CN102379846A - Fluticasone propionate aerosol preparation with hydrofluoroalkane and polyethylene glycol as auxiliary materials - Google Patents
Fluticasone propionate aerosol preparation with hydrofluoroalkane and polyethylene glycol as auxiliary materials Download PDFInfo
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Abstract
The invention discloses a fluticasone propionate aerosol preparation with a hydrofluoroalkane and polyethylene glycol as auxiliary materials. The aerosol preparation comprises: a medicine particle of fluticasone propionate, a physiologically acceptable salt thereof and a solvate thereof; a hydrofluoroalkane propellent; and a surfactant with the weight of not more than 1.0% of the weight of the preparation, wherein the traditional Chinese medicinal particle of the invention is prepared by airflow crushing. The aerosol preparation provided by the invention is a medical aerosol preparation with good stability, and a process for preparing the aerosol preparation is completed by a one-step or two-step canning method.
Description
Technical field
The invention belongs to technical field of medicine, more particularly, a kind of is that hydrofluoroalkane is that propellant, Polyethylene Glycol are the FLUTICASONE PROPIONATE aerosol of surfactant with non-Freon.
Background technology
The aerosol medicine is a kind of preparation through the respiratory tract administration approach.
The basic goal of respiratory tract administration technology is to make the medicine porous to pulmonary and be deposited on outer peripheral areas, has quick-acting, target spot administration and avoids advantages such as gastrointestinal tract first pass effect, side effect is little, dosage is little, has obtained internationally recognized.
The respiratory tract administration approach for treatment asthma and chronic obstructive pulmonary disease, reaches treatments such as those diseases that need the quick administration of general such as Cystic fibrosis, huge superiority is not only arranged, and be a kind of important therapeutic modality.But be different from general pharmaceutical preparation, the drug development that pulmonary absorbs has bigger technological challenge.Such as, the rational faculty of aerosol drug particles distributes, and the compatibility of drug particles and adjuvant and container all has high technical difficulty with the control of stability.The size that sucks microgranule is one of key issue that influences the aerosol preparations curative effect, and the suction granule of great majority above 5 microns will be trapped in the oral cavity or be stuck on the spout.Therefore, ideal inhalant particle size on average should reach the 2-3 micron, and 90% should be less than 5 microns.Yet; Even drug particles satisfies the particle diameter requirement of aerosol preparations, still exist effect suction microgranule to trend towards caking because of cohesiveness, form big granule; With the absorption affinity owing to other adjuvants in the microgranule, microgranule is adsorbed on the first-class technical bottleneck of the packing of product easily.
Therefore, for overcoming above-mentioned difficult point, in aerosol preparations, add surfactant and cosolvent usually.Surfactant can be stablized aerosol preparations drug particles or increase-volume medicine, also can play lubricated aerosol can and valve function.The cosolvent dispersion solvent of doing commonly used improves the dissolubility between surfactant and the propellant.For example U.S. Pat 5225183, US5439670, and what be primarily aimed at is drug molecules such as albuterol, beclometasone and ipratropium bromide.
In a word, the adaptability of contained concrete composition (comprising medicine, propellant, surfactant and cosolvent etc.) depends on the concrete selection of this special component in the whole preparation and suitability each other thereof in the aerosol preparations.
Yet those skilled in the art is difficult to infer whether certain drug molecule can form stable aerosol molecule under the situation that does not contain or contain cosolvent and/or surfactant, the very difficult stable aerosol formulation that obtains to meet clinical quality standard easily through the simple replacement of drug molecule.
About the disclosed patent of the aerosol preparations of FLUTICASONE PROPIONATE; For example RA Akehurst etc. discloses a kind of aerosol preparations that does not contain the FLUTICASONE PROPIONATE of surfactant, active component wherein in Chinese patent CN1075078---be micronized FLUTICASONE PROPIONATE.
RA Akehurst etc. discloses a kind of aerosol preparations that does not contain the surfactant and the FLUTICASONE PROPIONATE of the polar co-solvent that is no more than propellant 5% in Chinese patent CN1075079, active component wherein---be micronized FLUTICASONE PROPIONATE.
Johnson A.Keith etc. discloses a kind of aerosol preparations in U.S. Pat 5126123, it comprises the micronization FLUTICASONE PROPIONATE and dissolves in 1,1,1, the surfactant of 2-tetrafluoroethane etc.
K Bake Si Telan discloses a kind of medicinal aerosol formulations in Chinese patent CN1170356, it comprises HFA propellant, micronized active component, surfactant such as C8-C16 satisfied fatty acid or its salt etc.
In sum, the aerosol preparations instance of the disclosed micronization FLUTICASONE PROPIONATE of prior art is many not contain surfactant, and it is main not containing cosolvent.And, be that surfactant and/or the technical scheme that contains cosolvent do not have announcement with Polyethylene Glycol (PEG) etc. with micronized FLUTICASONE PROPIONATE.
Summary of the invention
The inventor has invented a kind of aerosol formulation of stable FLUTICASONE PROPIONATE astoundingly through a large amount of experiments, has successfully overcome some shortcomings of the prior art.
The aerosol that the purpose of this invention is to provide a kind of stable FLUTICASONE PROPIONATE.
Another object of the present invention provides the method for preparing of the aerosol of aforementioned stable.
Specifically, the present invention provides a kind of FLUTICASONE PROPIONATE aerosol, comprises the granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate; The hydrofluoroalkane propellant; And the surfactant polyethylene that is not more than preparation 1.0%w/w.
In embodiments of the invention, the invention provides a kind of FLUTICASONE PROPIONATE aerosol, comprise the granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate; The hydrofluoroalkane propellant; Be not more than the surfactant polyethylene of preparation 1.0%w/w; And polarity is higher than the polar cosolvent of propellant.Preferably, said cosolvent is not more than the 5.0%w/w (preferably being not more than the 2.5%w/w of propellant) of propellant.
In embodiments of the invention, the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is micronized, is obtained by the comminution by gas stream preparation.
In embodiments of the invention, the present invention provides a kind of FLUTICASONE PROPIONATE aerosol, comprises the granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate; The hydrofluoroalkane propellant; And the surfactant polyethylene that is not more than preparation 1.0%w/w; Here, the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is micronized, is obtained by the comminution by gas stream preparation.
In embodiments of the invention, the invention provides a kind of FLUTICASONE PROPIONATE aerosol, comprise the granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate; The hydrofluoroalkane propellant; Be not more than the surfactant polyethylene of preparation 1.0%w/w; And polarity is higher than the polar cosolvent of propellant; Here, the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is micronized, is obtained by the comminution by gas stream preparation.Preferably, said cosolvent is not more than the 5.0%w/w (preferably being not more than the 2.5%w/w of propellant) of propellant.
In embodiments of the invention; The air-flow micronization of the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate can adopt the method for prior art instruction, has just done all-side introduction to comminution by gas stream as the 15 piece in " newly organized crushing and grinding and the practical pandect of the mechanical Selection and Design of screening " (northern industrial publishing house publishes in June, 2006).In embodiments of the invention, this experiment air-flow microgranule prepares process: connect high-purity gas (like high pure nitrogen), open jet mill; Regulate vacuum pressure and ring internal pressure; Vacuum pressure is about 6-10bar, and the ring internal pressure is about 4-8bar, ventilates 1-3 minute; Guarantee whole line seal, air tight.With the drug particles that takes by weighing (like FLUTICASONE PROPIONATE) at the uniform velocity to add from charge door.Collect sample in the bottom collector, it is different according to material properties to get sample rate, is approximately 30%-90%.
In embodiments of the invention, the granulated drug of wherein said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is through surface modification, and like comminution by gas stream, its granular size 50% is less than 3um, and 90% less than 5um.In embodiments of the invention, described FLUTICASONE PROPIONATE and or its pharmaceutically acceptable salt or solvate account for the 0.01-5%w/w of preparation total amount, be preferably 0.01%-3%w/w, more preferably be 0.01%-1%w/w.
In embodiments of the invention, the propellant that said aerosol is selected for use can be hydrofluoroalkane or its mixture, and they should have enough vapour pressures so that as effective propellant, preferably; Said propellant is 1,1,1,2-tetrafluoroethane or 1; 1,1,2; 3,3,3-seven fluorine n-propanes or its mixture are formed.The content of propellant is the 89%-99.9%w/w of preparation.
In embodiments of the invention, described Polyethylene Glycol (being abbreviated as PEG, as follows) is PEG200～1800, can be PEG200, PEG300, PEG400, PEG1000; PEG1000 preferably.
In embodiments of the invention, said polarity is higher than the polar cosolvent of propellant, can be selected from propylene glycol or ethanol, more preferably is ethanol.
In embodiments of the invention, the invention provides a kind of FLUTICASONE PROPIONATE aerosol, comprise the granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate; The hydrofluoroalkane propellant; Be not more than the surfactant polyethylene of preparation 1.0%w/w; And the 5.0%w/w polarity that is not more than propellant is higher than the polar cosolvent of propellant; Here, the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is micronized, is obtained by the comminution by gas stream preparation;
Randomly, the granulated drug of said FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is through surface modification, and like comminution by gas stream, its granular size 50% is less than 3um, and 90% less than 5um;
Randomly, described FLUTICASONE PROPIONATE and or its pharmaceutically acceptable salt or solvate account for the 0.01-5%w/w of preparation total amount, be preferably 0.01%-3%w/w, more preferably be 0.01%-1%w/w;
Randomly, the propellant that said aerosol is selected for use can be hydrofluoroalkane or its mixture, and they should have enough vapour pressures so that as effective propellant, preferably, said propellant is 1; 1,1,2-tetrafluoroethane or 1,1,1; 2,3,3,3-seven fluorine n-propanes or its mixture are formed; The content of propellant is the 89%-99.9%w/w of preparation;
Randomly, described Polyethylene Glycol is PEG200～1800, can be PEG200, PEG300, PEG400, PEG1000; PEG1000 preferably;
Randomly, said polarity is higher than the polar cosolvent of propellant, can be selected from propylene glycol or ethanol, more preferably is ethanol.
In embodiments of the invention, said aerosol also can contain salmaterol or its physiologically acceptable salt.
In embodiments of the invention, " contain low quantity of surfactant " and be meant that the content of its surfactant polyethylene of preparation is not more than the 1.0%w/w of preparation.
In embodiments of the invention, " containing small amounts of co-solvents " is meant that preparation contains polarity and is higher than the polar liquid component of propellant, and ethanol for example preferably is not more than the 2.5%w/w of propellant.
In embodiments of the invention, said FLUTICASONE PROPIONATE drug molecule is prepared by comminution by gas stream.When taking this aerosol preparations, require all medicines should suck in the lung basically, therefore, with less than 10 microns for well, 1-5 micron preferably.Aerosol preparations of the present invention has the particle size distribution of good stable property and aerosol preparations under the situation with small amounts of co-solvents and surfactant.Technical process can be used a step or canned method of two steps.
The medicine that is used for aerosol preparations can be to be used to treat respiratory disorder (for example asthma or chronic obstructive pulmonary disease etc.) etc.; The short acting beta agonists trachea expanding agent is arranged; Like albuterol, terbutaline, isoproterenol etc., also can be the long acting beta agonists trachea expanding agent, for example salmaterol, formoterol; Also have steroid hormone such as beclometasone, fluticasone and non-steroidal hormone cromoglicic acid etc., also comprise cholinolytic trachea expanding agent ipratropium bromide etc. simultaneously.
Though the said medicine molecule all can be used for treating respiratory disorder, no matter it on structure, on physiologically acceptable salt or acid group or the base, still can have multiple variation in route of administration and pharmaceutical preparation.
Omitting under cosolvent and the surfactant component situation, FLUTICASONE PROPIONATE, salmaterol can form stable aerosol preparations (CN1075078), and its technical process can be used canned method of a step, and process equipment requires height relatively.Technical research through this patent; Under the situation that contains low quantity of surfactant Polyethylene Glycol and cosolvent; The granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate can form the same stable aerosol preparations of optimizing that reaches; Its technical process can be used canned method of two steps, and process equipment is simplified relatively.
According to the characteristics of aerosol preparations self, the size that sucks microgranule is the key factor that influences the aerosol curative effect, and it will directly influence the aerosol preparations medicine maybe can breathe part at the deposition of pulmonary.Aerosol preparations can be breathed the ratio that part accounts for the medicine total amount; Be often referred to droplet distribution tests index, promptly Fine Particle Fraction (FPF%) generally requires between 20-70%; Ideal between 30-60%, be the important indicator of investigating aerosol preparations.And the technological means of measuring FPF% can be to collide (ACI) or binary collision technology or impinger of future generation (NGI) step by step, in conjunction with the HPLC analytical method.
Aerosol preparations provided by the invention, through after collision is measured with HPLC step by step, it optimizes the FPF% value of writing out a prescription all more than 30%-40%, can stablize repetition.
The specific embodiment
Further specify technical scheme of the present invention through embodiment below.Alcoholic acid weight percent is the percentage ratio with respect to propellant in the following example.
In the following example, the micronized preparation process of air-flow: connect high-purity gas (like high pure nitrogen), open jet mill; Regulate vacuum pressure and ring internal pressure, vacuum pressure is about 6-10bar, and the ring internal pressure is about 4-8bar; Ventilated 1-3 minute, and guaranteed whole line seal, air tight.With the drug particles that takes by weighing (like FLUTICASONE PROPIONATE) at the uniform velocity to add from charge door.Collect sample in the bottom collector.
In addition, in following embodiment, like not specially provided for, represented " % " is " % " of weight ratio in the component.
Embodiment 1 is propellant+FLUTICASONE PROPIONATE only
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, and each the unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is about 20-40%.
Embodiment 2 0.15% cetomacrogol 1000s+FLUTICASONE PROPIONATE
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add Surfactant PEG 1000 then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 0.15%w/w PEG1000.The each unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is between the 40-50%.
Embodiment 3 0.1% cetomacrogol 1000+2.5% ethanol+FLUTICASONE PROPIONATEs
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add Surfactant PEG 1000 and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 0.1%w/w PEG1000, and 2.5%w/w ethanol, the each unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is about 40%.
Embodiment 4 0.1%w/w Liquid Macrogol+2.0% ethanol+FLUTICASONE PROPIONATEs
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add Surfactant PEG 300 and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 0.1%PEG300, and 2.0% ethanol, the each unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is about 40%.
Embodiment 5 0.1% PEG400+2.0% ethanol+FLUTICASONE PROPIONATEs
Micronized FLUTICASONE PROPIONATE of air-flow and salmaterol are directly weighed in the aluminium pot of clean dried, add Surfactant PEG 400 and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
FLUTICASONE PROPIONATE and the 0.038%w/w former times that the gained aerosol contains 0.19%w/w be sour salmaterol how, 0.1%PEG400,2.0% ethanol, each open provide～125ug FLUTICASONE PROPIONATE and～25ug former times sour salmaterol how.The FLUTICASONE PROPIONATE of this aerosol preparations and salmaterol, its FPF% is about 45%.
Embodiment 6 0.1% cetomacrogol 1000+2.5% ethanol+FLUTICASONE PROPIONATE+salmaterol
Micronized FLUTICASONE PROPIONATE of air-flow and salmaterol are directly weighed in the aluminium pot of clean dried, add Surfactant PEG 1000 and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains FLUTICASONE PROPIONATE and the 0.04%w/w salmaterol of 0.19%w/w, 0.1%PEG1000, and 2.5% ethanol, the each unlatching provides～125ug FLUTICASONE PROPIONATE and～25ug salmaterol.The FPF% of this aerosol preparations FLUTICASONE PROPIONATE and salmaterol is about 40%.
Embodiment 7 2.5% ethanol+FLUTICASONE PROPIONATE
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 2.5% ethanol, and each the unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is about 30%.
Embodiment 2-7 compares with embodiment 1; Micronized FLUTICASONE PROPIONATE of air-flow and salmaterol comprise PEG1000 containing surfactant polyethylene; PEG300; PEG400 is or/and contain when being no more than 2.5% cosolvent such as ethanol, and its aerosol preparations FPF% value is equal to or is superior to only containing the aerosol preparations of propellant.The aerosol preparations FPF% good reproducibility that contains Polyethylene Glycol, Polyethylene Glycol play the effect of raising and stable FPF%.
Embodiment 8 0.1% cetomacrogol 1000+5.0% ethanol+FLUTICASONE PROPIONATEs
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add Surfactant PEG 1000 and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 0.1%PEG1000, and 5.0% ethanol, the each unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is about 33%.
Embodiment 8 confirms; Micronized FLUTICASONE PROPIONATE of air-flow and salmaterol contain be no more than in addition 5.0%w/w cosolvent such as ethanol with contain surfactant polyethylene and comprise PEG1000; PEG300; During PEG400, its aerosol preparations FPF% value still is similar to and does not contain alcoholic acid aerosol preparations.
Embodiment 9 0.1% oleic acid+2.5% ethanol+FLUTICASONE PROPIONATEs
The micronized FLUTICASONE PROPIONATE of air-flow is directly weighed in the aluminium pot of clean dried, add surfactant oleic acid and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains the FLUTICASONE PROPIONATE of 0.19%w/w, 0.1% oleic acid and 2.5% ethanol, and each the unlatching provides～the 125ug FLUTICASONE PROPIONATE.The FPF% of this aerosol preparations is between the 20-30%.
Embodiment 10 0.1% oleic acid+2.5% ethanol+FLUTICASONE PROPIONATE+salmaterol
Micronized FLUTICASONE PROPIONATE of air-flow and salmaterol are directly weighed in the aluminium pot of clean dried, add surfactant oleic acid and cosolvent ethanol then, seal bottle rapidly, add 1,1,1 through metering valve, the 2-tetrafluoroethane with metering valve.Then with ultrasonic 30 seconds of populated aerosol jar.
The gained aerosol contains FLUTICASONE PROPIONATE and the 0.04%w/w salmaterol of 0.19%w/w, 0.1% oleic acid, and 2.5% ethanol, the each unlatching provides～125ug FLUTICASONE PROPIONATE and～25ug salmaterol.Its FPF% of the FLUTICASONE PROPIONATE of this aerosol preparations and salmaterol is about 25%.
Embodiment 9-10 compares with embodiment 1, and the micronized FLUTICASONE PROPIONATE of air-flow is containing 2.5%w/w ethanol, and oleic acid is the aerosol preparations of surfactant, and its FPF% value is not because oleic acid increases.
By on can know, aerosol provided by the invention, its drug particles is prepared by comminution by gas stream, under the situation that contains Polyethylene Glycol and/or small amounts of co-solvents, is superior to containing cosolvent and oleic preparation, preparation process can use one the step or two the step canned method.
Above-described is according to preferred embodiment of the present invention, is not in order to limiting scope of the present invention, and the above embodiment of the present invention can also be made various variations.Be that every simple, equivalence of doing according to the claims and the description of application of the present invention changes and modification, all fall into claim protection domain of the present invention.The present invention not technology contents of detailed description is those skilled in the art's a common practise.
Claims (10)
1. hydrofluoroalkane FLUTICASONE PROPIONATE aerosol comprises:
The granulated drug of FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate;
The hydrofluoroalkane propellant;
With the Polyethylene Glycol of the 1.0%w/w that is not more than preparation be surfactant.
2. aerosol as claimed in claim 1 randomly, also comprises the cosolvent that polarity is higher than propellant.
3. aerosol as claimed in claim 2, wherein, said cosolvent is not more than the 5.0%w/w of propellant.
4. according to claim 1 or claim 2 aerosol, the granulated drug of described FLUTICASONE PROPIONATE and physiologically acceptable salt and solvate is micronized, by the comminution by gas stream preparation and obtain.
5. according to claim 1 or claim 2 aerosol, wherein, said propellant is 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-seven fluorine n-propanes or its mixture are formed.
6. like claim 2 or 3 described aerosols, wherein, polarity is higher than the polar cosolvent of propellant, can be selected from propylene glycol or ethanol, more preferably is ethanol.
7. according to claim 1 or claim 2 aerosol formulation, wherein Polyethylene Glycol is PEG200～1800, can be PEG200, PEG300, PEG400, PEG1000; PEG1000 preferably.
8. according to claim 1 or claim 2 aerosol, wherein said FLUTICASONE PROPIONATE and physiologically acceptable salt thereof and solvate account for the 0.01-3%w/w of preparation total amount.
9. aerosol as claimed in claim 1, it comprises salmaterol or its physiologically acceptable salt further.
10. device that is used for the said aerosol of the arbitrary claim of claim 1-9, it comprises a container that can bear used propellant vapour pressure, wherein said container is a kind of do not have coating or cated jar of inner surface; This container seals with a metering valve, and its nozzle diameter is between 0.2-0.6mm.
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| CN201110322180.1A CN102379846B (en) | 2011-10-21 | 2011-10-21 | Fluticasone propionate aerosol preparation with hydrofluoroalkane and polyethylene glycol as auxiliary materials |
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| CN201110322180.1A CN102379846B (en) | 2011-10-21 | 2011-10-21 | Fluticasone propionate aerosol preparation with hydrofluoroalkane and polyethylene glycol as auxiliary materials |
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| CN1284330A (en) * | 1992-02-06 | 2001-02-21 | 格拉克索公司 | Medicinal aerosol preparation, its preparing method and release |
| WO2001019342A2 (en) * | 1999-09-11 | 2001-03-22 | Glaxo Group Limited | Pharmaceutical formulation of fluticasone propionate |
| WO2001047493A1 (en) * | 1999-12-24 | 2001-07-05 | Glaxo Group Limited | Pharmaceutical aerosol formulation of salmeterol and fluticasone propionate |
| CN1328445A (en) * | 1998-11-25 | 2001-12-26 | 奇斯药制品公司 | Pressurised metered dose inhalers |
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2011
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1284330A (en) * | 1992-02-06 | 2001-02-21 | 格拉克索公司 | Medicinal aerosol preparation, its preparing method and release |
| CN1328445A (en) * | 1998-11-25 | 2001-12-26 | 奇斯药制品公司 | Pressurised metered dose inhalers |
| WO2001019342A2 (en) * | 1999-09-11 | 2001-03-22 | Glaxo Group Limited | Pharmaceutical formulation of fluticasone propionate |
| WO2001047493A1 (en) * | 1999-12-24 | 2001-07-05 | Glaxo Group Limited | Pharmaceutical aerosol formulation of salmeterol and fluticasone propionate |
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| Title |
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| 《RESPIRATORY MEDICINE》 20011231 M.AUBIER，et.al Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800mug day-1) versus HFA-fluticasone propionate (1000 mug day-1) in patients with asthma 第212-220 1-10 , 第95期 * |
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