CN1204509A - Pharmaceutical aerosol formulation - Google Patents
Pharmaceutical aerosol formulation Download PDFInfo
- Publication number
- CN1204509A CN1204509A CN 98108908 CN98108908A CN1204509A CN 1204509 A CN1204509 A CN 1204509A CN 98108908 CN98108908 CN 98108908 CN 98108908 A CN98108908 A CN 98108908A CN 1204509 A CN1204509 A CN 1204509A
- Authority
- CN
- China
- Prior art keywords
- aerosol
- propellant
- beconase nasal
- solvate
- nasal syray
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
This invention relates to novel aerosol formulations for administering drugs, in particular for administration of a beclomethasone ester by inhalation. In particular the invention provides novel aerosol formulations consisting essentially of (a) beclomethasone dipropionate in the form of a solvate with 1,1,1,2-tetrafluoroethane (CF3CH2F) and one or more fluorocarbon or hydrogen-containing chlorofluorocarbon propellants or (b) anhydrous beclomethasone dipropionate and 1,1,1,2,3,3,3-heptafluoro-n-propane as propellant.
Description
The present invention relates to be used for administration, particularly use a kind of novel aerosol of beclomethasone ester with inhalation.
Beconase Nasal Syray is 9 α-chloro-16 Beta-methyls-1,4-pregnen diethylene-11 β, 17 α, 21-triol-3,20-diketone 17 α, 21-dipropionate, and available formula (I) expression.
The corticosteroid of formula (I) is known to be had typical anti-inflammatory activity and is used for the treatment of asthma symptom, particularly uses with the form of aerosol.The use of this class preparation is existing the description in GB-1429184; wherein also show when being incorporated into micronized anhydrous Beconase Nasal Syray in the aerosol formulations that contains the chlorofluorocarbon propellant; because the cause that solvation forms is easy to occur the phenomenon that crystal generates.Proved that particle volume can not be penetrated in the bronchi greater than 20 microns crystal is too big, and the obstruction that is easy to cause quantitative valve makes them be not suitable for inhalation to use.
Many possible solution have been tested at this problem.These solution comprise the use of the micronize solvate of Beconase Nasal Syray, chloro-containing fluorocarbon solvent (GB-1429184) for example, ethyl acetate solvent (DE-3018550OS), C
5-8Two diisopropyl ether solvents of alkane solvent (EP-0039369) (EP-0172672) and C
1-5Alcohols solvent (WO86/03750).GB-2076422A discloses a kind of method for preparing the chlorofluorocarbon aerosol, and it comprises a step that allegedly also can stop the low temperature (5 to 40 ℃) of crystal generation.
Generate problem at crystal in the aerosol formulations that contains Beconase Nasal Syray, WO92/06675 discloses another kind of solution recently.Described the ethanol liquid that contains Beconase Nasal Syray in this document, done the preparation of the aerosol of propellant coexistence with hydrofluorocarbon 134a (1,1,1, the 2-tetrafluoroethane) or hydrofluorocarbon 227 (1,1,1,2,3,3, the 3-heptafluoro-propane).Because in this aerosol, used the ethanol liquid of Beconase Nasal Syray rather than the suspension of graininess Beconase Nasal Syray, do not need to prepare solvate or its meticulous procedure of processing of active component before in mixing aerosol formulations.
Although ethanol is pharmaceutically acceptable and is commonly considered as safe that it also has many shortcomings that limit its use.Particularly, give do not drink or alcohol dependence person or child use that to contain alcoholic acid product be unfavorable.
Many other patent applications described contain medicine and fluorocarbon propellant and with one or more preparations of other adding as the aerosol of the adjuvant coexistence of surfactant.For example, WO91/14422 has described and has contained Beconase Nasal Syray with 1,1,1,2-tetrafluoroethane cage type inclusion form and with 1,1,1, the preparation of the aerosol of 2-tetrafluoroethane and the coexistence of various surface activity diffusant.
Our the specific novel fog agent prescription of having found to contain the graininess Beconase Nasal Syray does not use under the situation of adjuvant or cosolvent stable out of a clear sky in said composition now.
Thereby the invention provides a kind of Beconase Nasal Syray that contains graininess or its a kind of pharmaceutically acceptable solvate and with the medicinal aerosol formulations of a kind of fluorocarbon or the coexistence of hydrogenous chlorofluorocarbon propellant, said preparation is substantially free of surfactant.Be meant with " being substantially free of surfactant " and contain the not surfactant of significant quantity, for example be less than 0.0001% of Beconase Nasal Syray weight.
