CN101642441A - Cefsulodine sodium freezedrying powder and preparation and preparation method thereof - Google Patents
Cefsulodine sodium freezedrying powder and preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a cefsulodine sodium freezedrying powder in which cefsulodine sodium accounts for 99.0wt% of the anhydrous substance after the freezedrying powder is place at 40 DEG C for 6 months under the relative humidity of 75%; and related materials account for 1wt%. In addition, the invention also discloses a preparation method of the freezedrying powder and particularly relates to amethod for freezedrying cefsulodine sodium at -60 DEG C to 60 DEG C by using water as solvent. The cefsulodine sodium freezedrying product of the invention has simple production process, less organicresidual solvent, stable drug quality and convenient transportation and storage.
Description
Technical field
The present invention relates to cephalosporins medicine and preparation, more particularly, relate to a kind of cefsulodin sodium freeze dry, its preparation and preparation method.
Technical background
The chemistry of cefsulodine sodium by name (6R, 7R)-3-[(4-carbamyl yl pyridines-1--1-yl) methyl]-the 8-oxo-7-[[(2R)-2-phenyl-2-sulfonic group acetyl] amino]-5-sulfur-1-azabicyclo [4.2.0] oct-2-ene-2-sodium formate, molecular formula is C
22H
19N
4NaO
8S
2, CAS RN:52152-93-9, its structural formula is as follows:
Cefsulodine sodium is a narrow spectrum, semisynthetic third generation cephalosporins by the exploitation of Japanese Takeda company.The clinical charrin's disease that is exclusively used in, aminoglycosides antibiotics such as its antibacterial action and gentamycin, dibekacin much at one, and and their no cross resistances; Than the strong 16-32 of Carbenicillin doubly, strong approximately 10 times than sulbenicillin.A plurality of countries (comprising Britain, France, Germany etc.) listing in the world afterwards obtained clinical practice widely as far back as Switzerland's listing in 1980.As the antibiotic that bacillus pyocyaneus is had certain specificity, its clinical efficacy is definite, and toleration is better, and side effect is little, and is nontoxic substantially to kidney, use separately or and other medicines unite use and on the anti-infective clinical treatment, occupy very consequence.
The technology bibliographical information of relevant cefsulodin is fewer both at home and abroad at present.See 1974 the earliest, Japanese Wu Tian company is at J.Med.Chem.1974, (12), the argumentation among the 1312-1315, it is a starting material with D (-)-α-sulphur phenyllacetyl chloride, with after the 7-ACA condensation in the presence of Pyrazinamide and excessive KSCN reaction promptly get target product.But the purification of this target product is the method by recrystallize behind the column chromatography to be obtained, and too high because of column chromatography cost on commercial production, feasibility is very little; Though and crystallization process is with low cost, quality is better relatively, use a large amount of organic solvents in crystallization process, thereby formed the environmental pollution threat, and residual organic solvent more or less directly has influence on the quality of product.
Summary of the invention
The inventor has been surprisingly found out that a kind of steady quality, cefsulodin sodium freeze dry that dissolubility is good, preparation and preparation method thereof through repeatedly experiment, has successfully overcome in the prior art to have problems, and has more advantage than crystallization process.
The purpose of this invention is to provide a kind of cefsulodine sodium freeze-dried powder.
Another object of the present invention provides a kind of preparation of above-mentioned cefsulodin sodium freeze dry.
Another object of the present invention provides the preparation method of above-mentioned cefsulodin sodium freeze dry or its preparation.
In one embodiment of the present invention, the invention provides a kind of cefsulodin sodium freeze dry, zero timing point after making the cefsulodine sodium freeze-dried powder, calculate with anhydride, the content of cefsulodine sodium is greater than 99.5 weight % in the cefsulodin sodium freeze dry, preferably, and greater than 99.6 weight %; The content of related substance is less than 0.5 weight %, preferably, and less than 0.4 weight %; Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, under the condition of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, calculate with anhydride, the content of cefsulodine sodium is greater than 99.0 weight % in the cefsulodin sodium freeze dry, preferably, greater than 99.1 weight %; The content of related substance is less than 1.0 weight %, preferably, and less than 0.9 weight %.
