CN1726913A - Powder and injection preparation of ciprofloxacin hydrochloride, and preparing method - Google Patents
Powder and injection preparation of ciprofloxacin hydrochloride, and preparing method Download PDFInfo
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Abstract
A powder injection of mocixacine hydrochloride is disclosed. Its advantages are no first pass effect, high absorptive rate, and high stability.
Description
Technical field:
The invention belongs to the pharmaceutical chemistry technical field.Be specifically related to moxifloxacin hydrochloride injectable powder and preparation method.
Background technology:
Moxifloxacin hydrochloride is a super wide spectrum Comprecin of the 4th generation, and its has a broad antifungal spectrum is all effective to G-bacterium and G+ bacterium.This product all has good antibacterial action to streptococcus pneumoniae, hemophilus influenza, morazella catarrhalis, staphylococcus aureus, bacillus pyocyaneus, pneumobacillus, escherichia coli and other atypical intestinal Pseudomonas, tubercule bacillus, mycoplasma pneumoniae and Chlamydia pneumoniae, bacteroides fragilis etc., antibacterial to penicillin resistant, macrolide antibiotics is also effective, has the quick sterilization effect and produces antibiotic after effect.MIC
90Be 0.01-0.25 μ g/ml.This product has specially good effect to clinical pathogenic organisms of respiratory tract especially, and is stable to beta-lactamase, effective to the antibacterial of antibiotic of anti-beta-lactamase the and anti-macrolide antibiotics.Clinically every day 400mg dosage, be administered once, can oral also injectable, be 5 days the general course of treatment, the clinical effective rate height is up to 98%, no serious adverse effects, safety, better tolerance absorbs soon, distributes extensively in the body.In German Initial Public Offering, the dosage form of having gone on the market at present is 400mg tablet and injection in JIUYUE, 1999, uses patient and surpasses 6,000,000 people.The indication of FDA approval has: respiratory tract infection, i.e. acute episode of chronic bronchitis, acute bacterial sinusitis, community acquired pneumonia and uncomplicated skin and skin soft-tissue infection.
But tablet and injection still have certain defective aspect stable.
Summary of the invention:
Technical problem to be solved by this invention is to overcome above-mentioned defective, and design stability is good, stores novel form easily.
The invention provides a kind of moxifloxacin hydrochloride injectable powder, this injectable powder comprises as the moxifloxacin hydrochloride of active ingredient and pharmaceutic adjuvant and forming.
Another object of the present invention provides the preparation method of moxifloxacin hydrochloride injectable powder, and this method comprises the following steps:
1. moxifloxacin hydrochloride sterile solution preparation
The moxifloxacin hydrochloride adding is had in the reactor of 10～20 times of distilled water, stirring and dissolving, add 0.5～2 times of mannitol or lactose, it is dissolved fully, add 0.1～0.2 times of active carbon, decolorization filtering is with 10～20 times of distilled water wash charcoal cakes, filtrate gets the moxifloxacin hydrochloride sterile solution through 0.22 μ filtering with microporous membrane;
2. moxifloxacin hydrochloride injectable powder preparation
Gained moxifloxacin hydrochloride sterile solution is surveyed content, calculate the fill amount by content.In 100 grades of clean zones, in 25ml pharmaceutical antibiotics vial, vacuum lyophilization was taken out after 50～70 hours, rolled lid, got final product in fill under the laminar flow hood.
By the moxifloxacin hydrochloride injectable powder purity height that the inventive method makes, good stability sees Table 1.
Impurity content relatively before and after table 1 solvent crystal
| Sequence number | Before the lyophilization | After the lyophilization (the inventive method) | ||
| Content (%) | Total impurities (%) | Content (%) | Total impurities (%) | |
| 1 | 99.4 | 0.06 | 99.5 | 0.02 |
| 2 | 99.3 | 0.07 | 99.7 | 0.03 |
| 3 | 99.3 | 0.06 | 99.7 | 0.02 |
| 4 | 99.4 | 0.07 | 99.6 | 0.02 |
| 5 | 99.5 | 0.08 | 99.8 | 0.02 |
| 6 | 99.6 | 0.08 | 99.8 | 0.02 |
The moxifloxacin hydrochloride injectable powder and the stability of the moxifloxacin hydrochloride injection in the prior art comparative result that make with the inventive method see Table 2.