The granular size of graininess Beconase Nasal Syray can for example make it to reduce with micronize, fluid grinding (fluid energy milling) or ball milling with conventional method, and should guarantee that all medicines suck in the lung basically when using this aerosol.The Beconase Nasal Syray granular size is to be lower than 20 microns preferably, preferably is lower than 10 microns, and is best in 1 to 5 micrometer range.
The solvate of suitable pharmaceutically acceptable Beconase Nasal Syray comprises and chlorofluorocarbon ethyl acetate, alkane, ethers, the solvate of alcohols and water.Yet Beconase Nasal Syray preferably uses 1,1,1,2-tetrafluoroethane (CF
3CH
2F) solvate forms.
Terminology used here " Beconase Nasal Syray-1,1,1,2-tetrafluoroethane solvate " is meant any Beconase Nasal Syray and 1,1,1, the crystal that the 2-tetrafluoroethane links to each other.The ratio of this steroidal and this solvent based does not need stoichiometry, and does not have the special mechanism that links.This solvent can comprise that for example, about 20 to 1,1,1 of about 30% weight portion, the 2-tetrafluoroethane, and this accurate consumption depends on used specific preparation method.
Preferably with mixing Beconase Nasal Syray and 1,1,1 fully, the method that the 2-tetrafluoroethane forms a kind of recrystallisation solvent thing prepares this solvate.This method is to carry out in the presence of other possible solvent such as water, alcohol, chlorofluorocarbon, ethyl acetate, alkane and the diisopropyl ether not having ideally.Therefore, for example, micronized Beconase Nasal Syray can with 1,1,1 of exsiccant preferred liquid state, the coupling of 2-tetrafluoroethane.Can obtain formed recrystallisation solvent thing with conventional method as filtering with dry.
We have found Beconase Nasal Syray-1,1,1, and 2-tetrafluoroethane solvate is stable unexpectedly under ambient temperature and pressure.Especially, found Beconase Nasal Syray-1,1,1,2-tetrafluoroethane solvate is being stable up to 65 ℃ of left and right sides temperature.The granular size of this recrystallisation solvent thing can for example be used micronize with conventional method, and fluid grinds or ball milling makes it to reduce, and all medicines are sucked in the lung basically.Preferably, reduce the particle volume of this solvate under 2-tetrafluoroethane gas or its portion gas 1,1,1.This solvate of micronize form is mixed in the aerosol, unexpectedly is any significant crystal not occur to generate or condense.And, this solvate seemingly than anhydrous or other knownly can be prepared as 1,1,1 of aerosol, the Beconase Nasal Syray solvate of 2-tetrafluoroethane is easier to be moistening, and has the diffusion property of improvement.
Thereby, a particular aspects of the present invention provides a kind of graininess Beconase Nasal Syray-1,1,1 contained, 2-tetrafluoroethane solvate and the medicinal aerosol formulations that coexists with a kind of fluorocarbon or hydrogenous chlorofluorocarbon propellant, said preparation is substantially devoid of surfactant.
Being used for propellant of the present invention can be to have an enough air pressure to make them become either carbon fluorine compounds or hydrochlorofluorocarsolvent or its mixture of effective propellant.Preferred propellant right and wrong concerning medicine are deliquescent.Suitable propellant comprises as C
1-4Hydrochlorofluorocarsolvent such as CH
2ClF, CClF
2CHClF, CF
3CHClF, CHF
2CClF
2, CHClFCHF
2, CF
3CH
2Cl and CClF
2CH
3, C
1-4Hydrogenous fluorocarbon such as CHF
2CHF
2, CF
3CH
2F, CHF
2CH
3And CF
3CHFCF
3And C
1-4Perfluocarbon such as CF
3CF
3And CF
3CF
2CF
3
If use the mixture of perfluorocarbon or hydrochlorofluorocarsolvent here, they can be the above-mentioned chemical compound of indicating mixture or with other hydrofluorocarbons or hydrochlorofluorocarsolvent such as CHClF
2, CH
2F
2And CF
3CF
3Mixture, preferred binary mixture.
