CN105055307A - Meglumine adenosine cyclophosphate injection and preparation method thereof - Google Patents
Meglumine adenosine cyclophosphate injection and preparation method thereof Download PDFInfo
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- CN105055307A CN105055307A CN201510489942.5A CN201510489942A CN105055307A CN 105055307 A CN105055307 A CN 105055307A CN 201510489942 A CN201510489942 A CN 201510489942A CN 105055307 A CN105055307 A CN 105055307A
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Abstract
The invention belongs to the field of medicines, and particularly relates to a meglumine adenosine cyclophosphate injection and a preparation method thereof. The meglumine adenosine cyclophosphate injection comprises raw materials in parts by weight as follows: 0.68-0.84 parts of adenosine cyclophosphate, 0.39-0.49 parts of meglumine and 200 parts of water for injection. Meglumine is adopted as a cosolvent and a pH regulator, and the problem that meglumine adenosine cyclophosphate is precipitated gradually is solved through optimization of prescription and preparation technology without introduction of other auxiliary materials; the injection is a sterile injection preparation prepared by adopting a modern sterile filling technology in combination of a final sterilization technology and has the advantages of direct and fast effect, high sterility assurance level and the like, and further, the product has fewer side effects and can be transported and stored at normal temperature, so that the stability and the safety of the product are improved. The invention further provides a preparation method of the meglumine adenosine cyclophosphate injection. The process is simple, the medication is safe, and the quality is stable.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of meglumine cyclic adenosine injection and preparation method thereof.
Background technology
Adenosine cyclophosphate is protein kinase activator, is the derivant of nucleotide.It is a kind of important substance with physiologically active extensively existed in human body, generates, can regulate the multifunctional movable of cell by under the catalysis of adenosine triphosphate cyclase.Hormonal regulation physiological function and substance metabolism effect is played in cell, the function of cell membrane can be changed, the calcium ion impelling net agonistic muscle to starch in matter enters muscle fiber, thus enhancing myocardial contraction, and the oxidasic activity of respiratory chain can be promoted, improve myocardial ischemia, alleviate coronary heart disease symptom and improve electrocardiogram.In addition, the synthesis adjustment etc. of sugar, lipid metabolism, nucleic acid, protein is played an important role.For angina pectoris, myocarditis and cardiogenic shock.Cardiopalmus, the symptom such as out of breath, uncomfortable in chest of improving rheumatic heart disease are had certain effect.Can curative effect be improved to acute leukemia in conjunction with chemotherapy, also can be used for the inducer remission of acute leukemia.In addition, also certain curative effect is had to senile chronic bronchitis, various hepatitis and psoriasis.
At present, adenosine cyclophosphate has injectable powder and aqueous injection clinically.Because adenosine cyclophosphate is slightly soluble in water, easily separate out when being made into aqueous solution, make aqueous injection also more difficult; In adenosine cyclophosphate, add meglumine can increase its dissolubility, but in meglumine adenosine cycle phosphate solution, along with the prolongation meglumine adenosine cycle phosphate of holding time can be separated out gradually, make medicinal liquid rotten, muddy, thus affect the curative effect of medicine and the safety of medication.
In order to improve the safety of medication, meglumine adenosine cycle phosphate is all made lyophilized formulations by many medicine enterprises, so that preserve.Publication number is that the patent of invention of CN579413A discloses a kind of meglumine cyclic adenosine for injecta and preparation technology thereof.But the preparation technology of lyophilized formulations is very complicated, sometimes also has meglumine adenosine cycle phosphate after redissolution and separate out gradually.Therefore invent that a kind of technique is simple, the injection that can effectively prevent meglumine adenosine cycle phosphate from separating out and preparation method thereof will be highly profitable.
Publication number is disclose a kind of meglumine adenosine cyclophosphate composition injection and preparation method thereof in the patent of invention of CN102600070B, although this meglumine adenosine cyclophosphate composition injection clarity is good, have good stability, but it introduces the cosolvents such as the pH adjusting agent such as citric acid, sodium hydroxide and sodium benzoate in prescription, brings risk to a certain extent to drug safety.
Summary of the invention
The object of this invention is to provide a kind of meglumine cyclic adenosine injection, when not introducing other adjuvants, solving the difficult problem that meglumine adenosine cycle phosphate is separated out gradually, stability and the safety of product are high; The present invention also provides its preparation method, and technique is simple, drug safety, steady quality.
Meglumine cyclic adenosine injection of the present invention, comprises the raw material of following parts by weight:
Adenosine cyclophosphate 0.68-0.84 part
Meglumine 0.39-0.49 part
Water for injection 100 parts.
Wherein:
The pH of meglumine cyclic adenosine injection is 6.0-6.5, regulates the pH of meglumine cyclic adenosine injection with meglumine.
The charcoal treatment of every 100 weight portion meglumine cyclic adenosine injection 0.05-0.15 weight portions, to remove impurity wherein.
The preparation method of described meglumine cyclic adenosine injection, comprises the following steps:
(1) get partial syringe water, add meglumine stirring and make it dissolve;
(2) add adenosine cyclophosphate, stir;
(3) add active carbon charcoal slurry, stir;
(4) add remaining water for injection, stir evenly;
(5) add meglumine and make pH to 6.0-6.5, filter;
(6) by filter after liquid medicine filling in ampoule bottle;
(7) intermediate products after embedding are carried out sterilizing and leak detection;
(8) intermediate products after sterilizing are carried out by an inspection by lamp inspection.
Wherein:
The dissolubility of meglumine in water is larger, its course of dissolution is less by the impact of course of dissolution parameter, the dissolubility of adenosine cyclophosphate in water is less, although the dissolubility in meglumine solution increases, but its course of dissolution is also relatively slow, select appropriate process parameter to ensureing that the dissolving of adenosine cyclophosphate is also very important.The preferred technological parameter of the present invention is as follows:
Mixing speed in step (1) and step (2) is 10-180rpm.
The temperature 50-90 degree Celsius of the water for injection in step (1) and step (4), preferably 70 degrees Celsius.
Mixing time in step (3) is 5-30min, is preferably 15min.
In step (3), the ratio of active carbon and water for injection gross weight is 0.05-0.15:100.
Step (1) is 2:1 with the addition ratio of water for injection in step (4).
Step is filtered in (5): the microporous filter membrane decarburization first using 0.45um, and the microporous filter membrane then through 0.22um carries out aseptic filtration.
The temperature that insulation in step (6) stores is 25-40 degree Celsius.
In step (7), ampoule bottle is glass ampule or the plastic ampoule bottle of below 20ml.
In described step (8), sterilising temp is 100-121 degree Celsius, and be preferably 121 degrees Celsius, sterilization time is 8-30min, is preferably 15min.
The present invention compared with prior art, has following beneficial effect:
(1) the present invention utilizes meglumine as cosolvent and pH adjusting agent, when not introducing other adjuvants, by optimization formulation and preparation technology, solves the difficult problem that meglumine adenosine cycle phosphate is separated out gradually.
(2) present invention process simple, drug safety, steady quality.
(3) meglumine cyclic adenosine injection prepared of the present invention, it is the aseptic injection preparation adopting modern sterile filling technique to make in conjunction with final sterilization technique, it not only has effect directly, fast, Sterility Assurance value advantages of higher, and this product untoward reaction is few, can transport, preserve by room temperature, thus improve stability and the safety of this product.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1-5
Add the water for injection of institute's vehicle cumulative volume 2/3, add meglumine 42g, be stirred to dissolving.Add adenosine cyclophosphate 75g, be stirred to dissolving.PH to 6.0-6.5 is regulated with meglumine.Take active carbon 10g, join in above-mentioned solution, stir 15min.Inject water to 10000ml, stir evenly.Medicine liquid irrigation after filtering is enclosed in 5ml glass ampoule bottles.Intermediate products after embedding are carried out sterilizing (121 DEG C of 15min) and leak detection.
Mixing speed when adding meglumine in embodiment 1-5 and add adenosine cyclophosphate and adenosine cyclophosphate all dissolve required time in table 1.
Data as can be seen from table 1, embodiment 1 best performance.
In table 1 embodiment 1-5, mixing speed and adenosine cyclophosphate all dissolve required time
Embodiment 6-10
Add 70 DEG C of waters for injection of institute's vehicle cumulative volume 2/3, add meglumine 42g, 100rpm stirs 15min.Add adenosine cyclophosphate 75g, 100rpm stirs 15min.PH to 6.0-6.5 is regulated with meglumine.Take the active carbon of recipe quantity, join in above-mentioned solution, stir.Inject water to 10000ml, stir evenly.Medicine liquid irrigation after filtering is enclosed in 5ml glass ampoule bottles.Intermediate products after embedding are carried out sterilizing (121 DEG C of 15min) and leak detection.
In embodiment 6-10, the labelled amount of activated carbon dosage and meglumine adenosine cycle phosphate is in table 2.
Data as can be seen from table 2, embodiment 7 best performance.
The labelled amount of activated carbon dosage and meglumine adenosine cycle phosphate in table 2 embodiment 6-10
Embodiment 11-13
Add 70 DEG C of waters for injection of institute's vehicle cumulative volume 2/3, add meglumine 42g, 100rpm stirs 15min.Add adenosine cyclophosphate 75g, 100rpm stirs 15min.PH to 6.0-6.5 is regulated with meglumine.Take active carbon 10g, and join in above-mentioned solution, stir.Inject water to 10000ml, stir evenly.Deposit at different temperatures for the ease of medicinal liquid, by liquid medicine filling in 5ml glass ampule, at each temperature, deposit 500.
