AP382A - A pharmaceutical composition comprising a benzopyran-3-OL. - Google Patents

A pharmaceutical composition comprising a benzopyran-3-OL. Download PDF

Info

Publication number
AP382A
AP382A APAP/P/1992/000454A AP9200454A AP382A AP 382 A AP382 A AP 382A AP 9200454 A AP9200454 A AP 9200454A AP 382 A AP382 A AP 382A
Authority
AP
ARIPO
Prior art keywords
pharmaceutically acceptable
compound
pharmaceutical composition
acceptable salt
administration
Prior art date
Application number
APAP/P/1992/000454A
Other versions
AP9200454A0 (en
Inventor
Jonathan Robert Sanders Arch
Nicholas Edward Bowring
Original Assignee
Smithkline Beecham Plc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from GB919125862A external-priority patent/GB9125862D0/en
Priority claimed from GB929213042A external-priority patent/GB9213042D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Publication of AP9200454A0 publication Critical patent/AP9200454A0/en
Application granted granted Critical
Publication of AP382A publication Critical patent/AP382A/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A pharmaceutical composition comprising trans

Description

pharmAceutical composition
This invention relates to a pharmaceutical composition, to processes for the preparation of such a composition and to the use of such a composition in medicine.
European Patent Application, Publication Number 0376524 discloses certain benzopyran derivatives which are stated inter alia to be potentially useful as bronchodilators in the treatment of disorders of the respiratory tract, such as reversible airways obstruction and asthma, and also in the treatment of hypertension.
EP 0376524 also discloses trans (3S, 4R)-3,4-dihydro-2,2dimethyl-4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-l- benzopyran-3-ol ( Compound Γ).
It has now been discovered that a discrete and particular pharmaceutical composition comprising Compound I or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, is particularly useful for the treatment in humans of disorders of the respiratory tract, such as reversible airways obstruction and asthma: the hypotensive activity of such composition is largely reduced.
Accordingly, in one aspect the present invention provides a pharmaceutical composition comprising Compound I or, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and optionally a pharmaceutically acceptable carrier therefore, characterised in that the composition comprises 0.2 to 0.9 mg or
1.1 to 1.9 mg or 2.1 to 3.0 mg of Compound I.
Particular compositions comprise 0.3 to 0.8 mg, 0.4 to 0.7 mg, 0.2 to 0.5 mg, 0.5 to 0.9 mg, 1.1 to 1.5 mg, 1.5 to 1.9 mg, 2.1 to 2.5 mg or 2.5 to 3.0 mg of active compound.
Examples of compositions are those comprising 0.2, 0.3, 0.4, 0.5, 0.6, 0.7,
0.8,0.9,1.1, 1.5, 1.9, 2.1, 2.5 or 3.0 mg of active compound.
Suitable pharmaceutically acceptable salts include those described in
BAD ORIGINAL
P30208
AP 0 0 0 3 8 2
-2EP0376524. Generally, Compound I is not in a salted form.
Suitable pharmaceutically acceptable solvates include those described in EP0376524, in particular hydrates.
Compound I or, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, may be prepared using known methods, for example those disclosed in EP0376524. The disclosures of EP0376524 are incorporated herein by reference.
In one aspect, the invention provides a process for preparing a pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to 1.9 mg or
2.1 to 3.0 mg of Compound I, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and optionally a pharmaceutically acceptable carrier therefor, which process comprises formulating Compound I, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof and optionally comprises admixing the pharmaceutically acceptable carrier.
The composition of the invention is preferably adapted for oral administration. However, it may be adapted for other modes of administration, for example parenteral administration, sublingual or transdermal administration.
The compositions may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, reconstitutable powders, or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
In order to obtain consistency of administration it is preferred that a composition of the invention is in the form of a unit dose.
Unit dose presentation forms for oral administration may be tablets and capsules and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline bad
ORIGINAL
P30208
AP000382
-3cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
The solid oral compositions may be prepared by conventional methods of 5 blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are of course conventional in the art. The tablets may be coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
Oral liquid preparations may be in the form of, for example, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution .- with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel, hydrogenated edible fats; emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid; and if desired conventional flavouring or colouring agents.
For parenteral administration, fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle, and, depending on the ( concentration used, can be either suspended or dissolved in the vehicle.
In preparing solutions the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, a preservative and buffering agents can be dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum. Parenteral suspensions are prepared in substantially the same manner, except that the compound is suspended in the vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration. The compound ran be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound
BAD ORIGINAL tf
P30208
APO00382
