[go: up one dir, main page]

WO1987000047A1 - Procede et composition de traitement d'affections pulmonaires obstructives chroniques - Google Patents

Procede et composition de traitement d'affections pulmonaires obstructives chroniques Download PDF

Info

Publication number
WO1987000047A1
WO1987000047A1 PCT/US1986/001419 US8601419W WO8700047A1 WO 1987000047 A1 WO1987000047 A1 WO 1987000047A1 US 8601419 W US8601419 W US 8601419W WO 8700047 A1 WO8700047 A1 WO 8700047A1
Authority
WO
WIPO (PCT)
Prior art keywords
calcium channel
channel blocker
verapamil
beta
composition
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.)
Ceased
Application number
PCT/US1986/001419
Other languages
English (en)
Inventor
Tahir Ahmed
Marvin Sackner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Key Pharmaceuticals Inc
Original Assignee
Key Pharmaceuticals Inc
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
Application filed by Key Pharmaceuticals Inc filed Critical Key Pharmaceuticals Inc
Priority to FI870731A priority Critical patent/FI870731A0/fi
Priority to KR1019870700179A priority patent/KR890004691B1/ko
Publication of WO1987000047A1 publication Critical patent/WO1987000047A1/fr
Priority to NO870827A priority patent/NO870827D0/no
Priority to DK103087A priority patent/DK103087A/da
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/275—Nitriles; Isonitriles
    • 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

