CN109091500A - A kind of children's compound electrolyte glucose injection and preparation method thereof - Google Patents
A kind of children's compound electrolyte glucose injection and preparation method thereof Download PDFInfo
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- CN109091500A CN109091500A CN201811174780.6A CN201811174780A CN109091500A CN 109091500 A CN109091500 A CN 109091500A CN 201811174780 A CN201811174780 A CN 201811174780A CN 109091500 A CN109091500 A CN 109091500A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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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
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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
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- 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
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
Abstract
The present invention relates to a kind of children's compound electrolyte glucose injections and preparation method thereof.The 1000ml injection includes: sodium chloride 0.1-0.3g, Sodium acetate trihydrate 2.5-3.0g, potassium chloride 1.1-1.4g, calcium chloride dihydrate 0.1-0.2g, magnesium chloride hexahydrate 0.2-0.4g, malic acid 0.02-0.03g, phosphoglycerol disodium salt pentahydrate 1.4-1.6g, glucose 45-55g, 25% hydrochloric acid 1.0-1.2g, pH adjusting agent 5.0-5.5.The preparation process of the injection include: with liquid, filtering, it is filling, roll lid, sterilizing, lamp inspection；Concentrated compounding is used to add with liquid dilute with the mode that combines, concentrated compounding uses low temperature in the process, is entirely protected from light protection with liquid process inflated with nitrogen, controls by reinforcement supplementary material and packaging material, can effectively avoid and have an impact using active carbon to injection quality.Using this method prepare electrolyte glucose injection medicine stability is good, side reaction is few, patient medication compliance and highly-safe is more suitable for newborn and children's peri-operation period fluid and electrolyte balance within 2 years old.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of children's compound electrolyte glucose injection and its preparation side
Method.
Background technique
Children's compound electrolyte glucose injection is suitable for newborn and children's peri-operation period water and electrolyte within 2 years old
Balance, part meet the needs of to glucose, avoid hypoglycemia, it may also be used for the carrier of electrolyte concentrate and compatible drug is molten
Liquid.Domestic existing children's electrolyte injection mainly contains glucose and sodium chloride at present, and comparison of ingredients is single, cannot be complete
Meet the needs of human body is to fluid and electrolyte balance, compared with the existing children's electrolyte compound solution in the current country, this product
Various electrolyte ions necessary to being formed containing human body fluid, such as sodium ion, magnesium ion, calcium ion, phosphate anion, organic
Acid ion etc..The Na of electrolyte in this product+,K+,Mg 2+,Ca 2+, and Cl-It can be used for keeping or correcting water-electrolyte balance
(influence including blood volume, osmotic equilibrium, acid-base status and specific ion).
Glucose is metabolism natural substrate generally existing in biological cell.Glucose is most important in physiological conditions
Energy resource supply carbohydrate, wherein the energy supply of nerve fiber, red blood cell and kidney medulla depend on glucose.In blood
The normal value of concentration of glucose is 50~95mg/100ml and 2.8~5.3mmol/L (fasting) in liquid.Children's compound electrolyte Portugal
Glucose is applied to children as carbon aquation and object in grape sugar injection.But in the injection containing glucose, glucose meeting
Dehydration forms 5 hydroxymethyl furfural, when the amount increase of the decomposition product 5 hydroxymethyl furfural of glucose can cause animal striated muscle numb
Numbness and visceral lesion.
According to the literature, dosing temperature is excessively high, too high or too low solution ph is all to influence 5- in glucose injection
The factor that hydroxymethylfurfural generates.Contain phosphatic electrolyte injection simultaneously, free phosphoric acid can be generated during the preparation process
Salt, and human body take in excessive free phosphorus hydrochlorate it is excessive when, the tricalcium orthophosphate for being insoluble in water can be combined into calcium, make intracorporal calcium without
Method is fully absorbed, is utilized, and easily causes fracture, loss of tooth and textured bone, long-term administration can cause serium inorganic phosphorus to increase, blood calcium drops
It is low.Therefore it needs effectively to control 5 hydroxymethyl furfural, free phosphate content in electrolyte process for preparation.
Pyrogen is adsorbed frequently with active carbon in electrolyte injection liquid preparing process, but active carbon removes bacterial endotoxin
Ability is not high, and is very easy to introduce new substance, such as impurity element, particulate matter etc., this technology is international
Market is phased out.And chemistry " it is imitative to be listed according to the publication of state food pharmaceuticals administration general bureau's drug evaluation center
Pharmacy (injection) Conformance Assessment technical requirements (exposure draft) " in " injection production in it is not recommended that using active carbon.For
It effectively removes pyrogen (bacterial endotoxin), the control to former auxiliary packet, production equipment etc. need to be reinforced.".Therefore electrolyte injection
Carry out heat of adsorption by active carbon preferably by reinforcing the control to former auxiliary packet, production equipment etc. in preparation process, rather than merely
It is former.
