CN1212118C - Powder-injections of cyclonorfloxacin and its salts and their preparation - Google Patents
Powder-injections of cyclonorfloxacin and its salts and their preparation Download PDFInfo
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- CN1212118C CN1212118C CN 02151606 CN02151606A CN1212118C CN 1212118 C CN1212118 C CN 1212118C CN 02151606 CN02151606 CN 02151606 CN 02151606 A CN02151606 A CN 02151606A CN 1212118 C CN1212118 C CN 1212118C
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Abstract
The present invention relates to an active medical preparation and a preparation field thereof, particularly to a ciprofloxacin and a power injection of corresponding salts of the ciprofloxacin. The present invention is characterized in that the power injection is composed of ciprofloxacin or salts of the ciprofloxacin, supporting agents and pH regulating agents, wherein the ciprofloxacin or salts of the ciprofloxacin are used as curative medicine, ciprofloxacin containing the ciprofloxacin or the salts of the ciprofloxacin is equivalent to 50-600 mg/ dosage, a solvent for injecting is 100 ml / dosage in the same package or bought another, and the ratio of the rest components by weight of ciprofloxacin or the slats of the ciprofloxacin: the supporting agents: the pH regulating agents is 1: 0 to 1.25: proper quantities. The power injection of the ciprofloxacin or the slats of the ciprofloxacin can not only prepare salt crystallization of the ciprofloxacin or crystalline powder, but also prepare ciprofloxacin salts in site by the ciprofloxacin and corresponding acids before injecting. The present invention has the advantages that the present invention develops the novel dosage form of the powder injection, solves the problems of the water injection in operation and transportation, and is suitable for occasions that the present invention can not be in oral admission.
Description
Technical field
The present invention relates to active agent formulation and preparation field thereof, be specifically related to a kind of method for making of synthetic quinolones broad spectrum antibiotic ciprofloxacin injectable powder and the product of preparation thereof.
Background technology
Ciprofloxacin (chemical name is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, and molecular formula is C
17H
18FN
3O
3, molecular weight is 331, English Ciprofloxacin by name) for synthesizing the quinolones extensive pedigree antibiotic, antibacterial activity is strong, gram positive bacteria and gram negative bacteria all there is antibacterial action, especially enterobacteriaceae lactobacteriaceae is particularly outstanding, Pseudomonas aeruginosa, staphylococcus aureus are also had good action, and especially the negative bacillus that drug resistance is strong still presents sensitivity to this medicine.Be applicable to clinically by sensitive bacterial caused in, the severe respiratory tract, digestive tract, urinary tract and skin, soft tissue infection, septicemia and abdominal cavity infection, bone joint infection, gonorrhea etc. and infected patient that can not oral medication.
At present, the dosage form of this kind clinical practice mostly is aqueous injection, and inconvenience is arranged in using and transporting more, especially is unwell to the transportation and the storage of the north and extremely frigid zones.So far, do not find ciprofloxacin injectable powder report.
Summary of the invention
The objective of the invention is to: not temperature influence of a kind of physical stability is provided, is convenient to operation, be suitable for the ciprofloxacin injectable powder of large-scale production, can supply the intravenous drip administration.
Technical scheme of the present invention is: develop a kind of method for making (lyophilization) of ciprofloxacin injectable powder, it is characterized in that getting described ciprofloxacin or ciprofloxacin salt and add 0.5～5 times of amount water for injection, transfer pH3.0～5.0, stir and make dissolving, make first liquid; Proppant adds 0.5～5 times of amount water for injection, stirs and makes dissolving, makes second liquid; The mixing of first, second two liquid is added needle-use activated carbon, heat 30～80 ℃, stir, decolouring 10～30min, filtrate is again through the filtering with microporous membrane degerming, add sterile water for injection to amount of calculation, after measuring content, fill makes every container include that medicinal liquid is equivalent to ciprofloxacin or its esters is equivalent to ciprofloxacin 50～600mg; Jump a queue, pre-freeze keeps 2～4h to-40～-50 ℃, the beginning lyophilizing, the vacuum parameter value is 10～50KPa, in 10～30h, temperature rises to-10～-5 ℃ gradually by-40～-50 ℃, in 3～8h, temperature rises to 30～80 ℃ gradually by-10～-5 ℃ again, continues to keep vacuum 1～5h, tamponade, take out, the jewelling lid gets finished product.
