CN104208699A - Compound oral preparation containing antibacterial drugs - Google Patents
Compound oral preparation containing antibacterial drugs Download PDFInfo
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Abstract
The invention relates to the components and applications of a compound oral preparation containing antibacterial drugs. When a trace amount of an antibacterial drug is compounded with a drug for treating asthma and chronic obstructive pneumonia, a good effect will be generated. The curative effect is more prominent, when an antibacterial drug is compounded with a leukotriene acceptor antagonist to form an oral compound preparation.
Description
Technical field:
The present invention relates to component and the purposes of the compound oral administration preparation containing anti-bacterial drug.
Background technology:
Anti-bacterial drug is general designation antibacterial to suppression and killing action material, mainly treats antibacterial to mammiferous infection.The main route of administration of anti-bacterial drug is oral or injection, the disease that also can will be caused by atomization inspiration treatment pulmonary bacterial.
Asthma, chronic obstructive pneumonia all belong to the flow limitation disease that respiratory inflammation causes, in recent years along with the impact of smoking, air, anaphylactogen increase etc., sickness rate improves year by year, above-mentioned disease number of patients is many, mortality rate is high, social economical burden weight, has become the important public health problem affecting human health.The treatment of current treatment asthma, chronic obstructive pneumonia is mainly based on inhalant, and compound medicine is then main based on glucocorticoid, epinephrine broxaterol.Also do not find at present anti-bacterial drug treatment non-microorganism infect cause asthma, use in chronic obstructive pneumonia.
Summary of the invention:
The discovery that we are surprised, produce when micro-antibacterial medicine forms compound recipe with the medicine for the treatment of asthma, chronic obstructive pneumonia and act on preferably, especially when the oral compound that antibacterial medicine and LTRA form jointly, curative effect is more obvious.
We think it may is because antibacterial medicine has carried out certain impact to respiratory tract cell, thus the medicine causing other treatment respiratory tract disease more easily curative effect occurs.
An oral compound medicament composition, is characterized in that by LTRA and anti-bacterial drug as active component, and and one or more be applicable to pharmaceutic adjuvants composition of oral administration.
Described LTRA is the one in zafirlukast, pranlukast, montelukast, tranilast, seratrodast.
Described pharmaceutical composition, described antibacterial medicine is one or more in cephalo-type, quinolone antibiotic, aminoglycosides, macrolide antibiotics.
Described macrolide antibiotics is one or more in 14-membered ring macrolides antibiotic.
Described macrolide antibiotics is the one in erythromycin propionate, aldehyde oleandomycin, dirithromycin, erythromycin ethylsuccinate, clarithromycin, Roxithromycin, azithromycin, clarithromycin or erythromycin estolate and optical isomer thereof.
Described aminoglycosides antibiotics medicine is the one in streptomycin, A Ka meter star, gentamycin, kanamycin, tobramycin, neomycin and optical isomer thereof.
Described cephalosporins is cephalothin sodium, cefalexin, cefadroxil, cefazolin sodium, cefradine, cefathiamidine, cefaclor, cefaloridine, cefaloglycin, cefacetrile, cefapirin, ceftezole, CEFUROXIME AXETIL, Cefuroxime Sodium, cefamandole, cefotiam, cefmetazole, cefoxitin, cefprozil, cefonicid, ceforanide, cefotaxime, cefoperazone, ceftazidime, ceftriaxone, ceftizoxime, cefmenoxime, cefpiramide cefotetan, cefixime, Cefpodoxime Proxetil, Ro-15-8075, cefodizime, ceftibuten, cefdinir, cefteram, how cephalo draws, latamoxef, ceftibuten, cefminox, cefprozil, cefepime, cefpirome, one in cefuzonam and optical isomer thereof.Be preferably the one in cefaclor, CEFUROXIME AXETIL, Cefuroxime Sodium, cefamandole, cefotiam, cefmetazole, cefoxitin, cefprozil, cefonicid, ceforanide, ceftazidime, ceftriaxone, cefepime, cefpirome, cefuzonam and optical isomer thereof.
Described quinolone antibiotic is the one in norfloxacin, ofloxacin, pefloxacin, rufloxacin, Sparfloxacin, lomefloxacin, tosufloxacin, enoxacin, ciprofloxacin, Gatifloxacin, Pazufloxacin, Moxifloxacin, trovafloxacin, grepafloxacin, prulifloxacin, clinafloxacin, Gemifloxacin and optical isomer thereof.
Aforementioned pharmaceutical compositions, is characterized in that described pharmaceutical composition is tablet or capsule.
Aforementioned pharmaceutical compositions, is characterized in that the D90 particle diameter of described active component is 5 ~ 30 μm.
Above-mentioned pharmaceutical composition, it is characterized in that described excipient substance to contain on galenic pharmacy one or more in required diluent, binding agent, disintegrating agent, lubricant, correctives, aromatic or antiseptic.Above-mentioned adjuvant in " pharmaceutics " (the 5th edition, People's Health Publisher publish) just all described in.
Aforementioned pharmaceutical compositions, is characterized in that preparing the application in treatment asthma, chronic backup pneumonia medicine.
Aforementioned pharmaceutical compositions, is characterized in that preparing the application in treatment aseptic asthma, chronic backup pneumonia medicine.
In this patent, the dosage of said medicine is with the weighing scale of medicine itself, does not comprise the weight of its salt or ester, such as MK 100mg, in fact refers to Montelukast 100mg, instead of the sodium salt 100mg of Montelukast.
Particle diameter in the present invention is equivalent volume footpath, is the diameter of the ball identical with actual particle volume.It is generally acknowledged that the diameter that laser method is surveyed is equivalent volume footpath.
Particle diameter corresponding when D90 particle diameter refers to that the cumulative particle sizes distribution number of a sample reaches 90%.Its physical significance be particle diameter be less than it amounts of particles account for 90%, this numerical value can be detected by laser particle instrument.
Mean diameter refers to meso-position radius, can detect with laser particle analyzer.
Detailed description of the invention
Micronization of the present invention can use known mechanical crushing method or spray drying method.Mechanical crushing method refers to and utilizes the method for fluid energy mill (using Nanjing Univ. Instrument Factory QM-3A) respectively medicine and/or carrier powder to be broken into required particle diameter.Spray drying method refers to and medicine and/or carrier is dissolved in organic solvent entirely as in ethanol, through spray dryer (as Buli Minispray, 190 types, Germany or QW-500, Xishan city Lin Zhou drying machine factory), solid material is made required particle diameter.Use during spray drying method and can also add surfactant as poloxamer etc.The process conditions of spray drying method can be: inlet temperature is 105 DEG C, and outlet temperature is 68 DEG C, throughput 90%, and jet expansion internal diameter is 0.1cm, nozzle air flow velocity 800ml/min, sample introduction speed 50mL/h.
Medicine mist (dripping) the grain abundance measured in embodiment below detects according to the method in 2010 editions pharmacopeia annex XH.
In an embodiment, active component 2 is the combination of following medicine, and wherein unit refers to administration unit minimum in medicine, and as capsule refers to grain, tablet is sheet, and oral liquid then refers to the minimum dosage specified in description.D90 particle diameter refers to that all medicines in active component 2 are as a sample, particle diameter corresponding when its cumulative particle sizes distribution number reaches 90%, its physical significance be particle diameter be less than it granule account for 90%.。
Example of formulations 1
Active component sees the following form
Adjuvant:
Active component, pregelatinized Starch, microcrystalline Cellulose, lactose is taken according to recipe quantity, cross 60-100 mesh sieves respectively, after mix homogeneously, add polyvidone aqueous solution soft material processed in right amount, 20 mesh sieve granules, drying, granulate, adds, magnesium stearate, carboxymethylstach sodium, micropowder silica gel, adopts applicable punch die to be pressed into tablet after mix homogeneously.
Example of formulations 2
Active component sees the following form
Adjuvant:
| Embodiment number | Active component 1 | Dosage (mg/ grain) | D90 particle diameter (μm) | Active component 2 |
| 2-1 | Gentamycin | 20 | 5.8 | M1-2 |
| 2-2 | Neomycin | 100 | 4.8 | M1-3 |
| 2-3 | Dirithromycin | 250 | 5.2 | M1-4 |
| 2-4 | Roxithromycin | 50 | 5.6 | M1-2 |
| 2-5 | Cefalexin | 125 | 4.7 | M1-3 |
| 2-6 | Cefaclor | 250 | 5.2 | M1-4 |
| 2-7 | Cefdinir | 100 | 4.8 | M1-2 |
| 2-8 | Levofloxacin | 100 | 5.3 | M1-3 |
| 2-9 | Ciprofloxacin | 100 | 4.9 | M1-4 |
| 2-10 | Gentamycin | 10 | 5.2 | M2-2 |
| 2-11 | Neomycin | 50 | 4.9 | M2-3 |
| 2-12 | Dirithromycin | 125 | 5.8 | M2-4 |
| 2-13 | Roxithromycin | 25 | 5.3 | M2-2 |
| 2-14 | Cefalexin | 62.5 | 4.3 | M2-3 |
| 2-15 | Cefaclor | 125 | 5.1 | M2-4 |
| 2-16 | Cefdinir | 50 | 4.9 | M2-2 |
| 2-17 | Levofloxacin | 50 | 5.2 | M2-3 |
| 2-18 | Ciprofloxacin | 50 | 4.8 | M2-4 |
| 2-19 | Gentamycin | 4 | 5.2 | M3-2 |
| 2-20 | Neomycin | 20 | 4.9 | M3-3 |
| 2-21 | Dirithromycin | 50 | 5.8 | M3-4 |
| 2-22 | Roxithromycin | 10 | 5.3 | M3-2 |
| 2-23 | Cefalexin | 25 | 4.3 | M3-3 |
| 2-24 | Cefaclor | 50 | 5.1 | M3-4 |
| 2-25 | Cefdinir | 20 | 4.9 | M3-2 |
| 2-26 | Levofloxacin | 20 | 5.2 | M3-3 |
| 2-27 | Ciprofloxacin | 20 | 4.8 | M3-4 |
Active component, microcrystalline Cellulose, lactose are crossed 80 mesh sieves respectively, after mix homogeneously, adds the magnesium stearate of recipe quantity, load in suitable capsule after mix homogeneously and get final product.
