CN1605342A - Breviscapine injection for perfusion and its preparing process - Google Patents
Breviscapine injection for perfusion and its preparing process Download PDFInfo
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- CN1605342A CN1605342A CN 200310100102 CN200310100102A CN1605342A CN 1605342 A CN1605342 A CN 1605342A CN 200310100102 CN200310100102 CN 200310100102 CN 200310100102 A CN200310100102 A CN 200310100102A CN 1605342 A CN1605342 A CN 1605342A
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Abstract
The breviscapine preparation for transfusion comprises breviscapine as effective component, and supplementary material including sodium chloride or glucose, polyglycol-400, glycylglycine, EDTA disodium salt, and injection water. The breviscapine preparation for transfusion has mixed solvent comprising polyglycol-400 and water and thus has high clarity and stability. The present invention also discloses the simple preparation process of the breviscapine preparation for transfusion.
Description
Invention field
The present invention relates to a kind of infusion preparation, relating to a kind of specifically is the intravenous transfusion preparation of main component with the breviscapine.The invention still further relates to the preparation method of this infusion preparation.
Background technology
Breviscapine is to fly the Flavonoid substances that paulin plant Herba Erigerontis [Erigron breviscapus (Vaniot) Hand Mazz] extracts by the short Roripa of Compositae, be mainly used in the treatment of cardiovascular and cerebrovascular disease, determined curative effect, to the diseases such as paralysis due to coronary heart disease, angina pectoris, cerebral thrombosis, the cerebral infarction, total effective rate reaches more than 90%.The clinical practice of breviscapine mainly is tablet, freeze-dried powder, little liquid drugs injection, is convenient and uses, avoid polluting, and stability and the clarity problem in order to improve the breviscapine injection in addition, thus carried out the research of breviscapine infusion preparation.
The patent application for " breviscapine infusion preparation and preparation method thereof " of No. 02155001.8 denomination of invention application number was disclosed is on June 25th, 2003, the described breviscapine infusion preparation of this application is to select for use propylene glycol and water to make the mixed solvent of breviscapine, and added L-arginine, triethylammonium tetrakis oxalic acid disodium as mixed stabilizer, also added the antioxidant sodium sulfite.Active carbon with 0.1% in preparation method is made with extra care, and to regulate pH with glacial acetic acid be 4.5-6.5.
However, the present invention has selected for use a kind of breviscapine infusion preparation prescription more reasonable, simpler another breviscapine infusion preparation of preparation process, thus finished the present invention.
Summary of the invention
The object of the present invention is to provide another heavy dose of breviscapine infusion preparation that uses.
Another object of the present invention provides the preparation method of this Herba Erigerontis transfusion.
Breviscapine infusion preparation of the present invention is to be effective ingredient with the breviscapine, and adjuvant is sodium chloride or glucose, Polyethylene Glycol-400, glycylglycine, disodiumedetate and water for injection.Wherein sodium chloride or glucose are that isotonic agent, Polyethylene Glycol-400 and water for injection are the mixing active ingredients solvent, and glycylglycine is the stabilizing agent of effective ingredient, and disodiumedetate is stabilizing agent and antioxidant.
The component consumption of breviscapine infusion preparation of the present invention is breviscapine 0.01～0.3g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.014～4ml/100ml, glycylglycine 0.08～0.4g/100ml, disodiumedetate 0.01～0.04g/100ml, and surplus is a water for injection.
Be preferably breviscapine 0.01～0.08g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.05～1.0ml/100ml, glycylglycine 0.1～0.36g/100ml, disodiumedetate 0.04g/100ml, surplus is a water for injection.
The best is breviscapine 0.01～0.05g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.1～0.7ml/100ml, glycylglycine 0.10～0.30g/100ml, disodiumedetate 0.04g/100ml, and surplus is a water for injection.
Use sodium chloride, be the transfusion of breviscapine sodium chloride; Use glucose, be the erigeron breviscapus glucese transfusion.Breviscapine infusion of the present invention is generally 500ml, 250ml, 100ml, 50ml are bottled.