-4Compositions of this invention, especially for the treatment of reversible airways obstruction and asthma, may also suitably be presented for administration to the respiratory tract as a snuff or an aerosol or solution for a nebulizer, or as a microfine powder for insufflation, alone or in combination with an inert carrier such as lactose. In such a case the particles of active compound suitably have diameters of less than 50 microns, preferably less than 10 microns for example diameters in the range of 1-50 microns, 1-10 microns or 1-5 microns. Where appropriate, small amounts of other anti-asthmatics and bronchodilators, for example sympathomimetic amines such as isoprenaline, isoetharine, salbutamol, phenylephrine and ephedrine; xanthine derivatives such as theophylline and aminophylline and corticosteroids such as prednisolone and adrenal stimulants such as ACTH may be included.
The compositions may contain from 0.1% to 99% by weight, preferably from 10-60% by weight, of the active material, depending upon the method of administration. A preferred range for inhaled administration is 10-99%, especially 60-99%, for example 90,95 or 99%.
The present invention further provides a pharmaceutical composition, in particular a composition for inhaled administration, which comprises 0.2 to 3.0 mg of Compound I or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, in the form of a microfine powder and optionally a pharmaceutically acceptable carrier. Suitable carriers are those used conventionally in the art, for example lactose.
Preferably the composition for inhaled administration comprises 0.2 to 0.9 mg for example 0.2 to 0.5 mg, or 0.2,0.3, 0.4 or 0.5 mg, of active compound.
Microfine powder formulations may suitably be administered in an aerosol as a metered dose or by means of a suitable breath-activated device.
Suitable metered dose aerosol formulations comprise conventional propellants, cosolvents, such as ethanol, surfactants such as oleyl alcohol, lubricants such as oleyl alcohol, desiccants such as calcium sulphate and density modifiers such as sodium chloride.
BAD ORIGINAL $
P30208
AP 0 0 0 3 8 2
-5Suitable solutions for a nebulizer are isotonic sterilised solutions, optionally buffered, at for example between pH 4-7, containing up to 20mg ml-1 of compound but more generally 0.1 to lOmg ml-1, for use with standard nebulisation equipment.
The compositions of the invention may be prepared and formulated according to conventional methods, such as those disclosed in standard reference texts, for example the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.), Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) and Harry's Cosmeticology (Leonard Hill Books).
The present invention further provides a method for the treatment of respiratory tract disorders, such as reversible airways obstruction and, especially asthma, in humans which method comprises administering a total daily dose of 0.2 to 0.9 mg or 1.1 to 1.9 mg or 2.1 to 3.0 mg of Compound I, or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, to a human in need thereof.
The medicament may be administered from 1 to 6 times a day, more usually from 2 to 4 times a day, preferably 1 or 2 times per day providing the total daily dose is 0.2 to 0.9 mg, 1.1 to 1.9 mg or 2.1 to 3.0 mg.
It will be appreciated that a unit dose for use in the method of the invention may comprise less than the stated total daily dose (e.g. less than 0.2 to 0.9 mg) of active compound in order to achieve the required total daily dose.
The present invention also provides a pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to 1.9 mg or 2.1 to 3.0 mg of Compound I or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefor, for use as an active therapeutic substance.
In particular, the present invention provides a pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to 1.9 mg or 2.1 to 3.0 mg of
Compound I, or a pharmaceutically acceptable salt thereof, or a
BAD ORIGINAL (, λ
P30208
ΑΡ ο Ο Ο 3 8 2
-6pharmaceutically acceptable solvate thereof, for use in the treatment of respiratory tract disorders. Also the present invention provides the use of a pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to 1.9 mg or
2.1 to 3.0 mg of Compound I, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefor for the manufacture of a medicament for the treatment of respiratory tract disorders.
The following Example illustrates the invention but does not limit it in 10 any way.
BAD ORIGINAL ...
P3020S
ΑΡ ο 0 0 3 8 2
-7Example
Male Sprague-Dawley rats were anaesthetized using urethane and prepared for determination of airways resistance (Raw), dynamic lung compliance (C^yu) and blood pressure as described by N.E. Bowring et al., 1991, Pulmonary Pharmacolgoy 4, 99-105.
The rats were challenged with an aerosol of methacholine for 2 minutes at 15 minute intervals using a concentration (0.25 to 2.5 mol) sufficient to raise resistance by about 100% and reduce compliance by about 40%. When consistent responses had been established Compound 1 was given intravenously 2 minutes before the methacholine challenge, the challenge being repeated at 15 minute intervals until its effect on Raw and C^yn had returned to near pre-Compound I values, after which point a higher dose of Compound I was given. Blood pressure was measured just prior to each methacholine challenge. When the dose of Compound I was sufficiently high to elicit an effect on blood pressure, this effect was maximal within 2 minutes. Results are means of 5 values ± S.E. and are expressed as percentage falls in blood pressure or inhibitions of preCompound I responses to the methacholine challenge.
bad original &
P30208
AP Ο Ο Ο 3 8 2
-8RESULTS
04 co ι- 31±9* 22±10
*
* ♦
οο r—w
•H -H
Γ Γ- r-~
co CO
<
* #
o ♦ ♦
+! ί c> -H
cm
+i Ή
CM o 00
co CO
#
«
* «
±7 51
f'-
CO CM
«
·—M «
^-4
-H -H O
oo in s
04 CO CM
o
Ό
-H +t
04 r-
co
CM ±8 ±7
Γ'· WO r-~
·“*
OO SI 4±5
cm 1 »—«
£
3
co
ε
c CL
Ό C (mi ί c I
ο α. > o co Λ & Ό O Lo
ε - Ο xk O Ό c ο c o §
r s °β w co a ibiti « LS υ ε
w =L υ « JZ e x: c 73
CO E tu
Ο Q H £ £
tn

Claims (11)

1. A pharmaceutical composition comprising trans (3S,4R>3,4dihydro-2,2-dimethyl~4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-lbenzopyran-3-ol ('Compound Γ), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefore, characterised in that, the composition comprises 0.2 to 0.9 mg or 1.1 to 1.9 mg or 2.1 to 3.0 mg of Compound I.
2. A composition according to claim 1, comprising 0.3 to 0.8 mg, 0.4 to 0.7 mg, 0.2 to 0.5 mg, 0.5 to 0.9 mg, 1.1 to 1.5 mg, 1.5 to 1.9 mg, 2.1 to 2.5 mg or 2.5 to 3.0 mg of active compound.
3. A composition according to claim 1 or claim 2, comprising 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8,0.9, 1.1, 1.5, 1.9, 2.1, 2.5 or 3.0 mg of active compound.
4. A composition according to any one of claims 1 to 3, adapted for oral administration, parenteral administration, sublingual or transdermal administration.
5. A composition according to any one of claims 1 to 4, adapted for oral administration.
6. A composition according to any one of claims 1 to 5, in the form of a unit dose.
7. A composition according to any one of claims 1 to 6, adapted for administration to the respiratory tract as a snuff, an aerosol, a solution for a nebulizer, or as a microfine powder for insufflation.
8. A pharmaceutical composition for inhaled administration, which comprises 0.2 to 3.0 mg of trans (3S,4R)-3,4-dihydro-2,2-dimethyl4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-l- benzopyran-3-ol (’Compound Γ), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, in the form of a microfine powder and optionally a pharmaceutically acceptable carrier.
BAD ORIGINAL
P30208/C
APO 0 0 3 8 2
Ο r
-29. A process for preparing a pharmaceutical composition as claimed in any one of claims 1 to 8, which process comprises formulating Compound I, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and optionally comprises admixing the pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to
1.9 mg or 2.1 to 3.0 mg of trans (3S,4R)-3,4-dihydro-2,2-dimethyl4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-l-benzopyran-3-ol ('Compound Γ), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefor, for use as an active therapeutic substance.
11. A pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to
1.9 mg or 2.1 to 3.0 mg of trans (3S,4R)-3,4-dihydro-2,2-dimethyl4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-l- benzopyran-3-ol ( Compound Γ), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, for use in the treatment of respiratory tract disorders.
12. The use of a pharmaceutical composition comprising 0.2 to 0.9 mg or 1.1 to 1.9 mg or 2.1 to 3.0 mg of trans (3S,4R)-3,4-dihydro-2,2-dimethyl4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-l- benzopyran-3-ol (’Compound Γ), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier therefor for the manufacture of a medicament for the treatment of respiratory tract disorders.
APAP/P/1992/000454A 1991-12-05 1992-12-04 A pharmaceutical composition comprising a benzopyran-3-OL. AP382A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB919125862A GB9125862D0 (en) 1991-12-05 1991-12-05 Pharmaceutical composition
GB929213042A GB9213042D0 (en) 1992-06-19 1992-06-19 Pharmaceutical composition

Publications (2)

Publication Number Publication Date
AP9200454A0 AP9200454A0 (en) 1993-01-31
AP382A true AP382A (en) 1995-05-03

Family

ID=26299960

Family Applications (1)

Application Number Title Priority Date Filing Date
APAP/P/1992/000454A AP382A (en) 1991-12-05 1992-12-04 A pharmaceutical composition comprising a benzopyran-3-OL.

