CN102451187A - High-energy nutrient infusion solution and preparation method thereof - Google Patents
High-energy nutrient infusion solution and preparation method thereof Download PDFInfo
- Publication number
- CN102451187A CN102451187A CN2010105294183A CN201010529418A CN102451187A CN 102451187 A CN102451187 A CN 102451187A CN 2010105294183 A CN2010105294183 A CN 2010105294183A CN 201010529418 A CN201010529418 A CN 201010529418A CN 102451187 A CN102451187 A CN 102451187A
- Authority
- CN
- China
- Prior art keywords
- weight portion
- weight portions
- potassium
- chloride
- add
- 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.)
- Granted
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a high-energy nutrient infusion solution and a preparation method thereof. The nutrient infusion solution is prepared from glucose, fructose, xylitol, calcium gluconate, sodium chloride, potassium chloride, magnesium sulfate, sodium citrate, citric acid, monopotassium phosphate, zinc sulfate, copper chloride, iron chloride, sodium bisulfite and the like. The high-energy nutrient infusion solution has the advantages of reasonable formula composition, scientific process control, obvious clinical effects and safety in use.
Description
Technical field
The present invention relates to a kind of transfusion and preparation method thereof, particularly a kind of high-energy nutrition transfusion and preparation method thereof.
Background technology
The transfusion of nutrition class is very extensive in the clinical practice of China; It plays the critical patient who can not oral administration absorbs nourishment and keeps, the effect of prolongation and save lives; Make and normally to take food or the metabolic patient of superelevation still can keep the good nutrition state, be able to correct negative nitrogen balance, promote wound healing and weight increase to improve survival rate.
At present, domestic hospital clinical uses maximum nutrition class transfusions to mainly contain glucose injection, fat emulsion injection, amino acid injection, vitamin and electrolyte injection four major types.Glucose is the main source of needed by human body energy, is oxidized to carbon dioxide and water in vivo, and supplies with heat simultaneously; Or store with the glycogen form; It can promote the function of detoxification of liver, and liver is had protective effect, low potassium, low sodium and hypophosphatemia can occur during long-term simple supply glucose; Low potassium, low sodium disease also can appear when hyperpotassemia, brittle diabetes patient applying high density glucose; Glucose must rely on just energy metabolism of insulin, and metabolism is slow in vivo; Hyperglycemia makes steatolysis receive to press down, and causes body the nitrogenize phenomenon to occur, and these drawbacks have caused traditional nutrition transfusion can not adapt to such as increasingly high clinical requirements of numerous hospital department such as department of endocrinology, hepatology, surgeries.
Xylitol is the normal intermediate of human body carbohydate metabolism.The people of a health even do not eat any food that contains xylitol, is also contained 0.03～0.06 milligram/100 milligrams xylitol in the blood.Lacking insulin in vivo influences under the carbohydrate metabolism situation, need not insulin and promotes, xylitol also can permeate through cell membranes, by the tissue absorption utilization, supplies cell with nutrition and energy; Xylitol can promote liver glycogen synthetic, and blood glucose can not rise, and the hepatopath is had the liver function of improvement and lipotropic effect.But the thermal source utilization rate of xylitol is not high, is merely the half the of glucose, can not to body energy be provided as thermal source separately; In addition, xylitol is mainly drained through kidney, and therefore, its injection speed, working concentration etc. all can be restricted in use, and is improper like control, is easy to occur side effect such as metabolic acidosis and kidney, cerebral lesion.
Fructose is the highest sugar of chemism in the saccharide, and calorific value is low, and metabolism is faster than glucose in vivo, is prone to absorbed by body, and does not rely on insulin, and is little to blood sugar influence, is applicable to glucose metabolism and hepatic insufficiency person makeup energy.It can be when replenishing the diabetics energy i (in vivo) fluctuation of effective blood sugar control concentration; As far as the hepatopath, do not rely on the fructose of insulin resistant, also can many-sided effectively remedy the obstacle that utilizes of its glucose.Metabolic stability is particularly suitable for wound and surgical patient and uses.Yet the researcheres of Georgia university are found, the too high spatial memory ability that impairs adult rat of fructose content in the diet.Drip that speed is too fast to cause that lactic acidosis, hyperuricemia and lipid metabolism are unusual; Excessive use can cause serious acidosis, so do not recommend place of glucose in the parenteral nutrition.
Electrolyte has important function in human body.Power and water is separated matter and extensively is distributed in inside and outside the cell, participate in many important function and metabolic activity in the body, and electrolyte plays important effect to keeping of normal activities.Water, metabolic disturbance of electrolyte can make the substance metabolism of whole body each tract, particularly cardiovascular system, neural physiological function and body that corresponding obstacle takes place, and seriously can cause death often.Human body except necessary sodium, potassium, magnesium, calcium, phosphorus, sulfur, carbon, hydrogen, oxygen, nitrogen, etc. element and people existence and healthy closely bound up; Trace element all also plays a part very important at aspects such as disease-resistant, anti-cancer, life lengthening, as zinc deficiency can cause mouthful, eye, anus or external genital is rubescent, pimple, warm rash.And for example ferrum is one of main component that constitutes hemoglobin, and iron deficiency can cause iron deficiency anemia.Report was abroad once arranged: iron content, copper, zinc total amount reduce in the body, all can weaken immunologic mechanism, reduce resistance against diseases, encourage bacterial infection, and metainfective mortality rate are also higher.
The present domestic all kinds of nutrition transfusions of producing basically; But kind and specification are also incomplete, as for merge the total parenteral nutrition transfusion of all kinds of nutritional labelings in one (Total Parenteral Nutrition, TPN); Domestic still awaiting researched and developed; Saccharide is to supply with organism metabolism energy needed and the required carbon atom of biosynthesis, in the TPN transfusion, uses maximum glucoses that is still, and 25～50% concentration commonly used are as the source of TPN heat.In addition, the utilization rate that is to improve sugar with reduce the side reaction of some patient to heavy dose, the mixed liquor of glucoses and fructose is adopted in indivedual TPN transfusions, even independent employing fructose is arranged.Being also noted that interaction and equilibrium relation between each element in addition. some element mutual interference mutually absorbs; Meeting out of proportion brings new element to lack. when once there are some researches show intravenous nutrition; As do not supply zinc; Copper etc., these constituent contents can the decline of carrying out property in the blood, after (being generally for 4 weeks) a series of symptoms can appear. comparatively obvious to children's.
Therefore, total parenteral nutrition is infused and is occupied consequence day by day in medical treatment in modern times and the fluid transport therapy, has played the dual function of nutrition and treatment.In order to develop China's transfusion kind, satisfy needs of medical treatment, catch up with international most advanced level, the utmost point is necessary to develop this series products to fill the domestic gaps.
Summary of the invention
The object of the present invention is to provide a kind of high-energy nutrition transfusion; Another object of the present invention is to provide the method for preparing of this nutrition transfusion.
The objective of the invention is to realize through following technical scheme:
The raw material of high-energy nutrition transfusion of the present invention consists of:
Potassium chloride 1.5～3.3 weight portions
Magnesium sulfate 0.3～1.5 weight portion
Citric acid 0.05～0.25 weight portion
Potassium dihydrogen phosphate 0.5～1.5 weight portion
Zinc sulfate 0.0045～0.0055 weight portion
Copper chloride 0.0005～0.0006 weight portion
Iron chloride 0.0005～0.0015 weight portion
Sodium sulfite 0.2 weight portion～0.8 weight portion
Add injection water to 1000 parts by volume.
