CN102274515B - Medicinal composition containing montelukast and statins medicament - Google Patents
Medicinal composition containing montelukast and statins medicament Download PDFInfo
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- CN102274515B CN102274515B CN 201110255919 CN201110255919A CN102274515B CN 102274515 B CN102274515 B CN 102274515B CN 201110255919 CN201110255919 CN 201110255919 CN 201110255919 A CN201110255919 A CN 201110255919A CN 102274515 B CN102274515 B CN 102274515B
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- rosuvastatin
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Abstract
The invention belongs to the technical field of medicaments, provides a medicinal composition containing montelukast and a statins medicament, and discloses application of the medicinal composition to the preparation of a medicament for treating asthma diseases. Specifically, the medicinal composition contains two medicinal active ingredients, i.e., montelukast and a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, wherein the mass ratio of the montelukast to the HMG-CoA reductase inhibitor is 1:(0.01-10). Moreover, a compound preparation can be prepared into an oral administration preparation or a parenteral administration preparation.
Description
Technical field
The invention belongs to medical technical field, specifically establish and the pharmaceutical composition of a kind of montelukast and statins.
Background technology
Bronchial asthma (abbreviation asthma), its sickness rate is year by year ascendant trend, and public health in serious threat.Asthma is a kind of chronic airway inflammation, is the respiratory tract chronic inflammation that is participated in by multiple inflammatory cell.It is characterized by Reversible airway obstruction and airway reactivity increases, the secretions increase that airway obstruction is caused by the bronchial mucosa inflammation, myxedema and two kinds of factors of inflammatory stimulus smooth muscle spasm cause; And airway reactivity to increase also be because the result of the bronchial epithelial cell damage that airway inflammation causes.It has been recognized that to only have the inflammation of control air flue mucosa, just can reach the purpose of final reduction airway hyperreactivity, relieving asthma symptoms, present research concentrates on air flue mostly, thinks that airway inflammation is the main pathogenesis of asthma.But in fact, the lung tissue of asthma patient also has pathological change, and its pathological change of dissimilar asthma patient is different.
Montelukast montelukast (trade name Singulair singulair) be at present commonly used be the leukotriene receptor depressant, improving pulmonary function, reducing airway hyperreactivity, suppressing Airway Remodeling and pulmonary fibrosis resistant, and all many-sides such as impact of inflammation and immunity are all being played a significant role.It has the various biological effect, can be combined with leukotriene receptor competitively, thereby inhibition leukotriene, the inflammatory effects of LTD-4 particularly, effectiveness prevents the air flue spasm because antigen, cold air suck and motion etc. is brought out, also can make asthmatic patient accept after the antigenic stimulus that eosinophilic granulocyte and other inflammatory cells reduce in the bronchoalveolar lavage fluid, can alleviate airway smooth muscle simultaneously and shrink, reduce airway hyperreactivity.The dual function that montelukast has antiinflammatory and relievings asthma, but its antiinflammatory action than glucocorticoid a little less than.
China's document " foreign medical science pharmacy fascicle " the 5th phase of the 30th volume October in 2003,284～287 disclose, Menglusitena and glucocorticoid are to the control effect of symptoms of asthma and similar to the inhibitory action of airway inflammation, and both have collaborative and vicarious function.Accept the asthmatic patient of Glucocorticoid Inhalation, adding the consumption that can reduce gradually glucocorticoid with montelukast.And Chinese document " practical clinical medical magazine " the 6th phase of the 10th volume in 2006, the research of the drug combination treatment asthma of montelukast and inhaled glucocorticoids is provided in 47～49, result of study shows that montelukast is united and inhales people's grain 17-hydroxy-11-dehydrocorticosterone and can effectively improve severe asthma patient's lung function index, relieving asthma symptoms, treatment asthma.But be oral medication at employed montelukast in the document.Dosage is larger, uses inconvenient.And a small amount of general action is arranged, gastrointestinal tract is had zest." adverse effect magazine " 7 volumes in 2005 2 phase 116-117 discloses in clinical research, and using montelukast has 1% left and right sides patient headache, dizziness, the stomachache relevant with medication to occur.