Be preferably and use single perfluorocarbon or hydrochlorofluorocarsolvent as propellant.Best propellant is a hydrofluorocarbon, particularly 1,1,1, and 2-tetrafluoroethane (CF
3CH
2F) and 1,1,1,2,3,3,3-seven fluoro-n-propane (CF
3CHFCF
3).
It is desirable to preparation of the present invention and do not contain the composition that can bring out the stratospheric ozone degraded.It would be desirable that said preparation is substantially free of particularly not hydrogenous chlorofluorocarbon of Chlorofluorocarbons (CFCs) such as CCl
3F, CCl
2F and CF
3CCl
3Here be meant that being lower than 1%w/w especially is lower than 0.5% used " not containing substantially ", as 0.1% or still less hydrofluorocarbons or hydrochlorofluorocarsolvent propellant.
This propellant can contain a kind of adjuvant that has than this propellant high polarity and/or higher arbitrarily.Operable polarity adjuvant comprises (as C
2-5) aliphatic alcohol and polyhydric alcohol such as ethanol, isopropyl alcohol and propylene glycol, preferred alcohol.Usually only need a spot of polarity adjuvant (as 0.05-3.0%w/w) to improve the stability of colloid solution.Using in addition can dissolved substance above the consumption of 5%w/w.Preferably contain according to preparation of the present invention and to be less than 1%w/w, according to appointment 0.1%w/w or polarity adjuvant still less.Suitable volatility adjuvant comprises saturated hydro carbons such as propane, normal butane, iso-butane, pentane and isopentane and alkane ether such as dimethyl ether.Usually, can contain a kind of volatility adjuvant up to the propellant of 50%w/w, as, 1 to 30%w/w the saturated C of a kind of volatility
1-6Hydro carbons.
However, be that preparation of the present invention does not contain other possible solvent such as chlorofluorocarbon, ethyl acetate, alkane substantially preferably, ether, alcohol and water, especially, said preparation is not moisture substantially, as contain and be less than 250ppm, be less than 100ppm for being less than 200ppm, being preferably preferably, as be less than the water of 50ppm.
It is a kind of mainly by Beconase Nasal Syray-1,1,1 that most preferred embodiment of the present invention provides, 2-tetrafluoroethane solvate and one or more hydrofluorocarbons or hydrochlorofluorocarsolvent propellant, particularly 1,1,1, the medicinal aerosol that the 2-tetrafluoroethane is formed.
In addition on the one hand, according to the Beconase Nasal Syray that can use anhydrous form in the present composition.Therefore, the present invention provides a kind of medicinal aerosol formulations that contains the anhydrous Beconase Nasal Syray of graininess and a kind of hydrofluorocarbons or the coexistence of hydrochlorofluorocarsolvent propellant on the other hand, and said preparation is substantially free of surfactant.
It is a kind of mainly by anhydrous Beconase Nasal Syray and 1,1,1,2,3,3 that most preferred embodiment of the present invention provides, the medicinal aerosol that 3-seven fluoro-n-propanes are formed as propellant.
Final aerosol formulations is the 0.005-10%w/w that comprises with respect to the prescription gross weight ideally, the Beconase Nasal Syray of preferred 0.005-5.0%w/w, particularly 0.01-1.0%w/w such as 0.01-0.5%w/w.
Those skilled in the art can be understood as aerosol formulations of the present invention, and work if desired can comprise one or more additional activity compositions.The aerosol formulations that contains two kinds of active component (in a conventional propellant system) is known, as, can be used for treating respiratory system disease as asthma.Thereby the present invention also provides the aerosol preparations that contains one or more additional certain drug.Medication can be selected from arbitrary other appropriate drug that is applicable to anapnotherapy, and this medicine can exist with the form that is insoluble to selected propellant basically fully.So appropriate drug is selected from as, analgesic, as codeine, paramorphane, Ergotamine, fentanyl or morphine; Persantin preparation such as sulfur nitrogen ketone; Anti-allergic drug, as cromoglycate, ketotifen or nedocromil; Anti-infective, as cephalosporins, penicillins, streptomycin class, sulfonamides, Tetracyclines and pentamidine; Antihistaminic, as, sleepwell; Anti-inflammatory agent, as fluticasone, 9-removes the fluorine fluocinonide, budesonide, tipredane, or the third scorching pine; Cough medicine, as, narcotine; Bronchodilator, as salmeterol, salbutamol, ephedrine, epinephrine, fenoterol, the formoterol isoproterenol, orciprenaline, phenylephrine, phenylpropanolamine, pyrrole butanols, D-1959, asmaten, terbutaline, neoisuprel, C-78, alotec or (-)-4-amino-3,5-two chloro-α-[[[6-[2-(the 2-pyridine radicals] ethyoxyl] hexyl] amino] methyl] benzyl alcohol; Diuretic is as amiloride; Anticholinergic agent, as Ipratropium Bromured, atropine or second scopolamine; Hormones, as cortisone, hydrocortisone or meticortelone; Horizontal purine class, as aminophylline, Oxtriphylline, lycine theophylline or theophylline; With treatment protein and polypeptide class, as, insulin or glucagon.Very at the appropriate time clear to those skilled in the art, can use this medicine salt (as make alkali metal or amine salt or as acid-addition salts) or esters (as, low alkyl group esters) or solvate (as hydrate) form bring into play the active and/or stability of this medicine and/or reduce the dissolubility of this medicine in propellant with the best to minimum.