The raw material composition of high-energy nutrition transfusion of the present invention is preferably:
Glucose 140.0 weight portions
Fructose 70.0 weight portions
Xylitol 35.0 weight portions
Calcium gluconate 1.5 weight portions
Sodium chloride 1.8 weight portions
Potassium chloride 3.2 weight portions
Magnesium sulfate 0.83 weight portion
Sodium citrate 1.4 weight portions
Citric acid 0.15 weight portion
Potassium dihydrogen phosphate 0.91 weight portion
Zinc sulfate 0.005 weight portion
Copper chloride 0.00057 weight portion
Iron chloride 0.0009 weight portion
Sodium sulfite 0.5 weight portion
Add injection water to 1000 parts by volume.
The raw material composition of high-energy nutrition transfusion of the present invention is preferably:
Glucose 120.0 weight portions
Fructose 90.0 weight portions
Xylitol 45.0 weight portions
Calcium gluconate 1.0 weight portions
Sodium chloride 1.2 weight portions
Potassium chloride 1.6 weight portions
Magnesium sulfate 1.4 weight portions
Sodium citrate 1.0 weight portions
Citric acid 0.08 weight portion
Potassium dihydrogen phosphate 1.42 weight portions
Zinc sulfate 0.0053 weight portion
Copper chloride 0.00052 weight portion
Iron chloride 0.0006 weight portion
Sodium sulfite 0.75 weight portion
Add injection water to 1000 parts by volume.
The raw material composition of high-energy nutrition transfusion of the present invention is preferably:
Glucose 190.0 weight portions
Fructose 55.0 weight portions
Xylitol 30.0 weight portions
Sodium chloride 2.8 weight portions
Potassium chloride 2.2 weight portions
Magnesium sulfate 0.43 weight portion
Sodium citrate 1.8 weight portions
Citric acid 0.20 weight portion
Potassium dihydrogen phosphate 0.6 weight portion
Zinc sulfate 0.0052 weight portion
Copper chloride 0.0006 weight portion
Iron chloride 0.0012 weight portion
Sodium sulfite 0.3 weight portion
Add injection water to 1000 parts by volume.
The raw material composition of high-energy nutrition transfusion of the present invention is preferably:
Glucose 167.0 weight portions
Fructose 83.0 weight portions
Xylitol 42.0 weight portions
Calcium gluconate 1.77 weight portions
Sodium chloride 2.2 weight portions
Potassium chloride 2.6 weight portions
Magnesium sulfate 1.0 weight portions
Sodium citrate 1.7 weight portions
Citric acid 0.18 weight portion
Potassium dihydrogen phosphate 1.3 weight portions
Zinc sulfate 0.0048 weight portion
Copper chloride 0.0006 weight portion
Iron chloride 0.0008 weight portion
Sodium sulfite 0.5 weight portion
Add injection water to 1000 parts by volume.
Get above-mentioned raw materials,, add conventional adjuvant, process high-energy nutrition transfusion according to common process.
The method for preparing of high-energy nutrition transfusion of the present invention is:
Take by weighing each raw material for standby by prescription; In Agitation Tank, adding 80% preparation total amount, temperature is the water for injection more than 80 ℃, adds calcium gluconate, and temperature is controlled at 60～90 ℃ (preferred 70～80 ℃), is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, citric acid, sodium citrate and sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 60～90 ℃ (preferred 70～80 ℃); Add 0.5～1% active carbon, in 60～90 ℃ of absorption 15～30 minutes (preferably adding 1% active carbon, 80 ℃ of absorption 20min); Using the citron acid for adjusting pH value is 4.2～5.0 (being preferably 4.7); Get solution and filter the back with ion-chromatographic determination anion, cations, the content of cation sodium, potassium, magnesium, calcium and anion chlorine, sulfur, phosphorus, glucose acid group, citric acid radical is all between labelled amount 95%～105%, through titanium rod filtering decarbonization; Press formula ratio and add zinc sulfate, copper chloride, iron chloride mixed solution, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and remaining oxygen is less than 3%, 121 ℃ of sterilization 8～18 minutes (preferred 121 ℃ of sterilizations 12 minutes) after the fill, and lamp inspection is qualified promptly to be got;
Wherein said cations assay method is:
Chromatographic condition and system suitability test: with IonPac SCS1 column (150～300mm; Be preferably 250mm) be chromatographic column; With 0.03%～0.06% (being preferably 0.04%) Loprazolam solution is mobile phase, and flow velocity is 0.5～1.0ml/min (being preferably 0.8ml/min), and column temperature is 20 ℃～40 ℃ (being preferably 30 ℃); Electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1～3ml of the present invention; (preferred precision is measured high-energy nutrition transfusion 1ml of the present invention) put in 5～50ml measuring bottle and (preferably put in the 10ml measuring bottle); Thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 66mg～192mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 132mg～376mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, are dissolved in water and are diluted to scale, shake up; Precision is measured 1～3ml, and (preferred precision is measured 1ml) put in 5～50ml measuring bottle and (preferably put in the 10ml measuring bottle), and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and each 5～20 μ l of need testing solution respectively; (preferably precision is measured reference substance solution and each 10 μ l of need testing solution respectively) injected ion chromatograph; Measure; External standard method is calculated each ion concentration, and cation sodium, potassium, magnesium, calcium are all between labelled amount 95%～105% as a result.Chromatogram is seen accompanying drawing 1,2.
Wherein said anion-content assay method is:
Chromatographic condition and system suitability test: with IonPac AS23 column (150～300mm; Be preferably 250mm) be chromatographic column, suppressor: ASRS
ULTRA II 4mm, KOH generator: DIONEX EGC II KOH RFIC; Mobile phase is potassium hydroxide solution; Gradient elution, eluting order is: the time: 0-6～12-6.1～12.5-20～30-20.1～30.5-25～40 minute, (preferred time: 0-6-6.1-20-20.1-25 minute; Time: 0-12-12.5-30-30.5-40 minute, the time was 0-10-10.2-28-28.5-35 minute) concentration of potassium hydroxide solution: 3～10-3～10-25～50-25～50-3～10-3～10mmol/L; (the concentration of preferred potassium hydroxide solution: 3-3-25-25-3-3mmol/L; The concentration of potassium hydroxide solution: 10-10-50-50-10-10mmol/L; The concentration of potassium hydroxide solution: 4-4-40-40-4-4mmol/L) (eluting order is preferably: the time: 0-8-8.1-25-25.1-30 minute, and the concentration of potassium hydroxide solution: 5-5-35-35-5-5mmol/L);
Gradient program such as following table:
Column temperature is 20 ℃～40 ℃ (being preferably 30 ℃), flow velocity: 0.5～1.0ml/min (being preferably 0.8ml/min), and electrochemical detector detects, and number of theoretical plate is pressed potassium (Cl
-) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1～3ml of the present invention (preferred precision is measured high-energy nutrition transfusion 1ml of the present invention); Put in 5～50ml measuring bottle and (preferably put in the 10ml measuring bottle); Thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 109mg～279mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 25mg～75mg, citric acid 38mg～84mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1～3ml, and (preferred precision is measured 1ml) put in 5～50ml measuring bottle and (preferably put in the 10ml measuring bottle), and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and need testing solution 5～20 μ l (preferred precision is measured reference substance solution and each 10 μ l of need testing solution); Inject ion chromatograph; Measure; External standard method is calculated each ion concentration, and anion chlorine, phosphorus, sulfur, glucose acid group, citric acid radical are all between labelled amount 95%～105% as a result.The result sees accompanying drawing 3,4.