The preparation method of the breviscapine infusion preparation that the present invention proposes is as follows:
Component dosage by infusion preparation takes by weighing each component;
Breviscapine is a mixed solvent with Polyethylene Glycol-400 and water for injection, add water-soluble amino acid, regulate pH with the pH regulator agent and 6.5～8.5 make it dissolving fully, add again after sodium chloride or glucose, disodiumedetate dissolve, filter, it is standby to be prepared into the breviscapine concentrated solution;
With breviscapine concentrated solution water for injection standardize solution, ultrafiltration, fill in 500ml, 250ml, 100ml, 50ml glass infusion bottle, blooming, jump a queue, roll lid, the sterilization, promptly.
The pH regulator agent is preferably sodium hydroxide, sodium bicarbonate or sodium carbonate in above-mentioned preparation method, and the best is a sodium hydroxide.
Breviscapine infusion preparation of the present invention has selected for use Polyethylene Glycol-400 and water as mixed solvent, makes the clarity of breviscapine infusion preparation be better than using in the prior art propylene glycol and water to make mixed solvent.
We do not adopt activated carbon decolorizing in the step of infusion preparation of the present invention, because we find to add 0.1% active carbon of liquor capacity in prerun, after stirring 20min, filter, solution colour is close to colourless, check related substance through high performance liquid chromatography, the result shows that the peak of scutellarin reduces greatly.The main cause that causes above result is the large usage quantity owing to active carbon, and adsorption causes excessively by force.It has not only adsorbed pigment, and has adsorbed most effective ingredient.Why use activated carbon decolorizing among the preparation technology of little pin, mainly contain two reasons, the one, because the active constituent content height, and the pH value meta-alkalescence, color is dark partially; The 2nd, active carbon has the former effect of good desuperheating.Yet after the transfusion that is mixed with 100ml:50mg, solution colour is very shallow; We are in process of the test simultaneously, the inspection of having compared pyrogen in the prescription that adds and do not add active carbon, find that the two pyrogen test is all qualified, so as long as effective clean level that guarantees in the preparation process, can be in the prescription without activated carbon decolorizing, this not only reduces the step of preparation process, and can ensure the stability of formulation content.
Herba Erigerontis infusion preparation of the present invention is 6.5-8.5 with pH regulator in preparation process, and this is that pH is too high and too low all can to stimulate blood vessel because the pH of injection should be as far as possible in neutrality, makes patient's compliance reduction.Character according to breviscapine shows through prerun, in the process with water for injection dissolving breviscapine, only needs to regulate pH at 6.5～7.5 o'clock, just can be molten entirely.Behind 110 ℃ of autoclaving 40min, the pH value of injection slightly descends.So selecting the pH of breviscapine sodium chloride injection is 6.5～8.5.
Used disodiumedetate to make oxidant in the Herba Erigerontis infusion preparation of the present invention.This is based on us the stability of breviscapine under the condition of pH6.8～8.0 is investigated, its trap was measured in the scope at 48 hours, the result shows: breviscapine is that stability is preferably arranged under about 6.8 the condition at pH, when pH value is 8.0 left and right sides, stability is affected, and trap has a spot of decline, simultaneously, with the content of its related substance of high performance liquid chromatography sync check, find that the peak area of impurity peaks increases to some extent.The results are shown in following table 1 and 2.
The investigation of table 1 breviscapine stability in p H=6.8 phosphate buffer
Time (h) 016 10 24 48 RSD (%)
Trap A 0.367 0.364 0.364 0.361 0.357 0.354 1.35
The investigation of table 2 breviscapine stability in the pH=7.8 phosphate buffer
Time (h) 016 10 24 48 RSD (%)
Trap A 0.346 0.345 0.343 0.334 0.318 0.307 4.87
Since the structure of adjacent two phenolic hydroxyl groups is arranged in the structure of breviscapine, very easily oxidized.In order to increase the stability of breviscapine in solution, we add a certain amount of antioxidant in solution, with reference to adding metal chelating Calcium Disodium Versenate (EDTA-2Na) in the small-volume injection, has certain antioxidant capacity, we add metal-chelator to it and have carried out study on the stability, the result shows: after adding metal-chelator, the stability of breviscapine is significantly improved, and the results are shown in Table 3 and 4.
