and citric acid have the effect of cosolvent and stabilizing agent for C14H25N4NaO11P2, can strengthen product stability, reduce the generation of related substance.Make product remain high-quality, high stability in production and storage process, be conducive to Clinical practice.
(2) citicoline sodium glucose injection production technology of the present invention is simple, main ingredient is cheap, can reduce production cost, bring benefit to the people.
Detailed description of the invention
Further illustrate the present invention by the following examples, but these embodiments do not limit the present invention in any way.
Embodiment 1 citicoline sodium glucose injection
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology:
Glucose is soluble in water 1., filter after then adding activated carbon adsorption, filtrate water is diluted to isotonic concentration, thus obtain the isotonic aqueous solution of glucose; Preferably, described water is water for injection;
2. in the isotonic aqueous solution obtained through step 1, add C14H25N4NaO11P2, glycine and citric acid, stir and make it dissolve, filter after then adding activated carbon adsorption, use 0.1N sodium hydroxide to regulate adjust ph to be 5.5-5.6, filtering with microporous membrane.
Embodiment 2
C14H25N4NaO11P2 3000mg
Glucose 40000mg
Citric acid 1300mg
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology: with embodiment 1.
Embodiment 3
C14H25N4NaO11P2 3000mg
Glucose 40000mg
Glycine 1800mg
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology: with embodiment 1.
Citicoline sodium glucose injection indices prepared by above-described embodiment meets 2010 editions Chinese Pharmacopoeias, two pertinent regulations.
Character: colourless clear liquid.
PH value: 5.5-5.6
Visible foreign matters: qualified
Sterility test: qualified
Particulate matter: qualified
Content: qualified
Related substance: single impurity is no more than 0.3%, other impurity are no more than 0.5%.
Citicoline sodium glucose injection stability test:
Comparative example 1
C14H25N4NaO11P2 2500mg
Glucose 50000mg
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology: with embodiment 1.
Comparative example 2
C14H25N4NaO11P2 3000mg
Glucose 40000mg
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology: with embodiment 1.
Comparative example 3
Use 0.1N sodium hydroxide adjust ph to be 5.7-6.3, inject water to 1000ml.
Preparation technology: see CN102144963B
Comparative example 4
Use 0.1N sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Preparation technology: with embodiment 1.
Stability test 1:
Be positioned in 60 DEG C of climatic chambers by the product that above-mentioned 3 embodiments and 4 comparative examples obtain, in sampling calibrating in the 5th, 10 day, result compared with 0 day:
Related substance, content are by high effective liquid chromatography for measuring (be shown in table 1).
Table 1
Result:
Embodiment 1-3: select glycine or citric acid or the compositions of the two to be cosolvent and stabilizing agent, regulates pH to 5.5-5.6.
Comparative example 1: do not use cosolvent and stabilizing agent
Comparative example 2: do not use cosolvent and stabilizing agent
Comparative example 3: use malic acid and sodium sulfite as cosolvent and stabilizing agent
Comparative example 4: use glycine and citric acid as cosolvent and stabilizing agent, but consumption is different from embodiment 1-3
Embodiment 1-3 compares with comparative example 1-4, pH, related substance, stable content have obvious advantage, select glycine and citric acid as cosolvent and stabilizing agent, regulate pH to 5.5-5.6, significantly can increase the dissolubility of C14H25N4NaO11P2 in water, and significantly improve the stability of Citicoline sodium injection.
Stability test 2: long-term stable experiment
The Citicoline sodium injection of the Citicoline sodium injection prepared by embodiment of the present invention 1-3 and comparative example 1-4 carries out long-time stability investigation (25 DEG C ± 2 DEG C, RH60% ± 10%), the results are shown in Table 2:
Table 2
Result:
Embodiment 1-3: select glycine or citric acid or the compositions of the two to be cosolvent and stabilizing agent, regulates pH to 5.5-5.6.
Comparative example 1: do not use cosolvent and stabilizing agent
Comparative example 2: do not use cosolvent and stabilizing agent
Comparative example 3: use malic acid and sodium sulfite as cosolvent and stabilizing agent
Comparative example 4: use glycine and citric acid as cosolvent and stabilizing agent, but consumption is different from embodiment 1-3
Embodiment 1-3 compares with comparative example 1-4, pH, related substance, stable content have obvious advantage, select glycine and citric acid as cosolvent and stabilizing agent, regulate pH to 5.5-5.6, significantly can increase the dissolubility of C14H25N4NaO11P2 in water, and significantly improve the stability of Citicoline sodium injection.