Example of formulations 3
Active component sees the following form
Adjuvant:
| Embodiment number | Active component 1 | Dosage (mg/ grain) | D90 particle diameter (μm) | Active component 2 |
| 3-1 | Gentamycin | 20 | 12.8 | M1-2 |
| 3-2 | Neomycin | 100 | 17.8 | M1-3 |
| 3-3 | Dirithromycin | 250 | 15.2 | M1-4 |
| 3-4 | Roxithromycin | 50 | 11.6 | M1-2 |
| 3-5 | Cefalexin | 125 | 17.7 | M1-3 |
| 3-6 | Cefaclor | 250 | 19.2 | M1-4 |
| 3-7 | Cefdinir | 100 | 15.8 | M1-2 |
| 3-8 | Levofloxacin | 100 | 13.3 | M1-3 |
| 3-9 | Ciprofloxacin | 100 | 16.9 | M1-4 |
| 3-10 | Gentamycin | 10 | 21.2 | M2-2 |
| 3-11 | Neomycin | 50 | 27.9 | M2-3 |
| 3-12 | Dirithromycin | 125 | 24.8 | M2-4 |
| 3-13 | Roxithromycin | 25 | 28.3 | M2-2 |
| 3-14 | Cefalexin | 62.5 | 21.3 | M2-3 |
| 3-15 | Cefaclor | 125 | 25.1 | M2-4 |
| 3-16 | Cefdinir | 50 | 21.9 | M2-2 |
| 3-17 | Levofloxacin | 50 | 20.2 | M2-3 |
| 3-18 | Ciprofloxacin | 50 | 24.8 | M2-4 |
| 3-19 | Gentamycin | 4 | 5.2 | M3-2 |
| 3-20 | Neomycin | 20 | 6.9 | M3-3 |
| 3-21 | Dirithromycin | 50 | 8.8 | M3-4 |
| 3-22 | Roxithromycin | 10 | 6.3 | M3-2 |
| 3-23 | Cefalexin | 25 | 9.3 | M3-3 |
| 3-24 | Cefaclor | 50 | 7.1 | M3-4 |
| 3-25 | Cefdinir | 20 | 7.9 | M3-2 |
| 3-26 | Levofloxacin | 20 | 9.2 | M3-3 |
| 3-27 | Ciprofloxacin | 20 | 5.8 | M3-4 |
Active component, pregelatinized Starch, microcrystalline Cellulose, lactose is taken according to recipe quantity, cross 60-100 mesh sieves respectively, after mix homogeneously, add polyvidone aqueous solution soft material processed in right amount, 20 mesh sieve granules, drying, granulate, adds, magnesium stearate, carboxymethylstach sodium, micropowder silica gel, adopts applicable punch die to be pressed into tablet after mix homogeneously.