Table 3 pH=6.8 phosphate buffer adds the investigation of stability among the 0.05%EDTA-Na
Time (h) 016 24 10 48 RSD
(％)
Trap A 0.372 0.369 0.369 0.369 0.368 0.368 0.40
Table 4 pH=7.8 phosphate buffer adds the investigation of stability among the 0.05%EDTA-Na
Time (h) 016 10 24 48 RSD
(％)
Trap A 0.359 0.357 0.358 0.358 0.359 0.359 0.23
As can be seen from the above results, the adding of metal-chelator has effectively increased the stability of breviscapine in solution.In addition, also because the trace metal ion that contains in complexing of metal ion agent and the solution generates stable water miscible complex, thereby stop oxidation deterioration, the variable color of solution and avoid effective ingredient to be subjected to ionic destruction.
About determining of antioxidant consumption, bibliographical information [8] consumption usually is 0.03～0.05%, but we are with reference to United States pharmacopoeia specifications, the consumption of EDTA-2Na is no more than 0.04mg/ml in the transfusion, still its consumption carried out single factor investigated, the result does not see significant difference, the results are shown in following table 5,6,7.Therefore, determine that finally its consumption is by transfusion volume calculation 0.04mg/ml.
The prescription design of table 5 antioxidant consumption
Write out a prescription 123
Breviscapine 500mg 500mg 500mg
Sodium chloride 9g 9g 9g
EDTA-2Na????????20mg????????30mg?????????40mg
The variation of pH before and after 100 ℃ of high pressure flowing steam sterilizations of table 6 30min
Write out a prescription 123
Sterilize preceding 8.0 8.2 8.0
Sterilization back 7.1 7.5 7.6
The variation of trap before and after 100 ℃ of autoclaving 30min of table 7
Write out a prescription 123
Sterilize preceding 0.375 0.369 0.382
Sterilization back 0.397 0.385 0.388
As can be seen from the above results, pH value and trap change more obvious before and after prescription 1 sterilization, and write out a prescription 3 before and after sterilization PH change less, its trap does not have the variation of significance, just some increases slightly, carries out the inspection of related substance by the HPLC method, finds that the content of related substance does not change, see the test protocol, so the consumption of final definite antioxidant is 0.04mg/ml..
In addition, clarity of the present invention and stability all are better than the breviscapine infusion preparation of prior art.Certainly, the transfusion of various capacity makes clinical extremely easy to use, avoided the operation link with little pin preparation transfusion, thereby the cross infection in having avoided making up a prescription has ensured drug safety.
The specific embodiment
Embodiment 1: breviscapine sodium chloride transfusion (500ml)
Breviscapine 5.0g
Sodium chloride 450.0g
PEG400 70ml
Glycylglycine 80.0g
Disodiumedetate 20.0g
Add water for injection to 50000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium bicarbonate, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 50000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 500ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 2: breviscapine sodium chloride transfusion (250ml)
Breviscapine 5.0g
Sodium chloride 225.0g
PEG400 50ml
Glycylglycine 35.0g
Disodiumedetate 10.0g
Add water for injection to 25000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium carbonate, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 25000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 250ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 3: breviscapine sodium chloride transfusion (100ml)
Breviscapine 5.0g
Sodium chloride 90.0g
PEG400 60ml
Glycylglycine 20.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 10000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 100ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 4: breviscapine sodium chloride transfusion (50ml)
Breviscapine 2.5g
Sodium chloride 45.0g
PEG400 30ml
Glycylglycine 10.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 5000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 50ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 5: breviscapine sodium chloride transfusion (50ml)
Breviscapine 5.0g
Sodium chloride 45.0g
PEG400 35ml
Glycylglycine 12.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 5000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 50ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 6: breviscapine sodium chloride transfusion (100ml)
Breviscapine 10.0g
Sodium chloride 90.0g
PEG400 60ml
Glycylglycine 30.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium bicarbonate, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 10000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 100ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 7: erigeron breviscapus glucese transfusion (500ml)
Breviscapine 5.0g
Glucose 2800.0g
PEG400 70ml
Glycylglycine 40.0g
Disodiumedetate 20.0g
Add water for injection to 50000ml.
