CN1830431A - Preparation method of potassium magnesium aspartate freeze dried powder injection - Google Patents
Preparation method of potassium magnesium aspartate freeze dried powder injection Download PDFInfo
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- CN1830431A CN1830431A CNA2005100514650A CN200510051465A CN1830431A CN 1830431 A CN1830431 A CN 1830431A CN A2005100514650 A CNA2005100514650 A CN A2005100514650A CN 200510051465 A CN200510051465 A CN 200510051465A CN 1830431 A CN1830431 A CN 1830431A
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Abstract
A freeze-dried powder injection of spartase for supplementing electrolyte and treating arrhythmia, myocarditis sequelae, congestive heart failure, myocardial infarction, etc is prepared through reaction between L-aminobutanedioic acid and magnesium oxide, ultrasonic treating, cold storage, ultrafiltration, adding the filtered liquid prepared from potassium hydroxide and mannitol, filling in containers in dark condition, freeze drying and sealing.
Description
Technical field
The present invention relates to a kind of preparation method of electrolyte complementary medical thing potassium magnesium aspartate for injection lyophilized injectable powder, specifically, relating to a kind of is the lyophilized injectable powder of main constituent with the Aspartic Acid.This method is pressed the ad hoc approach preparation with Aspartic Acid and magnesium oxide, and through ultrasonic, cold preservation, hyperfiltration technique processing, prepare jointly with the filtrate of potassium hydroxide and mannitol preparation again, the lucifuge fill, after lyophilization, rolling lid pack, make potassium magnesium aspartate for injection lyophilized injectable powder finished product, belong to the chemical preparation field.But this product intravenous drip, Aspartic Acid are the precursors of oxaloacetic acid in the body, play an important role in tricarboxylic acid cycle.Simultaneously, Aspartic Acid is also participated in ornithine cycle, promotes the metabolism of ammonia and carbon dioxide, makes it to generate carbamide, the content of ammonia and carbon dioxide in the reduction blood.Aspartic Acid and cell have very strong affinity, can be used as the carrier that potassium, magnesium ion enter cell, and potassium ion is returned in the cell, promote cell depolarization and cellular metabolism, keep its normal function.Magnesium ion is to generate glycogen and the indispensable material of energy-rich phosphate ester, can strengthen the therapeutical effect of Aspartic Acid potassium salt.Be mainly used in electrolyte and replenish, also can be used for hypokalemia, the arrhythmia that digitalism causes (mainly being ventricular arrhythmia), and the auxiliary treatment of myocarditis sequela, congestive heart failure, myocardial infarction.
Background technology
Motassium magnessium aspartate is the equal amount of mixture of potassium salt and magnesium salt.The Aspartic Acid chemical name is the L-2 aminosuccinic acid, and Aspartic Acid is the precursor of oxaloacetic acid in human body.In tricarboxylic acid cycle, play an important role, also participate in ornithine cycle simultaneously, make intravital ammonia (NH
3) and CO
2In conjunction with generating carbamide, this plays a part certain to the interior environment of stablizing human body.Potassium ion is the essential material of cells survival, also is the catalyst that high-energy phosphate compound is synthetic and decompose.Magnesium ion is the activator of plurality of enzymes, also can distend the blood vessels, help renal blood flow, diuresis reduces intracranial pressure, increases the blood circulation of cerebral tissue, improve metabolism, therefore hepatitis be can be used for the treatment of, hepatic disease recovery, bile secretion and drainage helped, so the clinical poisoning icterohepatitis that is used for the treatment of.
At present, aspartate for injection lyophilized injectable powder on the domestic market has many enterprises to produce, all adopt traditional handicraft formulated, problems such as the product stability of its existence is poor, zest strong, poor solubility, clarity disqualification rate height, curative effect instability can't solve all the time, its main cause is that partial impurities is not removed fully in preparation process, has influenced clinical practice.The breakthrough of this potassium magnesium aspartate freeze dried powder injection technology has fundamentally solved the problems referred to above.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of potassium magnesium aspartate freeze dried powder injection.
Preparation method of the present invention comprises the steps: to get fresh water for injection, after the Aspartic Acid dissolving in the adding prescription, adds the magnesium oxide in the prescription, supersound process, and cold preservation, ultrafiltration gets filtrate I.Get fresh water for injection, potassium hydroxide in the adding prescription and mannitol dissolving add active carbon, heated and boiled, and cooling, decarbonization filtering get filtrate II.Above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH, intermediate products after the assay was approved, through end-filtration, the lucifuge fill after the freeze-drying lyophilization, is rolled lid pack in cillin bottle, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder with medicinal liquid.