Example of formulations 4
Active component sees the following form
Adjuvant:
Lactose (particle diameter is D90 at the micropowder of 30 μm) 20g
Magnesium stearate 0.5g
Make 1000 altogether
| Embodiment number | Active component 1 | Dosage (mg/ grain) | D90 particle diameter (μm) | Active component 2 |
| 4-1 | Gentamycin | 20 | 12.8 | M1-2 |
| 4-2 | Neomycin | 100 | 17.8 | M1-3 |
| 4-3 | Dirithromycin | 250 | 15.2 | M1-4 |
| 4-4 | Roxithromycin | 50 | 11.6 | M1-2 |
| 4-5 | Cefalexin | 125 | 17.7 | M1-3 |
| 4-6 | Cefaclor | 250 | 19.2 | M1-4 |
| 4-7 | Cefdinir | 100 | 15.8 | M1-2 |
| 4-8 | Levofloxacin | 100 | 13.3 | M1-3 |
| 4-9 | Ciprofloxacin | 100 | 16.9 | M1-4 |
| 4-10 | Prulifloxacin | 100 | 17.1 | M1-1 |
| 4-11 | Gentamycin | 10 | 21.2 | M2-2 |
| 4-12 | Neomycin | 50 | 27.9 | M2-3 |
| 4-13 | Dirithromycin | 125 | 24.8 | M2-4 |
| 4-14 | Roxithromycin | 25 | 28.3 | M2-2 |
| 4-15 | Cefalexin | 62.5 | 21.3 | M2-3 |
| 4-16 | Cefaclor | 125 | 25.1 | M2-4 |
| 4-17 | Cefdinir | 50 | 21.9 | M2-2 |
| 4-18 | Levofloxacin | 50 | 20.2 | M2-3 |
| 4-19 | Ciprofloxacin | 50 | 24.8 | M2-4 |
| 4-20 | Prulifloxacin | 50 | 27.5 | M2-1 |
| 4-21 | Gentamycin | 4 | 5.2 | M3-2 |
| 4-22 | Neomycin | 20 | 6.9 | M3-3 |
| 4-23 | Dirithromycin | 50 | 8.8 | M3-4 |
| 4-24 | Roxithromycin | 10 | 6.3 | M3-2 |
| 4-25 | Cefalexin | 25 | 9.3 | M3-3 |
| 4-26 | Cefaclor | 50 | 7.1 | M3-4 |
| 4-27 | Cefdinir | 20 | 7.9 | M3-2 |
| 4-28 | Levofloxacin | 20 | 9.2 | M3-3 |
| 4-29 | Ciprofloxacin | 20 | 5.8 | M3-4 |
| 4-30 | Prulifloxacin | 20 | 8.5 | M3-1 |
Active component, lactose are crossed 80 mesh sieves respectively, after mix homogeneously, adds the magnesium stearate of recipe quantity, load in suitable capsule after mix homogeneously and get final product.
Example of formulations 5
Active component sees the following form
Adjuvant:
Active component, pregelatinized Starch, microcrystalline Cellulose, lactose is taken according to recipe quantity, cross 60-100 mesh sieves respectively, after mix homogeneously, add polyvidone aqueous solution soft material processed in right amount, 20 mesh sieve granules, drying, granulate, adds, magnesium stearate, carboxymethylstach sodium, micropowder silica gel, adopts applicable punch die to be pressed into tablet after mix homogeneously.
Preparations. Control embodiment 1a
Preparations. Control embodiment 1a-1 to 1a-30 is prepared according to corresponding active component (active component only adds active component 1), ratio of adjuvant and preparation method in embodiment 1-1 to 1-30.
Preparations. Control embodiment 1b
Preparations. Control embodiment 1b-1 to 1b-30 is prepared according to corresponding active component (active component only adds active component 2), ratio of adjuvant and preparation method in embodiment 1-1 to 1-30.
Preparations. Control embodiment 2a
Preparations. Control embodiment 2a-1 to 2a-27 is prepared according to corresponding active component (active component only adds active component 1), ratio of adjuvant and preparation method in embodiment 2-1 to 2-27.
Preparations. Control embodiment 2b
Preparations. Control embodiment 2b-1 to 2b-27 is prepared according to corresponding active component (active component only adds active component 2), ratio of adjuvant and preparation method in embodiment 2-1 to 2-30.
Preparations. Control embodiment 3a
Preparations. Control embodiment 3a-1 to 3a-27 is prepared according to corresponding active component (active component only adds active component 1), ratio of adjuvant and preparation method in embodiment 3-1 to 3-27.
Preparations. Control embodiment 3b
Preparations. Control embodiment 3b-1 to 3b-27 is prepared according to corresponding active component (active component only adds active component 2), ratio of adjuvant and preparation method in embodiment 3-1 to 3-30.
Preparations. Control embodiment 4a
Preparations. Control embodiment 4a-1 to 4a-30 is prepared according to corresponding active component (active component only adds active component 1), ratio of adjuvant and preparation method in embodiment 4-1 to 4-30.
Preparations. Control embodiment 4b
Preparations. Control embodiment 1b-1 to 1b-30 is prepared according to corresponding active component (active component only adds active component 2), ratio of adjuvant and preparation method in embodiment 4-1 to 4-30.
The explanation of matched group situation
The medicine composition of matched group does not contain active component 1 or active component 2 compared with the Example formulations of corresponding group number, that is the active component in the active component of matched group and the embodiment of corresponding group number is different, but excipient substance, proportioning, preparation technology is identical, such as embodiment 1-3 group is dirithromycin containing active component 1, active component 2 is M1-1 and pharmaceutic adjuvant, corresponding matched group 1a-3 is then only containing active component 1 and excipient substance, not containing active component 2, active component 1(M1-1) with the amount of excipient substance and the active component 2(M1-1 of embodiment 1-3 group) identical with the amount of excipient substance, corresponding matched group 1b-3 is then only containing active component 2 and excipient substance, not containing active component 1, active component 2(M1-1) with the amount of excipient substance and the active component 2(M1-1 of embodiment 1-3 group) identical with the amount of excipient substance.There is several duplicate experimental grouies in matched group b, reality is only done one group and is represented other identical group, but group number retains, the matched group 1b-1 to 1b-10 that illustrates is identical, so only prepare 1b-1 group, retain 1b-2 to 1b-10 group number, when relating to the experiment of 1b-2 to 1b-10 group, also use 1b-1 group.
