CN1927206A - Lornoxicam composition for injection and preparation process thereof - Google Patents
Lornoxicam composition for injection and preparation process thereof Download PDFInfo
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- CN1927206A CN1927206A CN 200510029452 CN200510029452A CN1927206A CN 1927206 A CN1927206 A CN 1927206A CN 200510029452 CN200510029452 CN 200510029452 CN 200510029452 A CN200510029452 A CN 200510029452A CN 1927206 A CN1927206 A CN 1927206A
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Abstract
The invention provides a lornoxicam injection combination, including injection and freeze-dried powder. The combinations contain 0.86-4.3 weight portion of lornoxicam and pharmaceutically acceptable basic amino acids, and the weight rate of lornoxicam and basic amino acids is 1:0.5-20, the present invention also provides corresponding preparation methods. The said combination has good solubility in solution, high stability and it improves the convenience and safety of clinical use.
Description
Technical field
The present invention relates to a kind of field of pharmaceutical preparations, relate more specifically to Lornoxicam composition for injection and preparation method thereof.
Background technology
Lornoxicam; chemical name is 6-chloro-4-hydroxy-2-methyl-3-(2-pyridine carbamoyl)-2H-thieno [2; 3-e]-1; 2-thiazine-1; the 1-dioxide; belong to nonsteroidal anti-inflammatory analgetic; it is the thiazide derivant; have stronger analgesia and antiinflammatory action; to severe pain, acute sciatica and lumbago, ache in late cancer, also can be used for the treatment of chronic back pain, osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in can be used for that department of obstetrics and gynecology, oral cavity exodontia, orthomorphia and surgical postoperative acute pain, wound cause.The lornoxicam parenteral administration is the same with morphine, pethidine and tramadol effective aspect the alleviation postoperative pain, but the toleration of lornoxicam is better than morphine and tramadol.The cancer pain patient, lornoxicam can also reduce the consumption of morphine as auxiliary analgesic.
Lornoxicam is the molten material of shipwreck, and the dissolubility in water is about 20ug/ml, when being made into injecting medicine-feeding form, needs to adopt suitable method to increase the dissolubility of lornoxicam in water.Contain trometamol as cosolvent in the prescription in the external injection lornoxicam, but because the slow and gained medicinal liquid muddiness of trometamol dissolving lornoxicam process, and trometamol chance sodium chloride precipitates, make the lornoxicam injectable powder that contains trometamol can not be dissolved in sodium chloride injection, before injection, must adopt dedicated solvent (sterilized water for injection) dissolving in advance, carry out intravenous injection with sodium chloride injection or other infusion solutions mix homogeneously again, therefore the application method step is many, increase the chance of clinical microbiological contamination, limited its use.
Publication number is the Chinese patent of CN1228710A, discloses a kind of technical scheme that solves the lornoxicam clarity of injection by the method that adds an amount of EDTA-2Na.Yet, well-knownly be, EDTA-2Na can with the calcium ion complexation in the blood plasma, cause human calcium's ion to run off, have bigger side effect and potential harm.
Therefore this area presses for and seeks a kind of dissolubility height, clarity is good, stable and lornoxicam injection agent applied widely.
Summary of the invention
The purpose of this invention is to provide clear and bright composition for injection of a kind of lornoxicam and preparation method thereof.
In a first aspect of the present invention, a kind of lornoxicam injection solution type compositions is provided, it contains following component:
(a) 1.72mg/ml-8.6mg/ml lornoxicam is by the cumulative volume of dissolving back injection;
(b) the acceptable basic amino acid of pharmacy, the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1;
(c) pharmaceutically acceptable diluent.
The weight ratio of wherein said basic amino acid and lornoxicam is preferably 0.5-5: 1, and more preferably 0.8-2: 1; Described diluent is water, normal saline or glucose sugar aqueous solution; Described basic amino acid is selected from: arginine, lysine or its combination; The pH value of described injection is 7.5-9.5, and that better is 8.5-9.0.