Wherein, the relation of above-mentioned weight portion and parts by volume is the relation of g/ml.
Wherein, above-mentioned need testing solution and reference substance solution concentration are consistent.
The present invention supplies with as energy with a certain proportion of glucose, fructose and xylitol, is specially adapted to anti-sugar and measures TNP patient low and needs increase energy, can easily carry out glycemic control; And can improve the rate of ultilization of amino acid that feeds; Under the prerequisite that guarantees the human body energy supply, less to the carbohydrate metabolism influence, fructose is promptly under the insulin deficit situation in filling a prescription simultaneously; Also can play the energy supply effect; The effectively fluctuation of blood sugar control concentration simultaneously, effectively remedy the obstacle that utilizes of its glucose, therefore, when critical illness patient fluid-supplement therapy; The mixed sugar of forming with glucose, fructose and xylitol replaces glucose effectively to reduce blood glucose fluctuation, reduces other metabolism complication that single monosaccharide energy supply brings; And the present invention also replenishes zwitterions such as sodium, potassium, magnesium, calcium, zinc, ferrum, copper, chlorine, sulfur, phosphorus, glucose acid group and citric acid radical in makeup energy and moisture.With guarantee the health electrolyte balance, keep body fluid acid-base balance, necessary nutrient is provided, visible the present invention fills a prescription screening rationally, forms the proportioning science, clinical efficacy is remarkable, and is safe in utilization controlled.
Method for preparing of the present invention takes into full account dissolubility difference and energy efficiency, utilizes water for injection at first to dissolve calcium gluconate, dissolves other inorganic salts again, is xylitol, glucose then, is fructose at last; Whole dosing process does not need heating and cooling basically, avoids thermally sensitive saccharide simultaneously because the long-time decomposes of high temperature; Because it is unstable that glucose, fructose high temperature are met oxygen, so nitrogen is filled in dosing, fill overall process, the control remaining oxygen is less than 3%, and other adds 0.05% antioxidant, to guarantee the not oxidized decomposition variable color of fructose and glucose, generation 5-HMF (blood vessel is had zest); Because microelement concentration is extremely low, and is prone to by activated carbon adsorption, after decarburization, add again to avoid loss so process mixed solution; Packing adopts advanced polypropylene upright flexible bag, safety, the convenient use; Whole process of production is implemented meticulous control; Except pH value of solution, insoluble trace, visible foreign matters etc., also adopt the advanced chromatography of ions, once measure contained whole cationes or anion, quick, exclusive, accurate in the prescription simultaneously; And can not carry out accurate fast measuring to each composition in the intermediate simultaneously with additive method; This technological invention can ensure fully that dosing is accurate, scientific, this shows, advanced, the middle control method of preparation technology of the present invention is accurate, package design is novel.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
The screening test of experimental example 1 antioxidant and preparation technology's the nitrogen that fills is tested
(1) screening test of antioxidant
Prepare high-energy nutrition transfusion by table 1 prescription, embodiment 1 method,
The different formulations of table 1 high-energy nutrition transfusion
After each composition dissolving fully, filter in waiting to fill a prescription, be sub-packed in the 100ml infusion bottle, roll lid, 121 ℃ of sterilization 12min detect each item key index, and the result sees table 2,3:
Table 2 each item index testing result
The result shows that it is necessary adding antioxidant in the prescription, and sodium sulfite preferably, and consumption is 0.5%～1.0%;
Table 3 sample fills nitrogen and whether compares
The result shows that filling nitrogen is that technology is necessary, and particularly nitrogen is filled in fill, confirms that remaining oxygen is less than 3%.
The investigation experiment of experimental example 2 cations assay methods
(1) detectability, quantitative limit and the range of linearity are investigated
Instrument: ICS-90 Chromatography System
Chromatographic column: DIONEX Ionpac SCS1 4*250mm+SCG1 4*50mm
Mobile phase: 0.04% Loprazolam
Flow velocity: 0.8ml/min, column temperature: 30 ℃, sample size: 10 μ l.
Take by weighing sodium chloride 51.42mg, potassium dihydrogen phosphate 91.76mg, magnesium sulfate 25.42mg and calcium gluconate 50.73mg, put in the 50ml measuring bottle, be dissolved in water and be diluted to scale; And the mixed standard solution of stepwise dilution to variable concentrations; Sample introduction is analyzed, statistics, and the result sees table 4:
Detectability, quantitative limit, the range of linearity of table 4 cations assay method
Result of the test shows, cations assay method of the present invention highly sensitive, and the range of linearity is wide, can satisfy each ion quantitative assay requirement.
(2) precision is investigated
Precision is measured by each three parts of high-energy nutrient fluid 1ml, 0.75ml and the 1.3ml of embodiment 1 method preparation, and thin up with the concentration reference substance solution, is measured and indicated content with the legal system phasing to 10ml, and external standard method is calculated, as a result table 5:
The precision of table 5 cations assay method is investigated the result
The above results shows that the precision of the inventive method is good.
(3) accuracy is investigated
Precision takes by weighing sodium chloride, potassium dihydrogen phosphate, magnesium sulfate and calcium gluconate each 9 parts (80%, 100% and 120% each 3 parts); Put in the 25ml measuring bottle, the adjuvant blank solution that adds formula ratio is diluted to scale, and precision is measured 1ml; Thin up is to 10ml; With the concentration reference substance solution, measure the response rate, table 6 as a result with the legal system phasing:
The accuracy of table 6 cations assay method is investigated result-response rate
The above results shows that the accuracy of the inventive method is good.
(4) serviceability test
Instrument: ICS-90 Chromatography System
Chromatographic column: DIONEX Ionpac SCS1 4*250mm+SCG1 4*50mm
Reference substance solution: take by weighing sodium chloride 118mg, potassium dihydrogen phosphate 338mg, magnesium sulfate 42mg and calcium gluconate 75mg, put in the 50ml measuring bottle, add water 40ml; 60 ℃ of ultrasonic 30min make dissolving fully; Be dissolved in water and be diluted to scale, precision is measured 1ml, puts in the 10ml measuring bottle; Thin up is to scale, as reference substance solution;
Need testing solution: precision is measured the high-energy nutrient fluid 1.0ml by the preparation of embodiment 1 method, puts in the 10ml measuring bottle, and thin up is to scale, as need testing solution.
Chromatographic condition: concentration, column temperature and the flow velocity etc. of Loprazolam in the fine setting mobile phase, get need testing solution and the analysis of reference substance solution sample introduction, the result sees table 7:
Table 7 cations mensuration-serviceability test result
Result of the test shows that through regulating buffer salinity, flow velocity and column temperature isochromatic spectrum condition in the mobile phase, four kinds of cation separation are good, and assay is basically identical as a result, the good tolerance of cations assay method of the present invention.