By aforementioned stable contrast test, can find that glycine and citric acid significantly can increase the dissolubility of C14H25N4NaO11P2 in water and the stability of injection.The technical scheme (corresponding to embodiment 1-3, restriction pH value is 5.5-5.6, using glycine and citric acid as cosolvent and stabilizing agent) of the application's claim request protection, has better dissolubility and stability relative to comparative example 1-4.
Claims (1)
1. a citicoline sodium glucose injection, it is made up of C14H25N4NaO11P2, glucose, glycine, citric acid, and wherein C14H25N4NaO11P2 is 3g, glucose is 40g, and glycine is 1.8g, and citric acid is 1.3g, use sodium hydroxide adjust ph to be 5.5-5.6, inject water to 1000ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410244261.8A CN104027304B (en) | 2014-06-04 | 2014-06-04 | Citicoline sodium glucose injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410244261.8A CN104027304B (en) | 2014-06-04 | 2014-06-04 | Citicoline sodium glucose injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104027304A CN104027304A (en) | 2014-09-10 |
| CN104027304B true CN104027304B (en) | 2015-05-27 |
Family
ID=51458455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410244261.8A Active CN104027304B (en) | 2014-06-04 | 2014-06-04 | Citicoline sodium glucose injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104027304B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104940133A (en) * | 2015-06-11 | 2015-09-30 | 山东新时代药业有限公司 | Fluconazole injection and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101675925B (en) * | 2008-09-17 | 2012-05-23 | 秦引林 | Dimethylaminoethyl ginkgolide B mesylate injection and preparation method thereof |
| CN102144963B (en) * | 2010-02-05 | 2013-04-10 | 四川科伦药物研究有限公司 | Citicoline sodium glucose injecta and preparation process thereof |
-
2014
- 2014-06-04 CN CN201410244261.8A patent/CN104027304B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104027304A (en) | 2014-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101455631B (en) | Meglumine cyclic adenosine injection and preparation technique thereof | |
| CN105193707A (en) | Ambroxol hydrochloride oral solution and preparation method thereof | |
| KR20130080422A (en) | Injection of enrofloxacin and producing method thereof | |
| CN105477012B (en) | A kind of Levetiracetam sodium chloride injection composition and preparation method thereof | |
| CN104027304B (en) | Citicoline sodium glucose injection | |
| CN105125485A (en) | Preparation method of injecting drug improving stability of puerarin drug injection preparation | |
| CN105919931A (en) | Stable fasudil hydrochloride injection and preparation method thereof | |
| CN103006554A (en) | Ornidazole injection and preparation method thereof | |
| CN1969847B (en) | Pharmaceutical composition | |
| US4289783A (en) | Etomidate-containing compositions | |
| CN105532646A (en) | Liver cell preserving fluid and preparation method and application | |
| CN103637980B (en) | A kind of preparation method of promethazine hydrochloride inj | |
| CN102144963A (en) | Citicoline sodium glucose injecta and preparation process thereof | |
| CN103467529A (en) | EDTA binuclear platinum coordination compound and preparation method thereof | |
| CN103637981B (en) | A kind of promethazine hydrochloride inj | |
| CN102166185A (en) | Isotonic naloxone injection and preparation method thereof | |
| CN102274123B (en) | Production process for mannanoligosaccharide liposome nano preparation | |
| CN102488649B (en) | Puerarin sodium chloride injection and preparation method thereof | |
| CN110151688A (en) | A kind of ambroxol hydrochloride injection composition and preparation method thereof | |
| CN103479641A (en) | Acyclovir composition | |
| CN104434815A (en) | Stable parecoxib sodium pharmaceutical composition for injection | |
| CN106344502A (en) | Pharmaceutical composition for injection capable of improving stability of leech drug injection preparation | |
| CN103142510A (en) | Injection containing moxifloxacin hydrochloride composition | |
| CN102784098A (en) | Magnesium valproate injection and preparation method thereof | |
| CN102727427A (en) | Isotonic naloxone injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 331800 No. 6, Dongshan Industrial Park, Dongxiang Economic Development Zone, Fuzhou, Jiangxi. Patentee after: HUIYINBI GROUP JIANGXI EAST ASIA PHARMACEUTICAL Co.,Ltd. Address before: 331800 Dongxiang Province Economic Development Zone, Dongshan Industrial Park, Fuzhou, Hui Road, No. 6, No. Patentee before: HUIYINBI GROUP (JIANGXI) EAST ASIA PHARMACEUTICAL CO.,LTD. |
|
| CP03 | Change of name, title or address | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Citicoline sodium glucose injection Effective date of registration: 20230926 Granted publication date: 20150527 Pledgee: Bank of China Limited Dongxiang sub branch Pledgor: HUIYINBI GROUP JIANGXI EAST ASIA PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980059384 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |