CN101011397A - Pantoprazole sodium freeze dried injection and preparation method thereof - Google Patents
Pantoprazole sodium freeze dried injection and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a method for preparing batoracosodium freeze dried, whose pH value is 9.5-11.5. And the invention comprises 1 deal of batoracosodium, 0.5-1 deals of supporting agent, 0-0.06 deals of weak-acid strong-alkali salt, and some inorganic alkali. And the preparation comprises that 1, preparing materials; 2, dissolving the supporting agent and weak-acid strong-alkali salt via injection water, using inorganic salt to adjust the pH value to 9.5-11.5, adding batoracosodium, dissolving and using inorganic salt to adjust the pH value to 9.5-11.5; 3, filtering; 4, freezing and drying to obtain the final product. The invention can be used treat peptic ulcer, ulcer bleed, or the like.
Description
Technical field
The present invention relates to medicine of freeze-dried powder dosage form and preparation method thereof, particularly relate to a kind of Pantoprazole Sodium Freezing Injectable Powder And Its Preparation Method.
Background technology
Pantoprazole Sodium (Pantoprazole Sodium), chemical name is: 5-difluoro-methoxy-2-[(3,4-dimethoxy-2-pyridine radicals) methyl]-sulfinyl-1H-benzimidazole sodium salt.Pantoprazole Sodium is a proton pump inhibitor class antiulcerative.The pantoprazole sodium injection is mainly used in digestive ulcerative bleeding, under acute gastric mucosa damage that nonsteroidal antiinflammatory drug causes and the stress state after ulcer massive hemorrhage and general anesthesia or the major operation and weak comatose patient prevent treatment of conditions such as regurgitation of gastric juice merging aspiration pneumonitis.The poor stability of Pantoprazole Sodium, all very sensitive to light, heat, oxygen, water etc., especially when acid condition, the destructive variation can take place in its chemical constitution, variable color and polymerism occur, thereby is unsuitable for making water agent for injecting, is fit to make lyophilized injectable powder.
In the patent documentation in the past, the report of existing many relevant freeze-dried powder injection of pantoprazole sodium, patent (the application number: disclosed 01819379.X) a kind of, and the freeze-dried powder injection of pantoprazole sodium made of the aqueous solution lyophilization of sodium hydroxide and/or sodium carbonate that is called " freeze-dried pantoprazole preparation and pantoprazole injection " as name with pantoprazole, ethylenediaminetetraacetic acid and/or its suitable salt; Name is called the patent application (application number: disclosed a kind of freeze-dried powder injection of pantoprazole sodium 99112872.9) of " Pantoprazole Sodium Freezing Injectable Powder And Its Preparation Method ", the prescription of this injection is by Pantoprazole Sodium (1 part), lyophilized powder proppant (1-5 part), complexing of metal ion agent (0.05-2 part) and pH regulator agent constitute; Name is called the patent application (application number: disclosed a kind of by Pantoprazole Sodium (1 part) 200510023469.8) of " Pantoprazole Sodium Freezing Injectable Powder And Its Preparation Method ", excipient (0-0.125 part), weak acid strong alkali salt (0.075-0.125 part), disodium edetate (0.025-0.375 part) and an amount of inorganic alkaline agent prepare the method for freeze-dried powder injection of pantoprazole sodium.In the above-mentioned report, application number is that the preparation method that discloses in 99112872.9 and 200510023469.8 patent applications all is added with edetic acid (being ethylenediaminetetraacetic acid) and/or its salt, its objective is that visible foreign matters and particulate matter in order to guarantee product can conform with the safety criterion that human body uses, and increase the stability of product in put procedure.But this point has the suspicion that conflicts with the patent (patent No. 01819379.X) that China has been authorized; And, edetic acid and/or its salt after infusion enters human body, have with blood in the calcium ion complexation cause the potential side effect of bone calcium loss.
Summary of the invention
The purpose of this invention is to provide the freeze-dried powder injection of pantoprazole sodium that a kind of side effect is little, stability is high, preparation cost is cheap.
For achieving the above object, the present invention takes following design: a kind of freeze-dried powder injection of pantoprazole sodium, pH value are 9.5-11.5, and its prescription comprises following components by weight portion:
1 part of Pantoprazole Sodium,
Proppant 0.5-1 part,
Weak acid strong alkali salt 0-0.06 part,
Inorganic base is an amount of;
Wherein, proppant can be water solublity proppant such as mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt can be sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate etc.; Inorganic base can be sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate or sodium hydrogen phosphate etc.
The pH value of described freeze-dried powder injection of pantoprazole sodium is preferably 10.5-11, and it is preferably filled a prescription and comprises following components by weight portion:
1 part of Pantoprazole Sodium,
0.89 part of proppant,
0.045 part of weak acid strong alkali salt,
Inorganic base is an amount of;
Wherein, proppant can be water solublity proppant such as mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt can be sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate etc.; Inorganic base can be sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium hydrogen phosphate etc.The preferred prescription of described freeze-dried powder injection of pantoprazole sodium comprises following components by weight portion:
1 part of Pantoprazole Sodium,
0.89 part in mannitol,
0.045 part of sodium citrate,
Sodium hydroxide is an amount of.
In above-mentioned prescription, the effect of inorganic base is used for adjusting pH value, and its consumption those skilled in the art can adjust according to practical situation, as long as the pH value of freeze-dried powder injection of pantoprazole sodium can be maintained 9.5-11.5.
Second purpose of the present invention provides a kind of preparation method of above-mentioned freeze-dried powder injection of pantoprazole sodium.
The preparation method of freeze-dried powder injection of pantoprazole sodium provided by the present invention may further comprise the steps:
1) gets material by following parts by weight proportioning: proppant 0.5-1 part, weak acid strong alkali salt 0-0.06 part, 1 part of Pantoprazole Sodium; Described proppant is mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt is sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate;
2) proppant and weak acid strong alkali salt are dissolved with water for injection, to 9.5-11.5, add Pantoprazole Sodium with the inorganic base adjust pH, the dissolving back uses the inorganic base adjust pH to 9.5-11.5; Described inorganic base is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate or sodium hydrogen phosphate;
3) filtration sterilization;
4) lyophilizing obtains freeze-dried powder injection of pantoprazole sodium.
In above-mentioned preparation method, proppant in the step 1), the ratio of weight and number of weak acid strong alkali salt and Pantoprazole Sodium is preferably 0.89: 0.045: 1; Proppant is preferably mannitol, and weak acid strong alkali salt is preferably sodium citrate, and inorganic base is preferably sodium hydroxide.
The Pantoprazole Sodium pH value is preferably 10.5-11.
The aperture of filtering used filter membrane in the step 3) is 0.1-0.3 μ m, is preferably 0.22 μ m.
Avoid the influence of air oxidation for the freeze-dried powder injection of pantoprazole sodium product that uses method for preparing, preferably with the airtight preservation of freeze-dried powder injection of pantoprazole sodium product that obtains in the described step 4), more preferably vacuum is preserved.
The present invention also provides a kind of pantoprazole sodium injection medicine box.
Pantoprazole sodium injection medicine box provided by the present invention includes above-mentioned freeze-dried powder injection of pantoprazole sodium.
Be convenient and use that described medicine box also includes solvent for injection, as the 0.9%NaCl injection etc.
The dosage of above-mentioned freeze-dried powder injection of pantoprazole sodium was generally 40-80mg/ days, and be 3-5 days the course of treatment.
The present invention provides a kind of Pantoprazole Sodium Freezing Injectable Powder And Its Preparation Method by meticulous screening, reasonable compatibility.Freeze-dried powder injection of pantoprazole sodium provided by the present invention has the following advantages: 1) supplementary product consumption is less: as shown in table 1, compare with existing freeze-dried powder injection of pantoprazole sodium, do not add the complexing of metal ion agent, relatively large frozen-dried supporting agents such as mannitol have been added, one side mannitol etc. are as frozen-dried supporting agent, make the mouldability of product relatively good, also reduce simultaneously the contact area of medicine and plug, avoided the influence of plug to medicine, on the other hand, mannitol etc. also can play the effect of complexing of metal ion agent, can reduce the influence of metal ion, the potential side effect of also having avoided ethylenediaminetetraacetic acid and/or its suitable complexing of metal ion agent such as salt to cause simultaneously to stability of drug products; In addition,, guaranteed that visible foreign matters (particulate matter) project of product is qualified, and guaranteed the stability of product effectively, avoided the generation of side effect by adding other composition; 2) stability is high: add inorganic bases such as an amount of sodium hydroxide, pH value is strict controlled between the 9.5-11.5, the consumption that improves simultaneously suitably frozen-dried supporting agent such as mannitol has all reduced separating out of Pantoprazole Sodium, experimental result show freeze-dried powder injection of pantoprazole sodium of the present invention stability significantly be better than existing like product; 3) with low cost: because except that frozen-dried supporting agents such as mannitol, the consumption of its adjuvant all is lower than existing like product, thereby low production cost, when having alleviated patient's slight illness, also can reduce patient's financial burden, is convenient to apply; 4) preparation technology is simple, and is low for equipment requirements, is easy to carry out suitability for industrialized production.The present invention will be at digestive ulcerative bleeding, plays a great role in the treatment of diseases such as ulcer massive hemorrhage under acute gastric mucosa damage that nonsteroidal antiinflammatory drug causes and the stress state.
The contrast of table 1 freeze-dried powder injection of pantoprazole sodium of the present invention and existing like product composition
| Product of the present invention (preferably) | 99112872.9 | 200510023469.8 | Germany's Byk Gulden pharmaceutical factory product | |
| Pantoprazole Sodium | 1 part | 1 part | 1 part | 1 part |
| Proppant (mannitol) | 0.89 part | 1 to 5 |
0 to 0.125 part | Do not have |
| Metal chelating agent | Do not have | 0.05 to 2 parts | EDTA0.025 part to 0.0375 part | EDTA0.0005 part to 0.25 part |
| Weak acid strong alkali salt (sodium citrate) | 1.0.045 part 2. does not add | Do not have | 0.075 part is to 0.125 part | Do not have |
| Inorganic base | Have | Have | Have | Have |
Below in conjunction with specific embodiment the present invention is described in further details.
Description of drawings
Fig. 1 is the technological process of production figure of freeze-dried powder injection of pantoprazole sodium
Fig. 2 is the freeze-drying curve of freeze-dried powder injection of pantoprazole sodium
The specific embodiment
Method therefor is conventional method if no special instructions among the following embodiment.
The preparation of embodiment 1, freeze-dried powder injection of pantoprazole sodium and detection thereof
One, preparation freeze-dried powder injection of pantoprazole sodium
With reference to process chart shown in Figure 1, with 1000 bottles of (labelled amount: contain the 40g Pantoprazole Sodium) freeze-dried powder injection of pantoprazole sodium of method preparation of the present invention, detailed process may further comprise the steps:
1) gets material by following weight: mannitol 40.00g, sodium citrate 2.00g, Pantoprazole Sodium 44.72g;
2) mannitol and sodium citrate are dissolved with 1800g water for injection, with 2mol/L sodium hydroxide solution adjust pH to 10.5, add Pantoprazole Sodium, fully dissolving back reuse 2mol/L sodium hydroxide solution adjust pH to 10.5 is added 4 ℃ of waters for injection at last to 2000g;
3) with the aperture be 2 degerming of membrane filtration of 0.22 μ m;
4) (specifications: in cillin bottle 10mL), plug partly falls filtrate to be sub-packed in 1000 bottles with automatic filling machine (KFG-300 of Nanjing Bojian Science Co., Ltd type orthoscopic partly falls to filling in aseptic filler) with the loading amount of 2g/ bottle;
5) with freeze drying box (the Edward sky sharp pharmacy GLZ-10 of System Co., Ltd type freeze dryer) lyophilizing, the lyophilizing program sees Table 1, and freeze-drying curve is seen Fig. 2, obtains freeze-dried powder injection of pantoprazole sodium, the vacuum tamponade, and outlet rolls aluminium lid.
Table 1 lyophilizing program
| Sequence number | Step | Temperature (℃) | Vacuum (mbar) | Persistent period (min) |
| 1 | Load | -35 | - | - |
| 2 | Pre-freeze | -40 | - | 1 |
| 3 | Pre-freeze | -40 | - | 120 |
| 4 | Find time | - | 0.150 | - |
| 5 | Dry | -8.0 | 0.150 | 600 |
| 6 | Dry | -4.0 | 0.150 | 60 |
| 7 | Dry | 8.0 | 0.1 50 | 120 |
| 8 | Dry | 35.0 | 0.150 | 90 |
| 9 | Dry | 35.0 | 0.150 | 60 |
| 10 | Dry | 35.0 | 0.000 | 450 |
Two, the stability experiment of freeze-dried powder injection of pantoprazole sodium of the present invention
Freeze-dried powder injection of pantoprazole sodium (called after LZ) with the inventive method preparation in the step 1 is carried out stability experiment, simultaneously with other three kinds of like products that gone on the market: ' the Pan Lisu (NS) 10404092 of Hangzhou Sino-U.S. East China pharmacy; Zhejiang medicine Pantoprazole Sodium lot number 040322 (GS1) of limited company, 040323 (GS2); The East China pharmacy of Hangzhou Sino-U.S. ' Pan Lisu " and 046645 (HS) for the contrast.Transfusion is 0.9%NaCl injection 100mL, 250mL (Yangtze River, Jiangsu pharmaceutical factory).
Experimental technique: get 10mL transfusion with the 10mL syringe respectively and push in the different pharmaceutical bottle, treat its dissolving after, inject different infusion bottles, mix homogeneously.Said medicine keeps in Dark Place at ambient temperature.And in different time observation medicinal liquid appearance luster and pH value.
Table 2 Pantoprazole Sodium 40mg mixes the back pH value to be changed with the 100mL0.9%NaCl injection
| Grouping | Standing time (hour) | |||||
| Experimental group | 1 | 2 | 4 | 6 | 8 | 12 |
| LZ | 9.20 | 9.15 | 9.11 | 9.03 | 8.89 | 8.85 |
| GS1 | 9.12 | 9.00 | 8.52 | 8.47 | 8.36 | 8.21 |
| GS2 | 9.61 | 9.31 | 9.03 | 8.88 | 8.74 | 8.42 |
| HS | 9.51 | 9.24 | 9.06 | 8.97 | 8.76 | 8.64 |
| NS | 9.30 | 9.11 | 9.04 | 9.01 | 8.86 | 8.55 |
Pantoprazole Sodium 40mg mixes 1,2,4,6,8, the 12 hour pH value result of variations in back with the 100mL0.9%NaCl injection as shown in table 2, than other like product that has gone on the market, freeze-dried powder injection of pantoprazole sodium of the present invention (LZ) pH value changes minimum, and stability is higher.
Table 3 Pantoprazole Sodium 40mg mixes the back pH value to be changed with the 250mL0.9%NaCl injection
| Grouping | Standing time (hour) | |||||
| Experimental group | 1 | 2 | 4 | 6 | 8 | 12 |
| LZ | 8.68 | 8.64 | 8.59 | 8.57 | 8.55 | 8.43 |
| GS1 | 8.14 | 8.00 | 7.76 | 7.75 | 7.64 | 7.35 |
| GS2 | 8.46 | 8.55 | 8.32 | 8.17 | 7.91 | 7.84 |
| HS | 8.54 | 8.32 | 8.12 | 8.06 | 7.94 | 7.82 |
| NS | 8.57 | 8.48 | 8.12 | 8.08 | 7.84 | 7.77 |
Pantoprazole Sodium 40mg mixes 1,2,4,6,8, the 12 hour pH value result of variations in back with the 250mL0.9%NaCl injection as shown in table 3, than other like product that has gone on the market, freeze-dried powder injection of pantoprazole sodium of the present invention (LZ) pH value changes minimum, and stability is higher.
Table 4 Pantoprazole Sodium 40mg mixes the back change color with the 250mL0.9%NaCl injection
| Grouping | Standing time (hour) | |||||
| Experimental group | 1 | 2 | 4 | 6 | 8 | 12 |
| LZ | i | i | i | i | i | i |
| GS1 | i | ii | ii | iii | iii | iii |
| GS2 | i | i | ii | iv | iv | iv |
| HS | i | ii | iii | iv | iv | iv |
| NS | i | ii | ii | iii | iii | iii |
Pantoprazole Sodium 40mg mixes 1,2,4,6,8, the 12 hour change color result in back, and as shown in table 4 (" i " expression is colourless with the 250mL0.9%NaCl injection, ii, iii, iv represent that color progressively deepens), it is the principal element that influences Pantoprazole Sodium stability that the height of pH value changes, pH value changes tangible GS, HS group, less stable, cause occurring variable color, produce short fiber shape material, than other like product that has gone on the market, freeze-dried powder injection of pantoprazole sodium visible foreign matters of the present invention (particulate matter) project is qualified, and has advantages of higher stability.
The preparation of embodiment 2, freeze-dried powder injection of pantoprazole sodium and detection thereof
With 1000 bottles of freeze-dried powder injection of pantoprazole sodium of method preparation of the present invention, detailed process may further comprise the steps:
1) gets material by following weight: dextran 24.00g, Pantoprazole Sodium 44.72g;
2) dextran is dissolved with 1800g water for injection, with 2mol/L disodium phosphate soln adjust pH to 9.5, add Pantoprazole Sodium, fully reuse 2mol/L disodium phosphate soln adjust pH to 9.5 after the dissolving is added 10 ℃ of waters for injection at last to 2000g;
3) with the aperture be 3 degerming of membrane filtration of 0.3 μ m;
4) (specifications: in cillin bottle 10mL), plug partly falls filtrate to be sub-packed in 1000 bottles with automatic filling machine (KFG-300 of Nanjing Bojian Science Co., Ltd type orthoscopic partly falls to filling in aseptic filler) with the loading amount of 2g/ bottle;
5) with freeze drying box (the Edward sky sharp pharmacy GLZ-10 of System Co., Ltd type freeze dryer) lyophilizing, the lyophilizing program is identical with embodiment 1, obtains freeze-dried powder injection of pantoprazole sodium, the vacuum tamponade, and outlet rolls aluminium lid.
The 2g/ bottle freeze-dried powder injection of pantoprazole sodium and the 10mL0.9%NaCl injection of above-mentioned preparation are packed jointly, promptly obtained pantoprazole sodium injection medicine box.Detect with the method identical with embodiment 1, the result is than other like product that has gone on the market, and freeze-dried powder injection of pantoprazole sodium pH value of the present invention changes minimum, no change color, and visible foreign matters (particulate matter) project is qualified, has advantages of higher stability.
The preparation of embodiment 3, freeze-dried powder injection of pantoprazole sodium and detection thereof
With 1000 bottles of freeze-dried powder injection of pantoprazole sodium of method preparation of the present invention, detailed process may further comprise the steps:
1) gets material by following weight: glucose 44.72g, potassium citrate 2.68g, Pantoprazole Sodium 44.72g;
2) glucose and potassium citrate are dissolved with 1800g water for injection, with 1mol/L potassium hydroxide solution adjust pH to 11.5, add Pantoprazole Sodium, fully dissolving back reuse 1mol/L potassium hydroxide solution adjust pH to 11.5 is added 6 ℃ of waters for injection at last to 2000g;
3) with the aperture be 2 degerming of membrane filtration of 0.1 μ m;
4) (specifications: in cillin bottle 10mL), plug partly falls filtrate to be sub-packed in 1000 bottles with automatic filling machine (KFG-300 of Nanjing Bojian Science Co., Ltd type orthoscopic partly falls to filling in aseptic filler) with the loading amount of 2g/ bottle;
5) with freeze drying box (the Edward sky sharp pharmacy GLZ-10 of System Co., Ltd type freeze dryer) lyophilizing, the lyophilizing program is identical with embodiment 1, obtains freeze-dried powder injection of pantoprazole sodium, the vacuum tamponade, and outlet rolls aluminium lid.
The 2g/ bottle freeze-dried powder injection of pantoprazole sodium and the 10mL0.9%NaCl injection of above-mentioned preparation are packed jointly, promptly obtained pantoprazole sodium injection medicine box.Detect with the method identical with embodiment 1, the result is than other like product that has gone on the market, and freeze-dried powder injection of pantoprazole sodium pH value of the present invention changes minimum, no change color, and visible foreign matters (particulate matter) project is qualified, has advantages of higher stability.
The preparation of embodiment 4, freeze-dried powder injection of pantoprazole sodium and detection thereof
With 1000 bottles of freeze-dried powder injection of pantoprazole sodium of method preparation of the present invention, detailed process may further comprise the steps:
1) gets material by following weight: NaCl22.36g, sodium hydrogen phosphate 1.5g, Pantoprazole Sodium 44.72g;
2) NaCl is dissolved with 1800g water for injection, with 1mol/L potassium bicarbonate solution adjust pH to 10, add Pantoprazole Sodium, fully reuse 1mol/L potassium bicarbonate solution adjust pH to 10 after the dissolving is added 10 ℃ of waters for injection at last to 2000g;
3) with the aperture be 3 degerming of membrane filtration of 0.22 μ m;
4) (specifications: in cillin bottle 10mL), plug partly falls filtrate to be sub-packed in 1000 bottles with automatic filling machine (KFG-300 of Nanjing Bojian Science Co., Ltd type orthoscopic partly falls to filling in aseptic filler) with the loading amount of 2g/ bottle;
5) with freeze drying box (the Edward sky sharp pharmacy GLZ-10 of System Co., Ltd type freeze dryer) lyophilizing, the lyophilizing program is identical with embodiment 1, obtains freeze-dried powder injection of pantoprazole sodium, the vacuum tamponade, and outlet rolls aluminium lid.
The 2g/ bottle freeze-dried powder injection of pantoprazole sodium and the 10mL0.9%NaCl injection of above-mentioned preparation are packed jointly, promptly obtained pantoprazole sodium injection medicine box.Detect with the method identical with embodiment 1, the result is than other like product that has gone on the market, and freeze-dried powder injection of pantoprazole sodium pH value of the present invention changes minimum, no change color, and visible foreign matters (particulate matter) project is qualified, has advantages of higher stability.
The efficacy experiment of embodiment 5, freeze-dried powder injection of pantoprazole sodium of the present invention
Being example with the pantoprazole sodium injection of embodiment 1 preparation detects the curative effect of freeze-dried powder injection of pantoprazole sodium of the present invention, and method is as follows:
Select the inpatient in 18-65 year, being admitted to hospital precedingly had the clinical manifestation of upper gastrointestinal hemorrhage in 2 days (according to clinical indices such as hematemesis, the stool blood positive, see projects such as the hemorrhage pathological changes or the stomach tube Extract occult blood test positive under the gastroscope), include in and do not use other antiulcer medicine the last week, compliance is good, oral informed consent.In addition, gastric cancer, pyloric obstruction, gastrinoma person, gestation, women breast-feeding their children, cardiopulmonary or hepatic and kidney function obstacle person merge liver cirrhosis esophageal varicosis, portal hypertension gastric mucosal lesion person, and such drug allergy or allergic constitution person are all foreclosed.
To meet by random table and to include the Study on standards object in and be divided into test group (68 example) and matched group (69 example) at random, the pantoprazole sodium injection (40mg/ days) of the test group injection embodiment of the invention 1 preparation, (Sweden Astra Pharmaceuticals Pty Ltd. produces matched group injection omeprazole injectable powder, every bottle of 40mg, lot number ZF2245) (40mg/ day), used medicine dilutes with normal saline (or 5% Glucose Liquid) 100mL, intravenous drip 1.5 hours, 5 days courses of treatment.Must not use other proton pump inhibitor, bisfentidine, growth hormone and derivant simultaneously during this, and all hemorrhage.No smoking in observation period, drink tea and drink coffee.The variation of every patient's symptom of itemized record, sign.
Before and after the treatment every patient all have a blood test, urine, stool routine examination, stool blood, liver, renal function.Gastroscopy record before the treatment: the pathological changes type has or not hemorrhage and hemorrhage scope.Extent of hemorrhage judge to be observed: slight, amount of bleeding is less than 500mL, the performance of no hypovolemia; Severe, amount of bleeding have the performance of obvious hypovolemia greater than 1000mL; Moderate is between between the two.The index of stopped bleeding: hematemesis stops, and it is yellow that stool changes; OB is cloudy to be changeed; Do not find hemorrhage sign through stomach tube suction or gastroscopy.
The curative effect judging standard produce effects: 3 days internal hemorrhages of medication stop; Effectively: 5 days internal hemorrhages of medication stop; Invalid: medication still continues hemorrhage more than 5 days.Because of the full person's experimental group of untoward reaction therapy discontinued or data is designated as invalidly, matched group is designated as effectively.
Analysis and statistical procedures: measurement data is checked with t, and enumeration data is checked with x2.
137 routine upper gastrointestinal hemorrhage patients of test group and matched group are aspect there was no significant difference (P＞0.05) such as hemoglobin level and gastroscope diagnosis before age, sex, the hemorrhage course of disease and the order of severity, treatment, experimental group and matched group respectively have 4 routine Clinical Laboratory data incomplete, none routine patient's therapy discontinued.The hematemesis patient is respectively 21 example and 23 examples before test group and the treatment of control group, the melena patient is respectively 68 example and 67 examples, treat that hematemesis all disappears after five days, test group has 1 routine melena not disappear, matched group has 2 examples, the melena disappearance rate is respectively 98.5% and 97.0%, two group of relatively there was no significant difference (P＞0.05).Stool blood is cloudy change and treatment before and after hematochrome change two groups of relatively there are no significant differences (P＞0.05) (seeing Table 5).
Stool blood and hematochrome change situation before and after table 5 treatment
| Project | The example number | Stool blood (example) | Hematochrome/gL -1My god ± SD | ||
| Before controlling | After controlling | Before controlling | After controlling | ||
| Test group | 64 | 63 | 1 | 95.56±32.15 | 103.50±30.48 |
| Matched group | 65 | 61 | 5 | 93.48±27.69 | 97.24±28.88 |
| Test value | x 2＝0.177 | x 2＝0.098 | t＝0.375 | t＝1.198 | |
Two groups of comprehensive therapeutic effect statistical results are as shown in table 6, and no difference of science of statistics (P＞0.05) shows that the curative effect of the upper gastrointestinal hemorrhage due to the diseases such as the treatment of pantoprazole sodium injection of the present invention and omeprazole injectable powder peptic ulcer and gastric mucosal lesion is close.
Table 6 liang group comprehensive therapeutic effect relatively
| Project | Total routine number | Produce effects/example | Effectively/example | Invalid/example | Total effective rate (%) |
| Test group | 68 | 51(75.0％) | 12(17.6％) | 5(7.4％) | 92.6 |
| Matched group | 69 | 46(66.7％) | 18(26.1％) | 5(7.2％) | 92.8 |
| x 2Value | 0.284 | 0.232 | 0.979 |
Two groups of adverse reaction rates are respectively 20.6% (test group) and 27.5% (matched group), there was no significant difference (x
2=0.342, P＞0.05).Untoward reaction does not all influence patient's feed and life.
Claims (8)
1, a kind of freeze-dried powder injection of pantoprazole sodium, its prescription comprises following components by weight portion:
1 part of Pantoprazole Sodium,
Proppant 0.5-1 part,
Weak acid strong alkali salt 0-0.06 part,
Inorganic base is an amount of,
pH 9.5-11.5；
Wherein, proppant is mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt is sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate; Inorganic base is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate or sodium hydrogen phosphate.
2, freeze-dried powder injection of pantoprazole sodium according to claim 1 is characterized in that: the pH value of described freeze-dried powder injection of pantoprazole sodium is 10.5-11, and its prescription is a following components by weight portion:
1 part of Pantoprazole Sodium,
0.89 part of proppant,
0.045 part of weak acid strong alkali salt,
Inorganic base is an amount of;
Wherein, proppant is mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt is sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate; Inorganic base is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate or sodium hydrogen phosphate.
3, freeze-dried powder injection of pantoprazole sodium according to claim 2 is characterized in that: the prescription of described freeze-dried powder injection of pantoprazole sodium is a following components by weight portion:
1 part of Pantoprazole Sodium,
0.89 part in mannitol,
0.045 part of sodium citrate,
Sodium hydroxide is an amount of.
4, a kind of method for preparing the described freeze-dried powder injection of pantoprazole sodium of claim 1 may further comprise the steps:
1) gets material by following parts by weight proportioning: proppant 0.5-1 part, weak acid strong alkali salt 0-0.06 part, 1 part of Pantoprazole Sodium; Described proppant is mannitol, glucose, dextran or NaCl; Weak acid strong alkali salt is sodium citrate, potassium citrate, sodium carbonate, sodium hydrogen phosphate or dipotassium hydrogen phosphate;
2) proppant and weak acid strong alkali salt are dissolved with water for injection, to 9.5-11.5, add Pantoprazole Sodium with the inorganic base adjust pH, the dissolving back uses the inorganic base adjust pH to 9.5-11.5; Described inorganic base is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate or sodium hydrogen phosphate;
3) filter;
4) lyophilizing obtains freeze-dried powder injection of pantoprazole sodium.
5, method according to claim 4 is characterized in that: described proppant, the ratio of weight and number of weak acid strong alkali salt and Pantoprazole Sodium are 0.89: 0.045: 1; Described proppant is a mannitol, and weak acid strong alkali salt is a sodium citrate; Described inorganic base is a sodium hydroxide.
6, method according to claim 4 is characterized in that: the temperature of water for injection is 4-10 ℃ described step 2); All be adjusted to 10.5-11 before and after the pH value.
7, method according to claim 4 is characterized in that: the aperture of filtering used filter membrane in the described step 3) is 0.1-0.3 μ m.
8, according to each described method of claim 4-7, it is characterized in that: the freeze-dried powder injection of pantoprazole sodium product vacuum that obtains in the described step 4) is preserved.
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| CN101961309A (en) * | 2010-09-15 | 2011-02-02 | 河南辅仁怀庆堂制药有限公司 | Process for preparing pantoprazole sodium for injection |
| CN101766615B (en) * | 2010-01-12 | 2011-06-08 | 邓学峰 | Pantoprazole sodium combined drug |
| CN102846559A (en) * | 2012-09-20 | 2013-01-02 | 浙江亚太药业股份有限公司 | Pantoprazole sodium freeze-dry preparation and preparation method thereof |
| CN102920668A (en) * | 2012-11-07 | 2013-02-13 | 南京正宽医药科技有限公司 | Pantoprazole sodium freeze-dried powder injection and preparation method thereof |
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| CN101961309B (en) * | 2010-09-15 | 2012-06-27 | 河南辅仁怀庆堂制药有限公司 | Process for preparing pantoprazole sodium for injection |
| CN101961309A (en) * | 2010-09-15 | 2011-02-02 | 河南辅仁怀庆堂制药有限公司 | Process for preparing pantoprazole sodium for injection |
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| CN103202816A (en) * | 2013-05-09 | 2013-07-17 | 成都天台山制药有限公司 | Pantoprazole sodium freeze-dried powder injection |
| CN104414979A (en) * | 2013-08-21 | 2015-03-18 | 哈药集团三精制药股份有限公司 | Pantoprazole sodium freeze-dried powder injection and preparation method thereof |
| CN107412171A (en) * | 2017-04-21 | 2017-12-01 | 湖南赛隆药业有限公司 | Injection Levpantoprazole Sodium continuous release microsphere lyophilized formulations and preparation method thereof |
| CN107412171B (en) * | 2017-04-21 | 2020-04-17 | 湖南赛隆药业有限公司 | Levo-pantoprazole sodium long-acting microsphere freeze-dried preparation for injection and preparation method thereof |
| CN113041226A (en) * | 2021-03-29 | 2021-06-29 | 海南锦瑞制药有限公司 | Preparation process of pantoprazole sodium for injection |
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