Pharmacological Examples 1 asthma pharmacological evaluation
1, animal model
Choose healthy male Wistar rat (there is antibacterial to checking out, the rat of bacteriological infection will not select), body weight is 200 ± 10g, put into the bell glass of about 5 liters, spray into 3% chlorination second phthalein choline and 0.1% histamine phosphate's volume mixed liquor 15 second with the pressure of 400mmHg.After spraying stops, observing the asthmatic latent period (namely asthma occur, breathe be the devil, until twitch time of falling) of rat, draw and breathe heavily the rat that the latent phase is less than 70 seconds or is greater than 120 seconds and will not select.
2, experimental technique
Learn from else's experience and measure the qualified rat of asthmatic latent period, random packet is carried out according to the group in following table, often organize 10, every day experimental group, matched group gives embodiment according to oral route, medicine in comparative examples, dosage sees the following form, model group 1 gives not containing the blank tablet (450mg/kg) of embodiment 3 prescription of active component according to oral route, within the 10th day of administration, give 0.3% 2 hydrochloric acid histamine when spraying after after giving whole medicine 1.5 hours, observe the change (draw animal when breathing heavily and do not occur in 6 minutes that to breathe heavily the volt phase be calculate for 360 seconds to the person of falling to draw) of asthmatic latent period and tic incidence rate before and after drug.
The dosage of experimental group, matched group a group is all as the criterion with antibacterium pharmaceutical quantities, and the dosage of the active component 2 that the drug dose in matched group b group gives according to corresponding experimental group gives.
3, experimentation and result: animal generation asthma until the time of falling of twitching see the following form.
Have multiple form to be the result of this experiment in the present embodiment, problem for convenience of explanation, splits experimental result.
Table 1-1 uses merely anti-bacterial drug experimental result (n=10, mean ± SD)
Prove that the asthmatic latent period of asthmatic model animal increases after giving the antibiolics of various dose by above-mentioned experimental data, but change is little, the comparative examples 1-21 to 1-30 of especially low dosage is with basically identical with not administration group, change performance, can illustrate that asthmatic model animal only gives anti-bacterial drug, only can mild prolonged Paroxysmal asthma during high dose, and the Paroxysmal asthma on statistical significance during low dosage, cannot be extended.
Table 1-2 contains the experimental result (n=10, mean ± SD) of the single preparations of ephedrine of LTRA
Prove that the asthmatic latent period of asthmatic model animal is significantly improved after giving the leukotriene antagonist of various dose by above-mentioned experimental data, and reduce gradually along with lessening the curative effect of dosage.
Table 1-3 contains the experimental result (n=10, mean ± SD) of compound preparation of anti-bacterial drug, LTRA
Proved by above-mentioned experimental data, the experimental result successful of the compound preparation of anti-bacterial drug, LTRA is better than the experimental result of the single preparations of ephedrine of anti-bacterial drug or LTRA; Along with the decline of antibacterials dosage, the decline of compound medicine curative effect is more obvious, especially antibacterials dose degradation to normal dose 20% time, although the curative effect of compound medicine is better than folk prescription medicine, but advantage not obvious; Experimental result after the dosage of the compound preparation of anti-bacterial drug, LTRA all declines all is better than the experimental result of the single preparations of ephedrine of anti-bacterial drug or LTRA.
Pharmacological Examples 2 chronic obstructive pulmonary disease pharmacological evaluation
1, chronic obstructive pulmonary disease animal:
Male secondary SD rat, Mus age 8 week age, body weight 150 ~ 170g.Animal is adopted instillation Porcine trypsin method in fumigation (Golden Bridge) gas-adding pipe, namely the 1st, 15 day is tested through trachea instillation Porcine trypsin 0.5mg/kg, start smoked 5% medicated cigarette next day, 1 hour every morning, until the last day of the 10th week.
2, experimental technique
Get healthy male secondary SD rat 10, Mus age 8 week age, body weight 150 ~ 170g, is set to model group 2, and every day gives not containing the blank tablet (450mg/kg) of embodiment 3 prescription of active component according to oral route, successive administration 14 days.
Get the rat of making Chronic obstructive pulmonary disease, random packet is carried out according to the group in following table, often organize 10, every day carries out administration in the bell glass of about 5 liters, experimental group gives the medicine in embodiment according to the arrangement oral route in following table, model group 1 gives not containing the blank tablet (450mg/kg) of embodiment 3 prescription of active component according to oral route, and matched group oral route gives corresponding dosage matched group medicine, the equal successive administration of experimental group, model group 1, matched group 14 days.