Described lornoxicam injection solution type compositions also can contain the acceptable water for injection dissolubility of pharmacy nonaqueous solvent, is selected from: the combination in any of ethanol, propylene glycol, Polyethylene Glycol, glycerol or above-mentioned 4 kinds of solvents;
In another aspect of this invention, provide a kind of lornoxicam injection freeze-dried powder, it contains following component:
(a) lornoxicam of 0.86-4.3 weight portion;
(b) pharmaceutically acceptable basic amino acid, the weight ratio of basic amino acid and lornoxicam are 0.5-20: 1;
(c) pharmaceutically acceptable carrier of 5-50 part weight.
The weight ratio of wherein said basic amino acid and lornoxicam is preferably 0.5-5: 1, and more preferably 0.8-2: 1; Described basic amino acid is selected from: arginine, lysine or its combination; Described carrier is selected from: mannitol, dextran, sodium chloride or its combination.
In another aspect of this invention, provide a kind of lornoxicam injection solution type preparation of compositions method, this method may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, basic amino acid and 800-1000 weight portion aqueous solvent, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1;
(b) the pharmaceutically acceptable water for injection dissolubility of 50-300 weight portion nonaqueous solvent is joined in the solution of step (b) stirring and dissolving;
(c) solution to step (b) carries out depyrogenation and sterilization, obtains the lornoxicam injection.
Wherein, the weight ratio of described basic amino acid and lornoxicam is preferably 0.5-5: 1, and more preferably 0.8-2: 1; Described basic amino acid is selected from: arginine, lysine or its combination; The acceptable water for injection dissolubility of described pharmacy nonaqueous solvent is selected from: the combination in any of ethanol, propylene glycol, Polyethylene Glycol, glycerol or above-mentioned 4 kinds of solvents.
Wherein, the middle sterilization of step (c) is the cellulose esters micro-filtration membrane filtration by 0.22 micron.
In another aspect of this invention, also provide a kind of preparation method of lornoxicam injection freeze-dried powder, this method may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, basic amino acid and 800-1000 weight portion aqueous solvent, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1;
(b) the pharmaceutically acceptable carrier of 5-50 weight portion is joined in the solution of step (b) stirring and dissolving;
(c) solution of step (b) is removed pyrogen and sterilization;
(d) solution to step (c) carries out lyophilization, obtains Lornoxicam freeze-dried injection.
The weight ratio of wherein said basic amino acid and lornoxicam is preferably 0.5-5: 1, and more preferably 0.8-2: 1; Described basic amino acid is selected from: arginine, lysine or its combination; Described carrier is selected from: mannitol, dextran, sodium chloride or its combination.
Wherein, the middle sterilization of step (c) is the cellulose esters micro-filtration membrane filtration by 0.22 micron.
Clear and bright, the good stability of Lornoxicam composition for injection solution provided by the present invention, and clinical widely applicable.
Description of drawings
Fig. 1 has shown injection a stability result in the embodiment of the invention 1.
Fig. 2 has shown the stability result of control sample.
The specific embodiment
The inventor find that basic amino acid is suitable as the cosolvent of lornoxicam very much, and by add solvent for injection in compositions, it is good to obtain clarity, stability-enhanced lornoxicam injection through groping in a large number and furtheing investigate.
On the one hand, drug solution type compositions of the present invention contains:
(a) lornoxicam of 0.86-4.3 weight portion;
(b) pharmaceutically acceptable basic amino acid, the weight ratio of basic amino acid and lornoxicam are 0.5-20: 1;
(c) pharmaceutically acceptable diluent.
Basic amino acid used in the present invention can be selected pharmaceutical field basic amino acid commonly used for use.Representational basic amino acid example comprises (but being not limited to): arginine, lysine or its combination.What these aminoacid were that pharmacy allows can intravenous aminoacid, records in Chinese Pharmacopoeia and other various countries' pharmacopeia.