Table 2 moxifloxacin hydrochloride injectable powder and moxifloxacin hydrochloride injection stability are relatively
| Time | The moxifloxacin hydrochloride injectable powder | The moxifloxacin hydrochloride injection | ||
| Content (%) | Total impurities (%) | Content (%) | Total impurities (%) | |
| 0 month | 100.4 | 0.02 | 99.9 | 0.06 |
| March | 100.2 | 0.03 | 99.7 | 0.06 |
| June | 100.1 | 0.04 | 99.6 | 0.07 |
| December | 99.8 | 0.04 | 99.4 | 0.09 |
The injectable powder that obtains with the inventive method is carried out hemolytic test, hypersensitive test and blood vessel irritation test, all do not detect any side reaction, prove preparation safety of the present invention.
Moxifloxacin of the present invention (200mg, every day 1 time, each 2 bottles, continuous 5d) and clarithromycin (500mg, every day 2 times, 7d continuously) compare treating acute episode of chronic bronchitis, Moxifloxacin is similar with the clinical effectiveness of clarithromycin at least, but bacterial inactivation rate is higher.
For acute sinusitis, Moxifloxacin of the present invention (200mg every day 1 time, each 2 bottles, 10d continuously) and cefuroxime (250mg every day 2 times, 10d continuously) are compared, and the Moxifloxacin height is effective, and bacterial inactivation rate is better than cefuroxime.Use Moxifloxacin 7d to compare with using cefuroxime 10d, Moxifloxacin effective percentage height is better than cefuroxime aspect killing bacteria.
The present invention is the adult (〉=(greater thanor equal to) 18 years old) who suffers from upper respiratory tract and lower respiratory infection, as acute sinusitis, acute episode of chronic bronchitis, community acquired pneumonia and skin and soft tissue infection, provide a kind of and had definite curative effect, low side effect, good stability and be beneficial to storage and the powder injection formulation of transportation.
Existing tablet of moxifloxacin hydrochloride injectable powder of the present invention and aqueous injection have following remarkable advantage:
(1) product is difficult for oxidizedly, helps the product long term store, can avoid medicine rotten because of hyperpyrexia decomposes;
(2) be beneficial to and ensure the quality of products in storage and the transportation;
(3) easy and simple to handle, the process conditions gentleness, with low cost, be fit to suitability for industrialized production;
(4) preparation of the present invention is beneficial to the allotment of clinical dosage;
(5) adopt cryodesiccated method to make powder ampoule agent for injection, compare no first pass effect, the degree that is absorbed by the body height with tablet;
(6) this product side effect is low, is generally accepted by patient easily;
(7) this product water solublity is better, and the injection energy quick control critically ill patient state of an illness can satisfy the needs that clinical critically ill patient is treated.
The specific embodiment
Embodiment 1
Take by weighing principal agent 60g, add 50 ℃ of water for injection 1000ml, heating and stirring make its dissolving, add 60g mannitol, it is dissolved fully, add the 6g needle-use activated carbon, stirred 20 minutes, coarse filtration adds the injection water to 2000ml, with 0.22 μ filtering with microporous membrane, survey content, calculate the fill amount by content, fill is in 25ml pharmaceutical antibiotics vial, and vacuum lyophilization was taken out after 50 hours, roll lid, get final product.
Embodiment 2
Take by weighing principal agent 60g, add 50 ℃ of water for injection 1200ml, heating and stirring make its dissolving, add the 60g lactose, it is dissolved fully, add the 5g needle-use activated carbon, stirred 20 minutes, coarse filtration adds the injection water to 2400ml, with 0.22 μ filtering with microporous membrane, survey content, calculate the fill amount by content, fill is in 25ml pharmaceutical antibiotics vial, and vacuum lyophilization was taken out after 65 hours, roll lid, get final product.
Embodiment 3 stability tests
One, sample source
1. test sample is originated: Shanghai Medicine Science ﹠ Technology Developing Co., Ltd.
2. sample lot number: I030901, I030902, I030903
Two, investigation project:
1. test objective: the moxifloxacin hydrochloride injectable powder is carried out influence factor's test (under the 4500Lx strong illumination, under 60 ℃ of high temperature and RH 92.5%, the RH75% high humidity), accelerated test, long term test are investigated, to determine its production technology, packing, storage requirement and effect duration.
2. investigation project and method
(1) appearance color is observed judgment experiment front and back sample appearance change in color.