The dosage of experimental group, matched group a group is all as the criterion with antibacterium pharmaceutical quantities, and the dosage of the active component 2 that the drug dose in matched group b group gives according to corresponding experimental group gives.
3, experimentation and result: experimental group, model group 1,2, rat was put to death in the 14th day after matched group administration, get the right lower lobe lung tissue of every rat, specimens paraffin embedding slices, carry out elastic fibers dyeing, carry out the mensuration of elastic fiber relative amount by HIPS-1000 multi-functional true color pathological picture and text analytical system, concrete data see the following form.
Have multiple form to be the result of this experiment in the present embodiment, problem for convenience of explanation, splits experimental result.
Table 2-1 uses merely anti-bacterial drug experimental result (n=10, mean ± SD)
| Comparative examples group | Medicine | Dosage every day (μ g/kg) | Elastic fiber relative amount (%) |
| 3a-1 | Gentamycin | 20 | 11.8±1.7 |
| 3a-2 | Neomycin | 100 | 11.7±1.6 |
| 3a-3 | Dirithromycin | 250 | 12.1±1.9 |
| 3a-4 | Roxithromycin | 50 | 12.0±1.8 |
| 3a-5 | Cefalexin | 125 | 11.7±1.6 |
| 3a-6 | Cefaclor | 250 | 11.9±1.5 |
| 3a-7 | Cefdinir | 100 | 12.2±1.5 |
| 3a-8 | Levofloxacin | 100 | 11.9±1.3 |
| 3a-9 | Ciprofloxacin | 100 | 12.1±1.6 |
| 3a-10 | Gentamycin | 10 | 12.3±1.8 |
| 3a-11 | Neomycin | 50 | 11.9±1.5 |
| 3a-12 | Dirithromycin | 125 | 11.9±1.6 |
| 3a-13 | Roxithromycin | 25 | 12.1±1.7 |
| 3a-14 | Cefalexin | 62.5 | 12.0±1.5 |
| 3a-15 | Cefaclor | 125 | 11.8±1.3 |
| 3a-16 | Cefdinir | 50 | 11.9±1.6 |
| 3a-17 | Levofloxacin | 50 | 12.2±1.6 |
| 3a-18 | Ciprofloxacin | 50 | 11.4±1.9 |
| 3a-19 | Gentamycin | 4 | 11.2±1.3 |
| 3a-20 | Neomycin | 20 | 11.1±1.6 |
| 3a-21 | Dirithromycin | 50 | 11.5±1.9 |
| 3a-22 | Roxithromycin | 10 | 11.4±1.9 |
| 3a-23 | Cefalexin | 25 | 11.2±2.1 |
| 3a-24 | Cefaclor | 50 | 11.4±1.7 |
| 3a-25 | Cefdinir | 20 | 11.6±1.5 |
| 3a-26 | Levofloxacin | 20 | 11.5±1.7 |
| 3a-27 | Ciprofloxacin | 20 | 11.6±1.9 |
| 1a-10 | Prulifloxacin | 100 | 12.2±2.1 |
| 1a-20 | Prulifloxacin | 50 | 11.9±1.2 |
| 1a-30 | Prulifloxacin | 20 | 11.3±1.6 |
| Model group 1 | Nothing | 11.5±1.4 | |
| Model group 2 | Nothing | 22.4±1.9 |
Prove that the elastic fiber relative amount of Chronic obstructive pulmonary disease animal does not have difference before administration afterwards by experiment by above-mentioned experimental data, basically identical with not administration group, can illustrate that Chronic obstructive pulmonary disease animal only gives anti-bacterial drug, the relative scale of lung fiber cannot be improved.
Table 2-2 uses merely the experimental result (n=10, mean ± SD) of the single preparations of ephedrine of LTRA
| Comparative examples group | Medicine | Dosage every day (mg/kg) | Elastic fiber relative amount (%) |
| 1b-1 | Menglusitena | 200 | 13.6±1.5 |
| 1b-11 | Menglusitena | 100 | 13.3±1.7 |
| 1b-21 | Menglusitena | 20 | 12.9±1.6 |
| 3b-1 | Zafirlukast | 40 | 13.4±1.6 |
| 3b-2 | Pranlukast | 200 | 13.6±1.9 |
| 3b-3 | Tranilast | 100 | 13.8±1.8 |
| 3b-10 | Zafirlukast | 20 | 13.2±1.9 |
| 3b-11 | Pranlukast | 100 | 13.1±2.1 |
| 3b-12 | Tranilast | 50 | 13.4±1.8 |
| 3b-19 | Zafirlukast | 8 | 12.7±1.8 |
| 3b-20 | Pranlukast | 40 | 12.5±2.1 |
| 3b-21 | Tranilast | 20 | 12.9±1.9 |
Prove that the Fibrosis levels of chronic obstructive pulmonary disease animal pattern declines to some extent after giving the leukotriene antagonist of various dose by above-mentioned experimental data, and gradually change along with the raising curative effect of dosage.
Table 2-3 contains the experimental result (n=10, mean ± SD) of compound preparation of anti-bacterial drug, LTRA
| Embodiment group | Medicine | Dosage every day (mg/kg) | Elastic fiber relative amount (%) |
| 3-1 | Gentamycin | 20 | 14.7±1.9 |
| 3-2 | Neomycin | 100 | 14.5±1.7 |
| 3-3 | Dirithromycin | 250 | 15.4±1.9 |
| 3-4 | Roxithromycin | 50 | 15.3±2.1 |
| 3-5 | Cefalexin | 125 | 14.6±1.6 |
| 3-6 | Cefaclor | 250 | 14.9±1.5 |
| 3-7 | Cefdinir | 100 | 15.3±1.4 |
| 3-8 | Levofloxacin | 100 | 14.1±1.5 |
| 3-9 | Ciprofloxacin | 100 | 14.3±1.5 |
| 3-10 | Gentamycin | 10 | 14.3±1.9 |
| 3-11 | Neomycin | 50 | 14.0±1.4 |
| 3-12 | Dirithromycin | 125 | 14.9±1.7 |
| 3-13 | Roxithromycin | 25 | 15.0±2.2 |
| 3-14 | Cefalexin | 62.5 | 14.2±1.7 |
| 3-15 | Cefaclor | 125 | 14.3±1.4 |
| 3-16 | Cefdinir | 50 | 14.6±1.8 |
| 3-17 | Levofloxacin | 50 | 13.9±2.2 |
| 3-18 | Ciprofloxacin | 50 | 13.9±1.8 |
| 1-10 | Prulifloxacin | 100 | 15.6±1.8 |
| 1-20 | Prulifloxacin | 50 | 14.9±1.5 |
| 5-13 | Dirithromycin | 125 | 15.1±1.8 |
| 5-17 | Cefdinir | 50 | 14.9±1.9 |
| 5-20 | Prulifloxacin | 50 | 15.1±2.1 |
| 5-23 | Dirithromycin | 50 | 14.9±1.8 |
| 5-27 | Cefdinir | 20 | 14.7±1.8 |
| 5-30 | Prulifloxacin | 20 | 14.9±1.6 |
Proved by above-mentioned experimental data, the experimental result effect of the compound preparation of anti-bacterial drug, LTRA is better than the experimental result of the single preparations of ephedrine of anti-bacterial drug or LTRA; Along with the decline of antibacterials dosage, the decline of compound medicine curative effect is comparatively slow, especially antibacterials dose degradation to normal dose 20% time, although the curative effect of compound medicine is better than folk prescription medicine, but advantage not obvious; Experimental result after the dosage of the compound preparation of anti-bacterial drug, LTRA all declines all is better than the experimental result of the single preparations of ephedrine of anti-bacterial drug or LTRA.
Claims (10)
1. an oral compound medicament composition, is characterized in that by LTRA and anti-bacterial drug as active component, and and one or more be applicable to pharmaceutic adjuvants composition of oral administration.
2. pharmaceutical composition as claimed in claim 1, is characterized in that described LTRA is the one in zafirlukast, pranlukast, montelukast, tranilast, seratrodast.
3. pharmaceutical composition as claimed in claim 1, is characterized in that described antibacterial medicine is one or more in cephalo-type, quinolone antibiotic, aminoglycosides, macrolide antibiotics.
4. pharmaceutical composition as claimed in claim 3, is characterized in that described macrolide antibiotics is one or more in 14-membered ring macrolides antibiotic.
5. pharmaceutical composition as claimed in claim 3, it is characterized in that described cephalosporins is cephalothin sodium, cefalexin, cefadroxil, cefazolin sodium, cefradine, cefathiamidine, cefaclor, cefaloridine, cefaloglycin, cefacetrile, cefapirin, ceftezole, CEFUROXIME AXETIL, Cefuroxime Sodium, cefamandole, cefotiam, cefmetazole, cefoxitin, cefprozil, cefonicid, ceforanide, cefotaxime, cefoperazone, ceftazidime, ceftriaxone, ceftizoxime, cefmenoxime, cefpiramide cefotetan, cefixime, Cefpodoxime Proxetil, Ro-15-8075, cefodizime, ceftibuten, cefdinir, cefteram, how cephalo draws, latamoxef, ceftibuten, cefminox, cefprozil, cefepime, cefpirome, one in cefuzonam and optical isomer thereof.
6. pharmaceutical composition as claimed in claim 3, is characterized in that described quinolone antibiotic is the one in norfloxacin, ofloxacin, pefloxacin, rufloxacin, Sparfloxacin, lomefloxacin, tosufloxacin, enoxacin, ciprofloxacin, Gatifloxacin, Pazufloxacin, Moxifloxacin, trovafloxacin, grepafloxacin, prulifloxacin, clinafloxacin, Gemifloxacin and optical isomer thereof.
