CN1709248A - Lansoprazole lyophilized powder injection and its preparing method - Google Patents
Lansoprazole lyophilized powder injection and its preparing method Download PDFInfo
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- CN1709248A CN1709248A CN 200510040368 CN200510040368A CN1709248A CN 1709248 A CN1709248 A CN 1709248A CN 200510040368 CN200510040368 CN 200510040368 CN 200510040368 A CN200510040368 A CN 200510040368A CN 1709248 A CN1709248 A CN 1709248A
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Abstract
The present invention relates to a lansoprazole freeze-dried powder injection and its preparation method. Said lansoprazole freeze-dried powder injection contains ethylene diamine tetraacetic acid (EDTA) and/or its salt, and is made up by using active component lansoprazole, ethylene diamine tetraacetic acid and/or its salt, stabilizing agent, excipient, pH regulator and injection water through a certain preparation process. Besides, said invention also provides the concrete steps of said preparation process.
Description
Technical field
What a kind of Lansoprazole freeze-dried injection of the present invention and preparation method thereof related to is a kind of Lansoprazole freeze-dried injection that contains ethylenediaminetetraacetic acid (EDTA) and/or its salt and preparation method thereof.
Background technology
The chemical structural formula of lansoprazole:
Chemical name: 2-{[[3-methyl-4-(2,2, the 2-trifluoro ethoxy)-the 2-pyridine] methylene] sulfoxide-1H-benzimidazole lansoprazole (Lansoprazole) be after omeprazole the exploitation the benzimidazole substituent, be the potent inhibitor of the most advanced and sophisticated secretion of parietal cell film inner proton pump, lansoprazole suppresses H specifically
+-K
+The activity of-ATP enzyme, this enzyme are the key enzymes that gastric acid generates.To basic gastric acid with by the irritability gastric acid branch that stimulation causes inhibitory action must be arranged.Lansoprazole is applicable to gastric ulcer, duodenal ulcer, erosive stomach-esophageal reflux disease, helicobacter pylori, Zollimger-ellison syndrome.What show clinical practice is lansoprazole tablet and the blue azoles enteric coated capsule that drawn.
Lansoprazole is unstable under acidic condition, and is destroyed easily in gastric acid, make sheet or capsule after oral absorption slower, and bioavailability is lower.
CN97199638 has disclosed the lyophilized formulations that contains lansoprazole, and its method adds mannitol and meglumin for lansoprazole is dissolved in sodium hydrate aqueous solution, regulates pH to 11.2, makes dried frozen aquatic products then according to a conventional method.
Summary of the invention
From pharmacology, pharmacokinetics angle analysis, by muscle or intravenous injection medication, can avoid Lansoprazole sodium oral destroyed in gastric acid, can make lansoprazole rapidly by blood absorption or directly enter blood again, improve the concentration of lansoprazole in blood and shorten peak time, utilized by human body rapidly, can reach the purpose of rapid onset and raising bioavailability.But because the character instability of lansoprazole own, in sour environment, destroy easily, its properties of Aqueous Solution is also very unstable, often there is the variable color situation to take place, because the influence of above factor brings very big difficulty for the formulating and the processing and preparing of such medicine injection preparation, up to the present, domestic do not have and can go on the market by practical injection preparation, though CN97199638 has disclosed the lyophilized formulations that contains lansoprazole, needs the dedicated solvent with its patent provided during administration.
The present invention seeks at above-mentioned weak point, a kind of Lansoprazole freeze-dried injection and preparation method thereof is provided, adding ethylenediaminetetraacetic acid (EDTA) and/or its salt can make the stability of the solution of preparation improve greatly when the lansoprazole lyophilizing, make lansoprazole after use, can reach rapid onset and the purpose that improves bioavailability, solve the stability problem of the lyophilized formulations of lansoprazole.
The invention provides a kind of new preparation that contains lansoprazole, it is active component with the lansoprazole, add specific stabilizing agent and an amount of excipient, pH regulator agent, water for injection is processed into, can be used for intravenous injection, lansoprazole preparation compositions adopted name is a kind of Lansoprazole freeze-dried injection.
A kind of Lansoprazole freeze-dried injection is characterized in that by active component lansoprazole, stabilizing agent, excipient, pH regulator agent, water for injection formulatedly, and the weight portion proportioning of its each component of raw material is:
Lansoprazole 1
Stabilizing agent 0.05-0.5
Excipient 1-10
PH regulator agent 1-2
The water for injection surplus.
The described stabilizing agent of the prescription of a kind of Lansoprazole freeze-dried injection of the present invention is ethylenediaminetetraacetic acid (EDTA) and/or its salt, select ethylenediaminetetraacetic acid (EDTA) and ethylenediaminetetraacetic acid (EDTA) disodium for use, with ethylenediaminetetraacetic acid (EDTA) disodium the best.
The described excipient of the prescription of a kind of Lansoprazole freeze-dried injection of the present invention, can select for use and be common to medicine injection excipient, select a kind of or mixture in mannitol, lactose, dextran, sorbitol, glucose or the sodium chloride etc. for use, through blood vessel irritation experiment and clinical pharmacodynamic experiment and stability experiment, preferred sodium chloride and mannitol, the analysis-by-synthesis of using.To select mannitol for use is the best.
The described pH regulator agent of the prescription of a kind of Lansoprazole freeze-dried injection of the present invention, can select a kind of or mixture in the sodium hydroxide that is common to the medicine injection, sodium carbonate, the sodium bicarbonate solution for use, through blood vessel irritation experiment and clinical pharmacodynamic experiment and stability experiment, preferably select sodium hydroxide solution for use.
The preparation method of a kind of Lansoprazole freeze-dried injection of the present invention is as follows:
Take by weighing a certain amount of active component lansoprazole, ethylenediaminetetraacetic acid (EDTA) and/or its salt, excipient, sterile water for injection mixing by aforementioned formula weight portion proportioning, regulate pH10.0～11.5 with the pH regulator agent, through the filtering with microporous membrane of 0.22 μ m, press the fill of preparation specification in vial down at aseptic.Send in the freezer dryer.Lyophilization, pre-freeze-40 ℃～-35 ℃, 5～7 hours, about 20～30 hours of the low-temperature vacuum drying that slowly heats up then continues to be warming up to 10 ℃, vacuum drying 2～4 hours again, make dried frozen aquatic products moisture reach standard-required, outlet, gland promptly get lansoprazole freeze-dried injection for injection.
Use prescription provided by the present invention and preparation method to make a kind of Lansoprazole freeze-dried injection and can be used for intravenous injection.
A kind of Lansoprazole freeze-dried injection of the present invention has good stability, and can reach the shelf-life more than 2 years, directly with water for injection or sodium chloride for injection dissolving, has avoided the use dedicated solvent during use.
A kind of Lansoprazole freeze-dried injection of the present invention is compared with the sheet (or enteric coated capsule) of prior art, has the following advantages:
1, Lansoprazole freeze-dried injection of the present invention is rapid-action.Lansoprazole 10mg is used in general intravenous injection, lansoprazole blood drug level in the blood reaches peak concentration rapidly, Lansoprazole for injecting 10mg is used in intramuscular injection, peak reaching time of blood concentration is 0.5 hour, and the peak time of the blood drug level of the Lansoprazole enteric-coated tablet of use Isodose is 2 hours.
2, Lansoprazole freeze-dried injection of the present invention is faster to the healing speed of patients with peptic ulcer, and cure rate is also higher.In 1 week, the cure rate of Lansoprazole for injecting is 61%, is 35% and use the cure rate of the lansoprazole tablet of Isodose, and when 2 weeks, the cure rate of Lansoprazole for injecting is 84%.
3, preparation of the present invention is the injection freeze-dried product, and moisture is low, and acid or alkali environment is constant, and stability of formulation improves.The content of catabolite is less than 1% in two years.
4, preparation production technique of the present invention is simple, and quality is controlled easily.
5, preparation of the present invention is easy to carry, stores and transports.
The specific embodiment:
Now the specific embodiment of the present invention is described with embodiment.
Embodiment 1:30mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 30g
EDTA disodium 5g
Mannitol 50g
Sodium hydroxide 30g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium hydroxide.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
Embodiment 2:10mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 10g
EDTA disodium 0.5g
Mannitol 100g
Sodium hydroxide 10g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium hydroxide.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
Embodiment 3:60mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 60g
EDTA disodium 30g
Mannitol 120g
Sodium hydroxide 120g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium hydroxide.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
Embodiment 4:30mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 30g
Ethylenediaminetetraacetic acid 5g
Dextran 50g
Sodium bicarbonate solution 30g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium bicarbonate solution.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
Embodiment 5:10mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 10g
Ethylenediaminetetraacetic acid 0.5g
Sorbitol 100g
Sodium carbonate 10g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium carbonate.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
Embodiment 6:60mg/ bottle specification, 1000 Lansoprazole freeze-dried injection prescriptions:
Lansoprazole 60g
Ethylenediaminetetraacetic acid 30g
Glucose or sodium chloride 120g
Sodium carbonate, sodium bicarbonate solution 120g
Water for injection adds to 2000ml, makes 1000 altogether
Its preparation process is as follows:
A. press preparation prescription batching, add 1600ml water for injection after, stir, be adjusted to pH10.0～11.5, stirring and dissolving with pH regulator agent sodium carbonate, sodium bicarbonate solution.
B. with the solution of pH10.0～11.5 that prepare, with 0.22 μ m filtering with microporous membrane degerming, be stored in the receiver, measure intermediate content, add injection water 400ml to recipe quantity at aseptic condition.
C. medicinal liquid is sub-packed in the 10ml cillin bottle every bottled 2ml, half tamponade; sabot is sent in the freeze drying box, opens freeze dryer; utilize conduction oil that the product relaxing the bowels with purgatives of warm nature is fallen, reduce to-30～35 ℃, kept this temperature 2 hours when temperature; shut down coldly, the open cold condenser is when condenser temperature is lower than-40 ℃; open vacuum system, open butterfly valve, begin the distillation that heats up; per hour heat up and be advisable, when the final drying temperature is 30 ℃, be incubated 2～4 hours until drying at 2～4 ℃.From plug, put vacuum, outlet, gland is promptly made Lansoprazole freeze-dried injection, checks packing.
1. the lansoprazole freeze-dried injection for injection of producing with above-mentioned preparation method is pressed Lansoprazole for injecting quality standard (draft) check, the results are shown in Table 1.
Three batches of assays of table 1 lansoprazole freeze-dried injection for injection
| Lot number | Outward appearance | Clarity | PH value | Moisture (%) | Labelled amount (%) | Related substance (HPLC, %) |
| 20030822 20030828 20030903 | White loose block and powder white loose block and powder white loose block and powder | Up to specification up to specification | 10.81 10.94 11.05 | ??2.54 ??2.09 ??2.38 | ??99.54 ??101.7 ??98.64 | 0.35 0.34 0.35 |
2, the lansoprazole freeze-dried injection for injection stability test that carries out according to the Lansoprazole for injecting quality standard the results are shown in Table 2, table 3, table 4.
Table 2 lansoprazole freeze-dried injection for injection influence factor tests stability (lot number: 20030822)
| The placement condition | Standing time (my god) | Character | Clarity of solution and color | Basicity | Labelled amount (%) | Related substance (%) |
| Illumination | ??0 ??5 ??10 | White loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification is colourless | ?10.81 ?10.84 ?10.82 | ??99.54 ??99.22 ??99.75 | ??0.35 ??0.47 ??0.52 |
| ? 40℃ ? | ??5 ? ??10 | White loose block and powder white loose block and powder | The clarification achromaticity and clarification is colourless | ?10.81 ? ?10.83 | ??99.55 ? ??99.48 | ??0.48 ? ??0.47 |
| ? 60℃ ? | ??5 ? ??10 | White loose block and powder white loose block and powder | The clarification achromaticity and clarification is colourless | ?10.80 ? ?10.82 | ??99.61 ? ??99.29 | ??0.47 ? ??0.50 |
| ? 4℃ ? | ??5 ? ??10 | White loose block and powder white loose block and powder | The clarification achromaticity and clarification is colourless | ?10.82 ? ?10.81 | ??99.34 ? ??99.68 | ??0.48 ? ??0.50 |
The accelerated test stability of table 3 lansoprazole freeze-dried injection for injection (40 ℃ ± 2 ℃, RH75% ± 5%)
| Lot number | Standing time (moon) | Character | Clarity of solution and color | Basicity | Labelled amount (%) | Related substance (%) |
| ? ? ??20030822 ? ? | 0 1 2 3 6 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??10.81 ??10.83 ??10.80 ??10.81 ??10.82 | ??99.54 ??99.36 ??99.78 ??99.24 ??99.68 | ??0.35 ??0.34 ??0.42 ??0.39 ??0.33 |
| ? ? ??20030828 ? ? | 0 1 2 3 6 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??10.94 ??10.92 ??10.89 ??10.95 ??10.87 | ??101.7 ??101.5 ??101.8 ??101.6 ??101.7 | ??0.34 ??0.34 ??0.41 ??0.40 ??0.34 |
| ? ? ??20030903 ? ? | 0 1 2 3 6 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??11.05 ??11.03 ??11.07 ??11.04 ??11.09 | ??98.64 ??98.44 ??98.77 ??98.85 ??98.24 | ??0.35 ??0.36 ??0.40 ??0.43 ??0.34 |
The long term test stability of table 4 lansoprazole freeze-dried injection for injection
| Lot number | Standing time (moon) | Character | Clarity of solution and color | Basicity | Labelled amount (%) | Related substance (%) | Aseptic |
| ? ? 20030822 ? ? | 0 3 ? 6 9 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??10.81 ??10.83 ? ??10.82 ??10.80 | ??99.54 ??99.44 ? ??99.35 ??99.58 | ??0.35 ??0.44 ? ??0.34 ??0.35 | Up to specification |
| ? 20030828 ? ? | 0 3 ? 6 9 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??10.94 ??10.95 ? ??10.89 ??10.90 | ??101.7 ??101.4 ? ??101.3 ??101.6 | ??0.34 ??0.43 ? ??0.35 ??0.35 | Up to specification |
| ? 20030903 ? ? | 0 3 ? 6 9 | White loose block and powder white loose block and powder white loose block and powder white loose block and powder | Clarification achromaticity and clarification achromaticity and clarification achromaticity and clarification is colourless | ??11.05 ??11.07 ? ??11.03 ??11.06 | ??98.64 ??98.53 ? ??98.74 ??98.48 | ??0.35 ??0.43 ? ??0.35 ??0.33 | Up to specification |
3, the stability test of lansoprazole freeze-dried injection for injection in transfusion sees Table 5
3.1 the stability of lansoprazole freeze-dried injection for injection in 0.9% sodium chloride injection
Get 1 of lansoprazole freeze-dried injection for injection, join in 100ml 0.9% sodium chloride injection, place under the room temperature, solution appearance character, clarity, pH value, content and related substance inspection were investigated in sampling respectively in the 0th, 1,2,4,6,8 hour.The results are shown in Table 5
Study on the stability (the lot number: 20030822) of table 5 lansoprazole freeze-dried injection for injection in sodium chloride injection
| Time (h) | Appearance character | Clarity | PH value | Labelled amount (%) | Related substance (%) |
| ????0 ????1 ????2 ????4 ????6 ????8 | Colorless cleared solution colorless cleared solution colorless cleared solution colorless cleared solution colorless cleared solution colorless cleared solution | Up to specification up to specification | ??9.92 ??9.90 ??9.94 ??9.95 ??9.93 ??9.92 | ????100.0 ????100.2 ????100.0 ????99.59 ????99.98 ????99.86 | ????0.26 ????0.24 ????0.27 ????0.24 ????0.24 ????0.26 |
Experimental result shows: lansoprazole freeze-dried injection for injection is placed in 8 hours every investigation index and is not seen significant change in the 100ml0.9% sodium chloride injection under room temperature.
3.2 the stability of lansoprazole freeze-dried injection for injection in 5% glucose injection
Get 1 of lansoprazole freeze-dried injection for injection, join in 100ml 5% glucose injection, place under the room temperature, solution appearance character, clarity, pH value, content and related substance inspection were investigated in sampling respectively in the 0th, 2,4,6,8 hour.The results are shown in Table 6.
Study on the stability (the lot number: 20030822) of table 6 lansoprazole freeze-dried injection for injection in glucose injection
| Time (h) | Appearance character | Clarity | PH value | Labelled amount (%) | Related substance (%) |
| ????0 ????2 ????4 ????6 ????8 | The little yellow settled solution of the little yellow settled solution of the little yellow settled solution of colorless cleared solution colorless cleared solution | Up to specification up to specification | ????8.89 ????8.91 ????8.90 ????8.88 ????8.92 | ????100.0 ????100.2 ????99.52 ????99.71 ????99.71 | ????0.43 ????0.31 ????0.32 ????0.37 ????0.34 |
Experimental result shows: lansoprazole freeze-dried injection for injection is dissolved in the 100ml5% glucose injection, places 2 hours down in room temperature condition, and every investigation index is not seen significant change; After room temperature condition is down placed 4 hours, slightly change except that color, 4.7 ' peak slightly increases in the related substance, all other are investigated indexs and are not seen significant change.
