CN107303279A - A kind of aspartate for injection potassium freeze-dried powder and preparation method thereof - Google Patents
A kind of aspartate for injection potassium freeze-dried powder and preparation method thereof Download PDFInfo
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- CN107303279A CN107303279A CN201610249438.2A CN201610249438A CN107303279A CN 107303279 A CN107303279 A CN 107303279A CN 201610249438 A CN201610249438 A CN 201610249438A CN 107303279 A CN107303279 A CN 107303279A
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- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 238000002347 injection Methods 0.000 title claims abstract description 25
- 239000007924 injection Substances 0.000 title claims abstract description 25
- 239000000843 powder Substances 0.000 title claims abstract description 16
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 229940009098 aspartate Drugs 0.000 title claims abstract description 12
- 239000011591 potassium Substances 0.000 title claims abstract description 12
- 229910052700 potassium Inorganic materials 0.000 title claims abstract description 12
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 27
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 27
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 21
- 239000008101 lactose Substances 0.000 claims abstract description 21
- 238000009472 formulation Methods 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 238000010792 warming Methods 0.000 claims description 21
- 238000003756 stirring Methods 0.000 claims description 18
- 239000008215 water for injection Substances 0.000 claims description 17
- 238000004108 freeze drying Methods 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- 239000003002 pH adjusting agent Substances 0.000 claims description 8
- 230000001954 sterilising effect Effects 0.000 claims description 8
- 239000003610 charcoal Substances 0.000 claims description 7
- 238000007689 inspection Methods 0.000 claims description 7
- 239000012263 liquid product Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 230000001186 cumulative effect Effects 0.000 claims description 6
- 238000011049 filling Methods 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 abstract description 17
- 229940079593 drug Drugs 0.000 abstract description 9
- 239000003182 parenteral nutrition solution Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 4
- 229940068988 potassium aspartate Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- -1 carbohydrate salt Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005262 decarbonization Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 208000021264 digitalis poisoning Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- NFFJLMKHRCXLJO-UHFFFAOYSA-L magnesium;2-aminobutanedioate Chemical compound [Mg+2].[O-]C(=O)C(N)CC([O-])=O NFFJLMKHRCXLJO-UHFFFAOYSA-L 0.000 description 1
- LVBRFZFUCKKGDJ-HJWRJIQTSA-J magnesium;dipotassium;(2s)-2-aminobutanedioate;hydron Chemical compound [Mg+2].[K+].[K+].OC(=O)[C@@H](N)CC([O-])=O.OC(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC(O)=O.[O-]C(=O)[C@@H](N)CC(O)=O LVBRFZFUCKKGDJ-HJWRJIQTSA-J 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940111263 potassium magnesium aspartate Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
Classifications
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a kind of aspartate for injection potassium freeze-dried powder, the preparation by weight, is prepared from by the supplementary material including following components：Aspartic acid:Lactose=5:（2~3）.Lyophilized formulations of the present invention have the advantages that prescription is simple, preparation method is scientific and reasonable, so that lyophilized obtained medicine bulk multi-hole, so that it has high solubility in Clinical practice, simultaneously, supplementary product consumption is low, species it is few on the premise of compared to parenteral solution, the stability of product is improved, the drug safety of patient is ensured that.
Description
Technical field
The present invention relates to field of medicaments, specifically, it is related to a kind of aspartate for injection potassium freeze-dried powder and preparation method thereof.