In a preferred embodiment of the invention, the invention provides a kind of cefsulodin sodium freeze dry, zero timing point after making the cefsulodin sodium freeze dry, calculate with anhydride, the content of cefsulodine sodium is greater than 99.5 weight % in the cefsulodin sodium freeze dry, and the content of related substance is less than 0.5 weight %; Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, under the condition of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, calculate with anhydride, the content of cefsulodine sodium is greater than 99.0 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 1.0 weight %.
In a preferred embodiment of the invention, the invention provides a kind of cefsulodin sodium freeze dry, zero timing point calculates with anhydride after making the cefsulodin sodium freeze dry, and the content of cefsulodine sodium is greater than 99.6 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 0.4%; Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, under the condition of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, calculate with anhydride, the content of cefsulodine sodium is greater than 99.1 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 0.9 weight %.
In above-mentioned cefsulodin sodium freeze dry provided by the present invention, this powder is unbodied, and preferably, it comprises the X powder diffraction (Fig. 3) and the infrared ray diffraction (Fig. 4) of following feature further:
On the other hand, the invention provides a kind of pharmaceutical preparation, above-mentioned cefsulodin sodium freeze dry is equipped with in each preparation unit, and preferably 0.5 to 5g, more preferably 0.5g and 1.0g.
On the other hand, the invention provides a kind of preparation method of above-mentioned cefsulodin sodium freeze dry, comprise the steps:
(1) under 0～10 ℃ of condition, with cefsulodine sodium crude product water for injection stirring and dissolving;
(2) add the medical active carbon decoloring, filter;
(3) filtrate is cooled to-60 ℃～-10 ℃ and makes it to solidify, under fine vacuum, slowly be warming up to 0～60 ℃ stage by stage then, make water sublimed and desorption, strict simultaneously control freeze-drying curve finally obtains the cefsulodine sodium powder that lyophilization prepares.
No matter this freeze drying process is deep bid lyophilizing or bottle lyophilizing, can implement.
In preparation method of the present invention, randomly, step (1) is that sodium carbonate or sodium bicarbonate is soluble in water, stir down, gradation adds and above-mentioned sodium carbonate or the equimolar approximately cefsulodin acid of sodium bicarbonate, and control PH is 3.3-4.8, temperature is 0～10 ℃, preferably, and 0～5 ℃.
Preferred manufacturing procedure of the present invention is:
(1) under 0 ℃～10 ℃ conditions, in reaction bulb, drops into the cefsulodine sodium crude product that purification is crossed, with the water for injection stirring and dissolving;
(2) added activated carbon decolorizing 10～40 minutes, filter, wash with water;
(3) will filtrate and washing liquid put into the freeze dryer charging tray after mixing, be cooled to-60 ℃～-10 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing.Slowly heat up 2～10 hours to 0 ℃～10 ℃, keep this temperature lyophilizing and slowly heated up again in 1～5 hour 2～4 hours to 30 ℃～60 ℃, kept 30 ℃～60 ℃ continuation vacuum dryings 4～6 hours.
In preferred manufacturing procedure, the present invention can slowly cool to-20 ℃～-30 ℃ and make it primary solidification putting into the freeze dryer charging tray after filtrate and the washing liquid mixing, is cooled to-45 ℃～-60 ℃ more rapidly and makes it full solidification.Start freeze dryer, under 10 millibars of vacuums, slowly heat up 4～8 hours to-10 ℃～-20 ℃, keep-10 ℃～-20 ℃ lyophilizing and slowly heated up again in 3～5 hours 3～8 hours to 25 ℃～60 ℃ and continued dryings 1～6 hour.
In aforesaid preparation method, by weight, cefsulodine sodium is 1: 1～1: 10 with the ratio of the consumption of water for injection, preferred 1: 2～1: 5.
In aforesaid preparation method, by weight, cefsulodine sodium is 1: 0.01～1: 0.1 with the ratio of the consumption of medicinal carbon, preferred 1: 0.01～1: 0.05.
In aforesaid preparation method, the time of activated carbon decolorizing is 10～40 minutes, preferred 20～35 minutes, and most preferably 25 minutes.
The preferred cefsulodine sodium method for preparing freeze-dried powder of the present invention is:
Under (1) 0 ℃～10 ℃ conditions, the cefsulodine sodium crude product is dissolved with water for injection;
(2) added the medical active carbon decoloring 25 minutes, filter, wash with water;
(3) will put into the freeze dryer charging tray after filtrate and the washing liquid mixing, being cooled to-42 ℃ rapidly makes it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing, slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours.