Solution storage temperature in embodiment 11-13 pouring process, time and test are in table 3.
Data as can be seen from table 3, the having good stability of cyclic AMP injecta in embodiment 11-13, in 3 months, nodeless mesh is separated out, and pouring process is without control temperature.Cyclic AMP injecta of the present invention, solves the problem deposited process Raw and separate out.
Solution storage temperature in table 3 embodiment 11-13 pouring process, time and test
Embodiment 14-16
Add 70 DEG C of waters for injection of institute's vehicle cumulative volume 2/3, add meglumine 42g, 100rpm stirs 15min.Add adenosine cyclophosphate 75g, 100rpm stirs 15min.PH to 6.0-6.5 is regulated with meglumine.Take active carbon 10g, join in above-mentioned solution, stir.Inject water to 10000ml, stir evenly.Medicine liquid irrigation after filtering is enclosed in 5ml glass ampoule bottles.Intermediate products after embedding are carried out sterilizing and leak detection.
The preparation of sterilization process to injection is most important, and good sterilization process effectively can ensure the aseptic of injection.
Embodiment 14-16 meglumine cyclic adenosine injection sterilization process temperature and time is in table 4.
Table 4 embodiment 14-16 meglumine cyclic adenosine injection sterilization process temperature and time
Check according to the sample of state food drug surveilance office standard YBH02992006 to prescription 14-16, the results are shown in Table 5.
The testing result of sample under the different sterilising conditions of table 5
Data as can be seen from table 5, along with the rising of sterilising temp, the degradation amount of main component increases, and the amplitude that pH value raises increases, but all within the prescribed limit of YBH02992006, conformance with standard specifies.Preferred sterilising conditions is 121 DEG C of 15min.
Also carried out steriling test according to the relevant regulations of 2010 editions Chinese Pharmacopoeias to the sample of embodiment 14-16, result all conforms with the regulations simultaneously.
Claims (10)
1. a meglumine cyclic adenosine injection, is characterized in that: the raw material comprising following parts by weight:
Adenosine cyclophosphate 0.68-0.84 part
Meglumine 0.39-0.49 part
Water for injection 100 parts.
2. meglumine cyclic adenosine injection according to claim 1, is characterized in that: the pH of meglumine cyclic adenosine injection is 6.0-6.5, regulates the pH of meglumine cyclic adenosine injection with meglumine.
3. meglumine cyclic adenosine injection according to claim 1, is characterized in that: the charcoal treatment of every 100 weight portion meglumine cyclic adenosine injection 0.05-0.15 weight portions, to remove impurity wherein.
4. a preparation method for the arbitrary described meglumine cyclic adenosine injection of claim 1-3, is characterized in that: comprise the following steps:
(1) get partial syringe water, add meglumine stirring and make it dissolve;
(2) add adenosine cyclophosphate, stir;
(3) add active carbon charcoal slurry, stir;
(4) add remaining water for injection, stir evenly;
(5) add meglumine and make pH to 6.0-6.5, filter;
(6) by filter after liquid medicine filling in ampoule bottle;
(7) intermediate products after embedding are carried out sterilizing and leak detection;
(8) intermediate products after sterilizing are carried out by an inspection by lamp inspection.
5. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: the mixing speed in step (1) and step (2) is 10-180rpm; The temperature 50-90 degree Celsius of the water for injection in step (1) and step (4).
6. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: the mixing time in step (3) is 5-30min; In step (3), the ratio of active carbon and water for injection gross weight is 0.05-0.15:100.
7. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: step (1) is 2:1 with the addition ratio of water for injection in step (4).
8. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: step is filtered in (5): the microporous filter membrane decarburization first using 0.45um, and the microporous filter membrane then through 0.22um carries out aseptic filtration.
9. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: in step (7), ampoule bottle is glass ampule or the plastic ampoule bottle of below 20ml.
10. the preparation method of meglumine cyclic adenosine injection according to claim 4, is characterized in that: in described step (8), sterilising temp is 100-121 degree Celsius, and sterilization time is 8-30min.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102283804A (en) * | 2010-06-18 | 2011-12-21 | 山东方明药业股份有限公司 | Meglumine adenosine cyclophosphate injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102283804A (en) * | 2010-06-18 | 2011-12-21 | 山东方明药业股份有限公司 | Meglumine adenosine cyclophosphate injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| RAYMOND C ROWE ETAL: "《Handbook of Pharmaceutical Excipients》", 31 December 2009 * |
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