Background technology
Aspartic acid is carbohydrate salt and acid-base balance regulating, and for arrhythmia cordis caused by hypopotassaemia, low potassium and digitalis poisoning, virus hepatitis, hepatic sclerosis closes the treatment of hepatic encephalopathy.The aspartic acid of current clinical practice is generally liquid drugs injection, easily causes secondary pollution in Clinical practice, and the problem of there is easily damaged, shipping storage inconvenience and relatively poor stability.In addition, prior art also discloses the technical scheme that said preparation is prepared into injection freeze-dried powder by some, such as：
China's application 201210355164.7 discloses a kind of preparation method of potassium aspartate injection, and described preparation method detailed process is as follows：（a）Total water for injection with liquid product 60 ~ 70% is added into dense preparing tank；（b）Aspartic acid is added in dense preparing tank, after stirring 20 ~ 30 minutes, whole dissolvings is treated, detects and adjust pH value to 4.5 ~ 9.5；（c）Medical charcoal is added, stirs 20 ~ 40 minutes under the conditions of 70 ~ 90 DEG C, is while hot filled into decoction in dilute preparing tank by decarbonization filtering device, accurate filter；（d）Water for injection is added into dense preparing tank, is delivered to by filter in dilute preparing tank, the decoction of dilute preparing tank is reached that defined liquid of always matching somebody with somebody is accumulated；（e）Medicinal liquid agitating in dilute preparing tank is allowed to uniform in 5 ~ 10 minutes, and then by decoction through sterilizing filter, intermediate inspection is done in sampling；（f）Embedding, sterilizing.
Aspartic acid is prepared into liquid drugs injection by the above method, and ampoule needs opening when using, and makes decoction exposure in atmosphere, increases secondary pollution risk, and the cracky during shipping storage, liquid drugs injection less stable.
The content of the invention
The first object of the present invention is to provide a kind of aspartate for injection potassium freeze-dried powder, more preferable stability is made it have, further to improve the curative effect of preparation, so as to ensure the validity and security of medicine.
In order to realize foregoing invention purpose, the present invention is adopted the following technical scheme that：
A kind of potassium magnesium aspartate for injection freeze-dried powder, the preparation by weight, is prepared from by the supplementary material including following components：Aspartic acid:Lactose=5 (2 ~ 3) part.
Preparation of the present invention is based on g, and the amount ratio of aspartic acid and water for injection is 1:10~1:15.
It is preferred that the raw material that the preparation is consisted of is prepared into 10000 bottles：Aspartic acid 17000g, lactose 7000g, inject water to 200L.
Lyophilized formulations prescription of the present invention is simple, and only using lactose as unique auxiliary material, auxiliary material is few, it is meant that during production operation, it is possible to reduce batching step, is easy to operation, while the side effect for being difficult to expect that various accessory strips come can be avoided.Because supplementary material source is few, it can just reduce because of the increased possibility of relevant material that supplementary material is brought.So as to avoid because the hidden danger and active constituent content that relevant material increases and comes to patient medication safety belt decline the curative effect problem brought to patient.
In addition, conventional lyophilized formulations need to use outward appearance, solubility and the stability of various excipient to maintain preparation etc..Lactose often uses excipients as lyophilized formulations, is widely used, metastable system can be formed between aspartic acid, is beneficial to the stability for improving preparation, and the special construction of lactose, is beneficial to being uniformly distributed for main ingredient so that lyophilized forming, the cycle is short.The present invention reduces the consumption of excipient in order to strictly control the quality of preparation to try one's best, because of a kind of only excipient of lactose, therefore, and when specific freeze drying process directly affects the quality of dried frozen aquatic products for the consumption of active component and lactose.
On the basis of lot of experiments, inventor determines prescription of the present invention for aspartic acid:Lactose=5 (2 ~ 3) part.The present invention can significantly improve medicine stability simultaneously, and the freeze drying powder injection outward appearance prepared, relevant material, clarity, solubility etc. is reached requirement, obtain the freeze-dried powder of high-quality.
The second object of the present invention is the preparation method for providing above-mentioned preparation, and to realize the second purpose, the present invention is adopted the following technical scheme that：
The preparation method of aspartate for injection potassium freeze-dried powder as described above, methods described comprises the following steps：
（1）Total water for injection with liquid product 70% is added in dense preparing tank；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 6.0-8.0 after 20-40 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred under the conditions of 60-90 DEG C 30-40 minutes, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 5-10 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection;
（6）Carried out to bottling department filling；
（7）Freeze-drying, is produced.
Wherein, described pH adjusting agent is 10%（W/V）Sodium hydroxide or 10% watery hydrochloric acid.