The investigation experiment of experimental example 3 anion-content assay methods
(1) detectability, quantitative limit and the range of linearity are investigated
Instrument: ICS-90 Chromatography System
Chromatographic column: DIONEX Ionpac AS23 4*250mm+AG23 4*50mm
Suppressor: ASRS
RUltraII 4mm;
KOH generator: DIONEX EGC II KOH RFIC
Flow velocity: 0.8ml/min, column temperature: 30 ℃, sample size: 10 μ l.
Mobile phase is potassium hydroxide solution, gradient elution, and eluting order is seen table 8:
Table 8 mobile phase eluting order
Take by weighing sodium chloride 551.68mg, potassium dihydrogen phosphate 649.19mg, magnesium sulfate 390.74mg and calcium gluconate 850.68mg, citric acid 699.52mg; Put in the 50ml measuring bottle; Be dissolved in water and be diluted to scale, and the mixed standard solution of stepwise dilution to variable concentrations, the sample introduction analysis; Statistics, the result sees table 9:
Detectability, quantitative limit and the range of linearity of table 9 anion-content assay method
Result of the test shows, the inventive method highly sensitive, and the range of linearity is wide, can satisfy above-mentioned 5 kinds of anionic quantitative assay requirements.
(2) precision is investigated
Precision is measured by each three parts of high-energy nutrient fluid I 0.7ml, 1.0ml and the 1.3ml of embodiment 1 method preparation, and thin up with the concentration reference substance solution, is measured and indicated content with the legal system phasing to 10ml, and external standard method is calculated, as a result table 10:
The precision of table 10 anion-content assay method is investigated the result
The above results shows that the precision of the inventive method is good.
(3) accuracy is investigated
Take by weighing calcium gluconate 75mg, sodium chloride 215mg, magnesium sulfate 42mg, potassium dihydrogen phosphate 46mg and citric acid 58mg, to the 10ml measuring bottle, be dissolved in water and be diluted to scale, as storing solution, precision is measured 1ml, puts in the 10ml measuring bottle, as reference substance solution; Get contrast storing solution 0.4ml, 0.5ml, 0.7ml respectively and mix with high-energy nutrient fluid 0.3ml, 0.5ml, 0.6ml by the preparation of embodiment 1 method, thin up is to 10ml, and respectively three parts, the sample introduction analysis, calculate recovery rate, table 11 as a result:
The accuracy of table 11 anion-content assay method is investigated the result
The above results shows that the accuracy of the inventive method is good.
(4) serviceability test
Instrument: ICS-90 Chromatography System
Chromatographic column: DIONEX Ionpac AS23 4*250mm+AG23 4*50mm
Suppressor: ASRS
RUltraII 4mm;
KOH generator: DIONEX EGC II KOH RFIC
Reference substance solution: take by weighing sodium chloride 215mg, potassium dihydrogen phosphate 46mg, magnesium sulfate 42mg, calcium gluconate 75mg, citric acid 58mg, put in the 50ml measuring bottle, add water 40ml, 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1ml and is put in the 10ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Need testing solution: precision is measured the high-energy nutrient fluid 1.0ml by the preparation of embodiment 1 method, puts in the 10ml measuring bottle, and thin up is to scale, as need testing solution.
Chromatographic condition A:
Flow velocity: 0.7ml/min, column temperature: 25 ℃, sample size: 5 μ l.
Mobile phase: potassium hydroxide solution, gradient elution, eluting order is seen table 12:
Table 12: serviceability test A--mobile phase eluting order
Chromatographic condition B:
Flow velocity: 0.9ml/min, column temperature: 40 ℃, sample size: 20 μ l.
Mobile phase: potassium hydroxide solution, gradient elution, eluting order is seen table 13:
Table 13 serviceability test B--mobile phase eluting order
Get need testing solution and reference substance solution respectively by the condition sample introduction analysis of serviceability test A and serviceability test B, the result sees table 14:
Table 14 anion-content mensuration-serviceability test result
Experimental result shows: through changing chromatographic condition, adjust column temperature, flow velocity, sample size and eluent gradient, 6 kinds of aniones are separated well, and the assay result coincide, so the good tolerance of anion-content assay method.
Description of drawings
Fig. 1: cation reference substance chromatogram;
Fig. 2: cation sample chromatogram figure;
Fig. 3: anion reference substance chromatogram;
Fig. 4: anion sample chromatogram figure.
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1: the preparation of high-energy nutrition transfusion
Glucose 140.0kg
Fructose 70.0kg
Xylitol 35.0kg
Calcium gluconate 1.5kg
Sodium chloride 1.8kg
Potassium chloride 3.2kg
Magnesium sulfate 0.83kg
Sodium citrate 1.4kg
Citric acid 0.15kg
Potassium dihydrogen phosphate 0.91kg
Zinc sulfate 5.0g
Copper chloride 0.57g
Iron chloride 0.9g
Sodium sulfite 0.5kg
Add the injection water to 1000L;
Take by weighing each raw material for standby by prescription; In Agitation Tank, add 80% preparation total amount, temperature and be 80 ℃ water for injection, add calcium gluconate, temperature is controlled at 70 ℃, is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, sodium citrate, citric acid, sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 70 ℃; Add 1% active carbon, 70 ℃ of absorption 20 minutes; Using the citron acid for adjusting pH value is 4.6; Get and after solution filters anion, cation in the solution are carried out assay by the chromatography of ions, cation sodium is 100.1% of labelled amount, and potassium is 99.9%; Magnesium is 99.8%, and calcium is 99.6%, and anion chlorine is 100.1% of labelled amount; Phosphorus is 100.4%; Sulfur is 99.9%, and the glucose acid group is 98.8%, citric acid radical is 98.7%, through titanium rod filtering decarbonization; Press the mixed solution that formula ratio adds zinc sulfate, copper chloride, iron chloride, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and remaining oxygen is 1.9%, 121 ℃ of sterilization 12 minutes after the fill, lamp inspection, packing.
Embodiment 2: the preparation of high-energy nutrition transfusion
Glucose 120.0kg
Fructose 90.0kg
Xylitol 45.0kg
Calcium gluconate 1.0kg
Sodium chloride 1.2kg
Potassium chloride 1.6kg
Magnesium sulfate 1.4kg
Sodium citrate 1.0kg
Citric acid 0.08kg
Potassium dihydrogen phosphate 1.42kg
Zinc sulfate 5.3g
Copper chloride 0.52g
Iron chloride 0.6g
Sodium sulfite 0.75kg
Add the injection water to 1000L;
Appearance takes by weighing each raw material for standby by prescription; In Agitation Tank, add 80% preparation total amount, temperature and be 80 ℃ water for injection, add calcium gluconate, temperature is controlled at 60 ℃, is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, sodium citrate, citric acid, sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 60 ℃; Add 0.5% active carbon, 60 ℃ adsorbed 30 minutes; Using the citron acid for adjusting pH value is 4.2; Get and after solution filters anion, cation in the solution are carried out assay by the chromatography of ions; Cation sodium be labelled amount 100.7%, potassium is 101.4%, magnesium is 98.9%, calcium is 99.6%; Anion chlorine be labelled amount 99.4%, phosphorus is 97.8%, sulfur is 102.1%, the glucose acid group is 101.5%, citric acid radical is 98.7%, through titanium rod filtering decarbonization; Press the mixed solution that formula ratio adds zinc sulfate, copper chloride, iron chloride, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and 2.3%, 121 ℃ of sterilization of remaining oxygen is 8 minutes after the fill, lamp inspection, packing.