Country Status (15)

Country Link
EP (1) EP0615437A1 (en)
JP (1) JPH07501538A (en)
AP (1) AP382A (en)
AU (1) AU2954292A (en)
BR (1) BR9206845A (en)
CA (1) CA2125156A1 (en)
CZ (1) CZ136394A3 (en)
HU (1) HUT70745A (en)
IL (1) IL103952A0 (en)
MA (1) MA22731A1 (en)
MX (1) MX9206975A (en)
RU (1) RU94030464A (en)
SI (1) SI9200365A (en)
SK (1) SK65794A3 (en)
WO (1) WO1993010757A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0076075A1 (en) * 1981-09-25 1983-04-06 Beecham Group Plc Pharmaceutically active benzopyran compounds
EP0093535A1 (en) * 1982-04-28 1983-11-09 Beecham Group Plc Novel chromenes and chromans
EP0296975A1 (en) * 1987-06-23 1988-12-28 MERCK PATENT GmbH 2,2-Dimethyl-3-chromanol derivatives, process of their preparation and pharmaceutical compositions containing them
EP0376524A1 (en) * 1988-12-13 1990-07-04 Beecham Group Plc Benzopyran and related compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0076075A1 (en) * 1981-09-25 1983-04-06 Beecham Group Plc Pharmaceutically active benzopyran compounds
EP0093535A1 (en) * 1982-04-28 1983-11-09 Beecham Group Plc Novel chromenes and chromans
EP0296975A1 (en) * 1987-06-23 1988-12-28 MERCK PATENT GmbH 2,2-Dimethyl-3-chromanol derivatives, process of their preparation and pharmaceutical compositions containing them
EP0376524A1 (en) * 1988-12-13 1990-07-04 Beecham Group Plc Benzopyran and related compounds

Also Published As

Publication number Publication date
HUT70745A (en) 1995-10-30
WO1993010757A1 (en) 1993-06-10
CZ136394A3 (en) 1995-02-15
CA2125156A1 (en) 1993-06-10
MX9206975A (en) 1993-06-01
IL103952A0 (en) 1993-05-13
SK65794A3 (en) 1995-02-08
BR9206845A (en) 1996-01-02
AU2954292A (en) 1993-06-28
AP9200454A0 (en) 1993-01-31
JPH07501538A (en) 1995-02-16
MA22731A1 (en) 1993-07-01
RU94030464A (en) 1996-04-27
HU9401681D0 (en) 1994-09-28
EP0615437A1 (en) 1994-09-21
SI9200365A (en) 1993-06-30

Similar Documents

Publication Publication Date Title
JP4445590B2 (en) Oral liquid composition containing paroxetine-resin
US4891380A (en) Novel treatment
EP0277352A1 (en) Synergistic mixture of azelastine and theophylline or of azelastine and beta-mimetics
JP2008512429A (en) Combination of roflumilast and syk inhibitor and method of use thereof
EP0310999B1 (en) Pharmaceutical composition for piperidinoalkanol derivatives
AP382A (en) A pharmaceutical composition comprising a benzopyran-3-OL.
EP1720543A1 (en) Roflumilast and glycopryrronium combination
EP0222575A1 (en) Prazosin-pirbuterol combination for bronchodilation
EP2262485A1 (en) Modified release composition comprising doxofylline
US7932276B2 (en) Agent for curing chronic obstructive pulmonary disease
JPH07505381A (en) Treatment for airway inflammation and airway hyperresponsiveness
EP0848610A1 (en) Use of a carbostyril derivative for inhibiting carcinogenesis
JPH07138157A (en) Anti-ulcer agent
KR20150100902A (en) Methods and compositions for administration of oxybutynin
US6297268B1 (en) Imidazoles as cholesterol lowering agents
JPH085784B2 (en) Syrup
WO2000003717A1 (en) Method of treatment
AU2002317509B2 (en) Use of thiazole deirvatives for the manufacture of a medicament for the treatment of chronic obstructure pulmonary disease
CN113577059A (en) Active medicine for treating infantile asthma
JP2001089375A (en) Common cold composition
JP2003095946A (en) Famotidine tablet
JPH0776584A (en) Suppressor for endothelial cytotoxicity
JPH035425A (en) Anti-ulcer agent
CN1080171A (en) Pharmaceutical composition
US20080269179A1 (en) Use of Megestrol Acetate for the Treatment of Obstructive Pulmonary Diseases