This product can adopt 0.9% sodium chloride injection and 5% glucose injection dissolving posterior vein to instil when clinical use, but should use up in 2 hours when adopting the dissolving of 5% glucose injection.By aforementioned stable investigation and quality inspection, prove that the lansoprazole freeze-dried injection for injection quality is good, stability is high.
The animal safety result of the test of this lansoprazole freeze-dried injection for injection is as follows:
Test name: lansoprazole freeze-dried injection for injection local toxicity and safety testing
Test unit: Nanjing Medical University's clinical pharmacology institute
Pilot project: local vascular irritation test, hemolytic test, sensitivity test
Test method:
A. local vascular irritation test: by perusal rabbit auricular vein infusion injection Lansoprazole sodium medicinal liquid, its part has or not redness, hyperemia, blood vessel variable color, edema, scleroma and downright bad phenomenon and histopathologic examination to estimate this product local irritation.
B. hemolytic test: have or not haemolysis and agglutination to estimate to the rabbit erythrocyte that exsomatizes by observing medicine.
C. sensitivity test:, cause that the Cavia porcellus anaphylaxis estimates by observing guinea pig intraperitoneal injection Lansoprazole for injecting sodium freeze-dried powder injection medicinal liquid.
Result of the test shows that lansoprazole freeze-dried injection for injection is injected nonirritant to rabbit vein, and tame rabbit erythrocyte is not had haemolysis and agglutination, Cavia porcellus is injected this medicine do not have irritated reaction.
Claims (8)
1, a kind of Lansoprazole freeze-dried injection is characterized in that by active component lansoprazole, stabilizing agent, excipient, pH regulator agent, water for injection formulatedly, and the weight portion proportioning of its each component of raw material is:
Lansoprazole 1
Stabilizing agent 0.05-0.5
Excipient 1-10
PH regulator agent 1-2
The water for injection surplus.
2, a kind of Lansoprazole freeze-dried injection according to claim 1 is characterized in that described stabilizing agent is ethylenediaminetetraacetic acid and/or its salt.
3, a kind of Lansoprazole freeze-dried injection according to claim 2 is characterized in that described stabilizing agent selects ethylenediaminetetraacetic acid and disodiumedetate for use.
4, a kind of Lansoprazole freeze-dried injection according to claim 1 is characterized in that excipient in the described prescription selects a kind of or mixture in mannitol, lactose, dextran, sorbitol, glucose or the sodium chloride for use.
5, a kind of Lansoprazole freeze-dried injection according to claim 4 is characterized in that the excipient in the described prescription is selected mannitol for use.
6, a kind of Lansoprazole freeze-dried injection according to claim 1 is characterized in that pH regulator agent in the described prescription is a kind of or mixture in sodium hydroxide, sodium carbonate, the sodium bicarbonate solution.
7, a kind of Lansoprazole freeze-dried injection according to claim 6 is characterized in that sodium hydroxide solution is selected in the pH regulator agent in the described prescription for use.