(2) clarity, solution colour, acidity, related substance, moisture, sign assay are all investigated test with reference to the assay method of Chinese Pharmacopoeia regulation.
Three, experimental technique
1. this product (lot number: I030901) is got in influence factor's test, place respectively under strong illumination (4500Lx), 60 ℃ of high temperature and RH92.5%, RH75% high humidity (opening) condition and placed 10 days, difference sampling and measuring in the time of 5,10 days, and in 0 day with the batch sample data relatively, experimental result sees Table 3.
Table 3 moxifloxacin hydrochloride injectable powder influence factor tests and investigates result's (lot number: I030901)
| Condition | Natural law | Outward appearance | Acidity | Moisture (%) | Related substance (%) | Indicate content (%) | |
| Single impurity | Total impurities | ||||||
| 60 ℃ of high temperature | 0 day | Yellow block | 4.0 | 3.4 | Do not detect | Do not detect | 99.4 |
| 5 days | Yellow block | 3.9 | 2.5 | Do not detect | Do not detect | 99.4 | |
| 10 days | Yellow block | 3.8 | 2.0 | 0.04 | 0.07 | 99.7 | |
| RH 92.5％ | 0 day | Yellow block | 4.0 | 3.4 | Do not detect | Do not detect | 99.4 |
| 5 days | Faint yellow block | 3.9 | 3.1 | Do not detect | Do not detect | 99.8 | |
| 10 days | Faint yellow block | 3.9 | 2.4 | 0.02 | 0.03 | 99.3 | |
| RH75％ | 0 day | Yellow block | 4.0 | 3.4 | Do not detect | Do not detect | 99.4 |
| 5 days | Faint yellow block | 3.8 | 3.8 | Do not detect | Do not detect | 99.8 | |
| 10 days | Faint yellow block | 4.1 | 4.3 | 0.02 | 0.03 | 101.2 | |
| Strong illumination (4500Lx) | 0 day | Yellow block | 4.0 | 3.4 | Do not detect | Do not detect | 99.4 |
| 5 days | The buff block | 4.1 | 3.6 | 0.69 | 1.89 | 101.1 | |
| 10 days | The buff block | 4.1 | 3.7 | 1.08 | 4.78 | 99.2 | |
Above result shows: the sample under each influence factor's condition, after placing 5,10 days, with 0 day result relatively, other no significant changes related substance slightly increases except that high humidity (RH 92.5%) condition under, related substance slightly increases under moisture rising and illumination (4500Lx) condition.
2. accelerated test three batch samples (lot number: I030901, I030902, I030903, the simulation commercially available back), be placed on exsiccator top, it is 75% solution that relative humidity is put in the bottom, and exsiccator is moved in the calorstat, adjusts the temperature to 40 ℃, placed 6 months, the sampling and measuring respectively in 0,1,2,3,6 month, and with 0 month with the batch sample data relatively, result of the test sees Table 4.
Table 4 moxifloxacin hydrochloride injectable powder accelerated test is investigated the result
| Lot number | Time | Outward appearance | Acidity (pH) | Moisture (%) | Related substance (%) | Indicate content (%) | |
| Single impurity | Total impurities | ||||||
| I030901 | 0 | Yellow block | 4.0 | 3.4 | 0.02 | 0.04 | 99.7 |
| 1 | Yellow block | 4.0 | 3.8 | 0.06 | 0.17 | 100.4 | |
| 2 | Yellow block | 3.9 | 3.5 | 0.05 | 0.05 | 101.0 | |
| 3 | Yellow block | 3.9 | 3.9 | 0.04 | 0.11 | 101.8 | |
| 6 | Yellow block | 4.0 | 4.0 | 0.02 | 0.02 | 102.3 | |
| I030902 | 0 | Yellow block | 3.8 | 3.5 | 0.04 | 0.04 | 99.8 |
| 1 | Yellow block | 3.9 | 4.0 | 0.03 | 0.10 | 100.6 | |
| 2 | Yellow block | 3.8 | 3.9 | 0.04 | 0.07 | 99.2 | |
| 3 | Yellow block | 3.9 | 3.8 | 0.06 | 0.11 | 99.7 | |
| 6 | Yellow block | 3.9 | 3.8 | 0.04 | 0.04 | 100.9 | |
| I030903 | 0 | Yellow block | 3.9 | 3.4 | 0.03 | 0.06 | 100.7 |
| 1 | Yellow block | 3.8 | 3.9 | 0.05 | 0.17 | 99.9 | |
| 2 | Yellow block | 3.6 | 4.1 | 0.04 | 0.07 | 99.4 | |
| 3 | Yellow block | 3.5 | 4.1 | 0.09 | 0.12 | 99.7 | |
| 6 | Yellow block | 3.9 | 4.0 | 0.05 | 0.05 | 99.0 | |
Above result shows: accelerated test compared with 0 month result after 6 months, and except that related substance slightly increased, other no significant changes showed this product steady quality.