Statins is that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor is an effective treatment means that reduces coronary heart disease risk.Find that in pharmacological research statins not only has good effect for reducing blood fat, but also has the thrombotic effect of anti-inflammatory response, stabilize plaque and inhibition, its mechanism of action comprises: increase nitricoxide synthase (nitric oxide syn2thase, NOS) expression, reduce endothelin-1 (endothelin-1, ET-A) and reactive oxygen intermediate (reactive oxygen species, ROS) synthetic; Reduce the level of c reactive protein (C-reactive p rotein, CRP); Suppress the growth of macrophage and the migration of smooth muscle cell (vascular smooth muscle cell, VSMC).Be usually used at present clinical having: lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, newer in addition Rosuvastatin and Pitavastatin.Statins is evident in efficacy, side effect is little, has become the choice drug of transferring fat, and in clinical application research, has constantly found the purposes that it is new.
Thereby it is low to seek to develop a kind of side effect, and cost is low, and good effect can suppress the medicine of airway of patient with asthma reconstruct, fundamentally cures asthma, alleviates patient's misery and huge medical expense, and is significant.The people such as Li Lifang (" Ningxia Medical University's journal " 05 phase in 2011, montelukast is on impact and the meaning of atherosclerotic rat leukotriene) have inquired into montelukast sodium and simvastatin to atherosclerotic effect.And Menglusitena and statins have no report as the compound treatment respiratory tract disease in the prior art.
Summary of the invention
When the inventor finds Menglusitena and statins coupling unexpectedly on the basis of lot of experiments, not only have the stronger effect of relievining asthma, and the also significantly reinforcement of its antiinflammatory action, this compound recipe has good synergism.
The object of the present invention is to provide a kind of pharmaceutical composition of new treatment bronchial asthma, it contains the following active component of effective dose:
1) montelukast or its pharmaceutically acceptable salt; With
2) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.
Wherein the mass ratio of Menglusitena or its salt and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor is 1: 0.01-10.
In the above-mentioned pharmaceutical composition, described montelukast pharmaceutically acceptable salt is Menglusitena.
Affiliated HMG-CoA reductase inhibitor is one or more in lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, Rosuvastatin or the Pitavastatin, preferred Rosuvastatin.
The inventor is according to the result of clinical trial, and with suitable dosage ratio, it is manufactured becomes the compound preparation that makes things convenient for the patient to take with Menglusitena and statins class medicine.
Pharmaceutical composition recited above, preferred Menglusitena and Rosuvastatin weight ratio are 1: 0.1-1, most preferred Menglusitena and Rosuvastatin weight ratio are 1: 0.3.
In the pharmaceutical preparation that is prepared into according to pharmaceutical composition provided by the present invention, the effective dose that montelukast or its pharmaceutically acceptable salt are contained in each preparation unit is 1mg-5mg, and the effective dose that contains 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor is 0.05mg-10mg.In the pharmaceutical preparation that preferred pharmaceutical composition provided by the present invention is prepared into, the effective dose that Menglusitena is contained in each preparation unit is 1mg-5mg, and the effective dose that contains Rosuvastatin is 0.5mg-5mg.In the pharmaceutical preparation that further preferred pharmaceutical composition provided by the present invention is prepared into, the effective dose that Menglusitena is contained in each preparation unit is 5mg, and the effective dose that contains Rosuvastatin is 1.5mg.For a person skilled in the art, the administration frequency is determined after can considering according to combined factors such as state of an illness situation, ages.
Compound preparation of the present invention, oral administration and intestinal external administration can both reach good effect.Several dosage forms such as the preferred double-layer tablet of oral administration, slow releasing tablet, dispersible tablet, oral cavity disintegration tablet, capsule or drop pill wherein.
Double-layer tablet described above, dispersible tablet, capsule also comprises adjuvant commonly used such as starch, L-HPC (low-substituted hydroxypropyl cellulose), magnesium stearate, microcrystalline Cellulose, PVP (polyvinylpyrrolidone), micropowder silica gel, carboxymethyl starch sodium, the tertiary butyl-4-hydroxy methyl phenyl ethers anisole, Pulvis Talci, vitamin E, the Henan gelling starch, carboxymethyl starch sodium, lactose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, crospolyvinylpyrrolidone, in the crosslinked carboxymethyl fecula sodium adjuvant one or more.
Slow releasing tablet described above and slow releasing capsule are preferred following slow-release auxiliary material hexadecanol, octadecanol, HPMC-4M (hydroxypropyl emthylcellulose-4M), HPMC-15M (one or more in hydroxypropyl emthylcellulose-15M), glyceryl monostearate, ethyl cellulose, acrylic resin RS100, acrylic resin RL100, polyvinyl alcohol or the ethylene-vinyl acetate copolymer;
Preferred one or more in following adjuvant vitamin E, PEG400, PEG-3 oleate (Polyethylene Glycol-3 olein), glycerol, gelatin, propylene glycol or the PEG-60 glyceryl isostearate (Polyethylene Glycol-60 glyceryl isostearate) in the development of soft capsule;
Preferred one or more among following adjuvant PEG-1500 (PEG-4000), PEG-2000 (Polyethylene glycol-2000), PEG-4000 (PEG-4000) or the PEG-6000 (PEG-4000) in the development of drop pill.
Because asthma is a kind of chronic disease, needs long-term prescription.Asthmatic patient can produce repel psychology to Long-term taking medicine, for covering the bitterness of medicine, increases mouthfeel, and the inventor is also with the oral tablet coating, comprising: sweet tablet, film coating.Greatly increased patient's compliance behind the coating.
The intestinal external administration can be injection, injection powder pin, spray, aerosol, powder spray, buccal tablet.Its preparation method and pharmaceutic adjuvant are common method and adjuvant thereof.
Pharmaceutical composition of the present invention is mainly reflected in the following aspects in the advantage for the treatment of bronchial asthma fermentation:
The compound recipe that shows Menglusitena and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor by animal experimental data has good synergism, show evident in efficacy through a large amount of zooperies, and reduced the consumption (conventional amount used of using separately: Menglusitena 10mg/ days of Menglusitena, the conventional amount used of using of Menglusitena is 1-5mg/ days in the pharmaceutical composition of the present invention, the conventional amount used of using of Rosuvastatin is 0.1-5mg/ days), side effect significantly reduces, and has increased the safety of medication.
Secondly, pharmaceutical composition of the present invention is rapid-action, than Menglusitena folk prescription long action time; In the survival rate that has improved rat and prolonged to draw to breathe heavily aspect incubation period to compare with the Menglusitena folk prescription and have significant difference.Animal experiment shows that pharmaceutical composition of the present invention prolongs to draw to breathe heavily to compare with the montelukast folk prescription incubation period and has significant difference, compares with statins to have utmost point significant difference.
The 3rd, because when forming immobilised compound, the dosage of each single medicine all has minimizing, thereby the incidence rate of drug side effect reduces; About medical expense, reduce when using separately owing to used drug dose ratio, and production and packing cost reduction, therefore, medical expense not only can not increase, and has on the contrary decline, so that the benefit for the treatment of/expense ratio is significantly improved.Therefore patient's treatment compliance increases greatly, and quality of life also will obviously improve.
The 4th, pharmaceutical composition of the present invention, not only strong than the Menglusitena folk prescription effect of relievining asthma, and also its antiinflammatory action is compared with the Menglusitena folk prescription and is had significant difference.Pharmaceutical composition of the present invention is except can significantly reducing eosinophilic granulocyte among the mice BALF, lymphocyte, neutrophilic granulocyte number, the effect that more can beat all generation better reduces BALF macrophage number, thereby when treatment asthma, reach better therapeutic effect, for the treatment asthma has been opened up an a new direction.
The specific embodiment
For a better understanding of the present invention, below by the description to preferred embodiment of the present invention, the present invention that explains in detail, but do not limit in any form the present invention.
The preparation of embodiment 1 tablet
Preparation technology: pravastatin, Menglusitena and microcrystalline cellulose excipients, carboxymethyl starch sodium mix homogeneously, add an amount of starch slurry soft material processed, right mistake 16 mesh sieves are granulated.Wet granular is 60 ℃ of dryings, and dried granule is crossed 16 mesh sieve granulate, sifts out the fine powder in the dry granular, with the magnesium stearate mixing, and then with dried granule mixing, tabletting, and get final product.
The preparation of embodiment 2 tablets
Preparation technology: Rosuvastatin, Menglusitena and microcrystalline cellulose excipients, carboxymethyl starch sodium mix homogeneously, add an amount of starch slurry soft material processed, right mistake 16 mesh sieves are granulated.Wet granular is 60 ℃ of dryings, and dried granule is crossed 16 mesh sieve granulate, sifts out the fine powder in the dry granular, with the magnesium stearate mixing, and then with dried granule mixing, tabletting, and get final product.
The preparation of embodiment 3 tablets
Preparation technology: Rosuvastatin, zafirlukast sodium and microcrystalline cellulose excipients, carboxymethyl starch sodium mix homogeneously, add an amount of starch slurry soft material processed, right mistake 16 mesh sieves are granulated.Wet granular is 60 ℃ of dryings, and dried granule is crossed 16 mesh sieve granulate, sifts out the fine powder in the dry granular, with the magnesium stearate mixing, and then with dried granule mixing, tabletting, and get final product.
The preparation of embodiment 4 bilayer tablets
a、
Preparation technology: simvastatin is crossed 100 mesh sieves, hydroxypropyl cellulose-4M, microcrystalline Cellulose are crossed 80 mesh sieves, take by weighing the simvastatin of recipe quantity and hydroxypropyl cellulose-4M, microcrystalline Cellulose mix homogeneously, adding the 6%PVP ethanol solution granulates in right amount, 60 ℃ of dryings, the whole dried granule of 16 mesh sieves, the magnesium stearate of adding recipe quantity in the dried granule.
b、
Preparation technology: Menglusitena is crossed 100 mesh sieves, sodium carboxymethyl cellulose, lactose are crossed 80 mesh sieves, take by weighing the Menglusitena of recipe quantity and sodium carboxymethyl cellulose, lactose mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, the whole dried granule of 16 mesh sieves, the magnesium stearate of adding recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press punching press namely to get double-layer tablet.
The preparation of embodiment 5 bilayer tablets
a、
Preparation technology: Menglusitena is crossed 100 mesh sieves, lactose, hydroxypropyl emthylcellulose-15M cross 80 mesh sieves, take by weighing the Menglusitena of recipe quantity and lactose, hydroxypropyl emthylcellulose-15M mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, the whole dried granule of 16 mesh sieves, the Rikemal B 200 of adding recipe quantity in the dried granule.
b、
Preparation technology: atorvastatin is crossed 100 mesh sieves, hydroxypropyl cellulose, dextrin are crossed 80 mesh sieves, take by weighing the atorvastatin of recipe quantity and hydroxypropyl cellulose, dextrin mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, the whole dried granule of 16 mesh sieves, the Pulvis Talci of adding recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press punching press namely to get double-layer tablet.
The preparation of embodiment 6 capsules
A, Menglusitena 5g
Celphere 250g
7%PVP solution (solvent is 90% ethanol) 200g
Preparation technology: Menglusitena is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Open granulation coating machine (Taiwan unit becomes machinery plant), enter wind pressure 0.5bar, enter 30 ℃ of air temperatures, spray gun pressure (CYL) 3bar, atomizing pressure (CAP1) 0.8bar, pour celphere into, pelletize, blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 145rpm, spray 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 50 ℃ of oven dry, discharging.
B, lovastatin 1.5g
Celphere 90g
7%PVP solution (solvent is 90% ethanol) 50g
Preparation technology: lovastatin is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Open granulation coating machine, enter wind pressure 0.5bar, enter 30 ℃ of air temperatures, CYL3bar, CAP1 0.8bar pours celphere into, pelletize, blanking velocity 4rpm, the pump 6% of wriggling, rotary speed 160rpm, spray 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 45 ℃ of oven dry, discharging.
C, the piller that a and b are made adopts hard capsule medicine filling machine to be respectively 5mg according to the weight that contains Menglusitena and lovastatin in per two capsules and 1.5mg fills, and gets final product.
Embodiment 7 statinses and Menglusitena are united the pharmacodynamic experiment that uses experimental rat model of asthma
Experiment purpose:
Utilize induced lung body index before and after the determination experiment, the BALF of Rats classified counting of leucocyte is observed speed and is sent out the inhibitory action of investigating the bronchial asthma that Menglusitena and statins compound recipe bring out ovalbumin the incubation period of phase symptoms of asthma and asthma.
Tested medicine:
The pharmaceutical composition of Rosuvastatin and Menglusitena compound recipe
Group arranges:
Blank group, model group, Menglusitena, Rosuvastatin group, Menglusitena and Rosuvastatin compound recipe A, B, C amount group, compound recipe D group (Menglusitena and atorvastatin compound recipe group), compound recipe E organize (Menglusitena and simvastatin compound recipe group).
Gastric infusion dosage:
Menglusitena 0.75mg/kg,
Rosuvastatin 0.225mg/kg,
Menglusitena and Rosuvastatin compound recipe A, B, C group dosage are respectively: 0.75mg/kg Menglusitena+0.225mg/kg Rosuvastatin, 0.75mg/kg Menglusitena+0.225mg/kg Rosuvastatin, 0.75mg/kg Menglusitena+0.75mg/kg Rosuvastatin
Compound recipe D group: 0.75mg/kg Menglusitena+0.0075mg/kg atorvastatin compound recipe group,
Compound recipe E group: 0.15mg/kg Menglusitena+1.5mg/kg simvastatin compound recipe group.
Operating procedure:
The preparation of Rat Asthma Model: 96 SD rats, body weight are 200～240g, are divided at random 9 groups by body weight, 10 every group.Each group is 5% ovalbumin of the fresh preparation of lumbar injection (1ml/ only) respectively, and Normal group was strengthened once at intraperitoneal injection of saline lml in 5 days afterwards.Atomized afterwards in 10 days and suck 1% ovalbumin normal saline, once a day, 15min/ time, continuous 35 days.Each organizes respectively gastric infusion simultaneously, 10ml/kg, and gavage is 35 days continuously, and Normal group and model group give the normal saline gavage, 10ml/kg, gavage is 35 days continuously.
Rat speed is sent out bringing out of phase asthma: attack with 1% ovalbumin and the atomizing of 2% acetylcholine, bring out asthma, observe incubation period and the symptoms of asthma of each group.
Observation index:
Draw and breathe heavily incubation period, be placed on respectively each group rat in the hermetic container, put into 4 at every turn, again with 1% egg protein solution spray, appoint animal to suck voluntarily, until asthma attack, record the dyspneic time occurs from being atomised to, carry out this 5th, 10,15 day of detecting respectively at excitation phase, gets the meansigma methods that detects for three times and be drawing of every rat and breathe heavily incubation period.
Measure body weight and lung body index, put to death animal, cut off skin of chest, open the thoracic cavity, peel off lung tissue, take by weighing the lung tissue weight in wet base, and calculate lung body index.Computational methods are as follows: body weight before body weight after body weight difference=test-test; Lung body index=lung weighs/the rear body weight (g) * 100% of test.
The impact on the airway of mice inflammation is respectively organized in test: put to death animal, and carry out bronchoalveolar lavage and collect irrigating solution (BALF) and carry out the differential counting statistics.
Experimental result and statistical analysis:
1. preclinical impact after each Experimental agents group is attacked sensitized rats antigen
In the rat of test group, statins and Menglusitena have significant coordinate repression to symptoms of asthma, have greatly prolonged the incubation period of Bronchial Asthma.Especially Menglusitena and Rosuvastatin compound recipe group synergy are obviously better, and concrete experimental result sees Table 1.
Preclinical impact after table 1 Menglusitena and Rosuvastatin compound recipe are attacked sensitized rats antigen
*Compare P＜0.05 with model group,
※Compare P＜0.05 with the Menglusitena group,
﹠amp;Compare P＜0.05 with the Rosuvastatin group.
2. each Experimental agents group to Mus lung body index before and after the experiment relatively
As can be seen from Table 2: compare with Normal group, the lung body index of asthmatic model group is obviously greater than the former, and prompting Paroxysmal asthma lungs weight in wet base compared with normal increases, and exists obvious pulmonary edema; Compare with the asthmatic model group, the lung body index of each medication group all is significantly less than the former, compound recipe A, B, C, D, the E group is compared lung body index with the Menglusitena group that significant difference is arranged, all can effectively alleviate pulmonary edema, compound recipe A, B, C effect are better than compound recipe D, E group, take compound recipe A group as the optimal choice proportioning, the effect that alleviates pulmonary edema is better than other and respectively organizes compound recipe in each prescription compound recipe.
Table 2 induced lung body index
Annotate: respectively organizing lung body index after the experiment has significant difference (p＜0.05),
△Compared significant difference with the asthmatic model group,
●With the Menglusitena group significant difference is arranged relatively,
*Compared significant difference with Rosuvastatin group comparable group.
3. each Experimental agents group is on the impact of rat airway inflammation
Table 3 different pharmaceutical and pharmaceutical composition on the impact of BALF of Rats classified counting of leucocyte (
* 10
4Ml)
| Group | The eosinophilic granulocyte | Lymphocyte | Macrophage | Neutrophilic granulocyte |
| Normal group | 0.07±0.02 △＊& | 0.46±0.04 △＊& | 14.9±2.23 △＊& | 0.55±0.07 △＊& |
| The asthmatic model group | 55.45±11.01 △& | 8.88±1.29 △& | 75.3±10.44 △ | 16.36±1.47 △& |
| Rosuvastatin group group | 21.14±5.48 ＊& | 6.45±1.01 ＊& | 35.84±3.18 ＊& | 10.22±0.83 ＊& |
| The Menglusitena group | 13.24±2.01 ＊△ | 3.90±0.69 ＊△ | 72.1±9.84 △ | 5.39±1.12 ＊△ |
| Compound recipe A group | 5.51±0.82 ＊&△ | 1.80±0.21 ＊&△ | 17.56±2.22 ＊&△ | 3.45±0.58 ＊&△ |
| The Compound B group | 5.95±0.90 ＊&△ | 2.00±0.34 ＊&△ | 18.44±2.41 ＊&△ | 3.55±0.49 ＊&△ |
| Compound recipe C group | 5.66±0.79 ＊&△ | 1.95±0.35 ＊&△ | 17.20±2.02 ＊&△ | 3.46±0.71 ＊&△ |
| Compound recipe D group | 6.01±0.86 ＊&△ | 2.04±0.61 ＊&△ | 18.01±1.86 ＊&△ | 3.90±0.81 ＊&△ |
| Compound recipe E group | 6.64±0.77 ＊&△ | 2.49±0.83 ＊&△ | 16.91±1.94 ＊&△ | 4.00±0.55 ＊&△ |
*Compared significant difference with the asthmatic model group,
﹠amp;With the Menglusitena group significant difference is arranged relatively,
△Compared significant difference with Rosuvastatin group comparable group.
Can find out from the data of table 3, eosinophilic granulocyte, lymphocyte, neutrophilic granulocyte number and asthmatic model group among each administration group BALF more all have significance.Eosinophilic granulocyte, lymphocyte, neutrophilic granulocyte number among the BALF of each group of compound recipe and Rosuvastatin group or Menglusitena group more all have respectively significance (P＜0.05), have shown that each group of compound recipe has respectively synergism.Especially, when alone Menglusitena, among the Menglusitena group BALF among macrophage number and the asthmatic model group BALF macrophage number more do not have significance (P＞0.05), and during the coupling statins, the macrophage number that macrophage is counted among the comparison Menglusitena group BALF in the BALF of Rats has significance (P＜0.05), explanation, Menglusitena and statins compound recipe are except working in coordination with the eosinophilic granulocyte who reduces among the mice BALF, lymphocyte, outside the neutrophilic granulocyte number, more can beat all generation better reduce the effect of BALF macrophage number.
Claims (5)
1. pharmaceutical composition for the treatment of bronchial asthma is characterized in that being comprised of the following active component of effective dose:
1) Menglusitena; With
2) Rosuvastatin;
Wherein Menglusitena and Rosuvastatin weight ratio are 1: 0.1-1.
2. pharmaceutical composition as claimed in claim 1 is characterized in that Menglusitena and Rosuvastatin weight ratio are 1: 0.3.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the effective dose that Menglusitena is contained in each preparation unit is 1mg-5mg in the pharmaceutical preparation that described pharmaceutical composition is prepared into, and the effective dose that contains Rosuvastatin is 0.5mg-5mg.
4. pharmaceutical composition as claimed in claim 3 is characterized in that the effective dose that Menglusitena is contained in each preparation unit is 5mg in the pharmaceutical preparation that described pharmaceutical composition is prepared into, and the effective dose that contains Rosuvastatin is 1.5mg.
5. such as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that described pharmaceutical composition is oral formulations or intestinal external administration preparation, described oral formulations is double-layer tablet, dispersible tablet, capsule or drop pill; Described intestinal external administration preparation is injection, spray, aerosol, powder spray or buccal tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110255919 CN102274515B (en) | 2011-09-01 | 2011-09-01 | Medicinal composition containing montelukast and statins medicament |
Applications Claiming Priority (1)
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