Test of the present invention shows, arginine, lysine or its combination can increase the dissolubility of lornoxicam in water by the utmost point significantly, the dissolution velocity of lornoxicam in the basic amino acid aqueous solution is significantly higher than the dissolution velocity in trometamol solution, and gained solution clarity significantly is better than the trometamol solution of lornoxicam; And lornoxicam in the basic amino acid aqueous solution, add sodium chloride not precipitation separate out, enlarged the scope of application clinically.
The amino acid whose amount of neutral and alkali of the present invention reaches clinical desired drug level for making the lornoxicam dissolving, as the 1.72-8.6mg/ml lornoxicam.Usually, the weight ratio of lornoxicam and basic amino acid is 0.5-20: 1, be preferably 0.5-5: and 1, more preferably be 0.8-2: 1.
Described lornoxicam injection solution type compositions also can contain the acceptable water for injection dissolubility of pharmacy nonaqueous solvent, is selected from: the combination in any of ethanol, propylene glycol, Polyethylene Glycol, glycerol or above-mentioned 4 kinds of solvents; What these solvents were that pharmacy allows can intravenous water-soluble solvent, records in Chinese Pharmacopoeia and other various countries' pharmacopeia.Test shows, the adding of these solvents can the utmost point improves the clarity and the stability of lornoxicam in solution of solution significantly.
Also can contain materia medica various additives commonly used in the drug solution type compositions of the present invention, as long as this additive does not hinder the function of lornoxicam.Representational additive comprises (but being not limited to): buffer agent, osmotic pressure regulator, pH value regulator etc.
Usually, the pH value of drug solution type compositions of the present invention is 7.5-9.5, and that better is 8.5-9.0.
Usually, the present invention's method of preparing the lornoxicam solution type composition may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, pharmaceutically acceptable basic amino acid and 800-1000 weight portion aqueous solvent, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1, be preferably 0.5-5: and 1, be more preferred from 0.8-2: 1;
(b) the pharmaceutically acceptable water for injection dissolubility of 50-300 weight portion nonaqueous solvent is joined in the solution of step (b) stirring and dissolving;
(c) solution of step (c) is removed pyrogen and sterilization, obtain yellow clear and bright solution, be the lornoxicam injection.
Usually, whole process is carried out under aseptic condition.
In another preference, according to two appendix IX of Chinese Pharmacopoeia version in 2005 B method, the turbidity standard of the lornoxicam solution that adopts method for preparing and equivalent placed respectively pairedly observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution should be clear and bright with the water ratio, is not deeper than No. 1 than turbid liquid, is suitable for intramuscular injection and intravenous injection.
According to clinical using method, will inject 150ml sodium chloride with the lornoxicam solution (containing the 8.6-51.6mg lornoxicam) that said method makes, investigate the clarity of mixed solution.
On the other hand, the present invention also provides a kind of medicament freeze-drying powder pin, and it contains:
(a) lornoxicam of 0.86-4.3 weight portion;
(b) pharmaceutically acceptable basic amino acid, the weight ratio of basic amino acid and lornoxicam are 0.5-20: 1;
(c) pharmaceutically acceptable carrier of 5-50 part weight.
Identical with injection, employed basic amino acid also can be selected pharmaceutical field basic amino acid commonly used for use in the freeze-dried powder of the present invention.Representational basic amino acid example comprises (but being not limited to): arginine, lysine or its combination.Test shows, even make freeze-dried powder, after adding water for injection, still can increase the dissolubility of lornoxicam in water, and gained solution clarity significantly is better than the trometamol solution of lornoxicam with showing; And lornoxicam in the basic amino acid aqueous solution, add sodium chloride not precipitation separate out, enlarged the scope of application clinically.
In freeze-dried powder, the amount of basic amino acid reaches clinical desired drug level for making the lornoxicam dissolving, and usually, the weight ratio of lornoxicam and basic amino acid is 0.5-20: 1, be preferably 0.5-5: and 1, more preferably be 0.8-2: 1.
Carrier used in the present invention can be selected pharmaceutical field carrier commonly used for use, and representational example comprises that (but being not limited to) is selected from: mannitol, dextran, sodium chloride or its combination.
Also can contain materia medica various additives commonly used in the medicament freeze-drying powder pin of the present invention, as long as this additive does not hinder the function of lornoxicam.Representational additive comprises (but being not limited to): buffer agent, osmotic pressure regulator, pH value regulator etc.
Usually, medicament freeze-drying powder pin pH value of aqueous solution of the present invention is 7.5-9.5, more preferably is 8.5-9.0.
The present invention can make lyophilized injectable powder with conventional drying means (as lyophilization, vacuum drying etc.).
Usually, the present invention's method of preparing the lornoxicam freeze-dried powder may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, basic amino acid and 1000 weight portion aqueous solvents, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1, be preferably 0.5-5: and 1, be more preferred from 0.8-2: 1;
(b) the pharmaceutically acceptable carrier of 5-50 weight portion is joined in the solution of step (b) stirring and dissolving;
(c) solution of step (b) is removed pyrogen and sterilization;
(d) solution to step (c) carries out lyophilization, obtains Lornoxicam freeze-dried injection.
According to two appendix IX of Chinese Pharmacopoeia version in 2005 B method, with the Lornoxicam freeze-dried injection that adopts method for preparing add 2ml water for injection make behind the solution turbidity standard with equivalent place respectively paired than turbid with in the glass tubing, observe from horizontal direction under the daylight lamp, relatively.Lornoxicam solution should be clear and bright with the water ratio, is not deeper than No. 1 than turbid liquid, is suitable for intramuscular injection and intravenous injection.
According to clinical using method, lornoxicam solution (containing the 8.6-51.6mg lornoxicam) is injected 150ml sodium chloride, investigate the clarity of mixed solution.
Major advantage of the present invention is:
1. the injection that is obtained is stable;
2. dissolubility height;
3. clarity is good;
4. clinical applied widely, easy to use.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example is usually according to the normal condition or the condition of advising according to manufacturer.
The preparation of injection a
Lornoxicam 8.6mg
Arginine 13mg
Propylene glycol 0.3g
Sodium dihydrogen phosphate 6mg
Mannitol 80mg
Water for injection adds to 2ml
To filter through 0.22 μ m by the made lornoxicam solution of as above writing out a prescription.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To inject the 150ml sodium chloride injection by the made lornoxicam solution 8ml of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows, uses arginine and propylene glycol to prepare lornoxicam solution as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
The preparation of injection b
Lornoxicam 8.6mg
Arginine 12mg
Ethanol 0.1g
Lactic acid is an amount of
Mannitol 80mg
Water for injection adds to 1ml
To filter through 0.22 μ m by the made lornoxicam solution of as above writing out a prescription.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To inject the 150ml sodium chloride injection by the made lornoxicam solution 8ml of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows, uses arginine and ethanol to prepare lornoxicam solution as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
The preparation of injection c
Lornoxicam 8.6mg
Lysine 6.0mg
PEG400 0.15g
Lactic acid is an amount of
Mannitol 80mg
Water for injection adds to 5ml
To filter through 0.22 μ m by the made lornoxicam solution of as above writing out a prescription.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To inject the 150ml sodium chloride injection by the made lornoxicam solution 8ml of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows, uses lysine and Polyethylene Glycol to prepare lornoxicam solution as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
The preparation of injection d
Lornoxicam 8.6mg
Arginine 3mg
Lysine 3mg
PEG400 0.1g
Lactic acid solution is an amount of
Mannitol 80mg
Water for injection adds to 2ml
To filter through 0.22 μ m by the made lornoxicam solution of as above writing out a prescription.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To inject the 150ml sodium chloride injection by the made lornoxicam solution 8ml of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows that the combination of use arginine and lysine and Polyethylene Glycol prepare lornoxicam solution as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement equally.