7. pharmaceutical composition as claimed in claim 1, is characterized in that described pharmaceutical composition is tablet or capsule.
8. pharmaceutical composition as claimed in claim 1, is characterized in that the D90 particle diameter of described active component is 1 ~ 10 μm.
9. pharmaceutical composition as claimed in claim 1, it is characterized in that described excipient substance contains institute on galenic pharmacy must one or more in diluent, binding agent, disintegrating agent, lubricant, correctives, aromatic or antiseptic.
10. pharmaceutical composition as claimed in claim 1, is characterized in that preparing the application in treatment aseptic asthma, chronic backup pneumonia medicine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310205624.2A CN104208699A (en) | 2013-05-29 | 2013-05-29 | Compound oral preparation containing antibacterial drugs |
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|---|---|---|---|
| CN201310205624.2A CN104208699A (en) | 2013-05-29 | 2013-05-29 | Compound oral preparation containing antibacterial drugs |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105287562A (en) * | 2015-10-27 | 2016-02-03 | 白强 | Moxifloxacin hydrochloride composition and application of same in preparing medicine for treating lung injury |
| CN107312019A (en) * | 2017-06-16 | 2017-11-03 | 成都倍特药业有限公司 | A kind of Cefixime and its method for crystallising |
| WO2018086626A1 (en) * | 2016-11-14 | 2018-05-17 | 武汉华杰世纪生物医药有限公司 | Compound having anti-tumour effect |
| CN108926570A (en) * | 2017-05-27 | 2018-12-04 | 上海颢峰医药科技有限公司 | Cephalosporin analog antibiotic is preparing the application in preventing/treating pulmonary hypertension drug |
| WO2018219189A1 (en) * | 2017-05-27 | 2018-12-06 | 上海颢峰医药科技有限公司 | Application of cefmetazole in preparation of medicine for preventing/treating pulmonary hypertension |
| WO2018219188A1 (en) * | 2017-05-27 | 2018-12-06 | 上海颢峰医药科技有限公司 | Application of cefminox in preparation of medicine for preventing/treating pulmonary hypertension |
| CN108938644A (en) * | 2017-05-27 | 2018-12-07 | 上海颢峰医药科技有限公司 | Cefminox is preparing the application in preventing/treating pulmonary hypertension drug |
| CN108938643A (en) * | 2017-05-27 | 2018-12-07 | 上海颢峰医药科技有限公司 | Cefmetazole is preparing the application in preventing/treating pulmonary hypertension drug |
| WO2019122911A1 (en) * | 2017-12-22 | 2019-06-27 | Benevolentai Bio Limited | Tranilast for cystic fibrosis |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105287562A (en) * | 2015-10-27 | 2016-02-03 | 白强 | Moxifloxacin hydrochloride composition and application of same in preparing medicine for treating lung injury |
| WO2018086626A1 (en) * | 2016-11-14 | 2018-05-17 | 武汉华杰世纪生物医药有限公司 | Compound having anti-tumour effect |
| CN108926570A (en) * | 2017-05-27 | 2018-12-04 | 上海颢峰医药科技有限公司 | Cephalosporin analog antibiotic is preparing the application in preventing/treating pulmonary hypertension drug |
| WO2018219187A1 (en) * | 2017-05-27 | 2018-12-06 | 上海颢峰医药科技有限公司 | Application of cephalosporin antibiotics in preparation of medicine for preventing/treating pulmonary arterial hypertension |
| WO2018219189A1 (en) * | 2017-05-27 | 2018-12-06 | 上海颢峰医药科技有限公司 | Application of cefmetazole in preparation of medicine for preventing/treating pulmonary hypertension |
| WO2018219188A1 (en) * | 2017-05-27 | 2018-12-06 | 上海颢峰医药科技有限公司 | Application of cefminox in preparation of medicine for preventing/treating pulmonary hypertension |
| CN108938644A (en) * | 2017-05-27 | 2018-12-07 | 上海颢峰医药科技有限公司 | Cefminox is preparing the application in preventing/treating pulmonary hypertension drug |
| CN108938643A (en) * | 2017-05-27 | 2018-12-07 | 上海颢峰医药科技有限公司 | Cefmetazole is preparing the application in preventing/treating pulmonary hypertension drug |
| CN107312019A (en) * | 2017-06-16 | 2017-11-03 | 成都倍特药业有限公司 | A kind of Cefixime and its method for crystallising |
| CN107312019B (en) * | 2017-06-16 | 2019-06-25 | 成都倍特药业有限公司 | A kind of Cefixime and its method for crystallising |
| WO2019122911A1 (en) * | 2017-12-22 | 2019-06-27 | Benevolentai Bio Limited | Tranilast for cystic fibrosis |
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