Embodiment 3: the preparation of high-energy nutrition transfusion
Glucose 190.0kg
Fructose 55.0kg
Xylitol 30.0kg
Calcium gluconate 2kg
Sodium chloride 2.8kg
Potassium chloride 2.2kg
Magnesium sulfate 0.43kg
Sodium citrate 1.8kg
Citric acid 0.20kg
Potassium dihydrogen phosphate 0.6kg
Zinc sulfate 5.2g
Copper chloride 0.6g
Iron chloride 1.2g
Sodium sulfite 0.3kg
Add the injection water to 1000L;
Take by weighing each raw material for standby by prescription; In Agitation Tank, add 80% preparation total amount, temperature and be 80 ℃ water for injection, add calcium gluconate, temperature is controlled at 90 ℃, is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, sodium citrate, citric acid, sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 90 ℃; Add 0.5% active carbon, 90 ℃ adsorbed 15 minutes; Using the citron acid for adjusting pH value is 5.0; Get and after solution filters anion, cation in the solution are carried out assay by the chromatography of ions; Cation sodium be labelled amount 100.1%, potassium is 100.7%, magnesium is 99.9%, calcium is 98.6%; Anion chlorine be labelled amount 99.8%, phosphorus is 98.2%, sulfur is 101.0%, the glucose acid group is 100.2%, citric acid radical is 99.5%, through titanium rod filtering decarbonization; Press the mixed solution that formula ratio adds zinc sulfate, copper chloride, iron chloride, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and 2.8%, 121 ℃ of sterilization of remaining oxygen is 15 minutes after the fill, lamp inspection, packing.
Embodiment 4: the preparation of high-energy nutrition transfusion
Glucose 167.0kg
Fructose 83.0kg
Xylitol 42.0kg
Calcium gluconate 1.77kg
Sodium chloride 2.2kg
Potassium chloride 2.6kg
Magnesium sulfate 1.0kg
Sodium citrate 1.7kg
Citric acid 0.18kg
Potassium dihydrogen phosphate 1.3kg
Zinc sulfate 4.8g
Copper chloride 0.6g
Iron chloride 0.8g
Sodium sulfite 0.5kg
Add the injection water to 1000L;
Get above-mentioned raw materials,, add conventional adjuvant, process high-energy nutrition transfusion according to common process.
Embodiment 5: the assay of zwitterion
The cations assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac SCS1 column (200mm * 4mm i.d.) is chromatographic column, is mobile phase with 0.05% Loprazolam solution, and flow velocity is 0.7ml/min, and column temperature is 35 ℃, and electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: the high-energy nutrition transfusion 2ml of the present invention that precision is measured embodiment 1 preparation, to put in the 10ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: take by weighing calcium gluconate 75mg, sodium chloride 118mg, magnesium sulfate 42mg, potassium dihydrogen phosphate 338mg respectively, put in the 50ml measuring bottle, it is an amount of to add water, and 60 ℃ of ultrasonic 30min make dissolving fully, and thin up is to scale; Precision is measured 2ml, and to the 10ml measuring bottle, thin up is to scale, as reference substance solution;
Algoscopy: precision is measured each 20 μ l of reference substance solution and need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, the result contain sodium be labelled amount 100.7%, potassium is 99.3%, magnesium is 100.0%, calcium is 99.2%.
The anion-content assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac AS23 colu mn (200mm * 4mm i.d.) is chromatographic column, suppressor: ASRS
ULTRA II 4mm, the KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution; Gradient elution, eluting order is: the time is 0-10-10.2-28-28.5-35 minute, the concentration of potassium hydroxide solution is 4-4-40-40-4-4mmol/L; Column temperature is 35 ℃; Flow velocity: 0.7ml/min, electrochemical detector detects, and number of theoretical plate is pressed potassium (Cl
-) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: the high-energy nutrition transfusion 2ml of the present invention that precision is measured embodiment 1 preparation, to put in the 10ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 75mg, sodium chloride 215mg, magnesium sulfate 42mg, potassium dihydrogen phosphate 46mg, citric acid 58mg; Put in the 50ml measuring bottle, it is an amount of to add water, and 60 ℃ of ultrasonic 30min make dissolving fully; Thin up shakes up to scale; Precision is measured 2ml, puts in the 10ml measuring bottle, and thin up is to scale, as reference substance solution;
Algoscopy: precision is measured reference substance solution and each 10 μ l of need testing solution; Inject ion chromatograph; Measure, external standard method is calculated each ion concentration, the result chloride for labelled amount 100.1%, phosphorus is 100.9%, sulfur is 100.4%, the glucose acid group is 99.0%, citric acid radical is 98.6%.
Embodiment 6: the content assaying method of zwitterion
The cations assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac SCS1 column (150mm * 4mm i.d.) is chromatographic column, is mobile phase with 0.03% Loprazolam solution, and flow velocity is 1.0ml/min, and column temperature is 20 ℃, and electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: the high-energy nutrition transfusion 1ml of the present invention that precision is measured embodiment 2 preparations, to put in the 50ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg, sodium chloride 91mg, magnesium sulfate 70mg, potassium dihydrogen phosphate 217mg, puts in the 50ml measuring bottle, and it is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1ml, puts in the 50ml measuring bottle, and thin up is to scale; Shake up, process reference substance solution;
Algoscopy: precision is measured each 5 μ l of reference substance solution and need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, as a result sodium be labelled amount 102.7%, potassium is 101.0%, magnesium is 98.9%, calcium is 99.7%;
Wherein said anion-content assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac AS23 column (150mm * 4mm i.d.) is chromatographic column, suppressor: ASRS
ULTRA II 4mm, the KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution; Gradient elution, eluting order is: the time is 0-6-6.1-20-20.1-25 minute, the concentration of potassium hydroxide solution is 3-3-25-25-3-3mmol/L; Column temperature is 20 ℃; Flow velocity: 1.0ml/min, electrochemical detector detects, and number of theoretical plate is pressed potassium (Cl
-) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: the high-energy nutrition transfusion 1ml of the present invention that precision is measured embodiment 2 preparations, to put in the 50ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg, sodium chloride 123mg, magnesium sulfate 70mg, potassium dihydrogen phosphate 71mg, citric acid 40mg; Put in the 50ml measuring bottle, it is an amount of to add water, and 60 ℃ of ultrasonic 30min make dissolving fully; Thin up shakes up to scale; Precision is measured 1ml, puts in the 50ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and each 5 μ l of need testing solution; Inject ion chromatograph; Measure, external standard method is calculated each ion concentration, the result chloride for labelled amount 98.9%, phosphorus is 99.7%, sulfur is 101.0%, the glucose acid group is 102.1%, citric acid radical is 99.3%.
Embodiment 7: the content assaying method of zwitterion
The cations assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac SCS1 column (300mm * 4mm i.d.) is chromatographic column, is mobile phase with 0.06% Loprazolam solution, and flow velocity is 0.5ml/min, and column temperature is 40 ℃, and electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: the high-energy nutrition transfusion 3ml of the present invention that precision is measured embodiment 3 preparations, to put in the 5ml measuring bottle, thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 100mg, sodium chloride 166mg, magnesium sulfate 22mg, potassium dihydrogen phosphate 231mg, puts in the 50ml measuring bottle, and it is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 3ml, puts in the 5ml measuring bottle, and thin up is to scale; Shake up, process reference substance solution;
Algoscopy: precision is measured each 20 μ l of reference substance solution and need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, the result contain sodium be labelled amount 98.9%, potassium is 99.5%, magnesium is 101.1%, calcium is 100.0%.
The anion-content assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac AS23 column (300mm * 4mm i.d.) is chromatographic column, suppressor: ASRS
ULTRA II 4mm, the KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution, gradient elution; Eluting order is: the time is 0-12-12.5-30-30.5-40 minute, and the concentration of potassium hydroxide solution is 10-10-50-50-10-10mmol/L, and column temperature is 40 ℃; Flow velocity: 0.5ml/min, electrochemical detector detects, and number of theoretical plate is by potassium (Cl-) peak; Should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: the high-energy nutrition transfusion 3ml of the present invention that precision is measured embodiment 3 preparations, to put in the 5ml measuring bottle, thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 100mg, sodium chloride 226mg, magnesium sulfate 22mg, potassium dihydrogen phosphate 30mg, citric acid 74mg, puts in the 50ml measuring bottle, and it is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 3ml, puts in the 5ml measuring bottle, and thin up is to scale; Shake up, process reference substance solution;
Algoscopy: precision is measured reference substance solution and each 20 μ l of need testing solution; Inject ion chromatograph; Measure, external standard method is calculated each ion concentration, the result chloride for labelled amount 101.2%, phosphorus is 100.4%, sulfur is 98.7%, the glucose acid group is 98.5%, citric acid radical is 100.1%.
Embodiment 8: the content assaying method of zwitterion
The cations assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac SCS1 column (250mm * 4mm i.d.) is chromatographic column, is mobile phase with 0.04% Loprazolam solution, and flow velocity is 0.8ml/min, and column temperature is 30 ℃, and electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: the high-energy nutrition transfusion 1ml of the present invention that precision is measured embodiment 4 preparations, to put in the 10ml measuring bottle, thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 89mg, sodium chloride 141mg, magnesium sulfate 50mg, potassium dihydrogen phosphate 302mg, puts in the 50ml measuring bottle, and it is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1ml, puts in the 10ml measuring bottle, and thin up is to scale; Shake up, process reference substance solution;
Algoscopy: precision is measured each 10 μ l of reference substance solution and need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, the result contain sodium be labelled amount 99.6%, potassium is 99.2%, magnesium is 100.0%, calcium is 101.5%.
The anion-content assay method is:
Chromatographic condition and system suitability test: instrument: DIONEX ICS-90 Chromatography System; With IonPac AS23 column (250mm * 4mm i.d.) is chromatographic column, suppressor: ASRS
ULTRA II 4mm, the KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution, gradient elution; Eluting order is: the time is 0-8-8.1-25-25.1-30 minute, and the concentration of potassium hydroxide solution is 5-5-35-35-5-5mmol/L, and column temperature is 30 ℃; Flow velocity: 0.8ml/min, electrochemical detector detects, and number of theoretical plate is by potassium (Cl-) peak; Should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: the high-energy nutrition transfusion 1ml of the present invention that precision is measured embodiment 4 preparations, to put in the 10ml measuring bottle, thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 89mg, sodium chloride 212mg, magnesium sulfate 50mg, potassium dihydrogen phosphate 65mg, citric acid 70mg, puts in the 50ml measuring bottle, and it is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1ml, puts in the 10ml measuring bottle, and thin up is to scale; Shake up, process reference substance solution;
Algoscopy: precision is measured reference substance solution and each 10 μ l of need testing solution; Inject ion chromatograph; Measure, external standard method is calculated each ion concentration, the result chloride for labelled amount 100.2%, phosphorus is 99.7%, sulfur is 99.1%, the glucose acid group is 98.8%, citric acid radical is 100.6%.
Claims (9)
1. high-energy nutrition transfusion is characterized in that the raw material of this nutrition transfusion consists of:
Glucose 100～200 weight portions
Fructose 50～100 weight portions
Xylitol 25～50 weight portions
Calcium gluconate 1～2 weight portion
Sodium chloride 1～3 weight portion
Potassium chloride 1.5～3.3 weight portions
Magnesium sulfate 0.3～1.5 weight portion
Sodium citrate 1～2 weight portion
Citric acid 0.05～0.25 weight portion
Potassium dihydrogen phosphate 0.5～1.5 weight portion
Zinc sulfate 0.0045～0.0055 weight portion
Copper chloride 0.0005～0.0006 weight portion
Iron chloride 0.0005～0.0015 weight portion
Sodium sulfite 0.2 weight portion～0.8 weight portion
Add injection water to 1000 parts by volume.
2. high-energy nutrition transfusion as claimed in claim 1 is characterized in that the raw material of this nutrition transfusion consists of:
Glucose 140.0 weight portions
Fructose 70.0 weight portions
Xylitol 35.0 weight portions
Calcium gluconate 1.5 weight portions
Sodium chloride 1.8 weight portions
Potassium chloride 3.2 weight portions
Magnesium sulfate 0.83 weight portion
Sodium citrate 1.4 weight portions
Citric acid 0.15 weight portion
Potassium dihydrogen phosphate 0.91 weight portion
Zinc sulfate 0.005 weight portion
Copper chloride 0.00057 weight portion
Iron chloride 0.0009 weight portion
Sodium sulfite 0.5 weight portion
Add injection water to 1000 parts by volume.
3. high-energy nutrition transfusion as claimed in claim 1 is characterized in that the raw material of this nutrition transfusion consists of:
Glucose 120.0 weight portions
Fructose 90.0 weight portions
Xylitol 45.0 weight portions
Calcium gluconate 1.0 weight portions
Sodium chloride 1.2 weight portions
Potassium chloride 1.6 weight portions
Magnesium sulfate 1.4 weight portions
Sodium citrate 1.0 weight portions
Citric acid 0.08 weight portion
Potassium dihydrogen phosphate 1.42 weight portions
Zinc sulfate 0.0053 weight portion
Copper chloride 0.00052 weight portion
Iron chloride 0.0006 weight portion
Sodium sulfite 0.75 weight portion
Add injection water to 1000 parts by volume.
4. high-energy nutrition transfusion as claimed in claim 1 is characterized in that the raw material of this nutrition transfusion consists of:
Glucose 190.0 weight portions
Fructose 55.0 weight portions
Xylitol 30.0 weight portions
Calcium gluconate 2 weight portions
Sodium chloride 2.8 weight portions
Potassium chloride 2.2 weight portions
Magnesium sulfate 0.43 weight portion
Sodium citrate 1.8 weight portions
Citric acid 0.20 weight portion
Potassium dihydrogen phosphate 0.6 weight portion
Zinc sulfate 0.0052 weight portion
Copper chloride 0.0006 weight portion
Iron chloride 0.0012 weight portion
Sodium sulfite 0.3 weight portion
Add injection water to 1000 parts by volume.