3. long term test is investigated three batch samples (lot number: I030901, I030902, I030903, the simulation commercially available back), in 25 ℃ of temperature, relative humidity RH 60% places, respectively at 3,6,9,12,18,24 grades are period sampling measuring in the time of individual month, and compares with the batch sample data with 0 month, and result of the test sees Table 5.
Table 5 moxifloxacin hydrochloride injectable powder long term test is investigated the result
| Lot number | Time | Outward appearance | Acidity (pH) | Moisture (%) | Related substance (%) | Indicate content (%) | |
| Single impurity | Total impurities | ||||||
| I030901 | 0 | Yellow block | 4.0 | 3.4 | 0.02 | 0.04 | 99.7 |
| 3 | Yellow block | 4.1 | 3.8 | 0.02 | 0.05 | 99.3 | |
| 6 | Yellow block | 4.1 | 3.6 | 0.04 | 0.04 | 99.1 | |
| I030902 | 0 | Yellow block | 3.8 | 3.5 | 0.04 | 0.04 | 99.8 |
| 3 | Yellow block | 4.1 | 3.8 | 0.04 | 0.08 | 99.8 | |
| 6 | Yellow block | 4.0 | 4.0 | 0.03 | 0.03 | 101.6 | |
| I030903 | 0 | Yellow block | 3.9 | 3.4 | 0.03 | 0.06 | 100.7 |
| 3 | Yellow block | 3.8 | 3.9 | 0.03 | 0.05 | 101.0 | |
| 6 | Yellow block | 3.9 | 4.2 | 0.03 | 0.03 | 99.5 | |
Above result shows, after keeping sample 6 months for a long time, compares with 0 month data, and except that related substance slightly increased, other no significant changes showed this product steady quality.
Four, conclusion:
1. test by the influence factor, related substance slightly increases under high humidity (RH 92.5%) condition, moisture rises and illumination (4500Lx) condition under, accelerated test investigated in 6 months, long term test was investigated related substance slightly increases in 6 months, sample has no significant change, and shows that sample quality is stable.
2. investigated the result in 6 months by accelerated test 6 months, long term test and show that simulation commercially available back antibiotic does not have influence with vial (25ml) to sample.
Embodiment 4 hemolytic tests
One, test objective
Directly contact with blood by test sample, observe test sample and whether cause external haemolysis and cohesion.
Two, test material
1. test sample:
The name of an article: moxifloxacin hydrochloride injectable powder
Specification: 200mg/ bottle
Lot number: I030901
Sample source: Shanghai Medicine Science ﹠ Technology Developing Co., Ltd.
2. test liquid preparation
Get 1 bottle (0.2g/ bottle) and add the 3.5ml sterilized water for injection, after the dissolving, add the chlorination sodium injection and be diluted to 50ml, supply test behind the mixing.
Three, test method
The preparation of 1.2% Sanguis Leporis seu oryctolagi red blood cell suspension
Get one of healthy rabbits, it is an amount of that heart is gathered fresh blood, put into the conical flask jolting of bead, treat except that after defibrinating, doubling normal saline above mixes, with 3500 rev/mins centrifugal 15 minutes, remove supernatant, the normal saline mixing that sedimentary erythrocyte adds more than 1 times again is centrifugal, abandons supernatant.2～3 times so repeatedly, till being washed till supernatant and not taking on a red color, press the sedimentary red cell volume of gained, be mixed with 2% suspension with normal saline.
2. test procedure
Get 7 test tubes, add 2% red blood cell suspension successively by proportional quantity, distilled water, normal saline and given the test agent shake up, to 37 ℃ of water bath heat preservations.From beginning insulation by 0.5,1, observe it in 2,3 and 4 hours and have or not haemolysis, be transparent redness as supernatant, illustrate that this medicine has haemolysis; Otherwise, the same water white transparency of clear liquid on supernatant and the negative control saline tube, that just illustrates that this medicine does not have haemolysis; As the rufous flocculent deposit is arranged in the supernatant, represent that then this medicine has erythroagglutination.