The preparation of injection e
Lornoxicam 8.6mg
Arginine 85mg
Lysine 85mg
PEG400 0.1g
Lactic acid solution is an amount of
Mannitol 80mg
Water for injection adds to 2ml
To filter through 0.22 μ m by the made lornoxicam solution of as above writing out a prescription.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To inject the 150ml sodium chloride injection by the made lornoxicam solution 8ml of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows that the combination of use arginine and lysine and Polyethylene Glycol prepare lornoxicam solution as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement equally.
The preparation of freeze-dried powder a
Lornoxicam 8.6mg
Arginine 10mg
Sodium citrate 20mg
Mannitol 80mg
Lactic acid solution is an amount of
Water for injection adds to 2ml
To be dissolved in water for injection 2ml by the made lornoxicam freeze-dried powder of as above writing out a prescription, filter through 0.22 μ m.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To be dissolved in the 150ml sodium chloride injection by the made lornoxicam freeze-dried powder of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows, uses arginine and sodium citrate to prepare the lornoxicam freeze-dried powder as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
The preparation of freeze-dried powder b
Lornoxicam 8.6mg
Lysine 12mg
PEG400 0.1g
Sodium dihydrogen phosphate is an amount of
Dextran 80mg
Water for injection adds to 2ml
To be dissolved in water for injection 2ml by the made lornoxicam freeze-dried powder of as above writing out a prescription, filter through 0.22 μ m.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To be dissolved in the 150ml sodium chloride injection by the made lornoxicam freeze-dried powder of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows, uses lysine and PEG400 to prepare the lornoxicam freeze-dried powder as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
The preparation of freeze-dried powder c
Lornoxicam 8.6mg
Arginine 5mg
Lysine 5mg
Liquid Macrogol 0.1g
Sodium dihydrogen phosphate is an amount of
Mannitol 80mg
Water for injection adds to 2ml
To be dissolved in water for injection 2ml by the made lornoxicam freeze-dried powder of as above writing out a prescription, filter through 0.22 μ m.Place respectively with the turbidity standard of equivalent and pairedly to observe from horizontal direction under the daylight lamp with in the glass tubing, relatively than turbid.Lornoxicam solution is not deeper than No. 1 than turbid liquid as a result.
To be dissolved in the 150ml sodium chloride injection by the made lornoxicam freeze-dried powder of as above writing out a prescription, the result obtains clear and bright solution immediately, clarity less than No. 1 than turbid liquid.
The result shows that the combination of use arginine and lysine prepares the lornoxicam freeze-dried powder as the cosolvent of lornoxicam, can make the clarity of lornoxicam solution meet the injection requirement.
Performance test-stability
The injection a that embodiment 1 is made carried out accelerated test (30 ℃, 60%RH) six months, simultaneously, after adopting water for injection to dissolve, the lornoxicam powder pin (containing trometamol) that will go on the market is mixed with the injection of 4.3mg/ml, fill is in the brown ampoule of 2ml, in contrast, carried out accelerated test (30 ℃, 60%RH) six months with method.And content, pH value, impurity and the clarity of two kinds of samples compared.The results are shown in Table and Fig. 1 and 2 (material chromatogram).