8, the preparation method of the described a kind of Lansoprazole freeze-dried injection of claim 1 is characterized in that its preparation method is as follows:
Take by weighing a certain amount of active component with lansoprazole by formula ratio, ethylenediaminetetraacetic acid and/or its salt, excipient, sterile water for injection mixes, regulate pH10.0～11.5 with the pH regulator agent, membrane filtration through 0.22 μ m, press the fill of preparation specification in vial down at aseptic, send in the freezer dryer, lyophilization, pre-freeze-40 ℃～-35 ℃, 5～7 hours, about 20～30 hours of the low-temperature vacuum drying that slowly heats up then continued to be warming up to 10 ℃ again, vacuum drying 2～4 hours, make dried frozen aquatic products reach requirement, outlet, gland promptly gets Lansoprazole for injecting;
The weight portion proportioning of its each component of raw material is:
Lan Suola 1
Stabilizing agent 0.05-0.5
Excipient 1-10
PH regulator agent 1-2
The water for injection surplus,
Described stabilizing agent is ethylenediaminetetraacetic acid and/or its salt, select ethylenediaminetetraacetic acid and disodiumedetate for use, excipient in the described prescription is selected a kind of or mixture in mannitol, lactose, dextran, sorbitol, glucose or the sodium chloride for use, and the pH regulator agent in the described prescription is a kind of or mixture in sodium hydroxide, sodium carbonate, the sodium bicarbonate solution.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829065A (en) * | 2010-06-11 | 2010-09-15 | 山东罗欣药业股份有限公司 | Lansoprazole composition freeze-dried powder for injection |
| CN102151265A (en) * | 2011-05-10 | 2011-08-17 | 江苏奥赛康药业有限公司 | Lansoprazole composition for injection |
| CN102451181A (en) * | 2010-10-26 | 2012-05-16 | 海南中化联合制药工业股份有限公司 | Prescription and preparation method of injection lansoprazole |
| CN102617555A (en) * | 2012-03-20 | 2012-08-01 | 西藏易明西雅生物医药科技有限公司 | Preparation method of lansoprazole |
| CN101129368B (en) * | 2007-08-23 | 2012-10-10 | 常州市第四制药厂有限公司 | Freeze-dried powder needle containing lansoprazole |
| CN102920703A (en) * | 2011-12-06 | 2013-02-13 | 悦康药业集团有限公司 | Preparation method for lansoprazole for injection |
| CN103040737A (en) * | 2013-01-10 | 2013-04-17 | 罗诚 | Drug composition containing lansoprazole compound and preparation method of drug composition |
| CN104019635A (en) * | 2014-06-19 | 2014-09-03 | 上海慈瑞医药科技有限公司 | Drying process for lansoprazole bulk drug |
| CN105878193A (en) * | 2016-05-31 | 2016-08-24 | 济南康和医药科技有限公司 | Lansoprazole freeze-dried powder for injection and preparation method thereof |
-
2005
- 2005-06-02 CN CN 200510040368 patent/CN1709248A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129368B (en) * | 2007-08-23 | 2012-10-10 | 常州市第四制药厂有限公司 | Freeze-dried powder needle containing lansoprazole |
| CN101829065A (en) * | 2010-06-11 | 2010-09-15 | 山东罗欣药业股份有限公司 | Lansoprazole composition freeze-dried powder for injection |
| CN102451181A (en) * | 2010-10-26 | 2012-05-16 | 海南中化联合制药工业股份有限公司 | Prescription and preparation method of injection lansoprazole |
| CN102151265A (en) * | 2011-05-10 | 2011-08-17 | 江苏奥赛康药业有限公司 | Lansoprazole composition for injection |
| CN102920703A (en) * | 2011-12-06 | 2013-02-13 | 悦康药业集团有限公司 | Preparation method for lansoprazole for injection |
| CN102617555B (en) * | 2012-03-20 | 2014-05-21 | 北京易明康元医药科技有限公司 | Preparation method of lansoprazole |
| CN102617555A (en) * | 2012-03-20 | 2012-08-01 | 西藏易明西雅生物医药科技有限公司 | Preparation method of lansoprazole |
| CN103040737A (en) * | 2013-01-10 | 2013-04-17 | 罗诚 | Drug composition containing lansoprazole compound and preparation method of drug composition |
| CN103040737B (en) * | 2013-01-10 | 2014-06-18 | 罗诚 | Drug composition containing lansoprazole compound and preparation method of drug composition |
| CN104019635A (en) * | 2014-06-19 | 2014-09-03 | 上海慈瑞医药科技有限公司 | Drying process for lansoprazole bulk drug |
| CN104019635B (en) * | 2014-06-19 | 2015-05-27 | 上海慈瑞医药科技有限公司 | Drying process for lansoprazole bulk drug |
| CN105878193A (en) * | 2016-05-31 | 2016-08-24 | 济南康和医药科技有限公司 | Lansoprazole freeze-dried powder for injection and preparation method thereof |
| CN105878193B (en) * | 2016-05-31 | 2018-08-31 | 济南康和医药科技有限公司 | A kind of Lansoprazole freeze-dried powder for injection and preparation method thereof |
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