CN104013643A - Compound electrolyte invert sugar injection liquid - Google Patents
Compound electrolyte invert sugar injection liquid Download PDFInfo
- Publication number
- CN104013643A CN104013643A CN201410292695.5A CN201410292695A CN104013643A CN 104013643 A CN104013643 A CN 104013643A CN 201410292695 A CN201410292695 A CN 201410292695A CN 104013643 A CN104013643 A CN 104013643A
- Authority
- CN
- China
- Prior art keywords
- injection
- sodium
- preparation
- water
- chloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of invert sugar electrolyte injection liquid. The prescription of the injection liquid is as follows: each 1000ml of injection liquid comprises 50g of glucose, 50g of fructose, 1.46g of sodium chloride, 1.86g of potassium chloride, 2.80g of sodium lactate, 0.75g of sodium dihydrogen phosphate and 0.286g of magnesium chloride; water for injection is added to reach 1000ml. By adopting the compound electrolyte invert sugar injection liquid provided by the invention, the contradiction between an added stabilizing agent and an adverse reaction can be solved, namely that the hazards caused by the stabilizing agent contained in an invert sugar electrolyte solution in clinical applications can be reduced to a highest extent or even can be avoided, and meanwhile, the effects of the stabilizing agent on the stability of an injection in transportation and storage processes can be maintained.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of compound electrolyte invert srgar inj and preparation method.
Background technology
Inverted sugar electrolytes injection is the fructose of equivalent and the sterile water solution of glucose (Nulomoline), sodium chloride, potassium chloride, magnesium chloride, sodium dihydrogen phosphate and sodium lactate, can be patient water, electrolyte and energy are provided, and produce diuresis and metabolic alkalinization, its contained lactate generates glycogen at hepatic metabolism, at H
+under participation, finally generate CO
2and water.Be applicable to clinically to need parenteral approach to keep the skin wet or the energy and electrolytical patient's fluid-supplement therapy, at home and abroad use extensively, because it is respond well, safe, record into American Pharmacopeia.
Patent documentation CN101284014 discloses a kind of inverted sugar electrolytes injection, and its constituent is glucose, fructose, sodium chloride, potassium chloride, sodium lactate, sodium hydrogen phosphate, magnesium chloride and water for injection.The product of this invention is total intravenous nutrition injection, can be simultaneously for body provides multiple electrolyte and glucose and fructose, and can reach and supplement body body fluid, maintain fluid and electrolyte balance and the object of energy is provided.But document does not provide data and the announcement of the pH regulator in preparation preparation process.
(4 kinds of antibacterials of < < and inverted sugar electrolytes injection compatibility stability and the safety research > > such as Sun Chengchun, medicine Leader, the 9th phase in 2011) compatibility stability and the safety of Sulbactam/Cefoperazone, ceftriaxone, cefminox, Azithromycin 4 kind antibacterials and inverted sugar electrolytes injection have been investigated, for clinical rational drug use provides foundation.Method is: at 25 ℃, investigate respectively outward appearance, pH and changes of contents after 4 kinds of antibacterials and inverted sugar electrolytes injection compatibility; And observe compatibility solution to rabbit blood vessel irritation, whether can produce external haemolysis, and observe the allergy situation producing after animal duplicate injection compatibility solution.Result shows, 4 kinds of antibacterials and inverted sugar electrolytes injection compatibility 4 h outers, pH and content are all without significant change.Compatibility solution, to Sanguis Leporis seu oryctolagi pipe nonirritant, does not produce haemolysis and allergy.Conclusion is: 4 kinds of antibacterials and inverted sugar electrolytes injection compatibility safety, stable.
(there is incompatibility > > in < < Cefodizime Sodium and inverted sugar electrolytes injection to Zhang Yingmei, nursing journal, 2008, 15 (8): 67) report, the Cefodizime Sodium diluent 5ml that infusion is used directly mixes in aseptic dry test tube with inverted sugar electrolytes injection 5ml solution, after 5 min, find that mixed liquor becomes white opacity thing, standing 30 min still have white casse, after placing 24 h, there is Precipitation, show that Cefodizime sodium injection and inverted sugar electrolytes injection exist incompatibility.
Chinese patent CN102949413 has announced a kind of preparation method of inverted sugar electrolytes injection, discloses a kind of method that sucrose direct hydrolysis is prepared medicinal Nulomoline aqueous solution: water for injection adds 35% concentrated hydrochloric acid solution, adjusts pH value to suitable; Control temperature is suitable, adds appropriate medical cane sugar, reaction certain hour; Add 5 ~ 10 ℃ of water for injection fast coolings, obtain medicinal Nulomoline aqueous solution.Its medicinal Nulomoline aqueous solution preparing can be used for preparing medicinal invert srgar inj, medicinal inverted sugar electrolytes injection.It has solved the Cost Problems that Nulomoline is prepared electrolyte injection.