The method for making of ciprofloxacin injectable powder, it also can be boulton process, it is characterized in that getting under the aseptic condition described ciprofloxacin or ciprofloxacin salt and add 0.5～5 times of amount water for injection, be heated to 30～90 ℃, transfer pH3.0～5.0, stirring makes dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in-5～10 ℃, the vacuum parameter value is 10～80KPa drying, 2～10h, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 50～600mg; Again in 30～100 ℃, dry 1～5h, tamponade, the jewelling lid, finished product.
The method for making of the injectable powder of ciprofloxacin and corresponding salt thereof, also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt add lactic acid or citric acid or tartaric acid an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 50～600mg, jump a queue, the jewelling lid gets finished product.
The injectable powder of ciprofloxacin or its esters both can make ciprofloxacin saline crystallization or crystalline powder earlier; Also can make the ciprofloxacin salt in scene before injection by ciprofloxacin and respective acids.
According to the ciprofloxacin of above-mentioned all method preparations and the injectable powder of corresponding salt thereof, it is characterized in that: this injectable powder is to be combined by medicine ciprofloxacin or its esters, proppant and pH regulator agent; Wherein, containing ciprofloxacin or its esters is equivalent to ciprofloxacin 50～600mg/ and props up; Solvent for injection 100ml (same packing in or purchase separately); All the other composition weight proportionings are: ciprofloxacin or its esters are amounted to ciprofloxacin: proppant: pH regulator agent=1: 0～1.25: an amount of.
Above-mentioned ciprofloxacin salt can be nitrate, hydrochlorate, phosphate, sulfate, acetate, borate, lactate, aspartate, Lactobionate, gluconate, citrate salt, maleate, succinate, tartrate or other the medicinal organic acid and the inorganic acid salt of ciprofloxacin.
Or the injectable powder of a kind of ciprofloxacin and corresponding salt thereof, it is characterized in that: this injectable powder is to be combined by medicine ciprofloxacin injectable powder, solvent for injection, respective acids, proppant and pH regulator agent; Wherein, containing ciprofloxacin 50～600mg/ props up; Solvent for injection 100ml (same packing in or purchase separately); All the other composition weight proportionings are: ciprofloxacin injectable powder: respective acids: proppant: pH regulator agent=1: an amount of: 0～1.25: an amount of.
Above-mentioned respective acids can be medicinal nitric acid, hydrochloric acid, phosphoric acid, sulphuric acid, acetic acid, boric acid, lactic acid, Aspartic Acid, lactobionic acid, gluconic acid, citric acid, maleic acid, succinic acid, tartaric acid or other medicinal organic acid and mineral acid; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.
Above-mentioned proppant is selected from mannitol, glucose, NaCl, dextran, sucrose, lactose or gelatin hydrolysate.
Above-mentioned pH regulator agent is selected from lactic acid, hydrochloric acid, phosphoric acid, sulphuric acid, lactobionic acid, gluconic acid, citric acid or tartaric acid; The dosage of pH regulator agent is equivalent to ciprofloxacin injectable powder when dissolving medicinal liquid and is adjusted to pH3.0～5.0 dosage that some the pH regulator agent need be used.
Above-mentioned solvent for injection is selected from 0.9% sodium chloride injection, 5% or 10% glucose injection, 20% formula mannitol injection liquid, compound recipe Dextrose and Sodium Chloride Inj., low molecular dextran injection or lactated Ringer's injection; The control pH value is 3.0～5.0 during dissolving;
The proppant that uses among the present invention is the water solublity proppant, has characteristics easily molten in the water, and dissolving can clinical use rapidly when this preparation was used.
The pH value regulator that uses among the present invention is a water solublity or water-insoluble, purpose is to make the ciprofloxacin dissolving, and make the lyophilized injectable powder product, when diluting in 100ml0.9% sodium chloride injection, 5%, 10% glucose injection, 20% formula mannitol injection liquid, compound recipe Dextrose and Sodium Chloride Inj., low molecular dextran injection, lactated Ringer's injection, pH value is between 3.0～5.0.
Advantage of the present invention is:
1, opens up ciprofloxacin injectable powder novel form, solved the defective of this kind aqueous injection inconvenience in using and transporting;
2, be applicable to the occasion that the patient can not oral medication;
3, solvent for injection is selected for use multiplely, goes for various patients and occasion (diabetes, cerebrovascular accident etc.)