One skilled in the art will appreciate that for same preparation, even if active component is identical, changing the weight and consumption of auxiliary material can cause preparation method to be also required to make as the case may be and targetedly adjust.The present invention is due to extremely low as the consumption of excipient and lactose only with lactose, in order to obtain higher-quality dried frozen aquatic products, it is necessary to a kind of more preferably preparation method of design.
The present inventor gropes further across substantial amounts of experiment, further adjusts freeze-drying curve, can be in the case where reaching same degree of drying, it is to avoid influence of the higher temperature for product component so that the stability of medicine is improved.As a result show, take the freeze-drying method of the present invention, lyophilized obtained medicine more bulk multi-hole can be caused, its solubility in Clinical practice is significantly improved.
Wherein, described freeze-drying specifically includes following steps：
（7.1）Plate temperature sets less than -50 DEG C, is incubated 1-2 hours；
（7.2）Flaggy is heated, by temperature programming：0 DEG C is warming up in 3-4 hours；20 DEG C are continuously heating in 6-8 hours；60 DEG C are continuously heating in 4-8 hours, and is incubated 10-15 hours.
It is preferred that described freeze-drying specifically includes following steps：5.1 plate temperature set less than -55 DEG C, are incubated 2 hours；5.2 heating flaggies, by temperature programming：0 DEG C is at the uniform velocity warming up in 4 hours；20 DEG C were warming up to then at 6 hours；60 DEG C are at the uniform velocity warming up in 6 hours, and is incubated 12 hours.
As the preferred forms of the present invention, preferably methods described comprises the following steps：
（1）Total 70 DEG C of water for injection with liquid product 70% is added in dense preparing tank, the aspartic acid and lactose of recipe quantity are slowly added in tank successively, stirring and dissolving；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 7.0 after 30 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred 35 minutes under the conditions of 60 DEG C, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 5 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection;
（6）Filtering to bottling department carries out filling；
（7）Freeze-drying：
（7.1）Plate temperature sets less than -55 DEG C, is incubated 2 hours；
（7.2）Flaggy is heated, by temperature programming：0 DEG C is at the uniform velocity warming up in 4 hours；20 DEG C are at the uniform velocity warming up in 6 hours；Continue at the uniform velocity to be warming up to 60 DEG C in 6 hours, and be incubated 12 hours, produce.
Lyophilized formulations of the present invention have the advantages that prescription is simple, preparation method is scientific and reasonable, so that lyophilized obtained medicine more bulk multi-hole, significantly improve its solubility in Clinical practice, simultaneously, it is low in supplementary product consumption, the stability of preparation can also be improved on the premise of species is few, and avoid redissolution, the risk being exposed to using process Chinese medicine liquid in air, it is easy to storage and transport, ensures that the drug safety of patient.
Embodiment
It is explained in more detail explanation to technical scheme with embodiment below, but it is not limitation of the present invention.
Embodiment 1
Prescription：The raw material consisted of is prepared into 10000 bottles：Aspartic acid 17000g, lactose 7000g, inject water to 200L.；
Preparation method：
（1）Total 70 DEG C of water for injection with liquid product 70% is added in dense preparing tank, the aspartic acid and lactose of recipe quantity are slowly added in tank successively, stirring and dissolving；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 7.0 after 30 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred 35 minutes under the conditions of 60 DEG C, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 5 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection；
（6）Filtering to bottling department carries out filling；
（7）Freeze-drying：
（7.1）Plate temperature sets less than -55 DEG C, is incubated 2 hours；
（7.2）Flaggy is heated, by temperature programming：0 DEG C is at the uniform velocity warming up in 4 hours；20 DEG C are at the uniform velocity warming up in 6 hours；Continue at the uniform velocity to be warming up to 60 DEG C in 6 hours, and be incubated 12 hours, produce.
Embodiment 2
Prescription：The raw material consisted of is prepared into 10000 bottles：Aspartic acid 10000g, lactose 4000g, inject water to 120L；
Preparation method：
（1）Total 60 DEG C of water for injection with liquid product 70% is added in dense preparing tank, the aspartic acid and lactose of recipe quantity are slowly added in tank successively, stirring and dissolving；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 6.0 after 30 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred 30 minutes under the conditions of 55 DEG C, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 5 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection；
（6）Filtering to bottling department carries out filling；
（7）Freeze-drying：
（7.1）Plate temperature sets less than -55 DEG C, is incubated 2 hours；
（7.2）Flaggy is heated, by temperature programming：0 DEG C is at the uniform velocity warming up in 4 hours；20 DEG C are at the uniform velocity warming up in 6 hours；Continue at the uniform velocity to be warming up to 60 DEG C in 6 hours, and be incubated 12 hours, produce.
Embodiment 3
Prescription：The raw material consisted of is prepared into 10000 bottles：Aspartic acid 15000g, lactose 8000g, inject water to 200L；
Preparation method：
（1）Total 80 DEG C of water for injection with liquid product 70% is added in dense preparing tank, the aspartic acid and lactose of recipe quantity are slowly added in tank successively, stirring and dissolving；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 8.0 after 30 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred 30 minutes under the conditions of 60 DEG C, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 10 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection；
（6）Filtering to bottling department carries out filling；
（7）Freeze-drying：
（7.1）Plate temperature sets less than -55 DEG C, is incubated 2 hours；
（7.2）Flaggy is heated, by temperature programming：0 DEG C is at the uniform velocity warming up in 3 hours；20 DEG C are at the uniform velocity warming up in 8 hours；Continue at the uniform velocity to be warming up to 60 DEG C in 8 hours, and be incubated 10 hours, produce.
Embodiment 4
Compared with Example 1, the prescription that differs only in of the present embodiment is：The raw material consisted of is prepared into 10000 bottles：Aspartic acid 800g, Magnesium Aminosuccinate 800g and lactose 640g, inject water to 24L.
The present invention furthermore provides following test example, further to be illustrated to technical scheme.
Stability test
1. subjects
Experimental group 1：The product of the embodiment of the present invention 1；
Experimental group 2：The product of the embodiment of the present invention 2；
Experimental group 3：The product of the embodiment of the present invention 3；
Experimental group 4：The product of the embodiment of the present invention 4；
Control group 1：China's 201210355164.7 disclosed embodiments 1 of application；
Control group 2：Using the identical prescription of the embodiment of the present invention 1, distinctive points are that preparation technology is different, are specially：Water for injection is 20L, and freeze-drying process is：1st, plate temperature sets -40 DEG C, is incubated 2 hours；2nd, flaggy is heated, by temperature programming：18 DEG C/h are warming up to 0 DEG C；1 DEG C/h is warming up to 12 DEG C；6 DEG C/h are warming up to 20 DEG C, are incubated 2 hours；20 DEG C/h are warming up to 50 DEG C, are incubated 5 hours, produce.
2. the project of investigation and method
Investigation project：It is character, other amino acid, visible foreign matters, content, bacterial endotoxin, sterile.
Investigation method：National drug standards potassium aspartate injection YBH00102010, Chinese Pharmacopoeia（Version in 2010）.
3. content of the test and result
Accelerated test：Sample is taken, 40 DEG C ± 2 DEG C of temperature is placed in, placed 6 months under the conditions of relative humidity 75% ± 5%, is sampled respectively at the 1st, 2,3,6 months, is investigated indices, the results are shown in Table 1~2.
The long-term experiment that keeps sample：Sample is taken, 25 DEG C ± 2 DEG C are placed in, placed under the conditions of relative humidity 60% ± 10%, is sampled respectively at the 3rd, 6,9,12,18,24,36 months, is investigated indices, the results are shown in Table 3~4.
4. conclusion
Accelerated test result shows：Of the invention gained aspartate for injection potassium freeze drying powder injection and potassium aspartate injection liquid drugs injection under conditions of relative humidity 75% ± 5%, are placed 6 months, every Testing index meets the regulation of quality standard in 40 DEG C ± 2 DEG C of temperature.
The long-term result of the test that keeps sample shows：Gained aspartate for injection freeze-dried powder of the invention is in placement 36 months under room temperature condition, every Testing index was compared with 0 month, without significant changes, and compared with potassium aspartate injection liquid drugs injection, the stability of content has clear improvement compared with prior art, wherein with the best results of embodiment 1.
Claims (6)
1. a kind of aspartate for injection potassium freeze-dried powder, it is characterised in that the preparation by weight, is prepared from by the supplementary material including following components：Aspartic acid:Lactose=5:（2~3）.
2. lyophilized formulations according to claim 1, it is characterised in that：The preparation is based on g, and the amount ratio of aspartic acid and water for injection is 1:10~1:15.
3. lyophilized formulations according to claim 1, it is characterised in that：The supplementary material that the preparation is consisted of is prepared into 10000 bottles：Aspartic acid 17000g, lactose 7000g, inject water to 200L.
4. the preparation method of aspartate for injection potassium freeze-dried powder described in claim 1, it is characterised in that methods described comprises the following steps：
（1）Total water for injection with liquid product 70% is added in dense preparing tank；
（2）Dense preparing tank stirring is opened, load weighted aspartic acid is added in dense preparing tank, mixing speed is 15-20rmp, stirring and dissolving adjusts pH value to 6.0-8.0 after 20-40 minutes with pH adjusting agent；
（3）Volume ratio adds 0.1% medical charcoal by weight, keeps fluid temperature to be stirred under the conditions of 60-90 DEG C 30-40 minutes, decoction is passed through into accurate filter while hot（0.45μm）It is filled into dilute preparing tank；
（4）Water for injection is added into dilute preparing tank to defined cumulative volume.
（5）Medicinal liquid agitating in dilute preparing tank 5-10 minutes, decoction is through double sterilizing filters（0.22μm）, sample and do intermediate inspection;（6）Carried out to bottling department filling；
（7）Freeze-drying, is produced.
5. the preparation method of aspartate for injection potassium freeze-dried powder according to claim 4, it is characterised in that：Described pH adjusting agent is 10%（W/V）Sodium hydroxide or 10% watery hydrochloric acid.
6. the preparation method of aspartate for injection potassium freeze-dried powder according to claim 4, it is characterised in that：Described freeze-drying specifically includes following steps：
（1）Plate temperature sets less than -50 DEG C, is incubated 1-2 hours；
（2）Flaggy is heated, by temperature programming：0 DEG C is warming up in 3-4 hours；20 DEG C are continuously heating in 6-8 hours；60 DEG C are continuously heating in 4-8 hours, and is incubated 10-15 hours.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110464706A (en) * | 2019-07-19 | 2019-11-19 | 济南康和医药科技有限公司 | A kind of preparation method of potassium aspartate injection |
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|---|---|---|---|---|
| CN1351866A (en) * | 2001-11-22 | 2002-06-05 | 于航 | Levo-potassium magnesium aspartate freeze drying powder injection and preparing method |
| CN103110616A (en) * | 2013-03-14 | 2013-05-22 | 山西普德药业股份有限公司 | Potassium magnesium aspartate freeze-dried powder preparation for injection and preparation method of preparation |
| CN103655461A (en) * | 2012-09-24 | 2014-03-26 | 沈阳药联科技创新有限公司 | Method for preparing potassium aspartate injection |
| CN105055388A (en) * | 2015-08-11 | 2015-11-18 | 瑞阳制药有限公司 | Potassium magnesium aspartate injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1351866A (en) * | 2001-11-22 | 2002-06-05 | 于航 | Levo-potassium magnesium aspartate freeze drying powder injection and preparing method |
| CN103655461A (en) * | 2012-09-24 | 2014-03-26 | 沈阳药联科技创新有限公司 | Method for preparing potassium aspartate injection |
| CN103110616A (en) * | 2013-03-14 | 2013-05-22 | 山西普德药业股份有限公司 | Potassium magnesium aspartate freeze-dried powder preparation for injection and preparation method of preparation |
| CN105055388A (en) * | 2015-08-11 | 2015-11-18 | 瑞阳制药有限公司 | Potassium magnesium aspartate injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110464706A (en) * | 2019-07-19 | 2019-11-19 | 济南康和医药科技有限公司 | A kind of preparation method of potassium aspartate injection |
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