Above-mentioned cefsulodine sodium freeze-drying process is equally applicable to the bottle lyophilizing, concrete operational approach is: take by weighing non-sterile cefsulodine sodium by recipe quantity, dissolve activated carbon decolorizing 25 minutes, aseptic filtration under 0 ℃～10 ℃ conditions with water for injection, after filtrate is sub-packed in the cillin bottle, jump a queue, be cooled to-42 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing.Slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours, tamponade, roll lid promptly.
Cefsulodine sodium deep bid freeze-dried powder of the present invention can be directly used in aseptic subpackaged, concrete operational approach is: take by weighing the aseptic freeze-dried powder of a certain amount of cefsulodine sodium, operation according to shown in the aseptic freeze-dried powder packing of Fig. 1 cefsulodine sodium process chart is sub-packed in it in cillin bottle with 0.5g or 1.0g/ bottle respectively.
The product that the prepared cefsulodine sodium dried frozen aquatic products of the present invention obtains than crystallization process aspect stable improves greatly, freeze-drying prods of the present invention is done stability test, see embodiment 9 for details, from this experimental analysis, its stability is higher, placed at normal temperatures 30 months, every after testing index has no significant change.
The present invention is obtained that the cefsulodin sodium freeze dry improves greatly than the product that crystallization process obtains on rate of dissolution, the present invention is got freeze-drying prods and crystallization process products obtained therefrom do the rate of dissolution test, see embodiment 10 for details, from this analysis of experiments, its rate of dissolution is 10.8s only, and the rate of dissolution of crystallization process gained cefsulodine sodium is 12.6s.
Advantage of the present invention is: (1) yield height, and average yield can reach more than 97%; (2) because the cefsulodine sodium crude product is purified, so the quality of final products is guaranteed equally, and freeze-drying process is solvent with water only, and essentially no organic solvent is residual, becomes any threat to environment is not enough; (3) adopt the cefsulodine sodium dissolution velocity of lyophilization preparation fast, drug quality is stable, and it is convenient to transport, store.
Description of drawings
Fig. 1 is the process chart of the aseptic freeze-dried packing of cefsulodine sodium.
Fig. 2 is the cefsulodine sodium freeze-drying curve.
Fig. 3 is the X-ray powder diffraction pattern of cefsulodin sodium freeze dry.
Fig. 4 is cefsulodin sodium freeze dry infrared ray diffraction figure.
The specific embodiment
Further describe cefsulodin sodium freeze dry of the present invention and preparation method thereof by following specific embodiment, but and be not limited by the following examples.
1000ml water for injection is joined in the 2000ml reaction bulb, be chilled to 0～10 ℃ in advance, accurately take by weighing cefsulodine sodium crude product that the 500g purification crosses again in reaction bulb, stirring and dissolving, when dissolving crude product is clarified, added the 5g activated carbon decolorizing 35 minutes, filter, gained filtrate is transferred in the lyophilizing dish, is cooled to-45 ℃ rapidly and makes it to solidify, and starts freeze dryer, under 10 millibars of vacuums, slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours, get cefsulodine sodium freeze-dried powder 485.5g.M.p. be 180 ℃ (decomposition)
Embodiment 2
Accurately take by weighing cefsulodine sodium crude product that the 500g purification crosses in the 2000ml reaction bulb, under 0～10 ℃ of condition, with 1000ml water for injection stirring and dissolving, added the 7.5g activated carbon decolorizing 30 minutes, filter, gained filtrate is transferred in the lyophilizing dish, being cooled to-60 ℃ rapidly makes it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heated up 10 hours to 0 ℃, keep this temperature lyophilizing 3 hours, slowly heated up again 4 hours to 48 ℃, keep 48 ℃ of continuation vacuum dryings 5 hours, and got cefsulodine sodium freeze-dried powder 485.2g.
Accurately take by weighing cefsulodine sodium crude product that the 500g purification crosses in the 2000ml reaction bulb, under 0～10 ℃ of condition, with 1500ml water for injection stirring and dissolving, added the 10g activated carbon decolorizing 25 minutes, filter, gained filtrate is transferred in the lyophilizing dish, being cooled to-30 ℃ rapidly makes it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heated up 5 hours to 0 ℃, keep this temperature lyophilizing 3 hours, slowly heated up again 4 hours to 41 ℃, keep 41 ℃ of continuation vacuum dryings 5 hours, and got cefsulodine sodium freeze-dried powder 486.8g.