The specific embodiment
Set forth technical scheme of the present invention and design below by embodiment:
Embodiment 1 prepares its injectable powder by the ciprofloxacin salt
The ciprofloxacin salt of (proportioning) lactic acid or boric acid or Aspartic Acid or lactobionic acid or gluconic acid, the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.For example, if ciprofloxacin lactate salt is then used 254.4g; Hydrochloric acid is an amount of, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.Solvent for injection is selected from 0.9% sodium chloride injection 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets recipe quantity ciprofloxacin lactate salt, and adding the injection water consumption is 0.5 times of amount of ciprofloxacin salt, stirring and dissolving, add the 1mol/L hydrochloric acid solution and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 30 ℃ are stirred decolouring 10min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, behind the mensuration content, fill, every about 4ml is equivalent to ciprofloxacin 50mg, adds plug, give and freezing to-40 ± 5 ℃, insulation 2h, the beginning lyophilizing, the vacuum parameter value is 10KPa, in 10 hours, temperature rises to-5 ℃ by-40 ± 5 ℃, and in 3 hours, temperature rises to 30 ℃ by-5 ℃ again, continue to keep vacuum 1 hour, tamponade is taken out, jewelling cover finished product.
Embodiment 2 prepares its injectable powder by the ciprofloxacin salt
(proportioning) citric acid or maleic acid or succinic acid or tartaric ciprofloxacin salt, consumption reference example 1; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.The pH regulator agent is selected from lactic acid, and the dosage of pH regulator agent is equivalent to ciprofloxacin when dissolving medicinal liquid and is adjusted to pH3.0～5.0 dosage that some the pH regulator agent need be used.The water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.Solvent for injection is selected from 5% or 10% glucose injection 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets recipe quantity ciprofloxacin lactate salt, and adding the injection water consumption is 5 times of amounts of ciprofloxacin salt, stirring and dissolving, add lactic acid and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 80 ℃ are stirred decolouring 30min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, behind the mensuration content, fill, every about 4ml is equivalent to ciprofloxacin 600mg, adds plug, give and freezing to-45 ± 5 ℃, insulation 4h, the beginning lyophilizing, the vacuum parameter value is 50KPa, in 30 hours, temperature rises to-10 ℃ by-45 ± 5 ℃, and in 8 hours, temperature rises to 80 ℃ by-10 ℃ again, continue to keep vacuum 5 hours, tamponade is taken out, jewelling cover finished product.
Embodiment 3 prepares its injectable powder by the ciprofloxacin salt
The ciprofloxacin salt of (proportioning) medicinal hydrochloric acid or nitric acid or phosphoric acid or sulphuric acid or acetic acid, the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.The pH regulator agent is selected from hydrochloric acid, and the dosage of pH regulator agent is equivalent to ciprofloxacin when dissolving medicinal liquid and is adjusted to pH3.0～5.0 dosage that some the pH regulator agent need be used.The water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.Solvent for injection is selected from 20% formula mannitol injection liquid 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets recipe quantity ciprofloxacin lactate salt, and adding the injection water consumption is 2.5 times of amounts of ciprofloxacin salt, stirring and dissolving, add the 1mol/L hydrochloric acid solution and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 50 ℃ are stirred decolouring 20min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, behind the mensuration content, fill, every about 4ml is equivalent to ciprofloxacin 300mg, adds plug, give and freezing to-40 ± 5 ℃, insulation 4h, the beginning lyophilizing, the vacuum parameter value is 25KPa, in 20 hours, temperature rises to-7 ℃ by-40 ± 5 ℃, and in 5 hours, temperature rises to 50 ℃ by-7 ℃ again, continue to keep vacuum 3 hours, tamponade is taken out, jewelling cover finished product.