5. high-energy nutrition transfusion as claimed in claim 1 is characterized in that the raw material of this nutrition transfusion consists of:
Glucose 167.0 weight portions
Fructose 83.0 weight portions
Xylitol 42.0 weight portions
Calcium gluconate 1.77 weight portions
Sodium chloride 2.2 weight portions
Potassium chloride 2.6 weight portions
Magnesium sulfate 1.0 weight portions
Sodium citrate 1.7 weight portions
Citric acid 0.18 weight portion
Potassium dihydrogen phosphate 1.3 weight portions
Zinc sulfate 0.0048 weight portion
Copper chloride 0.0006 weight portion
Iron chloride 0.0008 weight portion
Sodium sulfite 0.5 weight portion
Add injection water to 1000 parts by volume.
6. like the arbitrary described high-energy nutrition transfusion of claim 1-5, it is characterized in that getting above-mentioned raw materials,, add conventional adjuvant, process high-energy nutrition transfusion according to common process.
7. like the method for preparing of the arbitrary described high-energy nutrition transfusion of claim 1-5, it is characterized in that this method is:
Take by weighing each raw material for standby by prescription; In Agitation Tank, adding 80% preparation total amount, temperature is the water for injection more than 80 ℃, adds calcium gluconate, and temperature is controlled at 60～90 ℃, is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, citric acid, sodium citrate and sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 60～90 ℃; Add 0.5～1% active carbon, 60～90 ℃ of absorption 15～30 minutes; Using the citron acid for adjusting pH value is 4.2～5.0; Get solution and filter the back with ion-chromatographic determination anion, cations, the content of cation sodium, potassium, magnesium, calcium and anion chlorine, sulfur, phosphorus, glucose acid group, citric acid radical is all between labelled amount 95%～105%, through titanium rod filtering decarbonization; Press formula ratio and add zinc sulfate, copper chloride, iron chloride mixed solution, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and remaining oxygen was less than 3%, 121 ℃ of sterilization 8～18 minutes after the fill, and lamp inspection is qualified promptly to be got;
Wherein said cations assay method is:
Chromatographic condition and system suitability test: with IonPac SCS1 column 150～300mm is chromatographic column; With 0.03%～0.06% Loprazolam solution is mobile phase, and flow velocity is 0.5～1.0ml/min, and column temperature is 20 ℃～40 ℃; Electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1～3ml of the present invention, puts in 5～50ml measuring bottle, and thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 66mg～192mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 132mg～376mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, are dissolved in water and are diluted to scale, shake up; Precision is measured 1～3ml, puts in 5～50ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and each 5～20 μ l of need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, and cation sodium, potassium, magnesium, calcium are all between labelled amount 95%～105% as a result;
Wherein said anion-content assay method is:
Chromatographic condition and system suitability test: with IonPac AS23 column 150～300mm is chromatographic column; Suppressor: ASRS ULTRA II 4mm; The KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution, gradient elution; Eluting order is: the time: 0-6～12-6.1～12.5-20～30-20.1～30.5-25～40 minute, the concentration of potassium hydroxide solution: 3～10-3～10-25～50-25～50-3～10-3～10mmol/L;
Column temperature is 20 ℃～40 ℃, flow velocity: 0.5～1.0ml/min, and electrochemical detector detects, and number of theoretical plate is pressed potassium (Cl
-) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1～3ml of the present invention, puts in 5～50ml measuring bottle, and thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 109mg～279mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 25mg～75mg, citric acid 38mg～84mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1～3ml, puts in 5～50ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and need testing solution 5～20 μ l, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, and anion chlorine, phosphorus, sulfur, glucose acid group, citric acid radical are all between labelled amount 95%～105% as a result.
8. the method for preparing of high-energy nutrition transfusion as claimed in claim 7 is characterized in that this method is:
Take by weighing each raw material for standby by prescription; In Agitation Tank, adding 80% preparation total amount, temperature is the water for injection more than 80 ℃, adds calcium gluconate, and temperature is controlled at 70～80 ℃, is stirred well to whole dissolvings; Open the nitrogen valve, in Agitation Tank, continue deaeration by nitrogen stripping; Add sodium chloride, potassium chloride, magnesium sulfate, potassium dihydrogen phosphate, citric acid, sodium citrate and sodium sulfite successively, stirring makes it to dissolve fully; Add xylitol, glucose and fructose more successively, be stirred to whole dissolvings, add to the full amount of water for injection, temperature is controlled at 70～80 ℃; Add 1% active carbon, 80 ℃ of absorption 20min; Using the citron acid for adjusting pH value is 4.7; Get solution and filter the back with ion-chromatographic determination anion, cations, the content of cation sodium, potassium, magnesium, calcium and anion chlorine, sulfur, phosphorus, glucose acid group, citric acid radical is all between labelled amount 95%～105%, through titanium rod filtering decarbonization; Press formula ratio and add zinc sulfate, copper chloride, iron chloride mixed solution, stirring and evenly mixing is through 0.22 μ m filtering with microporous membrane; Fill is in the polypropylene upright flexible bag, and fill is nitrogen filled protection simultaneously, and remaining oxygen was less than 3%, 121 ℃ of sterilization 12 minutes after the fill, and lamp inspection is qualified promptly to be got.