The method for preparing the erigeron breviscapus glucese transfusion is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium bicarbonate, fully stirring dissolves breviscapine fully, after adding glucose, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 50000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 500ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 8: erigeron breviscapus glucese transfusion (250ml)
Breviscapine 5.0g
Glucose 1200.0g
PEG400 50ml
Glycylglycine 35.0g
Disodiumedetate 10.0g
Add water for injection to 25000ml.
The method for preparing the erigeron breviscapus glucese transfusion is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium carbonate, fully stirring dissolves breviscapine fully, after adding glucose, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 25000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 250ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 9: erigeron breviscapus glucese transfusion (100ml)
Breviscapine 5.0g
Glucose 500.0g
PEG400 40ml
Glycylglycine 20.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
The method for preparing the erigeron breviscapus glucese transfusion is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding glucose, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 10000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 100ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 10: erigeron breviscapus glucese transfusion (50ml)
Breviscapine 2.5g
Glucose 240.0g
PEG400 30ml
Glycylglycine 14.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
The method for preparing the transfusion of breviscapine sodium chloride is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding glucose, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 5000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 50ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 11: erigeron breviscapus glucese transfusion (50ml)
Breviscapine 5.0g
Glucose 260.0g
PEG400 30ml
Glycylglycine 12.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
The method for preparing the erigeron breviscapus glucese transfusion is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium hydroxide, fully stirring dissolves breviscapine fully, after adding sodium chloride, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 5000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 50ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
Embodiment 12: erigeron breviscapus glucese transfusion (100ml)
Breviscapine 10.0g
Glucose 520.0g
PEG400 50ml
Glycylglycine 30.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
The method for preparing the erigeron breviscapus glucese transfusion is as follows:
The water-soluble amino acid that accurately takes by weighing recipe quantity is dissolved in an amount of water for injection, the Polyethylene Glycol that adds recipe quantity again, the breviscapine that adds recipe quantity is regulated pH=6～8 with sodium bicarbonate, fully stirring dissolves breviscapine fully, after adding glucose, the disodiumedetate dissolving of recipe quantity again, filter, it is standby to be prepared into the breviscapine concentrated solution.With breviscapine concentrated solution dilution with water for injection to 10000ml, ultrafiltration, after the inspection of semifinished product was qualified, fill was in the 100ml glass infusion bottle, blooming is jumped a queue, and rolls lid, 110 ℃ of sterilizations in 40 minutes promptly.
The test example 1 breviscapine sodium chloride injection clinical trial preliminarily stabilised test of medicine
The investigation method:
With under the terms of packing of medicine, (the 100ml lot number is 20020601,20020602,20020603 to three batches of breviscapine sodium chloride injections in clinical trial; The 50ml lot number is 20020606,20020607,20020608) by the requirement of new drug research preliminarily stabilised test, stored 12 months under the natural conditions, investigate once by the quality standard of working out preceding every month March, and investigate once year June in June, 2002 to 2003 investigation time every half a year after three months
The investigation project:
Character, discriminating, clarity, pyrogen, aseptic, pH value, assay etc.
Investigate the result
See the preliminarily stabilised test report of three batch samples
Conclusion:
By 12 months store naturally, the investigation result of the every quality index of breviscapine sodium chloride injection is shown: every quality index of said preparation met the quality standard of breviscapine sodium chloride injection, and preliminarily stabilised is good.