Embodiment 4 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin adds lactic acid or boric acid or Aspartic Acid or lactobionic acid or gluconic acid, and the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is 1.25 times of amounts of ciprofloxacin weight with mannitol or glucose, its consumption.For example, if ciprofloxacin 200g, then with proppant with mannitol or glucose 250g; The pH regulator agent is selected from sulphuric acid, and the dosage of pH regulator agent is equivalent to ciprofloxacin when dissolving medicinal liquid and is adjusted to pH3.0～5.0 dosage that some the pH regulator agent need be used.Water for injection adds to total amount 4000ml/ and prepares 1000 of injectable powder.Solvent for injection is selected from compound recipe Dextrose and Sodium Chloride Inj. 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets the recipe quantity ciprofloxacin and adds lactic acid or boric acid or Aspartic Acid or lactobionic acid or gluconic acid, and adding the injection water consumption is 0.5 times of amount of ciprofloxacin, and stirring and dissolving is a first liquid; Proppant is with mannitol or glucose, and adding the injection water consumption is 0.5 times of amount of proppant weight, and stirring and dissolving is a second liquid; Add dilution heat of sulfuric acid and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 80 ℃ are stirred decolouring 10min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, after measuring content, fill, every about 4ml, be equivalent to ciprofloxacin 50mg, add plug, give and freezing, insulation 2h to-40 ± 5 ℃, the beginning lyophilizing, the vacuum parameter value is 10KPa, and in 10 hours, temperature rises to-5 ℃ by-40 ± 5 ℃, again in 3 hours, temperature rises to 30 ℃ by-5 ℃, continues to keep vacuum 1 hour, tamponade, take out, jewelling cover finished product.
Embodiment 5 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin is with citric acid or maleic acid or succinic acid or tartaric acid, ciprofloxacin and consumption reference example 1; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is 1.25 times of amounts of ciprofloxacin weight with sucrose or lactose or NaCl, its consumption; All the other are with example 4.Solvent for injection is selected from low molecular dextran injection 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets the recipe quantity ciprofloxacin and adds citric acid or maleic acid or succinic acid or tartaric acid, and adding the injection water consumption is 5 times of amounts of ciprofloxacin, and stirring and dissolving is a first liquid; Proppant is with sucrose or lactose or NaCl, and adding the injection water consumption is 5 times of amounts of proppant weight, and stirring and dissolving is a second liquid; Add lactobionic acid solution and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 30 ℃ are stirred decolouring 30min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, after measuring content, fill, every about 4ml, be equivalent to ciprofloxacin 600mg, add plug, give and freezing, insulation 4h to-45 ± 5 ℃, the beginning lyophilizing, the vacuum parameter value is 50KPa, and in 30 hours, temperature rises to-10 ℃ by-45 ± 5 ℃, again in 8 hours, temperature rises to 80 ℃ by-10 ℃, continues to keep vacuum 5 hours, tamponade, take out, jewelling cover finished product.
Embodiment 6 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin adds medicinal hydrochloric acid or nitric acid or phosphoric acid or sulphuric acid or acetic acid, ciprofloxacin and consumption reference example 1; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is with dextran or gelatin hydrolysate.It is an amount of to add hydrochloric acid again, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.Solvent for injection is selected from lactated Ringer's injection injection 100ml, and the control pH value is 3.0～5.0 when dissolving with injectable powder.
(preparation technology) gets the recipe quantity ciprofloxacin and adds medicinal hydrochloric acid or nitric acid or phosphoric acid or sulphuric acid or acetic acid, and adding the injection water consumption is 2.5 times of amounts of ciprofloxacin, and stirring and dissolving is a first liquid; Proppant dextran or gelatin hydrolysate, adding the injection water consumption is 2.5 times of amounts of proppant weight, stirring and dissolving is a second liquid; Add gluconic acid solution again and transfer pH3.0～5.0, add 0.1% needle-use activated carbon again, 50 ℃ are stirred decolouring 20min, filter carbon removal, the degerming of reuse filtering with microporous membrane is added sterile water for injection to 4000ml, after measuring content, fill, every about 4ml, be equivalent to ciprofloxacin 300mg, add plug, give and freezing, insulation 4h to-40 ± 5 ℃, the beginning lyophilizing, the vacuum parameter value is 25KPa, and in 20 hours, temperature rises to-7 ℃ by-40 ± 5 ℃, again in 5 hours, temperature rises to 50 ℃ by-7 ℃, continues to keep vacuum 3 hours, tamponade, take out, jewelling cover finished product.
Embodiment 7 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt add lactic acid an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 50mg, jump a queue, the jewelling lid gets finished product.All the other are with example 4.
Embodiment 8 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt with citric acid an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 600mg, jump a queue, the jewelling lid gets finished product.All the other are with example 5.
Embodiment 9 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt tartarize an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 300mg, jump a queue, the jewelling lid gets finished product.All the other are with example 6.