Best aerosol comprises that salbutamol (as making free alkali or sulphate form) or Sal-meterol (as making xinafoate salt) are used in combination with Beconase Nasal Syray.Preferably Salmeterol Xinafoat and Beconase Nasal Syray are used in combination.
The present invention prescription can be used in the appropriate containers goes into method in the selected propellant to drug diffusion, for example, by sonicated, prepares.
Reduce in aerosol of the present invention and avoid using excipient such as surfactant as far as possible, cosolvent etc. are useful.Because it is the tasteless basically nothing of said preparation is smelt, littler and toxicity is lower than conventional formulation zest.
The chemistry of aerosol of the present invention and physical stability and medicine acceptability can be used the known technical measurement of those of skill in the art in this area.So, as after the product long term store, the chemical stability of this component can be measured with the HPLC detection method.The physical stability data can be from other conventional analysis technology as using leak test, and with valve start detection (the average ejaculation weight of every startup), the method that detects (every startup active component) and spray distribution analysis with the dosage repeatability obtains.
Preparation of the present invention can be charged into to be suitable for transporting in the container of medicinal aerosol.This class container often comprises container such as a kind of plastics that can tolerate used propellant air pressure or the vial of warding off plastics or preferred a kind of canister, can be painted by anodization arbitrarily and/or the aluminium pot of slush moulding as a kind of, and this container seals with proportional valve.This proportional valve is designed to start provide quantitative preparation and add a packing ring at every turn and passes through the valve seepage to prevent propellant.This packing ring can contain arbitrary suitable elastic material such as low-density polyethylene, chlorobutyl, black and white butadiene-acrylonitrile rubber, butyl rubber and neoprene.Suitable valve is that the producer of knowing from aerosol industry obtains commercial, as from Valois, France (as, DF10, DF30, DF60), Bespak Plc, (as BK300, BK356) with 3M-Neotechnic Ltd, UK (as Spraymiser TM) buys UK.
Can be used in the technical field of medicinal aerosol production and come large-scale commercial applications production canned products for known batch manufacturing method routinely of those of skill in the art and machinery.So, for example, in a kind of batch manufacturing method, proportional valve is crimped on forms empty on the aluminium pot.Form the processing bottle in this gas filling bottle pressing to insert in the graininess medicine adding gas filling bottle and liquefied propellant.This drug suspension mixes before being back to filling machine, by proportional valve drug suspension such as branch such as grade is packed into container then.Generally, in being prepared into medicinal batch, each weight of checking the container of filling out, the coding lot number is also put into the carriage storage before discharging test.
Every populated container often assembles a suitable lane device before use to form a metered dose suction apparatus, delivers medicine to patient's lung or nasal cavity.Suitable lane device comprises cylinder or the class circular cone passage that can be from populated container passes through during to patient's nose or oral area through proportional valve as a valve trigger and medicine, as, a hub cavity trigger.The metered dose suction apparatus is designed to each startup or " injection " carries the fixedly medicine of unit dose, as the medicine of every injection 10 to 5000 nanogram ranges.