Table 8 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020601 dates of manufacture: 2002/06/01
Specification: 100ml:50mg/ bottle
Conclusion: basicly stable
Table 9 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020602 dates of manufacture: 2002/06/02
Specification: 100ml:50mg/ bottle
| Look into | 7. 6.pH pyrogen 8. is aseptic | 7.62 it is up to specification | 7.59 it is up to specification | 7.60 it is up to specification | 7.58 it is up to specification | 7.60 it is up to specification | 7.56 it is up to specification |
| Assay | Lamp-dish flower acetic (mg/ bottle) | ???45.21 | ??45.04 | ??45.81 | ??45.37 | ??45.55 | ??44.92 |
Conclusion: basicly stable
Table 10 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020603 dates of manufacture: 2002/06/03
Specification: 100ml:50mg/ bottle
Conclusion: basicly stable
Table 11 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020606 dates of manufacture: 2002/06/05
Specification: 50ml:25mg/ bottle
| Differentiate | 1, chromogenic reaction 1, chromogenic reaction two | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation |
| Check | 5. clarity 6.pH 7. pyrogens 8. are aseptic | Up to specification 7.72 is up to specification | Up to specification 7.73 is up to specification | Up to specification 7.71 is up to specification | Up to specification 7.70 is up to specification | Up to specification 7.72 is up to specification | Up to specification 7.71 is up to specification |
| Assay | Lamp-dish flower acetic (mg/ bottle) | ??22.86 | ??22.78 | ??22.85 | ??22.81 | ??22.87 | ??22.73 |
Conclusion: basicly stable
Table 12 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020607 dates of manufacture: 2002/06/06
Specification: 50ml:25mg/ bottle
Conclusion: basicly stable
Table 13 preparation preliminarily stabilised investigation result
Sample title: breviscapine sodium chloride injection lot number: 20020608 dates of manufacture: 2002/06/07
Specification: 50ml:25mg/ bottle
| Character | Yellow clear liquid | Yellow clear liquid | Yellow clear liquid | Yellow clear liquid | Yellow clear liquid | Yellow clear liquid | |
| Differentiate | 1, chromogenic reaction 1, chromogenic reaction two | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation | Show orange red generation salmon precipitation |
| Check | 5. clarity 6.pH 7. pyrogens 8. are aseptic | Up to specification 7.82 is up to specification | Up to specification 7.81 is up to specification | Up to specification 7.81 is up to specification | Up to specification 7.81 is up to specification | Up to specification 7.81 is up to specification | Up to specification 7.81 is up to specification |
| Assay | Lamp-dish flower acetic (mg/ bottle) | ??23.02 | 23.02 | 22.91 | 22.87 | 22.51 | ??22.64 |
Conclusion: basicly stable
Claims (17)
1, a kind of breviscapine infusion preparation, it is characterized in that it is made up of the component of following consumption: breviscapine 0.01～0.3g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.014～4ml/100ml, glycylglycine 0.08～0.4g/100ml, disodiumedetate 0.01～0.04g/100ml, surplus is a water for injection.
2. according to the described Herba Erigerontis infusion preparation of claim 1, wherein the consumption of component is breviscapine 0.01～0.08g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.05～1.0ml/100ml, glycylglycine 0.1～0.36g/100ml, disodiumedetate 0.02～0.04g/100ml, and surplus is a water for injection.
3. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the consumption of component is breviscapine 0.01～0.05g/100ml, sodium chloride 0.85～0.95g/100ml or glucose 4.8～5.6g/100ml, Polyethylene Glycol-400 0.1～0.7ml/100ml, glycylglycine 0.10～0.30g/100ml, disodiumedetate 0.03～0.04g/100ml, and surplus is a water for injection.
4. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 500ml infusion preparations is:
Breviscapine 5.0g
Sodium chloride 450.0g
Polyethylene Glycol-400 70ml
Glycylglycine 80.0g
Disodiumedetate 20.0g
Add water for injection to 50000ml.
5. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 250ml infusion preparations is:
Breviscapine 5.0g
Sodium chloride 225.0g
Polyethylene Glycol-400 50ml
Glycylglycine 35.0g
Disodiumedetate 10.0g
Add water for injection to 25000ml.
6. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 100ml infusion preparations is:
Breviscapine 5.0g
Sodium chloride 90.0g
Polyethylene Glycol-400 60ml
Glycylglycine 20.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
7. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 50ml infusion preparations is:
Breviscapine 2.5g
Sodium chloride 45.0g
Polyethylene Glycol-400 30ml
Glycylglycine 10.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
8. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 50ml infusion preparations is:
Breviscapine 5.0g
Sodium chloride 45.0g
Polyethylene Glycol-400 35ml
Glycylglycine 12.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
9. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 100ml infusion preparations is:
Breviscapine 10.0g
Sodium chloride 90.0g
Polyethylene Glycol-400 60ml
Glycylglycine 30.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
10. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 500ml infusion preparations is:
Breviscapine 5.0g
Glucose 2800.0g
Polyethylene Glycol-400 70ml
Glycylglycine 40.0g
Disodiumedetate 20.0g
Add water for injection to 50000ml.
11. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 250ml infusion preparations is:
Breviscapine 5.0g
Glucose 1200.0g
Polyethylene Glycol-400 50ml
Glycylglycine 35.0g
Disodiumedetate 10.0g
Add water for injection to 25000ml.
12. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of l00ml infusion preparations is:
Breviscapine 5.0g
Glucose 500.0g
Polyethylene Glycol-400 40ml
Glycylglycine 20.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
13. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 50ml infusion preparations is:
Breviscapine 2.5g
Glucose 240.0g
Polyethylene Glycol-400 30ml
Glycylglycine 14.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
14. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 50ml infusion preparations is:
Breviscapine 5.0g
Glucose 260.0g
Polyethylene Glycol-400 30ml
Glycylglycine 12.0g
Disodiumedetate 2.0g
Add water for injection to 5000ml.
15. according to the described Herba Erigerontis infusion preparation of claim 2, wherein the component consumption of 100 bottles of 100ml infusion preparations is:
Breviscapine 10.0g
Glucose 520.0g
Polyethylene Glycol-400 50ml
Glycylglycine 30.0g
Disodiumedetate 4.0g
Add water for injection to 10000ml.
16. the preparation method as any one described breviscapine infusion preparation among the claim 1-15 is characterized in that concrete steps are as follows:
Component dosage by infusion preparation takes by weighing each component;
Breviscapine is a mixed solvent with Polyethylene Glycol-400 and water for injection, add glycylglycine, regulate pH with sodium hydroxide, sodium bicarbonate or the agent of sodium carbonate pH regulator and 6.5～8.5 make it dissolving fully, after adding sodium chloride or glucose, disodiumedetate dissolving again, filter, it is standby to be prepared into the breviscapine concentrated solution;
With breviscapine concentrated solution water for injection standardize solution, ultrafiltration, fill in 500ml, 250ml, 100ml, 50ml glass infusion bottle, blooming, jump a queue, roll lid, the sterilization, promptly.
17. according to the described preparation method of claim 16, wherein said pH regulator agent is sodium hydroxide, sodium bicarbonate or sodium carbonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310100102 CN1605342A (en) | 2003-10-08 | 2003-10-08 | Breviscapine injection for perfusion and its preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310100102 CN1605342A (en) | 2003-10-08 | 2003-10-08 | Breviscapine injection for perfusion and its preparing process |
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| CN1605342A true CN1605342A (en) | 2005-04-13 |
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| Application Number | Title | Priority Date | Filing Date |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100396289C (en) * | 2006-05-19 | 2008-06-25 | 昆明龙津药业有限公司 | Scutellarin injection preparation and its preparing method |
| CN1861087B (en) * | 2006-06-15 | 2010-11-24 | 正大青春宝药业有限公司 | High purity wild Radix scutellariae glucoside medicine composition, and application of making medicine to treat diseases of cardiovascular and cerebrovascular |
-
2003
- 2003-10-08 CN CN 200310100102 patent/CN1605342A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100396289C (en) * | 2006-05-19 | 2008-06-25 | 昆明龙津药业有限公司 | Scutellarin injection preparation and its preparing method |
| CN1861087B (en) * | 2006-06-15 | 2010-11-24 | 正大青春宝药业有限公司 | High purity wild Radix scutellariae glucoside medicine composition, and application of making medicine to treat diseases of cardiovascular and cerebrovascular |
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