Embodiment 10 prepares its injectable powder by the ciprofloxacin salt
The ciprofloxacin salt of (proportioning) lactic acid or boric acid or Aspartic Acid or lactobionic acid or gluconic acid, the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.For example, if ciprofloxacin lactate salt is then used 254.4g; Hydrochloric acid is an amount of, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.
(preparation technology) gets described ciprofloxacin salt and adds 0.5 times of amount water for injection under aseptic condition, be heated to 90 ℃, transfer pH3.0～5.0, stir and make dissolving with citric acid, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in 10 ℃, the vacuum parameter value is the dry 2h of 80KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 50mg; Again in 30 ℃, dry 5h, tamponade, the jewelling lid, finished product.
Embodiment 11 prepares its injectable powder by the ciprofloxacin salt
(proportioning) citric acid or maleic acid or succinic acid or tartaric ciprofloxacin salt, consumption reference example 10; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.Hydrochloric acid is an amount of, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.
(preparation technology) gets described ciprofloxacin salt and adds 5 times of amount waters for injection under aseptic condition, be heated to 30 ℃, transfer pH3.0～5.0, stir and make dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in-5 ℃, the vacuum parameter value is the dry 10h of 10KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 600mg; Again in 100 ℃, dry 1h, tamponade, the jewelling lid, finished product.
Embodiment 12 prepares its injectable powder by the ciprofloxacin salt
The ciprofloxacin salt of (proportioning) medicinal hydrochloric acid or nitric acid or phosphoric acid or sulphuric acid or acetic acid, the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Need not proppant.Hydrochloric acid is an amount of, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.
(preparation technology) gets described ciprofloxacin salt and adds 2.5 times of amount waters for injection under aseptic condition, be heated to 60 ℃, tartarize is transferred pH3.0～5.0, stirs and makes dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in 5 ℃, the vacuum parameter value is the dry 6h of 40KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 300mg; Again in 80 ℃, dry 3h, tamponade, the jewelling lid, finished product.
Embodiment 13 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin adds lactic acid or boric acid or Aspartic Acid or lactobionic acid or gluconic acid, and the dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is 1.25 times of amounts of ciprofloxacin weight with mannitol or glucose, its consumption.For example, if ciprofloxacin 50g, then with proppant with mannitol or glucose 62.5g; Hydrochloric acid is an amount of, and water for injection adds to total amount 4000ml/ and prepares 1000 of injectable powder.
(preparation technology) gets described ciprofloxacin salt and adds 0.5 times of amount water for injection under aseptic condition, be heated to 90 ℃, transfer pH3.0～5.0, stir and make dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in 10 ℃, the vacuum parameter value is the dry 10h of 10KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 50mg; Again in 30 ℃, dry 5h, tamponade, the jewelling lid, finished product.
Embodiment 14 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin is with citric acid or maleic acid or succinic acid or tartaric acid, ciprofloxacin and consumption reference example 10; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is 1.25 times of amounts of ciprofloxacin weight with sucrose or lactose or NaCl, its consumption; All the other are with example 10.
(preparation technology) gets described ciprofloxacin salt and adds 5 times of amount waters for injection under aseptic condition, be heated to 30 ℃, transfer pH3.0～5.0, stir and make dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in-5 ℃, the vacuum parameter value is the dry 2h of 80KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 600mg; Again in 100 ℃, dry 1h, tamponade, the jewelling lid, finished product.
Embodiment 15 adds respective acids by ciprofloxacin and prepares its injectable powder
(proportioning) ciprofloxacin adds medicinal hydrochloric acid or nitric acid or phosphoric acid or sulphuric acid or acetic acid, ciprofloxacin and consumption reference example 1; The dosage of respective acids is equivalent to ciprofloxacin and the required dosage of respective acids salify.Proppant is with dextran or gelatin hydrolysate.It is an amount of to add hydrochloric acid again, and the water for injection total amount adds to 4000ml/ and prepares 1000 of injectable powder.
(preparation technology) gets described ciprofloxacin salt and adds 2.5 times of amount waters for injection under aseptic condition, be heated to 60 ℃, transfer pH3.0～5.0, stir and make dissolving, filter, filtrate is left standstill, and natural cooling, crystallization are collected crystallization in 5～10 ℃, the vacuum parameter value is the dry 5h of 40KPa, quantitatively, packing includes every container to be equivalent to ciprofloxacin or the ciprofloxacin salt is equivalent to ciprofloxacin 300mg; Again in 80 ℃, dry 3h, tamponade, the jewelling lid, finished product.
Embodiment 16 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt add lactic acid an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 50mg, jump a queue, the jewelling lid gets finished product.All the other are with example 10.
Embodiment 17 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt with citric acid an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 300mg, jump a queue, the jewelling lid gets finished product.All the other are with example 11.
Embodiment 18 adds respective acids by ciprofloxacin and prepares its injectable powder
Also can be under aseptic condition, get described ciprofloxacin or ciprofloxacin salt tartarize an amount of (its pH regulator agent consumption should make this product when dissolving is used pH in 3.0～5.0 scopes), packing, every container includes ciprofloxacin or its esters is equivalent to ciprofloxacin 600mg, jump a queue, the jewelling lid gets finished product.All the other are with example 12.
Claims (3)
1. the method for making of the injectable powder of a ciprofloxacin and corresponding salt thereof is characterized in that getting described ciprofloxacin or ciprofloxacin salt and adds 0.5～5 times of amount water for injection, transfers pH3.0～5.0, stirs and makes dissolving, makes first liquid; Proppant adds 0.5～5 times of amount water for injection, stirs and makes dissolving, makes second liquid; First, second two liquid are mixed add needle-use activated carbon, heat 30～80 ℃, the 10～30min that stirs, decolours, filtrate is again through the filtering with microporous membrane degerming, add sterile water for injection to amount of calculation, after measuring content, fill makes every container include medicinal liquid and is equivalent to ciprofloxacin 50～600mg; Jump a queue, pre-freeze is to-40～-50 ℃, and the vacuum parameter value is that 10～50KPa keeps 2～4h, the beginning lyophilizing, in 10～30h, temperature rises to-10～-5 ℃ gradually by-40～-50 ℃, again in 3～8h, temperature rises to 30～80 ℃ gradually by-10～-5 ℃, continue to keep vacuum 1～5h, tamponade is taken out, the jewelling lid gets finished product.
2. according to the method for making of the injectable powder of described ciprofloxacin of claim 1 and corresponding salt thereof, the pH value after it is characterized in that dissolving is 3.0～4.5; Or when dissolving control pH value is 3.0～5.0.
According to the preparation of the described method of claim 1 ciprofloxacin and the injectable powder of corresponding salt, it is characterized in that:
This injectable powder is to be combined by medicine ciprofloxacin or its esters, proppant and pH regulator agent; Wherein, containing ciprofloxacin or its esters is equivalent to ciprofloxacin 50～600mg/ and props up; Solvent for injection 100ml;
All the other composition weight proportionings are:
Ciprofloxacin or its esters are amounted to ciprofloxacin: proppant: pH regulator agent=1: 0～1.25: an amount of;
The nitrate that described ciprofloxacin salt can be a ciprofloxacin, hydrochlorate, phosphate, sulfate, acetate, borate, lactate, aspartate, Lactobionate, gluconate, citrate salt, maleate, succinate, tartrate or other medicinal organic acid and inorganic acid salt;
Described proppant is selected from mannitol, glucose, sodium chloride, dextran, sucrose, lactose or gelatin hydrolysate;
Described pH regulator agent is selected from lactic acid, hydrochloric acid, phosphoric acid, sulphuric acid, lactobionic acid, gluconic acid, citric acid or tartaric acid; The dosage of pH regulator agent is equivalent to ciprofloxacin when dissolving medicinal liquid and is adjusted to pH3.0～5.0 dosage that some the pH regulator agent need be used;
Described solvent for injection is selected from 0.9% sodium chloride injection, 5% or 10% glucose injection, 20% formula mannitol injection liquid, compound recipe Dextrose and Sodium Chloride Inj., low molecular dextran injection or lactated Ringer's injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02151606 CN1212118C (en) | 2002-12-20 | 2002-12-20 | Powder-injections of cyclonorfloxacin and its salts and their preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02151606 CN1212118C (en) | 2002-12-20 | 2002-12-20 | Powder-injections of cyclonorfloxacin and its salts and their preparation |
Publications (2)
| Publication Number | Publication Date |
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| CN1424036A CN1424036A (en) | 2003-06-18 |
| CN1212118C true CN1212118C (en) | 2005-07-27 |
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