The medicine that uses can be indicated be used for the treatment of light, in or acute or chronic disease or be used for prophylactic treatment.Should be understood that the accurate dosage of being taken will depend on patient's age and situation, used specific graininess medicine and administration number of times, and finally according to medical worker's instrucion, when using medicinal mixture, the dosage of every kind of component often is the used amount of single time spent every kind of component in this mixture, usually, administration can be an one or many, and as every day 1 to 8 time, each administration is as spraying 1,2,3 or 4 times.
Suitable dosage every day is as the Beconase Nasal Syray in 100 to 2000 nanogram ranges, depends on the order of severity of disease.
So, can carry 50,100,200 or 250 milligrams Beconase Nasal Syray as each valve startup.Usually every filling containers that is used for quantitative inhalation dose comprises the quantitative or spray number of 100,160 or 240 medicines.
Filling containers as described herein and metered dose suction apparatus constitute another partial content of the present invention.
A further object of the invention comprises a kind of method for the treatment of respiratory system disease as asthma, and it comprises the preparation that uses effective dose as herein described with inhalation.
Following indefiniteness embodiment is used to describe in detail the present invention.Embodiment 1 Beconase Nasal Syray-1,1,1,2-tetrafluoroethane solvate
The micronized anhydrous Beconase Nasal Syray of weighing (25.2mg) is put into a clean dried slush moulding vial and is added exsiccant (＜50ppm H from a Dewar bottle
2O) 1,1,1,2-tetrafluoroethane (to 18.2g).This vial seals rapidly with an empty alumiseal cover.This bottle is placed under the ambient temperature.Several days after-filtration separate the crystallization of formed solvate.
Analyze the solvate that is obtained like this with various technology.
The microscopy of this solvate show this crystallization be column and prismatic and reach 500 to 1000 microns.
Analyze the solid-state infrared spectrum of this solvate.The most tangible difference is as follows between the infrared spectrum of this spectrum and solid-state anhydrous Beconase Nasal Syray:
(a) at 3300cm
-1Wide OH bands of a spectrum bring up to 3500cm
-1Near, and be sharp peak;
(b) at 1750cm
-1The carbonyl band at place is split into three tangible spikes of this solvation form of expression;
(c) 1,4-diene peak moves to about 1630cm
-1, with 1610cm
-1The peak separates significantly.
Other the difference also obviously show the whole zone of being checked after the solvation many positions and Strength Changes are arranged the peak.
Carry out the thermogravimetry and the differential scanning calorimetric of solvate under the atmospheric pressure with a Netzsch Simultaneous Thermal analyser STA409.1,1,1, being lost in 65 ℃ and beginning to take place of 2-tetrafluoroethane.Heat is inhaled to defend and is proceeded to about 90 ℃, and heat release at this moment changes makes 90 ℃ to be raised to 110 ℃, 1,1,1 of this and 120 ℃, and finishing of the loss of 2-tetrafluoroethane conforms to.This scattergram has different significantly with 30 ℃ of scattergrams that begin to take place the known Beconase Nasal Syray-trichlorine fluomethane solvate of trichlorine fluomethane loss.
Thermogravimetry shows heating Beconase Nasal Syray-1,1,1, total weight loss 23.1% during 2-tetrafluoroethane solvate, and this shows 1,1,1 of 3 molecules, the ratio of the Beconase Nasal Syray of 2-tetrafluoroethane and 2 molecules.Embodiment 2
Beconase Nasal Syray-1,1,1,2-tetrafluoroethane solvate
Micronized anhydrous Beconase Nasal Syray of weighing (24.1mg) and lecithin (3.3mg) join in the clean dry slush moulding vial, and add exsiccant (＜50ppm H from a Dewar bottle
2O) 1,1,1,2-tetrafluoroethane (being added to 18.2g).Of the alumiseal cover rapidly sealing of this vial with a sky.Place this bottle at ambient temperature.After several days, the crystallization of this solvate of isolated by filtration.The crystal shape of resulting solvate, the solvate basically identical of infrared spectrum and thermogravimetry and embodiment 1.Embodiment 3
Aerosol preparations
The prepared micronize Beconase Nasal Syray-1,1,1 of weighing embodiment 1 in a clean slush moulding vial of doing, 2-tetrafluoroethane solvate (31mg), and with exsiccant (＜50ppm H
2O) 1,1,1,2-tetrafluoroethane (18.2g) adds from a Dewar bottle.Seal this bottle rapidly with an empty alumiseal cover.Resulting aerosol comprises 0.138% (w/w) Beconase Nasal Syray (0.170%w/w solvate).Embodiment 4 aerosol formulations
A clean drying, the anhydrous Beconase Nasal Syray of weighing micronize (60mg) is also exsiccant (＜50ppm H in the slush moulding vial
2O) 1,1,1,2,3,3,3-seven fluorine normal butanes (18.2g) add from a Dewar bottle.Seal this bottle rapidly with an empty alumiseal cover.Resulting aerosol comprises 0.33% (w/w) Beconase Nasal Syray.
Claims (9)
1. medicinal aerosol, it contains the hydrofluorocarbons or the hydrogenous Chlorofluorocarbons (CFCs) propellant of the anhydrous Beconase Nasal Syray of graininess and a kind of coexistence, and said preparation is substantially free of surfactant.
2. aerosol as claimed in claim 1, propellant wherein are-1,1,1,2,3,3,3-seven fluoro-n-propanes.
3. as each aerosol among the claim 1-2, it contains the Beconase Nasal Syray that accounts for said preparation gross weight 0.005-5.0%W/W.
4. as each aerosol among the claim 1-3, the granular size of the two propionic esters of wherein anhydrous beclomethasone guarantees that all medicines suck in the lung basically when using this aerosol.
5. as each aerosol in the claim 1 to 4, it can also contain salbutamol.
6. medicinal aerosol, mainly by the anhydrous Beconase Nasal Syray and 1,1,1,2,3,3 of microgranule, 3-seven fluoro-n-propane propellants are formed for it.
7. container that is applicable to the transportation medicinal aerosol, it comprises a kind of container that can the used propellant air pressure of tolerance, this container is with quantitative valve sealing and include among the claim 1-6 each medicinal aerosol.
8. suction apparatus of measuring dosage, it comprises the described container of claim 7, and is assembled on the suitable lane device.
9. treat the method for calling out disease for one kind, it comprises with inhalation uses an effective dose and the medicinal aerosol fluorohydrocarbon coexistence or uses in the claim 1 to 6 each aerosol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 98108908 CN1204509A (en) | 1992-07-31 | 1998-05-14 | Pharmaceutical aerosol formulation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9216381.5 | 1992-07-31 | ||
| GB9216382.3 | 1992-07-31 | ||
| CN 98108908 CN1204509A (en) | 1992-07-31 | 1998-05-14 | Pharmaceutical aerosol formulation |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93116824A Division CN1052401C (en) | 1992-07-31 | 1993-07-30 | Medicaments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1204509A true CN1204509A (en) | 1999-01-13 |
Family
ID=5219797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 98108908 Pending CN1204509A (en) | 1992-07-31 | 1998-05-14 | Pharmaceutical aerosol formulation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1204509A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101028266B (en) * | 2006-03-02 | 2010-05-12 | 鲁南制药集团股份有限公司 | Lung medicine-feeding preparation containing Mulinong |
-
1998
- 1998-05-14 CN CN 98108908 patent/CN1204509A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101028266B (en) * | 2006-03-02 | 2010-05-12 | 鲁南制药集团股份有限公司 | Lung medicine-feeding preparation containing Mulinong |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1052401C (en) | Medicaments | |
| KR100375469B1 (en) | Medicaments | |
| RU2129424C1 (en) | Aerosol pharmaceutical composition, a method of treatment of patients with respiratory diseases | |
| EP0616525B1 (en) | Pharmaceutical aerosol formulation | |
| US5653962A (en) | Aerosol formulations containing P134a and particulate medicaments | |
| EP0616524B1 (en) | Medicaments | |
| US6919069B2 (en) | Aerosol formulation containing particulate formoterol, propellant and polar cosolvent | |
| CN1078633A (en) | pharmaceutical preparation | |
| US6013245A (en) | Aerosol formulation containing beclomethasone dipropionate and 1,1,1,2,3,3,3-heptafluoro-n-propane as propellant | |
| US5833950A (en) | Aerosol formulations containing beclomethasone dipropionate-1, 1, 1, 2-tetrafluoroethane solvate | |
| CN1204509A (en) | Pharmaceutical aerosol formulation | |
| CN1048627C (en) | Medicaments | |
| AU699677B2 (en) | Surfactant free aerosol formulations containing beclomathasone dipropionate | |
| CA2141039C (en) | Surfactant free aerosol formulations containing beclomethasone dipropionate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |