CN104606172A - Montelukast sodium inhalation aerosol powder as well as preparation method and application thereof - Google Patents
Montelukast sodium inhalation aerosol powder as well as preparation method and application thereof Download PDFInfo
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- CN104606172A CN104606172A CN201510063228.XA CN201510063228A CN104606172A CN 104606172 A CN104606172 A CN 104606172A CN 201510063228 A CN201510063228 A CN 201510063228A CN 104606172 A CN104606172 A CN 104606172A
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Abstract
The invention relates to the technical field of medicinal chemistry and in particular relates to montelukast sodium inhalation aerosol powder as well as a preparation method and an application thereof. The montelukast sodium inhalation aerosol powder comprises superfine montelukast sodium powder and pharmaceutically acceptable auxiliary materials, wherein the mean particle size of the superfine montelukast sodium powder is 1-5 microns, and the maximum particle size does not exceed 10 microns. According to the montelukast sodium inhalation aerosol powder provided by the invention, the superfine montelukast sodium powder can be well adsorbed to the surface of a carrier, the powder is inhaled through airflow during administration, is desorbed from the surface of the carrier with large particle size and enters the lung, the powder has high deposition rate, the drug is directly delivered to the lung to exert the effect, the first-pass effect of the liver is avoided, and the inhalation aerosol powder has the characteristics such as rapid drug absorption and high bioavailability in the treatment of asthma.
Description
Technical field
The present invention relates to field of pharmaceutical chemistry technology, particularly a kind of Menglusitena inhalation powder spray and its preparation method and application.
Background technology
Menglusitena, its chemistry [R-(E)]-1-[[[1-[3-[2-(the chloro-2-quinoline of 7-) vinyl] phenyl-3-[2-(1-hydroxyl-1-Methylethyl) phenyl] propyl group] sulfur] methyl] cyclopropaneacetic acid sodium by name.Molecular formula is C35H35ClNNaO3S, and molecular weight is 608.18.Mainly be applicable to prevention and the long-term treatment of more than 15 years old and 15 years old Adults Asthma, comprise prevention daytime and the symptoms of asthma at night, and alleviate the symptom (seasonal allergic rhinitis of being grown up for more than 15 years old and 15 years old and catarrhus perennialis) that allergic rhinitis causes.
Show the experimental study of MK at present, MK is a kind of medicine that significantly can improve inflammation of asthma index.Cysteinyl leukotriene (LTC4, LTD4, LTE4) is potent inflammatory mediator, is discharged by the various kinds of cell comprising mastocyte and eosinophilic granulocyte.Medium and cysteinyl leukotriene (CysLT) receptors bind before these important asthma.I type cysteinyl leukotriene (CysLT1) receptor is distributed in air flue (comprising airway smooth muscle cells and air flue macrophage) and other the proinflammatory cell (comprising eosinophilic granulocyte and some bone marrow stem cell) of human body.CysLTs is relevant to the pathophysiological process of asthma and allergic rhinitis.In asthma, the effect of leukotriene mediation comprises the reaction of a series of air flue, as bronchoconstriction, mucous secretion, vascular permeability increase and eosinophil accumulation.In allergic rhinitis, the speed after anaphylactogen exposes is sent out mutually and in late phase reaction, nasal mucosa all can discharge the CysLTs relevant to allergic rhinitis symptoms.Intranasal CysLTs excites the symptom that can increase nose airway resistance and nasal obstruction.Biochemistry and pharmacological bioassay display, montelukast has affinity and selectivity (the having the air flue receptor of pharmacology's significance such as prostanoid, cholinergic to compare with β-adrenergic receptor with other) of height to CysLT1 receptor.The physiological effect that montelukast can suppress LTC4, LTD4 and LTE4 and CysLT1 receptors bind to produce effectively and without any receptor agonist activity.Montelukast not antagonism CysLT2 receptor is thought in current research.
The dosage form of Menglusitena only has tablet and chewable tablet two kinds in the market, therefore, provides the MK inhalation powder spray that a kind of administration is convenient, bioavailability is high to have important practical significance.
Summary of the invention
In view of the deficiencies in the prior art, the present invention, by experimental study, provides a kind of particle diameter Menglusitena inhalation powder spray all within the scope of 1 μm ~ 5 μm and preparation method thereof.It is long-pending large that this Menglusitena inhalation powder spray has sorbent surface through Pulmonary inhalation, the advantages such as absorption site blood flow enriches, and can avoid the first pass effect of liver, bioavailability is high, and onset is rapid.
In order to realize foregoing invention object, the invention provides following technical scheme:
The invention discloses a kind of Menglusitena inhalation powder spray, comprise Menglusitena superfine powder and pharmaceutically acceptable adjuvant, the mean diameter of described Menglusitena superfine powder is 1 μm ~ 5 μm.
In some embodiments of the present invention, the maximum particle diameter of described Menglusitena superfine powder is no more than 10 μm.
In some embodiments of the present invention, described in Menglusitena inhalation powder spray, adjuvant comprises carrier and additives.
In some embodiments of the present invention, described carrier comprises a kind of or both the above mixture in saccharide, aminoacid and polyhydric alcohol.
In some embodiments of the present invention, described additives comprise a kind of or both the above mixture in surfactant, lubricant, antistatic additive.
In some embodiments of the present invention, carrier described in Menglusitena inhalation powder spray is lactose.
In certain preferred embodiments of the present invention, described lactose is particularly preferably grinding lactose, alpha-lactose monohydrate, β-Lactis Anhydrous, one or more in amorphous spray-dried lactose, crystallizing and drying lactose.
In some embodiments of the present invention, additives described in Menglusitena inhalation powder spray are PLURONICS F87.
In some embodiments of the present invention, adjuvant described in Menglusitena inhalation powder spray is micropowder, and the mean diameter of described adjuvant is 40 μm ~ 80 μm.
In some embodiments of the present invention, the maximum particle diameter of described adjuvant is no more than 120 μm.
In some embodiments of the present invention, Menglusitena described in Menglusitena inhalation powder spray and described adjuvant mass ratio are 1:71 ~ 1:17.
Preferably, Menglusitena described in Menglusitena inhalation powder spray and described adjuvant mass ratio are 1:17 ~ 1:35.
Preferred further, Menglusitena described in Menglusitena inhalation powder spray and described adjuvant mass ratio are 1:23 ~ 1:35.
Further preferred, Menglusitena described in Menglusitena inhalation powder spray and described adjuvant mass ratio are 1:71,1:35,1:23,1:17.
In some embodiments of the present invention, the shared mass percent in Menglusitena inhalation powder spray of PLURONICS F87 described in Menglusitena inhalation powder spray is 0.1% ~ 1%.
Preferred further, the shared mass percent in Menglusitena inhalation powder spray of PLURONICS F87 described in Menglusitena inhalation powder spray is 0.5% ~ 1%.
Further preferred, the shared mass percent in Menglusitena inhalation powder spray of PLURONICS F87 described in Menglusitena inhalation powder spray is 0.1%, 0.5% and 1%.
In some embodiments of the present invention, described in Menglusitena inhalation powder spray, the content of Menglusitena described in Menglusitena inhalation powder spray is 2.5mg ~ 10mg/180mg.
According to the safety using amount of Menglusitena, preferably, make containing principal agent composition 2.5mg, 5mg, 7.5mg and 10mg.
Present invention also offers the preparation method of Menglusitena inhalation powder spray, comprise the steps:
Step 1: get described Menglusitena through micronizing, obtains described Menglusitena superfine powder;
Step 2: get described adjuvant and pulverize;
Step 3: get adjuvant that described Menglusitena superfine powder and step 2 prepare pulverize after micropowder, by the mixing of equal increments method, capsule subpackage.
Equal increments method will be adopted when drug ratios differs greatly, practise and claim facing-up method.The present invention adopts equal increments method that principal agent Menglusitena is mixed homogeneously with adjuvant.Equal increments method concrete operation method is: get the component that the amount of component in a small amount and equivalent is large, be placed in mixing machinery mix homogeneously simultaneously, add the component mix homogeneously that the amount of same mixture equivalent is large again, times amount like this increases till adding the large component of whole amount.The Menglusitena inhalation powder spray made by the method effectively can improve the mixing uniformity of Menglusitena active substance and adjuvant.
Specific in embodiments more of the present invention, the preparation method of Menglusitena inhalation powder spray provided by the invention, comprises the steps:
Step 1: get described Menglusitena through micronizing, obtains described Menglusitena superfine powder;
Step 2: get described adjuvant and pulverize;
Step 3: get adjuvant that described Menglusitena superfine powder and step 2 prepare pulverize after micropowder, mix by equal increments method, namely the micropowder after the adjuvant pulverizing of Menglusitena superfine powder and equivalent is got, mix homogeneously obtains mixture simultaneously, add the micropowder mix homogeneously after with the adjuvant pulverizing of described mixture equivalent again, times amount like this increases till the micropowder after adding whole supplementary material pulverizing.Use suitable capsule subpackage.
In some embodiments of the present invention, the preparation method of a kind of Menglusitena inhalation powder spray of the present invention, comprises the following steps:
Step 1: by Menglusitena porphyrize, carries out micronizing with ultra micro disintegrating machine, obtains superfine powder;
Step 2: by the speed lapping pulverizer of the component in adjuvant, speed lapping is pulverized, and obtains micropowder;
Step 3: the Menglusitena superfine powder of recipe quantity and adjuvant micropowder are pressed equal increments method and mixes, fills suitable capsule.
In some embodiments of the present invention, in step 1, the mean diameter of the Menglusitena superfine powder obtained is 1 μm ~ 5 μm.
In some embodiments of the present invention, in step 2, the micropowder mean diameter of described adjuvant is 40 μm ~ 80 μm.
In some embodiments of the present invention, in step 3, gained Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method and mixes, carry out subpackage with the capsule of suitable model.
The Menglusitena inhalation powder spray made by the method effectively can improve the uniformity of the Menglusitena after pulverizing and adjuvant particle diameter, the uniformity coefficient that both raisings mix.
The method of micronization of Menglusitena of the present invention can adopt speed lapping method, fluid bed supersonic jet mill method, ball-milling method, fluid energy mill method, solvent method etc., preferred speed lapping method.
In case study on implementation more of the present invention, the using method of Menglusitena inhalation powder spray provided by the invention: when using Menglusitena inhalation powder spray provided by the present invention, point capsule installed is incapsulated in type powder vapor inhalator, patient uses the direct inhalation powder spray of the suction nozzle that capsule-type powder vapor inhalator is arranged, and powder spray can be taken directly pulmonary's onset.
The invention discloses a kind of Menglusitena inhalation powder spray, comprise Menglusitena superfine powder and pharmaceutically acceptable adjuvant, the mean diameter of described Menglusitena superfine powder is 1 μm ~ 5 μm; Wherein maximum particle diameter is no more than 10 μm.Menglusitena inhalation powder spray provided by the invention, Menglusitena superfine powder can be made well to be adsorbed on carrier surface, suck through air-flow during medication, from the carrier surface desorption that particle diameter is larger, enter pulmonary, have better deposition, the carrier micropowder of greater particle size is then trapped within a mouthful throat, avoids and sucks pulmonary's generation untoward reaction.The invention provides the unprecedented dosage form of a kind of Menglusitena and pulmonary administration mode, the medicine of Menglusitena inhalation powder spray provided by the invention initiatively sucks with micronized form, directly medicine is transported to pulmonary's onset, eliminate the liver first-pass effect of medicine, easy to use, the stability of medicine is also better.To the treatment of asthma disease have drug absorption rapidly, good stability, bioavailability high; Meanwhile, product of the present invention also has the not advantage such as moisture-sensitive.Capsule containing powder spray provided by the invention can adopt known powder spray capsule inhaler to suck.
Accompanying drawing explanation
The Menglusitena superfine powder electron-microscope scanning figure that Fig. 1 provides for embodiment 1;
The adjuvant micropowder electron-microscope scanning figure that Fig. 2 provides for embodiment 1;
The Concentration-time change broken line graph of Menglusitena in lung mucus that Fig. 3 provides for embodiment 8; Wherein,
show sodium intravenous group of montelukast;
show Menglusitena inhalation powder spray group prepared by embodiment 1.
Detailed description of the invention
Now further describe the present invention by following examples, embodiment only for the object of illustration, does not limit the scope of the invention, and the simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
The ultra micro that the present invention adopts shatters method, uses the WZJ500 type vibration type medicine ultra micro disintegrating machine of superfine powder engineering equipment research and development centre of Gulou, Nanjing Tontru that Menglusitena is ground into required particle diameter.The present invention adopts speed lapping pulverizer (Yanshan Mountain, Beijing Zheng De plant equipment company limited RT-34) that carrier powder is broken into required particle diameter.
Adopt No. 3 capsules (sino-america joint-venture Suzhou Capsule Co., Ltd produces, trade name: Vcaps) during subpackage of the present invention, each embodiment feeds intake according to 1000 capsules.The capsule loading bubble-cap type of powder spray is aluminum-plastic packaged, takes out, load powder spray inhaler (Shanghai Dongping pharmaceutical factory) and use during use.
Embodiment 1: the preparation of Menglusitena inhalation powder spray
By 2.5g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; 177.32g is ground lactose and 0.18g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 2.5mg.
The particle size distribution of Menglusitena superfine powder prepared by the present embodiment and adjuvant micropowder as illustrated in fig. 1 and 2.Fig. 1 is Menglusitena superfine powder electron-microscope scanning figure; Fig. 2 is adjuvant micropowder electron-microscope scanning figure.
Embodiment 2: the preparation of Menglusitena inhalation powder spray
By 5g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; By 174.82g alpha-lactose monohydrate and 0.18g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 5mg.
Embodiment 3: the preparation of Menglusitena inhalation powder spray
By 5g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; By 174.1g beta lactose and 0.9g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 5mg.
Embodiment 4: the preparation of Menglusitena inhalation powder spray
By 7.5g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; By 171.6g crystallizing and drying lactose and 0.9g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 7.5mg.
Embodiment 5: the preparation of Menglusitena inhalation powder spray
By 10g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; By 170.7g crystallizing and drying lactose and 1.8g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 10mg.
Embodiment 6: the preparation of Menglusitena inhalation powder spray
By 10g Menglusitena, carry out micronizing with super micron mill, obtain the ultra micro dry powder that average particle size is 1 μm ~ 5 μm, in described Menglusitena ultra micro dry powder, maximum particle diameter is no more than 10 μm; By unformed for 168.2g spray-dried lactose and 1.8g PLURONICS F87 speed lapping pulverizer, speed lapping is pulverized, and obtaining mean diameter is 40 μm ~ 80 μm micropowders, and in described adjuvant, maximum particle diameter is no more than 120 μm; Menglusitena superfine powder and adjuvant micropowder are pressed equal increments method mix, fill No. 3 capsules, fill 180mg for every, make 1000 capsules, the content obtaining every agent principal agent is the Menglusitena nebulizer of 10mg.
Embodiment 7: the mensuration of MK inhalation powder spray Emptying Rate
The Emptying Rate of powder spray is measured according to method disclosed in Chinese Pharmacopoeia 2010 editions annex I L.Get this product 10, accurately weighed respectively, be placed in suction apparatus by grain, the air-flow of 60L ± 5L per minute aspirates 4 times, each 1.5 seconds, and weighed weight wipes clean residual content with suitable apparatus, then distinguishes weighed softgel shell weight, obtains the Emptying Rate of every.
The Emptying Rate of the Menglusitena inhalation powder spray that embodiment 1 ~ 6 obtains is measured, the results are shown in Table 1:
The Emptying Rate measurement result of the Menglusitena inhalation powder spray that table 1 embodiment 1 ~ 6 is obtained
From table 1 data, the Emptying Rate of the Menglusitena inhalation powder spray that this law obtains is greater than 90%, meets the regulation of capsule type inhalation aerosol powder.
Embodiment 8: the mensuration of Menglusitena inhalation powder spray pulmonary deposition ratio
The Menglusitena inhalation powder spray that Example 1 ~ 6 is obtained respectively, each 20, measure the pulmonary deposition ratio of powder spray according to method disclosed in Chinese Pharmacopoeia 2010 editions annex Ⅹ H, often group is averaged.Get test sample 1 dosage, put in suction apparatus, after opening vacuum pump 10 second, start atomising device and make atomization, suction apparatus is that horizontal close connects through suitable rubbers interface with unit simulation throat B, closes atomising device, take off inhaler after waiting for for 5 seconds after 60 seconds.Repeat aforesaid operations, survey 20 Dose Results altogether in table 1 by the regulation under kind item:
The pulmonary deposition ratio of the Menglusitena inhalation powder spray that table 1 embodiment 1 ~ 6 is obtained
From table 1 data, effective deposition of the Menglusitena inhalation powder spray that this law obtains is greater than 15%, meets the regulation of capsule type inhalation aerosol powder.
Embodiment 9: different route of administration is on the impact of Menglusitena bioavailability
Method: SD rat 12, body weight 160 ~ 200g, male and female are not limit, and are divided into Menglusitena inhalation powder spray group prepared by oral group of Menglusitena and embodiment 1 ~ 6, often organize 6, Menglusitena sheet used and the principal agent of Menglusitena powder spray all containing 10mg.
The route of administration of Menglusitena inhalation powder spray: the dosage needed for experiment is placed in the suitable rifle head that front end sleeve has PE pipe, and the rifle headgear of medicated powder will be housed on suitable syringe.After rat anesthesia, with suitable pipe, the upper jaw and the lower jaw of rat are opened, when animal inhales, utilize syringe holder medicated powder to be blown in the trachea of rat.
The route of administration of Menglusitena sheet: MK sheet is managed with PF the gastric directly pouring into rat with in right amount mixing to blend.
After administration terminates, implant microdialysis probe, pour into the microdialysis probe in induced lung with 0.01mol/l isotonic phosphate buffer liquid (pH=7.3), collect dialysate every 5min.Adopt the concentration of high effective liquid chromatography for measuring Montelukast in lung rete malpighii.
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia two V D in 2010).Chromatographic condition and system suitability: be filler with octadecylsilane chemically bonded silica; 0.02mol/L phosphate buffered solution (pH=7.0 ± 0.05)-acetonitrile (90:10) is mobile phase; Determined wavelength is 256nm; Flow velocity is 1mL/min; Column temperature is room temperature sampling volume is 20 μ l.Often to organize concentration (mg/ml) meansigma methods of experiment for vertical coordinate, the time (min) be abscissa mapping, result as shown in Figure 3, wherein, the curve that peak concentration is high
represent the oral cell mean of Menglusitena sheet; The curve that peak concentration is low
represent Menglusitena inhalation powder spray cell mean prepared by embodiment 1 ~ 6.
As seen from Figure 3, after Menglusitena sheet is poured into rat stomach, the less speed of medicine is very fast, has substantially just monitored less than Montelukast after 25min in lung mucus; But after Menglusitena inhalation powder spray prepared by embodiment 1 ~ 6 containing equivalent medicine is blown into rat trachea, in holdup time of pulmonary than the holdup time significant prolongation (P < 0.05) of tablet.Research shows, medicine increases the absorption that can promote medicine in the holdup time of pulmonary, is conducive to significantly improving (P < 0.05) of bioavailability.Judge thus to show that the bioavailability of Menglusitena inhalation powder spray provided by the invention is significantly higher than montelukast sodium tablet (P < 0.05).
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (10)
1. a Menglusitena inhalation powder spray, is characterized in that, comprises Menglusitena superfine powder and adjuvant, and the mean diameter of described Menglusitena superfine powder is 1 μm ~ 5 μm.
2. Menglusitena inhalation powder spray according to claim 1, is characterized in that, described adjuvant comprises carrier and additives.
3. Menglusitena inhalation powder spray according to claim 2, is characterized in that, described carrier comprise in saccharide, aminoacid and polyhydric alcohol one or more.
4. the Menglusitena inhalation powder spray according to any one of claim 2, is characterized in that, described additives comprise in surfactant, lubricant and antistatic additive one or more.
5. the Menglusitena inhalation powder spray according to any one of claim 1 to 2, is characterized in that, described adjuvant is micropowder, and the mean diameter of described adjuvant is 40 μm ~ 80 μm.
6. the Menglusitena inhalation powder spray according to any one of claim 1 to 2, is characterized in that, the mass ratio of described Menglusitena and described adjuvant is 1:71 ~ 1:17.
7. Menglusitena inhalation powder spray according to claim 4, is characterized in that, described additives are PLURONICS F87.
8. the Menglusitena inhalation powder spray according to any one of claim 1 to 2, is characterized in that, described in described Menglusitena inhalation powder spray, the content of Menglusitena is 2.5mg ~ 10mg/180mg.
9. a preparation method for Menglusitena inhalation powder spray, is characterized in that, comprises the steps:
Step 1: get described Menglusitena through micronizing, obtains described Menglusitena superfine powder;
Step 2: get described adjuvant and pulverize, obtain described adjuvant micropowder;
Step 3: get the adjuvant micropowder that described Menglusitena superfine powder and step 2 prepare, by the mixing of equal increments method, capsule subpackage; Wherein, the mean diameter of described Menglusitena superfine powder is 1 μm ~ 5 μm.
10. the preparation method of a Menglusitena inhalation powder spray according to claim 1 or Menglusitena inhalation powder spray according to claim 9 is prevented in preparation or is treated the application in the medicine of asthma.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1457796A (en) * | 2003-04-28 | 2003-11-26 | 南昌弘益科技有限公司 | Ribavirin inhalation powder atomizing agent and its preparing process and anti-virus infection use |
| WO2006128674A2 (en) * | 2005-05-31 | 2006-12-07 | Novartis Ag | Combinations of indacaterol derivatives and other agents for the treatment of airway diseases |
| CN101347618A (en) * | 2007-07-20 | 2009-01-21 | 天津药业集团有限公司 | Medicament composition for treating respiratory disease |
| CN102973574A (en) * | 2011-09-02 | 2013-03-20 | 北京燕锋晨医药技术发展有限公司 | Pharmaceutical composition for treating asthma and preparation method thereof |
-
2015
- 2015-02-06 CN CN201510063228.XA patent/CN104606172A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1457796A (en) * | 2003-04-28 | 2003-11-26 | 南昌弘益科技有限公司 | Ribavirin inhalation powder atomizing agent and its preparing process and anti-virus infection use |
| WO2006128674A2 (en) * | 2005-05-31 | 2006-12-07 | Novartis Ag | Combinations of indacaterol derivatives and other agents for the treatment of airway diseases |
| CN101347618A (en) * | 2007-07-20 | 2009-01-21 | 天津药业集团有限公司 | Medicament composition for treating respiratory disease |
| CN102973574A (en) * | 2011-09-02 | 2013-03-20 | 北京燕锋晨医药技术发展有限公司 | Pharmaceutical composition for treating asthma and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 邓铁宏，等: "《药剂学》", 31 August 2011, 清华大学出版社 * |
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Application publication date: 20150513 |