Table 6 rabbit erythrocyte hemolytic test
| The test tube numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Given the test agent | 0.5 | 0.4 | 0.3 | 0.2 | 0.1 | 0 | 0 |
| Normal saline (ml) | 2.0 | 2.1 | 2.2 | 2.3 | 2.4 | 2.5 | 0 |
| Distilled water (ml) | 0 | 0 | 0 | 0 | 0 | 0 | 2.5 |
| 2% red blood cell suspension (ml) | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 |
3. result
The moxifloxacin hydrochloride injectable powder did not all have haemolysis in 0.5,1,2,3 and 4 hours to rabbit erythrocyte hemolytic test.The results are shown in Table 7.
Table 7 hemolytic test observed result
| Observing time (h) | The test tube numbering | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| 0.5 | - | - | - | - | - | - | + |
| 1 | - | - | - | - | - | - | + |
| 2 | - | - | - | - | - | - | + |
| 3 | - | - | - | - | - | - | + |
| 4 | - | - | - | - | - | - | + |
Four, conclusion: the moxifloxacin hydrochloride injectable powder does not have haemolysis and coacervation.
Embodiment 5 hypersensitive tests
One, test objective: observe the animal duplicate injection and tried the anaphylaxis situation that produced behind the thing.
Two, test material
1. test sample:
The name of an article: moxifloxacin hydrochloride injectable powder
Specification: 200mg/ bottle
Lot number: I030901
Sample source: Shanghai Medicine Science ﹠ Technology Developing Co., Ltd.
2. control sample
Negative control: normal saline
Source: Shanghai Long March rich people pharmaceutcal corporation, Ltd
Lot number: 03112201
Positive control: 1: 10 Ovum Gallus domesticus album physiological salt liquid
Preparation: get one in egg, abandon egg yolk and get Ovum Gallus domesticus album.Inhale Ovum Gallus domesticus album 2ml and add normal saline 20ml, put 4 ℃ of refrigerators and preserve standby.
3. laboratory animal
Animal: Cavia porcellus
Body weight: 250～300g
Sex: male
The source: the Shanghai Songjiang district joins real animal field
The quality certification number: the moving word 02-52-2 that closes in Shanghai
Every treated animal number: 6
Three, experimental technique
Get 18 of healthy guinea pigs, body weight is 250～300g, is divided into three groups at random, 6 every group, is respectively negative control group, positive controls and given the test agent group.Three groups of Cavia porcelluss are intraperitoneal injection of saline, Ovum Gallus domesticus album physiological salt liquid and each 0.5ml of moxifloxacin hydrochloride injectable powder of 1: 10 every other day respectively, injects altogether 3 times.In injecting the back the 14th day and 21 days first, get 3 Cavia porcelluss for every group, negative control group intravenous injection normal saline 1ml, 1: 10 Ovum Gallus domesticus album physiological salt liquid 1ml of positive controls intravenous injection, given the test agent group intravenous injection moxifloxacin hydrochloride injectable powder 1ml, observe that Cavia porcellus has or not anaphylaxiss such as scratching nose, sneeze, perpendicular hair, tic, dyspnea and shock in the injection back 15～30 minutes, according to the form below is chosen the anaphylactoid progression of Cavia porcellus.
Table 8 Cavia porcellus anaphylaxis progression
| The order of reaction | Reaction symptom |
| 0 | No significant reaction |
| 1 | Have only and slightly grab nose |
| 2 | Cough is several times arranged, grab nose, tremble or perpendicular hair |
| 3 | Repeatedly or continuously cough, with dyspnea or spasm, tic etc. |
| 4 | Spasm, tic, gatism, shock death |
Four, experimental result
Aggressive reaction in the time of 14 days: three Cavia porcelluss of negative control normal saline group do not have irritated reaction; Behind 1: 10 Ovum Gallus domesticus album physiological salt liquid 1ml of three Cavia porcelluss of positive controls injection, all spasm, tic and death in 3 minutes; The given the test agent group is behind injection moxifloxacin hydrochloride injectable powder 1ml, and three Cavia porcelluss are not found any allergic symptom yet.