Preparation method detailed process of the present invention is as follows:
1) get 70～90%80～90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 30～60 minutes, 0～10 ℃ of cold preservation 12～48 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 5000～10000, filtrate I.
2) get 10～30%80～90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.05～0.5% active carbon, heated and boiled 10～30 minutes, circulation is cooled to 30～50 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH5.5～7.5, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
More preferred manufacturing procedure comprises the steps:
1) get 80%90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 40 minutes, 4 ℃ of cold preservation 24 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 8000, filtrate I.
2) get 10%90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 20 minutes, circulation is cooled to 50 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH5.8～6.5, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
In the above-mentioned preparation method, the amount of the used water for injection of formulated product is 70～90% in the step 1), and temperature is 80～90 ℃, and preparation is in proper order for adding magnesium oxide behind the dissolving Aspartic Acid earlier.
In the above-mentioned preparation method, for making constant product quality, the supersound process time is 30～60 minutes, and refrigerated storage temperature is 0～10 ℃, and cold preservation time is 12～48 hours.
In the above-mentioned preparation method, used pH value regulator is 10% sodium hydroxide solution or 10% hydrochloric acid solution, and pH value is strict controlled in 5.8～6.5.
In the above-mentioned preparation method, adopting the molecular weight that dams is 5000～10000 ultrafilter membrane ultrafiltration, is the controlled step of invalid components in institute's preparating liquid, and used ultrafilter membrane is the commercially available prod.Its manufacturer should be the production unit of industry approval.
In the above-mentioned preparation method, lucifuge gas condition is the committed step of medicinal liquid preparation, pouring process.
In the above-mentioned preparation method, the employed filter membrane of terminal aseptic filtration aperture is 0.22 μ m.For making constant product quality, filter membrane should be as far as possible by fixedly manufacturer's supply.
During potassium magnesium aspartate for injection lyophilized injectable powder clinical practice of the present invention, intravenous drip, one time 1 bottle (being equivalent to L-Aspartic Acid 1.70g), and add slowly intravenous drip among 5% glucose injection 250ml or the 500ml, once a day, or follow the doctor's advice.
Potassium magnesium aspartate for injection lyophilized injectable powder of the present invention, being mainly used in electrolyte replenishes, also can be used for hypokalemia, the arrhythmia that digitalism causes (mainly being ventricular arrhythmia), and the auxiliary treatment of myocarditis sequela, congestive heart failure, myocardial infarction.
The present invention is Aspartic Acid and the preparation of magnesium oxide employing ad hoc approach in preparation process, and through ultrasonic, cold preservation, hyperfiltration technique processing, efficiently solve magnesian solubility problem, guaranteed that invalid components is removed fully, reduced the related substance in the preparation, made that the preparation quality made is loose, dissolubility is good, stability increases, zest reduces, and clarity is improved, stable curative effect.
The specific embodiment
Further describe the present invention with embodiment below, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1
1) get 75%85 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 60 minutes, 4 ℃ of cold preservation 12 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 5000, filtrate I.
2) get 30%90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.1% active carbon, heated and boiled 15 minutes, circulation is cooled to 40 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH5.8, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
Embodiment 2
1) get 80%90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 30 minutes, 6 ℃ of cold preservation 24 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 10000, filtrate I.
2) get 25%85 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.05% active carbon, heated and boiled 30 minutes, circulation is cooled to 30 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH6.3, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
Embodiment 3
1) get 70%80 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 40 minutes, 0 ℃ of cold preservation 24 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 8000, filtrate I.
2) get 10%80 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.3% active carbon, heated and boiled 20 minutes, circulation is cooled to 35 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH6.0, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
Embodiment 4
1) get 85%85 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 30 minutes, 10 ℃ of cold preservation 36 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 6000, filtrate I.
2) get 20%90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.5% active carbon, heated and boiled 10 minutes, circulation is cooled to 50 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH6.2, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
Embodiment 5
1) get 90%90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 50 minutes, 8 ℃ of cold preservation 48 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 10000, filtrate I.
2) get 15%80 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 25 minutes, circulation is cooled to 45 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II.
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH6.5, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
Experimental example 1
This experimental example is the detection of every gainer relevant under the character of the prepared potassium magnesium aspartate for injection lyophilized injectable powder of the present invention, acid-base value, clarity and color, moisture, dissolubility and the injection item.
Character: this product is white or off-white color block, and is up to specification.
Acid-base value: get this product, be dissolved in water and make the solution that contains Aspartic Acid 85mg among every 1ml approximately, measure (two appendix VIH of Chinese Pharmacopoeia version in 2000) in accordance with the law, pH value should be 5.5～7.5, and is up to specification.
The clarity of solution and color: get this product, be dissolved in water and make the solution that contains Aspartic Acid 85mg among every 1ml approximately, solution should be clarified colourless; As colour developing, compare with yellow No. 1 standard color solution (two appendix IXA first methods of Chinese Pharmacopoeia version in 2000), must not be darker, up to specification.
Moisture: get this product, check (two appendix VIIIM first methods of Chinese Pharmacopoeia version in 2000) in accordance with the law, contain moisture and do not cross 4.0%, up to specification
Dissolubility: get 1 bottle of this product, add 10ml water for injection, dissolving fully is up to specification in 10 minutes.
Other: meet every regulation relevant under the injection item (two appendix IB of Chinese Pharmacopoeia version in 2000).
Experimental example 2
This experimental example is the qualitative determination of the prepared potassium magnesium aspartate for injection lyophilized injectable powder of the present invention.
Differentiate: it is an amount of that (1) gets this product, makes the solution that contains Aspartic Acid 8.5mg among every 1ml approximately with the 1mol/L hydrochloric acid solution, as need testing solution.It is an amount of that other gets L-Aspartic Acid reference substance, makes the solution that every 1ml contains 8mg with the 1mol/L hydrochloric acid solution, in contrast product solution.Test according to thin layer chromatography (two appendix VB of Chinese Pharmacopoeia version in 2000).Draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with n-butyl alcohol-acetic acid-water (5: 2: 1) is developing solvent, after the expansion, take out, dry, spray is with the acetone soln of 2% 1,2,3-indantrione monohydrate, 80 ℃ of heating 5 minutes, test sample the color of apparent principal spot should be identical with the position with the principal spot of reference substance, up to specification.(2) this product shows the identification (two appendix III of Chinese Pharmacopoeia version in 2000) of potassium salt, magnesium salt, and is up to specification.
The prepared potassium magnesium aspartate for injection lyophilized injectable powder of above description of test the present invention contains definite component.
Experimental example 3
This experimental example is the quantitative assay of the prepared potassium magnesium aspartate for injection lyophilized injectable powder key component of the present invention.
Content standard: the L-Aspartic Acid is got the content under the content uniformity item, and precision takes by weighing in right amount (being equivalent to L-Aspartic Acid 255mg approximately), measures according to N2 method (two appendix VIID first methods of Chinese Pharmacopoeia version in 2000).The sulphuric acid volumetric solution (0.05mol/L) of every 1ml is equivalent to the C of 13.31mg
4H
7NO
4
Potassium is got the content under the content uniformity item, precision takes by weighing in right amount (being equivalent to potassium 20mg approximately), add water 2ml dissolving after, add spirit of vinegar 2ml, slowly add 1% sodium tetraphenylborate solution 30ml, stir evenly, placed 30 minutes, filter with No. 4 sintered glass crucibles that are dried to constant weight, precipitation is washed with 1% sodium tetraphenylborate solution 20ml gradation, reuse water 10ml gradation washing is dried to constant weight at 105 ℃, and accurate the title decides; Gained precipitation weight and 0.1091 multiplies each other, and promptly gets for the weight that contains potassium (K) in the examination amount.
Magnesium is got the content under the content uniformity item, precision takes by weighing in right amount (being equivalent to magnesium 20mg approximately), after adding water 40ml dissolving, ammonification-ammonium chloride buffer (pH10.0) 10ml and chromium black T indicator a little, change blueness with Calcium Disodium Versenate volumetric solution (0.05mol/L) titration to solution into by aubergine.The Calcium Disodium Versenate volumetric solution (0.05mol/L) of every 1ml is equivalent to the Mg of 1.2153mg.
Standard code: contain Aspartic Acid (C
4H
7NO
4), potassium (K), magnesium (Mg) all should be 93.0%～107.0% of labelled amount.
Assay by three batches the results are shown in following table:
Experimental example 4
This experimental example is the safety indexes inspection of the prepared potassium magnesium aspartate for injection lyophilized injectable powder of the present invention.
Pyrogen: get this product, make the solution that contains Aspartic Acid 42.5mg among every 1ml with sterile saline dissolving and dilution.Check in accordance with the law (two appendix XID of Chinese Pharmacopoeia version in 2000) that dosage is slowly injected 2ml by the every 1Kg of rabbit body weight, and is up to specification.
Aseptic: get 1 of this product, add water 20ml dissolving, check (two appendix XIH of Chinese Pharmacopoeia version in 2000) in accordance with the law, up to specification.
Long term toxicity is measured: successive administration was observed blood, urine index in three months, and pathologic finding there is no unusually.
Safety by the prepared potassium magnesium aspartate for injection lyophilized injectable powder of above description of test the present invention meets the injection requirement, does not have any toxic action, uses human body safety.
Comparative example 1
The clarity of the potassium magnesium aspartate for injection lyophilized injectable powder that this comparative example explanation the present invention is prepared is better than producing with conventional preparation method.
The clarity criterion:
1) finds foreign body to be arranged or only be with micro-white point person, the lattice theory of making a match.
2) every bottle contains the hair that is shorter than 0.5cm and the white point of 0.1～0.2mm, white piece or color dot sum above 5 persons, the lattice theory of making a match.
3) disqualification rate surpasses 5%, this batch product lattice theory of making a match.
Relevant notion:
White piece: mean with the inspection method of regulation, can see the whiteness that tangible plane or corner angle are arranged.
White point: can not differentiate plane or corner angle by white point.
Trace white point: in official hour, only see 3 or 3 following white point persons.
Foreign body: comprise chips of glass, fiber, color dot, color lump and other external foreign body.
Inspection method:
Get respectively and adopt prepared potassium magnesium aspartate for injection lyophilized injectable powder of the present invention and each 200 bottles of the products that adopts the common process preparation,, the results are shown in following table by " clarity test detailed rules and regulations and criterion " and above standard inspection.
| Group | The trace white point | White point | White piece | Foreign body | Number of non-compliances | Disqualification rate | Qualification rate | Conclusion |
| The invention group | 4 bottles | 2 bottles surpass 5 | 0 | 0 | 2 bottles | 1％ | 99.0 ％ | Qualified |
| Conventional group | 56 bottles | 8 bottles surpass 5 | 2 bottles surpass 5 | 0 | 10 bottles | 5％ | 95％ | Qualified |
Clarity by the prepared potassium magnesium aspartate for injection lyophilized injectable powder of above description of test the present invention obviously is better than producing with conventional preparation method.
Comparative example 2
The dissolubility of the potassium magnesium aspartate for injection lyophilized injectable powder that this comparative example explanation the present invention is prepared is better than producing with conventional preparation method.
Inspection method: get respectively and adopt prepared potassium magnesium aspartate for injection lyophilized injectable powder of the present invention and each 100 bottles of the products that adopts the common process preparation, in every bottle, add 10ml water for injection, observe and write down its dissolution time.
Criterion: with the dissolution time is standard.
Good: dissolving fully in 5 minutes;
Qualified: dissolving fully in 10 minutes;
Defective: as to surpass 10 minutes and dissolve fully.
Experimental result sees the following form:
| Group | Good number | Passing number | Number of non-compliances | Sum | Acceptance rate | Total qualification rate |
| The invention group | 99 | 1 | 0 | 100 | 99％ | 100％ |
| Conventional group | 12 | 75 | 13 | 100 | 12％ | 87％ |
Dissolubility by the prepared potassium magnesium aspartate for injection lyophilized injectable powder of above description of test the present invention obviously is better than producing with conventional preparation method.
Comparative example 3
This comparative example illustrates that the prepared potassium magnesium aspartate for injection lyophilized injectable powder zest when clinical practice of the present invention is less.
| Group | The invention group | Conventional group |
| Usage and dosage | Intravenous drip, one time 1 bottle (being equivalent to L-Aspartic Acid 1.70g), add slowly intravenous drip among 5% glucose injection 250ml or the 500ml, once a day, or follow the doctor's advice. | Intravenous drip, one time 1 bottle (being equivalent to L-Aspartic Acid 1.70g), add slowly intravenous drip among 5% glucose injection 250ml or the 500ml, once a day, or follow the doctor's advice. |
| Clinical practice | 85 routine poisoning icterohepatitises | 25 routine poisoning icterohepatitises |
| Zest is observed | No pain and untoward reaction phenomenon | Pain is all arranged, and 32 examples have untoward reaction |
Comparative example 4
The prepared potassium magnesium aspartate for injection lyophilized injectable powder of this comparative example explanation employing the present invention compares with the stability of the potassium magnesium aspartate for injection lyophilized injectable powder that adopts conventional preparation method to produce by six months accelerated tests, the results are shown in following table.