Embodiment 4
Accurately take by weighing cefsulodine sodium crude product that the 500g purification crosses in the 1000ml reaction bulb, under 0～10 ℃ of condition, with 500ml water for injection stirring and dissolving, added the 5g activated carbon decolorizing 30 minutes, filter, gained filtrate is transferred in the lyophilizing dish, slowly cools to-30 ℃ and makes it to solidify, and is cooled to-60 ℃ more rapidly and makes it full solidification.Start freeze dryer, slowly heated up 6 hours to-10 ℃ under 10 millibars of vacuums, keep-10 ℃ of lyophilizing and slowly heated up in 3 hours 6 hours to 40 ℃ again, drying got cefsulodine sodium freeze-dried powder 485.6g in 3 hours.
Embodiment 5
Accurately take by weighing cefsulodine sodium crude product that the 500g purification crosses in the 2000ml reaction bulb, under 0～10 ℃ of condition with 900ml water for injection stirring and dissolving, added the 5g activated carbon decolorizing 25 minutes, filter, gained filtrate is transferred in the lyophilizing dish, slowly cool to-20 ℃ and make it to solidify, be cooled to-45 ℃ more rapidly and make it full solidification.Start freeze dryer, slowly heated up 5.5 hours to-20 ℃ under 10 millibars of vacuums, keep-20 ℃ of lyophilizing and slowly heated up in 4 hours 5 hours to 40 ℃ again, drying got cefsulodine sodium freeze-dried powder 486.1g in 3 hours.
Embodiment 6
Accurately take by weighing 500g cefsulodine sodium crude product in the 3000ml reaction bulb, under 0～10 ℃ of condition with 1800ml water for injection stirring and dissolving, added the 6g activated carbon decolorizing 25 minutes, filter, gained filtrate and washing liquid are transferred in the lyophilizing dish, slowly cooled to-30 ℃ and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing.Slowly heated up 5 hours to-10 ℃, keep this temperature lyophilizing and slowly heated up again in 4.5 hours 4 hours to 42 ℃, kept 42 ℃ of continuation vacuum dryings 6 hours, get cefsulodine sodium freeze-dried powder 486.0g.
Embodiment 7
Take by weighing cefsulodine sodium by recipe quantity, an amount of water for injection dissolving, activated carbon decolorizing 25 minutes, aseptic filtration, after filtrate is sub-packed in the cillin bottle, jump a queue, be cooled to-42 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing.Slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours, tamponade, roll lid promptly.
The 157.7g sodium bicarbonate is joined in the 4L water for injection, stirring and dissolving, the control temperature is at 0～5 ℃, gradation adds cefsulodin acid 1kg, stirring and dissolving, control PH is 3.3-4.8, adds active carbon 25g, decolours 30 minutes, filter, gained filtrate is directly transferred in the lyophilizing dish, be cooled to-45 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours, get cefsulodine sodium freeze-dried powder 972.30kg.
Embodiment 9
The 99.5g sodium carbonate is joined in the 4L water for injection, stirring and dissolving, the control temperature is at 0～5 ℃, gradation adds cefsulodin acid 1kg, stirring and dissolving, control PH is 3.3-4.8, adds active carbon 25g, decoloured 30 minutes, filter, gained filtrate is directly transferred in the lyophilizing dish, be cooled to-60 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heated up 10 hours to 0 ℃, keep this temperature lyophilizing 3 hours, slowly heated up again 4 hours to 48 ℃, keep 48 ℃ of continuation vacuum dryings 5 hours, and got cefsulodine sodium freeze-dried powder 974.60g.
Indoor in the sterile working, take by weighing the aseptic cefsulodine sodium 1000g that is up to the standards, according to the operational approach shown in the accompanying drawing 1 cefsulodine sodium is distributed into the 1.0g/ bottle.
Cefsulodine sodium (in dry product, cefsulodin) 1000g
?????????????????????????????????????????????????????????????????
Make 1000 bottles
Embodiment 11
This experimental example is the stability test of product of the present invention
1, accelerated test
Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, the cefsulodine sodium that cefsulodine sodium that lyophilization is produced and crystallization process (method by document US 4245088 makes) obtain, under identical terms of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, respectively at sampling at 0,1,2,3,6 the end of month once, measure by the high spot reviews project, as shown in Table 1 and Table 2:
Particulate matter evaluation criterion: contain the above microgranule of 10 μ m in every 5g sample and must not cross 6000, contain the above microgranule of 25 μ m and must not cross 600.
Embodiment 12
Present embodiment is the solubility test
The solubility experimental technique: the cefsulodine sodium that lyophilization and crystallization process (method by document US 4245088 makes) are obtained waits quality to get 5 bottles respectively, is designated as No. 1, No. 2, No. 3, No. 4, No. 5 with the made lyophilized powder of freeze-dry process of the present invention; The cefsulodine sodium that obtains with crystallization process is designated as No. 6, No. 7, No. 8, No. 9, No. 10, and the dissolving method by clinical application injects 10ml water for injection respectively, it is jolted on eddy mixer, and be index to dissolve clear and bright fully, calculate dissolution velocity (seeing Table 3)
Table 3 cefsulodin sodium freeze dry and the crystal powder dissolution velocity in water for injection
Simultaneously, other parameter of the cefsulodine sodium powder of two kinds of prepared is investigated, seen Table 4
Other parameter of the cefsulodine sodium powder of two kinds of explained hereafter of table 4
| Process | Average yield | Moisture | Color and luster distributes | The solution clarity |
| Lyophilization | ??97.6％ | ??0.56％ | Color and luster is even | Clear and bright |
| Crystallization process | ??93.5％ | ??0.49％ | The bottom is dark slightly partially | Clear and bright |
Embodiment 11
Present embodiment is cefsulodine sodium influence factor's test
Table 5 cefsulodine sodium freeze-dried powder factors influencing
Table 6 cefsulodine sodium crystalline powder factors influencing
The result shows, investigates ten days under high temperature and illumination condition, and the cefsulodine sodium that lyophilization obtains is compared than the cefsulodine sodium that crystallization process (method by document US 4245088 makes) obtains, and the product quality that lyophilization obtains is obviously better.
Claims (15)
1. cefsulodin sodium freeze dry, zero timing point calculates with anhydride after making the cefsulodin sodium freeze dry, and the content of cefsulodine sodium is greater than 99.5 weight % in the cefsulodin sodium freeze dry, and the content of related substance is less than 0.5 weight %; Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, under the condition of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, calculate with anhydride, the content of cefsulodine sodium is greater than 99.0 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 1.0 weight %.
2. lyophilized powder according to claim 1, zero timing point calculates with anhydride after making the cefsulodin sodium freeze dry, and the content of cefsulodine sodium is greater than 99.6 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 0.4%; Requirement according to Chinese Pharmacopoeia second edition appendix in 2005 medicine stability test guideline, under the condition of packing, be that 40 ℃, relative humidity are to place 6 months under 75% the condition simultaneously in temperature, calculate with anhydride, the content of cefsulodine sodium is greater than 99.1 weight % in the cefsulodin sodium freeze dry; The content of related substance is less than 0.9%.
3. lyophilized powder according to claim 2, its X powder diffraction as shown in Figure 3, infrared ray diffraction is as shown in Figure 4.
4. preparation that comprises the described lyophilized powder of arbitrary claim in the claim 1 to 3,0.5 to 5g cefsulodin sodium freeze dry is equipped with in each preparation unit.
5. preparation according to claim 4, wherein, 0.5g or 1.0g cefsulodine sodium are equipped with in each preparation unit.
6. the manufacture method of the described cefsulodin sodium freeze dry of arbitrary claim in the claim 1 to 5, it comprises the steps:
Under (1) 0 ℃～10 ℃ conditions, with water for injection with the cefsulodine sodium stirring and dissolving; Perhaps, sodium carbonate or sodium bicarbonate is soluble in water, to stir down, gradation adds and above-mentioned sodium carbonate or the equimolar approximately cefsulodin acid of sodium bicarbonate, and the control pH value is 3.3-4.8, and temperature is 0～10 ℃, preferred 0～5 ℃;
(2) added the medical active carbon decoloring 10～40 minutes, filter, wash with low amounts of water;
(3) solution is cooled to-60 ℃～-10 ℃ and makes it to solidify, under high vacuum condition, slowly be warming up to 0～60 ℃ stage by stage then, make water sublimed and desorption, strict simultaneously control freeze-drying curve gets the cefsulodine sodium powder of lyophilization preparation.
7. according to the preparation method of claims 6 described cefsulodin sodium freeze dries, wherein, described step (3) adopts deep bid lyophilizing or bottle lyophilizing.
8. preparation method according to claim 6, wherein, in the step (1), by weight, the amount of coming into operation of cefsulodine sodium is 1: 1～10 with the ratio of the amount of water for injection, preferred 1: 2～5.
9. preparation method according to claim 6, wherein, in the step (1), by weight, the amount of coming into operation of cefsulodine sodium is 1: 0.01～0.1 with the ratio of the amount of medicinal carbon, preferred 1: 0.01～0.05.
10. preparation method according to claim 6, wherein, the time of decolouring is 10～40 minutes in the step (2), preferred 20～35 minutes, most preferably 25 minutes.
11. the preparation method of a cefsulodin sodium freeze dry comprises:
(1) in reaction bulb, drops into the cefsulodine sodium crude product that purification is crossed, dissolve with water for injection;
(2) added activated carbon decolorizing 10～40 minutes, filter, wash with water;
(3) will filtrate and washing liquid put into the freeze dryer charging tray after mixing, be cooled to-60 ℃～-10 ℃ rapidly and make it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing.
12. according to claims 11 described preparation methoies, wherein, it is characterized in that: start freeze dryer, under 10 millibars of vacuums, slowly heat up 2～10 hours to 0 ℃～10 ℃, keep 0 ℃～10 ℃ lyophilizing and slowly heated up again in 1～5 hour 2-4 hour to 30 ℃～60 ℃, continued vacuum drying 4～6 hours.
13. according to claims 11 described preparation methoies, wherein, step (3) slowly cools to-20 ℃～-30 ℃ and makes it primary solidification for putting into the freeze dryer charging tray after filtrate and the washing liquid mixing, is cooled to-45 ℃～-60 ℃ more rapidly and makes it full solidification.
14. according to claims 12 described preparation methoies, wherein, start freeze dryer, under 10 millibars of vacuums, slowly heat up 4～8 hours to-10 ℃～-20 ℃, keep-10 ℃～-20 ℃ lyophilizing and slowly heated up again in 3～5 hours 3～8 hours to 25 ℃～60 ℃ and continued dryings 1～6 hour.
15. the preparation method of a cefsulodin sodium freeze dry comprises the steps:
(1) under 0 ℃～10 ℃ conditions, the cefsulodine sodium crude product is dissolved with an amount of water for injection;
(2) added the medical active carbon decoloring 25 minutes, filter, wash with water;
(3) will put into the freeze dryer charging tray after filtrate and the washing liquid mixing, being cooled to-42 ℃ rapidly makes it to solidify, start freeze dryer, under 10 millibars of vacuums, slowly heat up, slowly heat up again after keeping lyophilizing, slowly heated up 6 hours to 10 ℃, keep this temperature lyophilizing and slowly heated up again in 3.5 hours 2.5 hours to 38 ℃, kept 38 ℃ of continuation vacuum dryings 5 hours.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101904817A (en) * | 2010-07-27 | 2010-12-08 | 海南永田药物研究院有限公司 | Cefsulodin sodium liposome injection |
| CN101974022A (en) * | 2010-09-27 | 2011-02-16 | 重庆福安药业(集团)股份有限公司 | Process for purifying cefsulodin sodium by solvent crystallization method |
| CN108567970A (en) * | 2018-05-25 | 2018-09-25 | 福安药业集团湖北人民制药有限公司 | High stable glutathione for injection |
-
2009
- 2009-08-31 CN CN200910171830A patent/CN101642441A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101904817A (en) * | 2010-07-27 | 2010-12-08 | 海南永田药物研究院有限公司 | Cefsulodin sodium liposome injection |
| CN101974022A (en) * | 2010-09-27 | 2011-02-16 | 重庆福安药业(集团)股份有限公司 | Process for purifying cefsulodin sodium by solvent crystallization method |
| CN108567970A (en) * | 2018-05-25 | 2018-09-25 | 福安药业集团湖北人民制药有限公司 | High stable glutathione for injection |
| CN108567970B (en) * | 2018-05-25 | 2021-09-24 | 福安药业集团湖北人民制药有限公司 | Preparation method of reduced glutathione for injection |
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