In sucrose hydrolysis reaction, at certain acidity and temperature, the concentration of sucrose solution has a significant impact the speed of reaction, with the augmenting response speed of concentration, increases equally.But along with the increase of (concentration of sucrose represents with hammer degree Bx) of sucrose solution hammer degree, the color of reactant liquor can be deepened.Sucrose hydrolysis reaction is (if pH value is 1.0) in low acidity situation, and sucrose is easy to variable color in hydrolysis, causes quality of products; When the increase along with acidity, sucrose hydrolysis rate reduction, hydrolysis time lengthens, and causes related substance to increase.In sucrose hydrolysis reaction, along with the raising of reacting liquid temperature, hydrolysis rate obviously increases, and hydrolysising balance moves to Nulomoline direction simultaneously, but after reaction temperature is higher than 100 ℃, reactant liquor color is significantly deepened, and along with the increase of temperature, in reactant liquor, impurity content increases simultaneously.
Solve the problem of injection stability, the conventional method in this area is to add appropriate stabilizing agent in prescription, and still, about stabilizing agent, query is endured in the application in injection to the fullest extent at present, sulphite anaphylaxis, and rapid onset, is in a bad way.In injection, do not advocate use stabilizing agent.In injection preparation, for reaching injection transportation and depositing character, keep stable effect, unavoidablely will apply stabilizing agent.Therefore the predicament that, solution stabilizing agent is applied in Nulomoline electrolyte solution is that this area faces major issue.
Summary of the invention
The invention provides a kind of preparation method of inverted sugar electrolytes injection, the prescription of described injection is, in 1000ml,
Glucose 50g
Fructose 50g
Sodium chloride 1.46g
Potassium chloride 1.86g
Sodium lactate 2.80g
Sodium dihydrogen phosphate 0.75g
Magnesium chloride 0.286g
Inject water to 1000ml.
The present invention also provides a kind of preparation method of inverted sugar electrolytes injection, the feeding intake by following formula of the preparation of described injection, and in the amount of 400L,
Single water glucose 22kg
Fructose 20kg
Sodium chloride 468g
Potassium chloride 744g
Magnesium chloride hexahydrate 244g
Sodium lactate (40.7%) 2.752kg
Sodium dihydrogen phosphate 300g
Sodium sulfite 208g
Hydrochloric acid (37%) 180-200g
It is characterized in that, preparation method is as follows:
(1) dense joining, take sodium chloride, sodium sulfite, other feeds intake by recipe quantity: single water glucose, fructose, potassium chloride, magnesium chloride hexahydrate, sodium dihydrogen phosphate, sodium lactate, add concentrated hydrochloric acid, add the water for injection of appropriate 40-80 ℃ to dissolve, pump into dense preparing tank, add water to 160L;
(2) depyrogenation, adds needle-use activated carbon 224-256g by the amount of 0.14-0.16% (W/V), circulation 30min, fine straining carbon removal;
(3) dilution, pumps into Agitation Tank by concentrated wiring liquid, injects and is diluted with water to 400L, circulation 30min, 0.22mm fine straining;
(4) fill, fine straining liquid, after clarity test, is filled into multi-layer co-extrusion infusion with in soft bag, 500ml/ bag.
(5) sterilizing, after fill, puts 115 ℃, sterilizing 30min.
Further, in step (1), hydrochloric acid adds concentrated hydrochloric acid 197g.
Preferably, in step (1), adding the temperature of water for injection is 70 ℃.
Preferably, in step (2), by the amount of 0.15% (W/V), add needle-use activated carbon 240g.
Owing to adopting technical scheme of the present invention, than prior art, the application controls the amount of sodium sulfite and hydrochloric acid, in storing and transporting, sodium sulfite and hydrochloric acid are converted into sodium chloride, eliminated the harm of sodium sulfite, in storing simultaneously and transporting, the stabilizer function of sodium sulfite still keeps, because of the HSO in sodium sulfite
3 -with H in hydrochloric acid
+in the preparation of injection and storage process, be consumed gradually, be therefore not counted in prescription, but Na
+with the Cl in hydrochloric acid
-count the total amount of sodium chloride.Because the sodium of system and the supplier of chlorine have produced variation, corresponding inventor has also carried out to osmotic pressure and pH value the amount that sodium sulfite and hydrochloric acid have finally been determined in checking repeatedly.
The specific embodiment
Embodiment 1
Prescription
Crude drug/adjuvant inventory (g)
Single water glucose 22kg
Fructose 20kg
Sodium chloride 468g
Potassium chloride 744g
Magnesium chloride hexahydrate 244g
Sodium lactate (40.7%) 2.752kg
Sodium dihydrogen phosphate 300g
Sodium sulfite 208g
Hydrochloric acid (37%) 197g.
Step: by inventory, take each component, add the water for injection of appropriate 70 ℃ to dissolve, pump into dense preparing tank, add water to 160L(total amount 40%).0.15% (W/V) by amount of liquid adds needle-use activated carbon 240g, circulation 30min, absorption pyrogen, coarse filtration carbon removal.Concentrated wiring liquid is pumped into Agitation Tank, inject and be diluted with water to 400L, circulation 30min, 0.22mm fine straining.Fine straining liquid, after clarity test, is filled into multi-layer co-extrusion infusion with in soft bag, 500ml/ bag.Put 115 ℃, sterilizing 30min.Obtain compound electrolyte invert srgar inj.
Embodiment 2
Crude drug/adjuvant inventory (g)
Single water glucose 22kg
Fructose 20kg
Sodium chloride 468g
Potassium chloride 744g
Magnesium chloride hexahydrate 244g
Sodium lactate (40.7%) 2.752kg
Sodium dihydrogen phosphate 300g
Sodium sulfite 208g
Hydrochloric acid (37%) 180g.
Step: by inventory, take each component, add the water for injection of appropriate 40 ℃ to dissolve, pump into dense preparing tank, add water to 160L(total amount 40%).0.14% (W/V) by amount of liquid adds needle-use activated carbon 224g, circulation 30min, absorption pyrogen, coarse filtration carbon removal.Concentrated wiring liquid is pumped into Agitation Tank, inject and be diluted with water to 400L, circulation 30min, 0.22mm fine straining.Fine straining liquid, after clarity test, is filled into multi-layer co-extrusion infusion with in soft bag, 500ml/ bag.Put 115 ℃, sterilizing 30min.Obtain compound electrolyte invert srgar inj.
Embodiment 3
By following formula, feed intake, in the amount of 400L,
Single water glucose 22kg
Fructose 20kg
Sodium chloride 468g
Potassium chloride 744g
Magnesium chloride hexahydrate 244g
Sodium lactate (40.7%) 2.752kg
Sodium dihydrogen phosphate 300g
Sodium sulfite 208g
Hydrochloric acid (37%) 200g
It is characterized in that, preparation method is as follows:
(1) dense joining, take sodium chloride, sodium sulfite, other feeds intake by recipe quantity: single water glucose, fructose, potassium chloride, magnesium chloride hexahydrate, sodium dihydrogen phosphate, sodium lactate, add concentrated hydrochloric acid, add the water for injection of appropriate 80 ℃ to dissolve, pump into dense preparing tank, add water to 160L;
(2) depyrogenation, adds needle-use activated carbon 256g by the amount of 0.16% (W/V), circulation 30min, fine straining carbon removal;
(3) dilution, pumps into Agitation Tank by concentrated wiring liquid, injects and is diluted with water to 400L, circulation 30min, 0.22mm fine straining;
(4) fill, fine straining liquid, after clarity test, is filled into multi-layer co-extrusion infusion with in soft bag, 500ml/ bag.
(5) sterilizing, after fill, puts 115 ℃, sterilizing 30min.
The Nulomoline aqueous solution that sucrose direct hydrolysis method provided by the present invention obtains, although also used stabilizing agent sodium sulfite, it can neutralize with hydrochloric acid in transportation with in storing, and the effect that improves stability that has to injection.Inventor gets its " 5 hydroxymethyl furfural " and carries out contrast test, to further illustrate beneficial effect of the present invention.