Chinese patent CN102755348B discloses a kind of carbohydrate-electrolyte solution and preparation method thereof, injection
Be by 30 parts of glucose, 15 parts of fructose, 7.5 parts of xylitol, 0.73 part of sodium chloride, 0.41 part of sodium acetate, 0.185 part of calcium chloride,
0.255 part of magnesium chloride, 0.87 part of dipotassium hydrogen phosphate, 0.0007 part of zinc sulfate, 0.21 part of sodium hydrogensulfite, 250 parts of water for injection.
Its preparation process are as follows: by glucose, fructose, xylitol and electrolyte supplementary material, 75-85 DEG C of injection of configuration amount 90% is added
In water, stirring is made it completely dissolved, and obtains mixed solution；Needle-use activated carbon, 55-65 DEG C of insulated and stirred 10- is added in above-mentioned solution
20 minutes, decarburization was filtered while hot；It adds to the full amount of water for injection, uses pH adjusting agent tune pH to 5.1-5.5；With 0.45 μm of micropore
The above-mentioned solution of filter membrane refined filtration；Packing, sterilizing to get.It is carried out using 75-85 DEG C of water for injection with liquid, dosing temperature in the patent
Higher, the easy high temperature of glucose generates impurity 5 hydroxymethyl furfural, while high temperature dosing can make free phosphate content in electrolyte
It increases.In addition, the patent is complete in supplementary material dissolution, after charcoal absorption, then regulation system pH, easily make glucose solution by pH value shadow
It rings and generates 5 hydroxymethyl furfural.Chinese patent CN103385889B is 70 DEG C using water for injection temperature with liquid, same temperature mistake
High glucose impurity 5 hydroxymethyl furfural easily generated.Patent CN102755348B and patent CN103385889B preparation process simultaneously
In all non-inflated with nitrogen, prepare solution in have oxygen residual, be unfavorable for the long-term storage of product.In addition, Chinese patent
All contain active carbon in CN102755348B, CN102935087B and patent CN103385889B preparation process, is still deposited after filtering
In residual risk.
Compound electrolyte glucose in injection is larger at present, the related substance in preparation and storage
It will increase, how to effectively control related content of material, extend stability of drug products, and improving drug safety is to be badly in need of the pass to be solved
Key problem.
Summary of the invention:
In view of the deficiencies of the prior art, the present invention provides a kind of children's compound electrolyte glucose injection and its preparations
Method.The injection achromaticity and clarification, side reaction is few, and stability of drug products is good, the medication compliance of patient and highly-safe, is suitable for
Newborn and children's peri-operation period fluid and electrolyte balance within 2 years old, part meet the needs of to glucose, avoid hypoglycemia,
It can also be used in the carrier solution of electrolyte concentrate and compatible drug.The technical scheme adopted by the invention is as follows:
A kind of children's compound electrolyte glucose injection is with sodium chloride, Sodium acetate trihydrate, potassium chloride, two water chlorinations
Calcium, magnesium chloride hexahydrate, malic acid, phosphoglycerol disodium salt pentahydrate, glucose, 25% hydrochloric acid are active constituent, with pharmacy
The sterile solution for injection of upper acceptable pH adjusting agent and water for injection composition, specifically includes following component:
PH adjusting agent adjusts pH to 5.0-5.5
Water for injection adds to 1000ml；
Above-mentioned pH adjusting agent is citric acid, formic acid, acetic acid, carbonic acid, meta-aluminic acid, sodium citrate, sodium hydroxide, potassium hydroxide
One of or their mixture.
Preferably, which is made of the substance of following weight proportion:
PH adjusting agent adjusts pH to 5.0
Water for injection adds to 1000ml；
A kind of preparation method of children's compound electrolyte glucose injection the following steps are included:
(1) 70% recipe quantity water for injection is weighed, 20-50 DEG C is kept the temperature, by recipe quantity sodium chloride, Sodium acetate trihydrate, chlorination
Potassium, calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid are in water for injection
In, stirring and dissolving；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.0-5.5；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.0-5.5, stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is dispensed, is jumped a queue, roll lid, 121 DEG C of moist heat sterilization 12-20min are got product.
Step (1), (2), (3) are with persistently oxygen in solution is discharged in inflated with nitrogen during liquid；This product preparation process whole process is kept away
Light.