Standard code:
Content: contain Aspartic Acid (C
4H
7NO
4), potassium (K), magnesium (Mg) all should be 93.0%～107.0% of labelled amount.
PH value: should be 5.5～7.5
Clarity: qualification rate should be not less than 95%
Character: this product is the loose block of white or off-white color.
| Time | Project | The invention group | Conventional group |
| 0 month | Aspartic Acid (%) | 102.8 | 102.5 |
| Potassium (%) | 100.5 | 100.8 | |
| Magnesium (%) | 101.4 | 101.3 | |
| PH value | 6.3 | 6.4 | |
| Clarity | 99％ | 98％ | |
| Character | The white loose block | The white loose block | |
| January | Aspartic Acid (%) | 102.4 | 101.6 |
| Potassium (%) | 100.2 | 99.9 | |
| Magnesium (%) | 101.0 | 100.3 | |
| PH value | 6.3 | 6.1 | |
| Clarity | 99％ | 97％ | |
| Character | The white loose block | The white loose block | |
| February | Aspartic Acid (%) | 102.0 | 100.7 |
| Potassium (%) | 99.9 | 99.0 | |
| Magnesium (%) | 100.6 | 99.3 | |
| PH value | 6.3 | 5.8 | |
| Clarity | 99％ | 95％ | |
| Character | The white loose block | The off-white color block that loosens | |
| March | Aspartic Acid (%) | 101.6 | 99.8 |
| Potassium (%) | 99.6 | 98.1 | |
| Magnesium (%) | 100.2 | 98.3 | |
| PH value | 6.2 | 5.5 | |
| Clarity | 98％ | 93％ | |
| Character | The white loose block | The off-white color block that loosens | |
| June | Aspartic Acid (%) | 101.0 | 98.3 |
| Potassium (%) | 99.0 | 96.6 | |
| Magnesium (%) | 99.6 | 96.8 | |
| PH value | 6.1 | 5.1 | |
| Clarity | 98％ | 90％ | |
| Character | The white loose block | Little yellow block that loosens |
By above experiment as can be seen, the invention group was passed through accelerated tests after six months, significant change does not take place in its content, pH value, clarity, color, and content, the pH value of conventional group all have obvious reduction, clarity, character are all against regulation, show that the stability of the potassium magnesium aspartate for injection lyophilized injectable powder that the present invention is prepared obviously is better than adopting conventional preparation method to be produced.
Claims (8)
1. the preparation method of an electrolyte complementary medical thing potassium magnesium aspartate for injection lyophilized injectable powder, described preparation method detailed process is as follows:
1) get fresh water for injection, after the Aspartic Acid dissolving in the adding prescription, add the magnesium oxide in the prescription, supersound process, cold preservation, ultrafiltration gets filtrate I;
2) get fresh water for injection, potassium hydroxide in the adding prescription and mannitol dissolving add active carbon, heated and boiled, and cooling, decarbonization filtering get filtrate II;
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH, intermediate products after the assay was approved, through end-filtration, the lucifuge fill after the freeze-drying lyophilization, is rolled lid pack in cillin bottle, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder with medicinal liquid.
2. according to claims 1 described preparation method, it is characterized in that comprising the steps:
1) get 70～90%80～90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 30～60 minutes, 0～10 ℃ of cold preservation 12～48 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 5000～10000, filtrate I;
2) get 10～30%80～90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.05～0.5% active carbon, heated and boiled 10～30 minutes, circulation is cooled to 30～50 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, filtrate II;
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH5.5～7.5, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
3. according to claims 1 described preparation method, it is characterized in that comprising the steps:
1) get 80%90 ℃ fresh water for injection of amount of preparation, add the Aspartic Acid stirring and dissolving in the prescription after, add the magnesium oxide in the prescription, supersound process 40 minutes, 4 ℃ of cold preservation 24 hours, with the ultrafilter membrane ultrafiltration of molecular cut off 8000, filtrate I;
2) get 10%90 ℃ fresh water for injection of amount of preparation, add potassium hydroxide and mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 20 minutes, circulation is cooled to 50 ℃, with 0.45 μ m microporous filter membrane decarbonization filtering, gets filtrate II;
3) above-mentioned medicinal liquid II is added among the medicinal liquid I, mix homogeneously, standardize solution is transferred pH5.8～6.5, intermediate products after the assay was approved, after terminal 0.22 μ m filter membrane aseptic filtration, the lucifuge fill is in cillin bottle with medicinal liquid, after the freeze-drying lyophilization, roll lid pack, promptly get the potassium magnesium aspartate for injection lyophilized injectable powder.