Aggressive reaction in the time of 21 days: behind 1: 10 Ovum Gallus domesticus album physiological salt liquid 1ml of three Cavia porcelluss of positive controls injection, all spasm, tic and death in 2 minutes 20 seconds; Each three Cavia porcellus of negative control normal saline group and given the test agent moxifloxacin hydrochloride injectable powder group all do not have irritated reaction.
The symptom that produces after the 14th day Cavia porcellus of table 9 excites
| Sample | Number of animals | Symptoms of allergic | The order of reaction |
| Given the test agent | 1 | The no abnormality seen reaction | 0 |
| 2 | The no abnormality seen reaction | 0 | |
| 3 | The no abnormality seen reaction | 0 | |
| 1: 10 egg white solution | 1 | Spasm, tic, death in 3 minutes | 4 |
| 2 | Spasm, tic, death in 3 minutes | 4 | |
| 3 | Spasm, tic, death in 3 minutes | 4 | |
| Normal saline solution | 1 | The no abnormality seen reaction | 0 |
| 2 | The no abnormality seen reaction | 0 | |
| 3 | The no abnormality seen reaction | 0 |
The symptom that produces after the 21st day Cavia porcellus of table 10 excites
| Sample | Number of animals | Symptoms of allergic | The order of reaction |
| Given the test agent | 1 | The no abnormality seen reaction | 0 |
| 2 | The no abnormality seen reaction | 0 | |
| 3 | The no abnormality seen reaction | 0 | |
| 1: 10 egg white solution | 1 | Spasm, tic, death in 2 minutes 20 seconds | 4 |
| 2 | Spasm, tic, death in 2 minutes 02 second | 4 | |
| 3 | Spasm, tic, death in 2 minutes 13 seconds | 4 | |
| Normal saline solution | 1 | The no abnormality seen reaction | 0 |
| 2 | The no abnormality seen reaction | 0 | |
| 3 | The no abnormality seen reaction | 0 |
Five, conclusion
The moxifloxacin hydrochloride injectable powder is negative to the anaphylaxis of Cavia porcellus.
The test of embodiment 6 blood vessel irritations
One, test objective:
Observe a certain amount of vascular stimulation response situation that produced behind the thing tried of animal intravenous injection.
Two, be subjected to the reagent thing:
1. test sample:
The name of an article: moxifloxacin hydrochloride injectable powder
Specification: 200mg/ bottle
Lot number: I030901
Sample source: Shanghai Medicine Science ﹠ Technology Developing Co., Ltd.
2. control sample
Negative control: normal saline
Source: Shanghai Long March rich people pharmaceutcal corporation, Ltd
Lot number: 03112201
3. laboratory animal: rabbit
Body weight: 2.5～3.0kg
Sex: male
Source: old capable warren
The quality certification number: Shanghai is moving closes word No. 112
Three, experimental technique
Get 3 of healthy rabbits, body weight 2.5～3.0kg.Left auricular vein 3 rabbit is slowly injected normal saline, auris dextra edge intravenous injection moxifloxacin hydrochloride injectable powder, volume injected is 2ml/kg, injected continuously 3 days, every day 1 time, after the last administration next day clip rabbit two auricular vein vessel segments, visual observations two ear edge intravascular injection positions stimulate situation, standards of grading according to the reaction of table 1 perusal vascular stimulation draw score value, fix with 10% formalin solution then, send pathology to do cut sections for microscopic examination.
The pathology microscopy: every rabbit cuts one section of 0.5cm rabbit ear edge vein tissue from distance ear distal-most end 1cm beginning every 1cm, gets 6 sections altogether, is marked with A～F identification respectively, then with 10% formaldehyde fixed, dehydration, embedding, section, H.E dyeing, last microscopy.