| Time (moon) | PH value | Content (%) | Impurity (%) | Clarity | |
| The injection a of | 0 | 8.63 | 101.8 | 0.86 | Yellow clear and |
| 1 | 8.59 | 100.8 | 1.03 | Yellow clear and | |
| 2 | 8.65 | 100.2 | 1.28 | Yellow clear and | |
| 3 | 8.67 | 98.69 | 1.49 | Yellow clear and | |
| 6 | 8.62 | 93.48 | 1.82 | Yellow clear and bright solution | |
| Matched | 0 | 8.89 | 99.68 | 0.67 | Yellow clear and |
| 1 | 8.78 | 95.26 | 0.96 | Yellow clear and | |
| 2 | 8.92 | 93.31 | 1.71 | Yellow clear and | |
| 3 | 8.84 | 90.22 | 2.88 | Yellow clear and | |
| 6 | 8.86 | 83.69 | 5.10 | Yellow clear and bright solution |
The result shows that the drug solution type compositions of the present invention that adopts 4.3mg/ml can improve the stability of lornoxicam.
Embodiment 10-13
Repeat the assay method of embodiment 9, difference only is, with injection b, c, d, the e replacement injection a of embodiment 2-5 preparation.
The result shows that these stability of sample all are better than matched group.
Embodiment 14-16
Repeat the assay method of embodiment 9, difference only is that freeze dried powder a, b, c that embodiment 6-8 is prepared are dissolved in water for injection, are mixed with the injection of 4.3mg/ml, replaces injection a with the aqueous solution that obtains.
The result shows that these stability of sample all are better than matched group.
The assay method of content and impurity is a high performance liquid chromatography in the stability test, and condition determination is as follows:
Chromatographic apparatus: Shimadzu VP HPLC instrument
Chromatographic column: Shimadzu VP-ODS (4.6 * 150mm, 5 μ m)
Mobile phase: 0.05mol/L sodium acetate solution (pH regulator to 5.8)/methanol=45:55 (V/V)
Measure wavelength: 290nm
Flow velocity: 1.0ml/min
Column temperature: 30 degree
Sample size: 20 μ l
Computational methods: calculate according to peak area with external standard method
Performance test-anaphylaxis, hemolytic, blood vessel irritation test
Embodiment 17
4.3mg/ml specification drug solution type of the present invention compositions (injection d) is applied to rabbit (accumulated dose is respectively 4.3mg and 8.6mg), observes the reaction of rabbit then.
The product of the present invention that the result shows 4.3mg/ml is the 0-1 level to the average response level of rabbit quadriceps femoris, and does not have anaphylaxis, hemolytic.
4.3mg/ml specification drug solution type of the present invention compositions (freeze dried powder c) is applied to rabbit (accumulated dose is respectively 4.3mg and 8.6mg), observes the reaction of rabbit then.
The product of the present invention that the result shows 4.3mg/ml is the 0-1 level to the average response level of rabbit quadriceps femoris, and does not have anaphylaxis, hemolytic.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. a lornoxicam injection solution type compositions is characterized in that, contains following component:
(a) 1.72mg/ml-8.6mg/ml lornoxicam is by the cumulative volume of dissolving back injection;
(b) the acceptable basic amino acid of pharmacy, the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1, preferred 0.5-5: 1, more preferably 0.8-2: 1;
(c) pharmaceutically acceptable diluent.
2. lornoxicam injection solution type compositions as claimed in claim 1 is characterized in that described diluent is water, sodium chloride solution or D/W.
3. lornoxicam injection solution type compositions as claimed in claim 1 is characterized in that described basic amino acid is selected from: arginine, lysine or its combination.
4. lornoxicam injection solution type compositions as claimed in claim 1, it is characterized in that, said composition still can contain the acceptable water for injection dissolubility of pharmacy nonaqueous solvent, is selected from: the combination in any of ethanol, propylene glycol, Polyethylene Glycol, glycerol or above-mentioned 4 kinds of solvents.
5. lornoxicam injection solution type compositions as claimed in claim 1 is characterized in that the pH value of described injection is 7.5-9.5, more preferably is 8.5-9.0.
6. a lornoxicam injection freeze-dried powder is characterized in that, contains following component:
(a) lornoxicam of 0.86-4.3 weight portion;
(b) pharmaceutically acceptable basic amino acid, the weight ratio of basic amino acid and lornoxicam are 0.5-20: 1, and preferred 0.5-5: 1, more preferably 0.8-2: 1;
(c) the pharmaceutically acceptable carrier of 5-50 part weight.