Test example 1
The impact of the inventory of hydrochloric acid on stabilizing agent effect
Sample is taken from embodiment 1 comparative example, and it is 170g that the prescription of comparative example 1 consists of hydrochloric acid addition, and all the other are with reference to embodiment 1 preparation, and it is 210g that comparative example 2 prescriptions consist of hydrochloric acid addition, and all the other are with reference to embodiment 1 preparation.Investigate the impact of high temperature on inverted sugar electrolytes injection stability.
test example 2
By two appendix XID pyrogen tests of < < Pharmacopoeia of People's Republic of China > > version in 2000, carry out successively.Every lot number compound electrolyte invert srgar inj is got 3 of rabbit, measure after normal body temperature in 15 minutes, by the dosage of 8.33ml/kg, from ear vein, slowly inject the need testing solution that is warmed to approximately 38 ℃, then every 30 minutes, measure its body temperature 1 time, survey altogether 6 times, with the highest normal body temperature that once deducts in 6 body temperature, be this rabbit body temperature rising temperature (℃).As having 1 fervescence in 3 rabbit more than 0.6 ℃ or 0.6 ℃, or 3 rabbit body temperatures raise all lower than 0.6 ℃, but the summation of fervescence reaches more than 1.4 ℃ or 1.4 ℃, should separately get 5 rabbit retrials.By result criterion, judge.
Test sample embodiment 1, embodiment 2, comparative example 1 and comparative example 2, comparative example 1 is on embodiment 1 and basis, will add needle-use activated carbon to be adjusted into 220g, comparative example 2 is on the basis of embodiment 2, will add needle-use activated carbon to be adjusted into 270g.
Compound electrolyte invert srgar inj (embodiment 1) pyrogen test result
Compound electrolyte invert srgar inj (embodiment 2) pyrogen test result
Compound electrolyte invert srgar inj (comparative example 1) pyrogen test result
The sample pyrogen test of comparative example 1 shows to number 8 rabbit body temperature and surpasses 0.6 ℃, and the summation of fervescence reaches 1.565 ℃, surpasses 1.4 ℃, separately gets 5 rabbit retrials, does not still meet heat source check regulation, is defined as pyrogen and exceeds standard.
Compound electrolyte invert srgar inj (comparative example 2) pyrogen test result
The pyrogen test result of comparative example 2 shows, the rabbit of numbering 10 and 12, and pyrogen test exceeds standard, and separately gets 5 rabbit retrials, does not still meet heat source check regulation, is defined as pyrogen and exceeds standard.
test example 3 is dense joins the impact that water for injection temperature produces 5 hydroxymethyl furfural
Get test sample 1ml, water for injection is diluted to 50ml, according to two appendix IV A spectrophotographys of < < Pharmacopoeia of People's Republic of China > > version in 2000, at 284nm wavelength place, measure trap, should be not more than 0.25.
Test liquid:
Embodiment 1
Embodiment 2
Embodiment 3
Comparative example 1, referring to embodiment 1 method preparation, difference is that dense to join that water for injection temperature controls be 50 ℃;
Comparative example 2, referring to embodiment 1 method preparation, difference is that dense to join that water for injection temperature controls be 90 ℃;
Test sample 5 hydroxymethyl furfural check result
Wavelength place according to spectrophotography at 284nm measures, and 5 hydroxymethyl furfural absorbance must not be greater than 0.25; The 5 hydroxymethyl furfural absorbance of documents 1,2 significantly raises, and documents 2 has exceeded standard prescribed limit, does not meet medicinal standard.
Above-mentioned detailed description is for the illustrating of one of them possible embodiments of the present invention, and this embodiment is not in order to limit the scope of the claims of the present invention, and the equivalence that all the present invention of disengaging do is implemented or change, all should be contained in the scope of technical solution of the present invention.
Claims (5)
1. a preparation method for inverted sugar electrolytes injection, the prescription of described injection is, in 1000ml,
Glucose 50g
Fructose 50g
Sodium chloride 1.46g
Potassium chloride 1.86g
Sodium lactate 2.80g
Sodium dihydrogen phosphate 0.75g
Magnesium chloride 0.286g
Inject water to 1000ml.
2. a preparation method for inverted sugar electrolytes injection, the formula that clicks of the preparation of described injection feeds intake, in the amount of 400L,
Single water glucose 22kg
Fructose 20kg
Sodium chloride 468g
Potassium chloride 744g
Magnesium chloride hexahydrate 244g
Sodium lactate (40.7%) 2.752kg
Sodium dihydrogen phosphate 300g
Sodium sulfite 208g
Hydrochloric acid (37%) 180-200g
It is characterized in that, preparation method is as follows:
(1) dense joining, take sodium chloride, sodium sulfite, other feeds intake by recipe quantity: single water glucose, fructose, potassium chloride, magnesium chloride hexahydrate, sodium dihydrogen phosphate, sodium lactate, add concentrated hydrochloric acid, add the water for injection of appropriate 40-80 ℃ to dissolve, pump into dense preparing tank, add water to 160L;
(2) depyrogenation, adds needle-use activated carbon 224-256g by the amount of 0.14-1.06% (W/V), circulation 30min, fine straining carbon removal;
(3) dilution, pumps into Agitation Tank by concentrated wiring liquid, injects and is diluted with water to 400L, circulation 30min, 0.22mm fine straining;
(4) fill, fine straining liquid, after clarity test, is filled into multi-layer co-extrusion infusion with in soft bag, 500ml/ bag;
(5) sterilizing, after fill, puts 115 ℃, sterilizing 30min.