9. the method for preparing of high-energy nutrition transfusion as claimed in claim 7 is characterized in that this method is:
Wherein said cations assay method is:
Chromatographic condition and system suitability test: with IonPac SCS1 column 250mm is chromatographic column, is mobile phase with 0.04% Loprazolam solution, and flow velocity is 0.8ml/min, and column temperature is 30 ℃, and electrochemical detector detects, and number of theoretical plate is pressed potassium (K
+) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: Na
+→ K
+→ Mg
2+→ Ca
2+
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1ml of the present invention, puts in the 10ml measuring bottle, and thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 66mg～192mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 132mg～376mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, are dissolved in water and are diluted to scale, shake up; Precision is measured 1ml, puts in the 10ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and each 10 μ l of need testing solution respectively, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, and cation sodium, potassium, magnesium, calcium are all between labelled amount 95%～105% as a result;
Wherein said anion-content assay method is:
Chromatographic condition and system suitability test: with IonPac AS23 column 250mm is chromatographic column; Suppressor: ASRS
ULTRA II 4mm; The KOH generator: DIONEX EGC II KOH RFIC, mobile phase is potassium hydroxide solution, gradient elution; Eluting order is: the time: 0-8-8.1-25-25.1-30 minute, and the concentration of potassium hydroxide solution: 5-5-35-35-5-5mmol/L;
Column temperature is 30 ℃, flow velocity: 0.8ml/min, and electrochemical detector detects, and number of theoretical plate is pressed potassium (Cl
-) the peak meter, should be no less than 5000, each peak-to-peak separating degree should meet the requirements peak sequence: C
12H
22O
14 -→ Cl
-→ S → P → C
6H
5O
7 3-
The preparation of need testing solution: precision is measured high-energy nutrition transfusion 1ml of the present invention, puts in the 10ml measuring bottle, and thin up shakes up to scale, processes need testing solution;
The preparation of reference substance solution: precision takes by weighing calcium gluconate 50mg～100mg, sodium chloride 109mg～279mg, magnesium sulfate 15mg～75mg, potassium dihydrogen phosphate 25mg～75mg, citric acid 38mg～84mg; Put in the 50ml measuring bottle; It is an amount of to add water; 60 ℃ of ultrasonic 30min make dissolving fully, and thin up shakes up to scale; Precision is measured 1ml, puts in the 10ml measuring bottle, and thin up shakes up to scale, processes reference substance solution;
Algoscopy: precision is measured reference substance solution and each 10 μ l of need testing solution, injects ion chromatograph, measures, and external standard method is calculated each ion concentration, and anion chlorine, phosphorus, sulfur, glucose acid group, citric acid radical are all between labelled amount 95%～105% as a result.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010529418 CN102451187B (en) | 2010-10-28 | 2010-10-28 | High-energy nutrient infusion solution and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010529418 CN102451187B (en) | 2010-10-28 | 2010-10-28 | High-energy nutrient infusion solution and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102451187A true CN102451187A (en) | 2012-05-16 |
| CN102451187B CN102451187B (en) | 2013-06-12 |
Family
ID=46035130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010529418 Active CN102451187B (en) | 2010-10-28 | 2010-10-28 | High-energy nutrient infusion solution and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102451187B (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102688187A (en) * | 2012-06-12 | 2012-09-26 | 湖北美林药业有限公司 | Fructose medicament composition injection and preparation method thereof |
| CN102793720A (en) * | 2012-08-17 | 2012-11-28 | 江苏正大丰海制药有限公司 | Method for solving crystal substance precipitation of mixed sugar electrolyte injection after disinfection |
| CN102846662A (en) * | 2012-09-18 | 2013-01-02 | 刘近标 | Oral body fluid replenisher |
| CN102846663A (en) * | 2012-09-18 | 2013-01-02 | 刘近标 | Intravenous drip type body fluid replenisher |
| CN107753505A (en) * | 2017-10-31 | 2018-03-06 | 华仁药业股份有限公司 | A kind of Multiple electrolytes injection |
| CN107898808A (en) * | 2017-10-31 | 2018-04-13 | 华仁药业股份有限公司 | Children are with intravenous nutrition preparation |
| 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 |
| CN109001340A (en) * | 2018-09-28 | 2018-12-14 | 湖北远大天天明制药有限公司 | A kind of rapid assay methods of low concentration salt flushing liquor multicomponent content |
| CN109507314A (en) * | 2018-10-29 | 2019-03-22 | 中科谱研（北京）科技有限公司 | The ion chromatography method of sodium, potassium, magnesium, calcium in Amino Acid Compound Injection |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278736A (en) * | 2008-03-28 | 2008-10-08 | 西安力邦制药有限公司 | Balanced enteral total nutrient preparation suitable for nutrition support of Asian population |
-
2010
- 2010-10-28 CN CN 201010529418 patent/CN102451187B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278736A (en) * | 2008-03-28 | 2008-10-08 | 西安力邦制药有限公司 | Balanced enteral total nutrient preparation suitable for nutrition support of Asian population |
Non-Patent Citations (1)
| Title |
|---|
| 李丽: "静脉营养在临床中的应用", 《辽宁药物与临床》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102688187A (en) * | 2012-06-12 | 2012-09-26 | 湖北美林药业有限公司 | Fructose medicament composition injection and preparation method thereof |
| CN102793720A (en) * | 2012-08-17 | 2012-11-28 | 江苏正大丰海制药有限公司 | Method for solving crystal substance precipitation of mixed sugar electrolyte injection after disinfection |
| CN102846662A (en) * | 2012-09-18 | 2013-01-02 | 刘近标 | Oral body fluid replenisher |
| CN102846663A (en) * | 2012-09-18 | 2013-01-02 | 刘近标 | Intravenous drip type body fluid replenisher |
| 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 |
| CN107753505A (en) * | 2017-10-31 | 2018-03-06 | 华仁药业股份有限公司 | A kind of Multiple electrolytes injection |
| CN107898808A (en) * | 2017-10-31 | 2018-04-13 | 华仁药业股份有限公司 | Children are with intravenous nutrition preparation |
| CN109001340A (en) * | 2018-09-28 | 2018-12-14 | 湖北远大天天明制药有限公司 | A kind of rapid assay methods of low concentration salt flushing liquor multicomponent content |
| CN109507314A (en) * | 2018-10-29 | 2019-03-22 | 中科谱研（北京）科技有限公司 | The ion chromatography method of sodium, potassium, magnesium, calcium in Amino Acid Compound Injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102451187B (en) | 2013-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102451187B (en) | High-energy nutrient infusion solution and preparation method thereof | |
| CN101721423B (en) | Bicarbonate physiological balanced solution and preparation method thereof | |
| Greenway et al. | Single-dose pharmacokinetics of different oral sodium nitrite formulations in diabetes patients | |
| MX2012007775A (en) | Nutritive compositions and methods of using same. | |
| CN105747208A (en) | Oral glucose liquid composition | |
| CN101254316B (en) | Blood filtering replacement liquid prescription special for anti congealing | |
| WO2012055371A1 (en) | Pulse-activating sports drink and preparation method therefor | |
| CN101947240A (en) | Mixed sugar electrolyte drug composite injection | |
| CN102451188B (en) | High-energy nutrient infusion solution and preparation method thereof | |
| CN103385889B (en) | Carbohydrate and electrolyte mixed injection and preparation method thereof | |
| CN103284261A (en) | Sports drink containing morinda officinalis and preparation method thereof | |
| CN101571522A (en) | Method for measuring content of taurine in food | |
| CN102526098A (en) | New application of compound sodium chloride potassium chloride injection | |
| CN103690561B (en) | Preparation method of oral liquid | |
| CN104337811A (en) | Repaglinide-metformin hydrochloride tablet and preparing method thereof | |
| CN103800285B (en) | A kind of sodium bicarbonate injection and preparation method thereof | |
| CN105661222A (en) | Whey protein compound drink suitable for drinking of sports groups | |
| CN102652744A (en) | Modified injection containing 13 compound vitamins and preparation method thereof | |
| CN106309481A (en) | Compound potassium aspartate-glucose injection and preparation method thereof | |
| CN102846662A (en) | Oral body fluid replenisher | |
| CN112315902B (en) | Preparation method of iron sucrose injection with low content of volatile iron | |
| CN101721424B (en) | Bicarbonate physiological balanced solution and preparation method thereof | |
| CN104721223B (en) | A kind of injection pharmaceutical composition of compound electrolyte and preparation method thereof | |
| CN105497061B (en) | A kind of electrolyte injection and preparation method thereof without glucose | |
| Tulikoura et al. | Effect of total parenteral nutrition on the zinc, copper, and manganese status of patients with catabolic disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: SICHUAN KELUN PHARMACEUTICAL RESEARCH INSTITUTE CO Free format text: FORMER NAME: KELUN PHARMACEUTICAL RESEARCH CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: 611138 Sichuan science and Technology Development Zone, Wenjiang District, Chengdu City, Xinhua Road, the central section of the two paragraph Patentee after: SICHUAN KELUN DRUG RESEARCH INSTITUTE CO., LTD. Address before: 610500 Sichuan province Chengdu City satellite city industrial development zone two South Road Patentee before: Kelun Pharmaceutical Research Co., Ltd. |