Table 11 perusal vascular stimulation reaction standards of grading
| The vascular stimulation reaction | Score value |
| No obvious stimulation reaction | 0 |
| Mild hyperaemia or hemorrhage | 1 |
| Gently, moderate hyperemia, swelling | 2 |
| Moderate, obviously hyperemia, swelling, ear are sagging | 3 |
| Same score value " 3 " has light, downright bad, the cyanosis of moderate | 4 |
| The same score value of pathological changes " 4 ", but more serious | 5 |
Four, result of the test
Table 12 perusal rabbit auricular vein vascular stimulation reaction scoring score value
| Number of animals | The sample title | The vascular stimulation reaction | Score value |
| 1 | Normal saline | No obvious stimulation reaction | 0 |
| Given the test agent | No obvious stimulation reaction | 0 | |
| 2 | Normal saline | No obvious stimulation reaction | 0 |
| Given the test agent | No obvious stimulation reaction | 0 | |
| 3 | Normal saline | No obvious stimulation reaction | 0 |
| Given the test agent | No obvious stimulation reaction | 0 |
The moxifloxacin hydrochloride injectable powder is to the perusal of rabbit auricular vein vascular stimulation: normal saline matched group and given the test agent moxifloxacin hydrochloride injectable powder group are in the mechanical damage of three rarely seen inserting needles in rabbit auricular vein injection site.Matched group and sample sets contrast no significant difference, choosing score value according to the standards of grading of table 1 perusal vascular stimulation reaction is 0.
The moxifloxacin hydrochloride injectable powder is to the microscopy of rabbit auricular vein vascular stimulation: there is no irritative responses such as edema, inflammation under matched group and each section of the administration group rabbit auricular vein angioscope, matched group and administration group contrast no significant difference.
Five, conclusion
The moxifloxacin hydrochloride injectable powder does not have stimulation to rabbit auricular vein blood vessel.
Claims (3)
1, a kind of moxifloxacin hydrochloride injectable powder is characterized in that this injectable powder comprises moxifloxacin hydrochloride and the pharmaceutic adjuvant composition as active ingredient.
2, a kind of preparation method of moxifloxacin hydrochloride injectable powder is characterized in that this method comprises the following steps:
1) moxifloxacin hydrochloride sterile solution preparation
The moxifloxacin hydrochloride adding is had in the reactor of 10～20 times of distilled water, stirring and dissolving, add 0.5～2 times of mannitol or lactose, it is dissolved fully, add 0.1～0.2 times of active carbon, decolorization filtering is with 10～20 times of distilled water wash charcoal cakes, filtrate gets the moxifloxacin hydrochloride sterile solution through 0.22 μ filtering with microporous membrane;
2) moxifloxacin hydrochloride injectable powder preparation
Gained moxifloxacin hydrochloride sterile solution is surveyed content, calculate the fill amount by content.In 100 grades of clean zones, in 25ml pharmaceutical antibiotics vial, vacuum lyophilization was taken out after 50～70 hours, rolled lid, got final product in fill under the laminar flow hood.
3, the preparation method of moxifloxacin hydrochloride injectable powder according to claim 2 is characterized in that wherein in the sterilized powder that single impurity is not more than 0.5%, total impurities is not more than 1.0%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102100666A (en) * | 2011-01-17 | 2011-06-22 | 南京新港医药有限公司 | New moxifloxacin hydrochloride injection |
| CN102688183A (en) * | 2011-03-21 | 2012-09-26 | 重庆医药工业研究院有限责任公司 | Stable moxifloxacin hydrochloride injection |
| CN103230372A (en) * | 2013-01-17 | 2013-08-07 | 辽宁亿灵科创生物医药科技有限公司 | Moxifloxacin hydrochloride freeze-dried powder injection and preparation method thereof |
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2004
- 2004-07-30 CN CN 200410053321 patent/CN1726913A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102100666A (en) * | 2011-01-17 | 2011-06-22 | 南京新港医药有限公司 | New moxifloxacin hydrochloride injection |
| CN102100666B (en) * | 2011-01-17 | 2012-07-18 | 南京新港医药有限公司 | New moxifloxacin hydrochloride injection |
| CN102688183A (en) * | 2011-03-21 | 2012-09-26 | 重庆医药工业研究院有限责任公司 | Stable moxifloxacin hydrochloride injection |
| CN102688183B (en) * | 2011-03-21 | 2016-04-06 | 重庆医药工业研究院有限责任公司 | A kind of stable moxifloxacin hydrochloride injection |
| CN103230372A (en) * | 2013-01-17 | 2013-08-07 | 辽宁亿灵科创生物医药科技有限公司 | Moxifloxacin hydrochloride freeze-dried powder injection and preparation method thereof |
| CN103230372B (en) * | 2013-01-17 | 2016-04-06 | 北京赛盟医药科技发展有限公司 | Lomefloxacin hydrochloride for injection powder pin and preparation method thereof |
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