7. lornoxicam injection freeze-dried powder as claimed in claim 6 is characterized in that described basic amino acid is selected from: arginine, lysine or its combination.
8. lornoxicam injection freeze-dried powder as claimed in claim 6 is characterized in that described carrier is selected from: mannitol, dextran, sodium chloride or its combination.
9. lornoxicam injection solution type preparation of compositions method as claimed in claim 1 is characterized in that this method may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, basic amino acid and 800-1000 weight portion aqueous solvent, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1, and preferred 0.5-5: 1, more preferably 0.8-2: 1;
(b) the pharmaceutically acceptable water for injection dissolubility of 50-300 weight portion nonaqueous solvent is joined in the solution of step (b) stirring and dissolving;
(c) solution to step (b) carries out depyrogenation and sterilization, obtains the lornoxicam injection.
10. the preparation method of lornoxicam injection freeze-dried powder as claimed in claim 6 is characterized in that, this method may further comprise the steps:
(a) mix 0.86-4.3 weight portion lornoxicam, basic amino acid and 800-1000 weight portion aqueous solvent, make the lornoxicam dissolving form solution, wherein the weight ratio of basic amino acid and lornoxicam is 0.5-20: 1, and preferred 0.5-5: 1, more preferably 0.8-2: 1;
(b) the pharmaceutically acceptable carrier of 5-50 weight portion is joined in the solution of step (b) stirring and dissolving;
(c) solution of step (b) is removed pyrogen and sterilization;
(d) solution to step (c) carries out lyophilization, obtains Lornoxicam freeze-dried injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100294523A CN100467024C (en) | 2005-09-07 | 2005-09-07 | Lornoxicam composition for injection and preparation process thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100294523A CN100467024C (en) | 2005-09-07 | 2005-09-07 | Lornoxicam composition for injection and preparation process thereof |
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| CN1927206A true CN1927206A (en) | 2007-03-14 |
| CN100467024C CN100467024C (en) | 2009-03-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2005100294523A Active CN100467024C (en) | 2005-09-07 | 2005-09-07 | Lornoxicam composition for injection and preparation process thereof |
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| Country | Link |
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| CN (1) | CN100467024C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846558A (en) * | 2012-09-20 | 2013-01-02 | 浙江亚太药业股份有限公司 | Lornoxicam freeze-drying preparation and preparation method thereof |
| CN106727364A (en) * | 2016-12-02 | 2017-05-31 | 苏州天马医药集团天吉生物制药有限公司 | A kind of lyophilized technique of injection Lornoxicam |
| CN109111469A (en) * | 2018-10-09 | 2019-01-01 | 中国药科大学 | A kind of amorphous compound altogether of lornoxicam |
-
2005
- 2005-09-07 CN CNB2005100294523A patent/CN100467024C/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846558A (en) * | 2012-09-20 | 2013-01-02 | 浙江亚太药业股份有限公司 | Lornoxicam freeze-drying preparation and preparation method thereof |
| CN102846558B (en) * | 2012-09-20 | 2014-08-20 | 浙江亚太药业股份有限公司 | Lornoxicam freeze-drying preparation and preparation method thereof |
| CN106727364A (en) * | 2016-12-02 | 2017-05-31 | 苏州天马医药集团天吉生物制药有限公司 | A kind of lyophilized technique of injection Lornoxicam |
| CN106727364B (en) * | 2016-12-02 | 2020-01-24 | 苏州天马医药集团天吉生物制药有限公司 | Freeze-drying process of lornoxicam for injection |
| CN109111469A (en) * | 2018-10-09 | 2019-01-01 | 中国药科大学 | A kind of amorphous compound altogether of lornoxicam |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100467024C (en) | 2009-03-11 |
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