It is that the present invention generates the utility model has the advantages that
1) the application injection contain human body fluid form necessary to various electrolyte ions, as sodium ion, magnesium ion,
Calcium ion, phosphate anion, organic acid anions etc..
2) malic acid is L MALIC ACID in the application injection.L MALIC ACID and D-malic acid are absorbed and utilized machine is intracorporal
There is significant difference, D-malic acid is not absorbed in vivo, and the malic acid that can be efficiently used in human body is only L MALIC ACID.L-
Malic acid is the utilizable form of organism, it is often equipped with moriamin-s (important nutritional medicine after operation)
In, to improve the utilization rate of amino acid, the postoperative weak and hepatosis patient of this opponent is even more important.L MALIC ACID is treatment
The good drug of hyperammonemia caused by hepatopathy, especially hepatosis.
3) chance that drug and oxygen contact can be preferably minimized, furthermore by present invention nitrogen charging before preparation process and encapsulating
It is protected from light from being weighed in process for preparation, to improve this product storage stability.
4) present invention matches liquid using low temperature, and dosing temperature is 20-50 DEG C, and glucose can be effectively prevent because of high temperature dosing process
It is pyrolyzed out 5 hydroxymethyl furfural, and reduces the generation of free phosphorus hydrochlorate.
5) glucose feeding sequence of the present invention is that can avoid after pH value of solution is adjusted since pH value is excessively high and too low leads to grape
The related substance 5 hydroxymethyl furfural content of sugar increases, patient medication compliance and highly-safe.
6) pyrogen is controlled by the control to former auxiliary packet, production equipment etc. in preparation process of the present invention, without using work
Property charcoal absorption, avoid and introduce the new remaining risk of impurity and active carbon.
Specific embodiment:
Below in conjunction with specific embodiment, the invention will be further described, and the following description is only intended to explain the invention,
Protection scope of the present invention is not limited to these examples, it should be understood by those skilled in the art that made by the content of present invention
Equivalent replacement, or be correspondingly improved, it still falls within protection scope of the present invention.
Embodiment 1:
Prescription (100 bottles): 250ml/ bottles of specification
| Ingredient | Effect | Inventory (100 bottles) |
| Sodium chloride | Active constituent | 5.31g |
| Potassium chloride | Active constituent | 30g |
| Sodium acetate trihydrate | Active constituent | 65g |
| Calcium chloride dihydrate | Active constituent | 3.75g |
| Magnesium chloride hexahydrate | Active constituent | 6.5g |
| Phosphoglycerol sodium salt pentahydrate | Active constituent | 37.25g |
| L MALIC ACID | Active constituent | 0.5g |
| 25% dilute hydrochloric acid | Active constituent | 27.6g |
| DEXTROSE ANHYDROUS | Active constituent | 1.13kg |
| Sodium hydroxide | PH adjusting agent | In right amount |
| Dilute hydrochloric acid | PH adjusting agent | In right amount |
| Water for injection adds to | Solvent | 25L |
Preparation method:
(1) weigh 70% recipe quantity water for injection, 25 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir in water for injection
Dissolution is mixed, and continues inflated with nitrogen, is protected from light；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.0；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.0, stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is filling (250ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 20min are got product.
Embodiment 2:
Prescription (100 bottles): 250ml/ bottles of specification
Preparation method
(1) weigh 70% recipe quantity water for injection, 35 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir in water for injection
Dissolution is mixed, and continues inflated with nitrogen, is protected from light；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.2；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.2, stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is filling (250ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 15min are got product.
Embodiment 3:
Prescription (100 bottles): 500ml/ bottles of specification
Preparation method
(1) weigh 70% recipe quantity water for injection, 50 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir in water for injection
Dissolution is mixed, and continues inflated with nitrogen, is protected from light；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.5；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.5, stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is filling (500ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 12min are got product.
Comparative example 1:
Prescription (100 bottles): 250ml/ bottles of specification
Preparation method
(1) weigh 70% recipe quantity water for injection, 25 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir in water for injection
Mix dissolution；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.0；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.0, stirring and dissolving；
(4) activated adoption, constant volume, decarburization, refined filtration；
(5) gained medical fluid is filling (250ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 15min are got product.
Comparative example 2:
Prescription (100 bottles): 250ml/ bottles of specification
Preparation method
(1) weigh 70% recipe quantity water for injection, 75 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir in water for injection
Mix dissolution；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.2；
(3) recipe quantity glucose is put into the solution of above-mentioned pH value 5.2, stirring and dissolving；
(4) activated adoption, constant volume, decarburization, refined filtration；
(5) gained medical fluid is filling (250ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 15min are got product.
Comparative example 3:
Prescription (100 bottles): 500ml/ bottles of specification
Preparation method
| Ingredient | Effect | Inventory (100 bottles) |
| Sodium chloride | Active constituent | 14.5g |
| Potassium chloride | Active constituent | 67g |
| Sodium acetate trihydrate | Active constituent | 136g |
| Calcium chloride dihydrate | Active constituent | 7.5g |
| Magnesium chloride hexahydrate | Active constituent | 15.5g |
| Phosphoglycerol sodium salt pentahydrate | Active constituent | 76.5g |
| L MALIC ACID | Active constituent | 1.35g |
| 25% dilute hydrochloric acid | Active constituent | 56.5g |
| DEXTROSE ANHYDROUS | Active constituent | 2.5kg |
| Sodium hydroxide | PH adjusting agent | In right amount |
| Dilute hydrochloric acid | Solvent | 50L |
(1) weigh 70% recipe quantity water for injection, 25 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid, glucose are in injection
In water, stirring and dissolving；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.5；
(3) activated adoption, constant volume, decarburization, refined filtration；
(4) gained medical fluid is filling (500ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 15min are got product.
Comparative example 4:
Prescription (100 bottles): 500ml/ bottles of specification
| Ingredient | Effect | Inventory (100 bottles) |
| Sodium chloride | Active constituent | 14.5g |
| Potassium chloride | Active constituent | 67g |
| Sodium acetate trihydrate | Active constituent | 136g |
| Calcium chloride dihydrate | Active constituent | 7.5g |
| Magnesium chloride hexahydrate | Active constituent | 15.5g |
| Phosphoglycerol sodium salt pentahydrate | Active constituent | 76.5g |
| L MALIC ACID | Active constituent | 1.35g |
| 25% dilute hydrochloric acid | Active constituent | 56.5g |
| DEXTROSE ANHYDROUS | Active constituent | 2.5kg |
| Sodium hydroxide | PH adjusting agent | In right amount |
| Dilute hydrochloric acid | Solvent | 50L |
Preparation method
(1) weigh 70% recipe quantity water for injection, 75 DEG C of heat preservations, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride,
Calcium chloride dihydrate, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid, glucose are in injection
In water, stirring and dissolving；
(2) pH adjusting agent is added by above-mentioned solution tune pH to 5.5；
(3) activated adoption, constant volume, decarburization, refined filtration；
(4) gained medical fluid is filling (500ml/ bottles), it jumps a queue, rolls lid, 121 DEG C of moist heat sterilization 15min are got product.
Test result:
For the characteristic and actual effect for examining children's electrolyte glucose injection of the invention to have, we are to said preparation
Long-time stability investigation is done.Comparative example 1,2,3,4 and 1,2,3 injection liquid samples of embodiment are set 25 ± 2 DEG C, 60% ± 10%
It is placed 6 months under the conditions of RH, related inspection target is measured by sampling respectively at January, 2 months, March, June, data are as shown in the table:
Table 6 months accelerated stability experimental results of 1 comparative example 1-4 and embodiment 1-3
The above result shows that:
1. passing through 6 months study on the stability, children's compound electrolyte glucose injection fluidity of Examples 1 to 3 preparation
Shape is colourless clear liquid, and related substance 5 hydroxymethyl furfural and free phosphoric acid sodium content are stablized, and is placed 6 months, without obvious
It increases.In addition, children's compound electrolyte glucose injection of Examples 1 to 3 preparation, is not removed by active carbon in configuration process
Pyrogen, but pyrogen is controlled using the supplementary material of bacterial endotoxin qualification and by control production equipment, obtained electrolysis
Matter glucose injection bacterial endotoxin meets regulation.
2. not being protected from light nitrogen charging gas shielded by electrolyte glucose injection prepared by comparative example 1 in process for preparation, being obtained
The related substance of finished product it is higher than Examples 1 to 3, and after storing 6 months, related substance 5 hydroxymethyl furfural and free phosphoric acid sodium
Content gradually rises, and character changes at 6 months.
3. high temperature is respectively adopted in process for preparation and is matched by electrolyte glucose injection prepared by comparative example 2, comparative example 3
Liquid, with liquid, first addition glucose adjusts pH value again in the process, and is not all protected from light inflated with nitrogen, after obtained finished product is placed 6 months, property
Shape changes, and related substance is higher than Examples 1 to 3.
4. being used high temperature dosing in process for preparation by electrolyte glucose injection prepared by comparative example 4, grape being first added
Sugar adjusts pH value again and is not protected from light nitrogen charging gas shielded, and the related substance of obtained finished product is than Examples 1 to 3 and comparative example 1~3
Will be high, and at study on the stability 3 months, character is yellowish clear liquid, and at study on the stability 6 months, character is yellow
Clear liquid, related substance 5 hydroxymethyl furfural and free phosphoric acid sodium content significantly increase.
5. it can be seen that Examples 1 to 3, at 25 ± 2 DEG C, quality is stablized after placing 6 months under the conditions of 60% ± 10%RH
Better than comparative example 1~4, it is protected from light with inflated with nitrogen during liquid, low temperature adjusts pH with liquid (20-50 DEG C of temperature), first and adds grape
The stability of compound electrolyte glucose injection can be improved in sugar.In addition, passing through the control by force to former auxiliary packet, production equipment etc.
The preparation of bacterium endogenous toxic material qualification also can be obtained in system.
Claims (7)
1. a kind of children's compound electrolyte glucose injection, it is characterised in that: the injection is by the group of following weight proportion
Divide and be made:
PH adjusting agent adjusts pH to 5.0-5.5
Water for injection adds to 1000ml.
2. a kind of children's compound electrolyte glucose injection according to claim 1, it is characterised in that: malic acid L-
Malic acid.
3. a kind of children's compound electrolyte glucose injection according to claim 1, pH adjusting agent is citric acid, first
One of acid, acetic acid, carbonic acid, meta-aluminic acid, sodium citrate, sodium hydroxide, potassium hydroxide or their mixture.
4. a kind of children's compound electrolyte glucose injection according to claim 1, it is characterised in that: it is preferred, it should
Injection is made of the component of following weight proportion:
PH adjusting agent adjusts pH to 5.0-5.5
Water for injection adds to 1000ml.
5. a kind of preparation method of children's compound electrolyte glucose injection as described in claim 1, it is characterised in that packet
Include following steps:
(1) 70% recipe quantity water for injection is weighed, 20-50 DEG C is kept the temperature, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride, two
Water calcium chloride, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid are in water for injection, stirring
Dissolution；
(2) pH adjusting agent is added and above-mentioned solution is adjusted into pH to 5.0-5.5；
(3) recipe quantity glucose is put into the solution of above-mentioned steps (2), stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is dispensed, is jumped a queue, roll lid, 121 DEG C of moist heat sterilization 12-20min are got product.
6. a kind of preparation method of children's compound electrolyte glucose injection according to claim 5, it is characterised in that:
Step (1), (2), (3) continue inflated with nitrogen with liquid in the process；It is protected from light during step (1)-(5).
7. a kind of preparation method of children's compound electrolyte glucose injection according to claim 6, it is characterised in that
The following steps are included:
(1) 70% recipe quantity water for injection is weighed, 25 DEG C are kept the temperature, by recipe quantity sodium chloride, Sodium acetate trihydrate, potassium chloride, two water
Calcium chloride, magnesium chloride hexahydrate, L MALIC ACID, phosphoglycerol disodium salt pentahydrate, 25% hydrochloric acid stir molten in water for injection
Solution；
(2) pH adjusting agent is added and above-mentioned solution is adjusted into pH to 5.2；
(3) recipe quantity glucose is put into the solution of above-mentioned steps (2), stirring and dissolving；
(4) constant volume, refined filtration；
(5) gained medical fluid is dispensed, is jumped a queue, roll lid, 121 DEG C of moist heat sterilization 15min are got product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811174780.6A CN109091500A (en) | 2018-10-09 | 2018-10-09 | A kind of children's compound electrolyte glucose injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811174780.6A CN109091500A (en) | 2018-10-09 | 2018-10-09 | A kind of children's compound electrolyte glucose injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109091500A true CN109091500A (en) | 2018-12-28 |
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Cited By (2)
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| CN109010362A (en) * | 2018-10-09 | 2018-12-18 | 济南康和医药科技有限公司 | A kind of children's compound electrolyte glucose injection and preparation method thereof |
| CN109432123A (en) * | 2018-11-23 | 2019-03-08 | 济南康和医药科技有限公司 | A kind of compound electrolyte glucose injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109010362A (en) * | 2018-10-09 | 2018-12-18 | 济南康和医药科技有限公司 | A kind of children's compound electrolyte glucose injection and preparation method thereof |
| CN109432123A (en) * | 2018-11-23 | 2019-03-08 | 济南康和医药科技有限公司 | A kind of compound electrolyte glucose injection and preparation method thereof |
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Application publication date: 20181228 |