3. according to the preparation method of the inverted sugar electrolytes injection of claim 2, it is characterized in that, in step (1), hydrochloric acid adds concentrated hydrochloric acid 197g.
4. according to the preparation method of the inverted sugar electrolytes injection of claim 2, it is characterized in that, the temperature that adds water for injection in step (1) is 70 ℃.
5. according to the preparation method of the inverted sugar electrolytes injection of claim 2, it is characterized in that, step adds needle-use activated carbon 240g by the amount of 0.15% (W/V) in (2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410292695.5A CN104013643A (en) | 2014-06-26 | 2014-06-26 | Compound electrolyte invert sugar injection liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410292695.5A CN104013643A (en) | 2014-06-26 | 2014-06-26 | Compound electrolyte invert sugar injection liquid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104013643A true CN104013643A (en) | 2014-09-03 |
Family
ID=51430826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410292695.5A Pending CN104013643A (en) | 2014-06-26 | 2014-06-26 | Compound electrolyte invert sugar injection liquid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104013643A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108113998A (en) * | 2016-11-28 | 2018-06-05 | 华仁药业股份有限公司 | A kind of preparation method of parenteral solution |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284014A (en) * | 2007-04-10 | 2008-10-15 | 扬子江药业集团上海海尼药业有限公司 | Inverted sugar electrolytes injection and preparation technique thereof |
| CN103860592A (en) * | 2012-12-18 | 2014-06-18 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of inverted sugar electrolyte injection |
-
2014
- 2014-06-26 CN CN201410292695.5A patent/CN104013643A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284014A (en) * | 2007-04-10 | 2008-10-15 | 扬子江药业集团上海海尼药业有限公司 | Inverted sugar electrolytes injection and preparation technique thereof |
| CN103860592A (en) * | 2012-12-18 | 2014-06-18 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of inverted sugar electrolyte injection |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108113998A (en) * | 2016-11-28 | 2018-06-05 | 华仁药业股份有限公司 | A kind of preparation method of parenteral solution |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102552127B (en) | Ornidazole injection | |
| KR102100103B1 (en) | Aqueous pectin solution | |
| CN102166360A (en) | Ibuprofen intravenously administrable preparation and preparation method thereof | |
| CN104586885A (en) | Compound sodium bicarbonate electrolyte injection composition and preparation method thereof | |
| CN101721423A (en) | Bicarbonate physiological balanced solution and preparation method thereof | |
| CN108066360A (en) | A kind of compound sodium acetate ringer's injection and preparation method thereof | |
| CN101007003A (en) | A stable torasemide injection and its preparation method | |
| CN105477012B (en) | A kind of Levetiracetam sodium chloride injection composition and preparation method thereof | |
| CN101032512B (en) | Medicine composition for expanding blood volume and the preparing method thereof | |
| CN102145009A (en) | Octadeca compound amino acid injection and preparation method thereof | |
| CN104013643A (en) | Compound electrolyte invert sugar injection liquid | |
| CN103381140A (en) | Inosine-common salt composition and preparation method thereof | |
| CN110538144A (en) | Ornidazole injection and S-ornidazole injection | |
| CN106309481A (en) | Compound potassium aspartate-glucose injection and preparation method thereof | |
| CN103800285B (en) | A kind of sodium bicarbonate injection and preparation method thereof | |
| CN103860592A (en) | Preparation method of inverted sugar electrolyte injection | |
| CN102526098A (en) | New application of compound sodium chloride potassium chloride injection | |
| CN104940135A (en) | Fluconazole injection and preparation method thereof | |
| CN102319258B (en) | 5 percent glucose substitution liquid and preparation method thereof | |
| CN104490902B (en) | A kind of composite vitamin for injection freeze drying powder injection composition and preparation method thereof | |
| CN102949413B (en) | Method for preparing invert sugar and electrolytes injection | |
| CN108451974A (en) | A kind of aspartic acid Multiple electrolytes injection and preparation method thereof | |
| CN102552314A (en) | Preparation method of compound sodium chloride-potassium chloride infusion solution | |
| CN105796487B (en) | Milrinone injection and preparation method thereof | |
| CN101766563A (en) | Combination use method of water-soluble vitamin injection and sodium chloride injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140903 |