4. according to claims 1,2 or 3 described preparation methoies, it is characterized in that the amount of the water for injection that formulated product in the step 1) is used is 70～90%, temperature is 80～90 ℃, preparation is in proper order for adding magnesium oxide behind the dissolving Aspartic Acid earlier.
5. according to claims 1,2 or 3 described preparation methoies, it is characterized in that the supersound process time is 30～60 minutes, refrigerated storage temperature is 0～10 ℃, and cold preservation time is 12～48 hours.
6. according to claims 1,2 or 3 described preparation methoies, it is characterized in that the employed ultrafilter membrane of ultrafiltration is that molecular cut off is 5000～10000 ultrafilter membrane.
7. according to claims 1,2 or 3 described preparation methoies, it is characterized in that used pH value regulator is 10% sodium hydroxide solution or 10% hydrochloric acid solution, pH value is strict controlled in 5.8～6.5.
8. according to claims 1,2 or 3 described preparation methoies, the condition that it is characterized in that preparing in the pouring process is a lucifuge.
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| CNA2005100514650A CN1830431A (en) | 2005-03-08 | 2005-03-08 | Preparation method of potassium magnesium aspartate freeze dried powder injection |
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| CNA2005100514650A CN1830431A (en) | 2005-03-08 | 2005-03-08 | Preparation method of potassium magnesium aspartate freeze dried powder injection |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100450476C (en) * | 2007-02-15 | 2009-01-14 | 北京京卫信康医药科技发展有限公司 | Electrolyte complementary medical combination for injection |
| CN102670645A (en) * | 2012-05-29 | 2012-09-19 | 海南卫康制药(潜山)有限公司 | Potassium magnesium aspartate lyophilized powder composition for injection and preparation method of potassium magnesium aspartate lyophilized powder composition |
| CN103536623A (en) * | 2013-10-15 | 2014-01-29 | 海南卫康制药(潜山)有限公司 | Potassium magnesium aspartate composition freeze-dried powder for injection |
| CN104352452A (en) * | 2014-10-09 | 2015-02-18 | 海南通用康力制药有限公司 | Potassium magnesium aspartate freeze-dried powder for injection and preparation method of potassium magnesium aspartate freeze-dried powder |
| CN113209032A (en) * | 2021-05-26 | 2021-08-06 | 海南通用康力制药有限公司 | Potassium magnesium aspartate freeze-dried powder injection for injection and preparation method thereof |
| CN114732825A (en) * | 2022-03-14 | 2022-07-12 | 山东德信拓达生物科技研究院有限公司 | Cardiac anti-stress product for livestock and poultry and preparation method thereof |
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2005
- 2005-03-08 CN CNA2005100514650A patent/CN1830431A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100450476C (en) * | 2007-02-15 | 2009-01-14 | 北京京卫信康医药科技发展有限公司 | Electrolyte complementary medical combination for injection |
| CN102670645A (en) * | 2012-05-29 | 2012-09-19 | 海南卫康制药(潜山)有限公司 | Potassium magnesium aspartate lyophilized powder composition for injection and preparation method of potassium magnesium aspartate lyophilized powder composition |
| CN103536623A (en) * | 2013-10-15 | 2014-01-29 | 海南卫康制药(潜山)有限公司 | Potassium magnesium aspartate composition freeze-dried powder for injection |
| CN103536623B (en) * | 2013-10-15 | 2015-07-08 | 海南卫康制药(潜山)有限公司 | Potassium magnesium aspartate composition freeze-dried powder for injection |
| CN104352452A (en) * | 2014-10-09 | 2015-02-18 | 海南通用康力制药有限公司 | Potassium magnesium aspartate freeze-dried powder for injection and preparation method of potassium magnesium aspartate freeze-dried powder |
| CN113209032A (en) * | 2021-05-26 | 2021-08-06 | 海南通用康力制药有限公司 | Potassium magnesium aspartate freeze-dried powder injection for injection and preparation method thereof |
| CN114732825A (en) * | 2022-03-14 | 2022-07-12 | 山东德信拓达生物科技研究院有限公司 | Cardiac anti-stress product for livestock and poultry and preparation method thereof |
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