Definitions

  • the present invention is directed to the treatment of chronic obstructive pulmonary diseases such as asthma and chronic bronchitis. More particularly, the present invention is directed to increasing the duration of action and the peak effect of conventional treatments, 10 so that treatment is more convenient and effective. It has been discovered that administering a calcium channel blocker with the standard beta-adrenergic agonist will result in greater bronchodilation and an increased acting time in treating chronic obstructive pulmonary 15 diseases.
  • a safe, effective treatment for patients suffering from chronic obstructive pulmonary diseases such as asthma and chronic bronchitis currently is the oral or 20 aerosol administration of a beta-adrenergic agonist.
  • the beneficial effect of this treatment wears off in about four hours, thus requiring the incon ⁇ venience of four to six treatments per day. It would be advantageous if three or fewer treatments were required 25 and nighttime coverage against potential bronchospasm would be ensured.
  • calcium channel blockers such as Verapamil and Nifedipine has been considered for treating allergen and antigen-induced bronchoconstric- 30 tions.
  • calcium channel blockers have not been considered as possible agents for increasing the duration of action and peak effectiveness in reducing ? bronchoconstriction for beta-adrenergic agonists.
  • the above objects and others are obtained by administering a calcium channel blocker with a beta- adrenergic agonist to a person suffering from a chronic obstructive pulmonary disease.
  • the use of the calcium channel blocker can as much as double the effective treatment time of the beta-agonist, thus reducing the number of daily dosages required and providing nighttime coverage.
  • a calcium channel blocker can be used to enhance the bronchodilation to increase the effective treating time of beta-agonists, presently used in treating chronic obstructive pulmonary diseases such as asthma, chronic bronchitis, and emphysema. It is believed that the increased effective ⁇ ness of the beta-adrenergic agonist is caused by the calcium channel blocker preventing reversal of the calcium depletion initiated by the beta-agonist.
  • this is only a proposed theory, and the present invention is not limited to this particular theory.
  • the calcium channel blocker may be administered concurrently with a beta-adrenergic agonist, using the same administration route as the beta-adrenergic agonist, i.e. aerosol, oral, parenteral, etc.
  • the amount of beta-adrenergic agonist administered at a given time is not changed from the levels presently known. However, the frequency of the administration may be decreased. It has been discovered that the calcium channel blocker doubles the effective treatment time of the beta-adrenergic agonist. Of course, it also would be possible to lower the dosage of beta-adrenergic agonist if, for some reason, more frequent adminis ⁇ tration is desired. For any given dosage of beta-adrenergic agonist, the calcium channel blocker increases the effective treatment time. 5 Any calcium channel blocker suitable for adminis ⁇ tration via the treatment routes mentioned heretofore is useful in the present invention. Two representative calcium channel blockers are Verapamil and Gallopamil. Nifedipine is an example of a calcium channel blocker
  • Nifedipine is inactivated by light, use of this compound in aerosol applications may be difficult.
  • any of the known beta- adrenergic agonists presently used in broncho-dilator is a known beta- adrenergic agonists presently used in broncho-dilator
  • beta-adrenergic agonists examples include Albuterol (Ventolin) , Isoetharine, Metaproterenol, and Isoproterenol. Aerosol administration is preferred, although other forms of administration, such as oral or
  • Aerosol administration may be through use of a metered dose inhaler, such as is commonly used in this type of therapy at present.
  • a preferred method for aerosol administration is use of a metered dose inhaler with the
  • the amount of calcium channel blocker in a given ⁇ dosage depends to some extent upon the method of admin ⁇ istration. For example, when a one-percent by weight
  • 35 solution of Verapamil in saline is to be delivered by nebulization, the amount of solution in a given dosage is chosen to provide about 10 to 20 milligrams of Verapamil. This has been found to provide an effective dose of about one-half milligram to the lungs. However, aerosol delivery using a metered dose inhaler and Freon results in a much greater amount of the active ingredient reaching the lungs. Thus, one-half to one milligram of Verapamil delivered in this fashion would be necessary to achieve the same effect as the 10-20 milligrams delivered via the nebulized saline solution. Dosages of other calcium channel blockers will depend upon their potency.
  • Gallopamil is more potent than Verapamil, so that a 5 or 10 milligram dose could be delivered via nebulized saline solution, preferably about J-1% by weight. 8 milligrams of Gallopamil in 2ml of saline (0.4%) solution is as effec- tive as 20 milligrams of Verapamil. Both Gallopamil and Verapamil prolong the effective bronchodilation of Ventolin to up to 10-11 hours. Also, the magnitude of Ventolin-induced bronchodilation is enhanced by both Gallopamil and Verapamil.
  • compositions according to the present invention comprise a beta-adrenergic agonist in an amount sufficient to relieve broncho constriction and a calcium channel blocker in an amount effective to increase the effective treating time provided by the beta-agonist.
  • suitable carriers, adjuvants and diluents also may be present in the composition of the present invention.
  • an oral dosage form could include known polymer matrix - forming compounds and suitable lubricants and tableting ingredients. Particles of given ingredients could be coated and provided in the form of capsules. Pulmonary introduction through an aerosol form can be accomplished using appropriate saline solutions, with known solubilizers if necessary for the specific active ingre- der.
  • the active ingredients alternatively could be dispersed in a carrier such as Freon.
  • the following example is provided to further illustrate the present invention.
  • a patient suffering from severe asthma is treated by administration of a total of 180 micrograms of Ventolin in two "puffs" through a metered dose inhaler connected to an inhaling device according to U.S. Patent 4,484,577.
  • Measurements of Forced Expired Volume in One Second (FEV..) are taken immediately after administration and at one-half hour intervals thereafter.
  • the bronchodilation effect (change in FEV..) is shown in Figure 1.
  • Significant bronchodilation effects last for about 5 hours.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Des affections pulmonaires obstructives chroniques sont traitées à l'aide d'un agoniste bêta-adrénergique et d'un agent de blocage de canal à base de calcium. L'agent de blocage de canal à base de calcium accroît l'effet de dilatation et prolonge la durée de l'efficacité du traitement à l'aide de l'agoniste bêta-adrénergique.
PCT/US1986/001419 1985-07-02 1986-07-01 Procede et composition de traitement d'affections pulmonaires obstructives chroniques Ceased WO1987000047A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
FI870731A FI870731A0 (fi) 1985-07-02 1986-07-01 Foerfarande och blandning foer behandling av kronisk obstruktiv lungaokomma.
KR1019870700179A KR890004691B1 (ko) 1985-07-02 1986-07-01 만성 폐색성 폐질환의 치료용 및 조성물
NO870827A NO870827D0 (no) 1985-07-02 1987-02-27 Fremgangsmaate og preparat for behandling av kronisk obstruerende lungesykdom.
DK103087A DK103087A (da) 1985-07-02 1987-02-27 Middel til behandling af kroniske tilstoppende lungesygdomme

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US75111485A 1985-07-02 1985-07-02
US751,114 1985-07-02

Publications (1)

Publication Number Publication Date
WO1987000047A1 true WO1987000047A1 (fr) 1987-01-15

Family

ID=25020531

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1986/001419 Ceased WO1987000047A1 (fr) 1985-07-02 1986-07-01 Procede et composition de traitement d'affections pulmonaires obstructives chroniques

Country Status (8)

Country Link
EP (1) EP0231266A1 (fr)
JP (1) JPS63500243A (fr)
KR (1) KR890004691B1 (fr)
AU (1) AU601695B2 (fr)
DK (1) DK103087A (fr)
FI (1) FI870731A0 (fr)
MY (1) MY100519A (fr)
WO (1) WO1987000047A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4430128A1 (de) * 1994-08-25 1996-02-29 Hoechst Ag Kombinationspräparat mit immunsuppressiven, kardiovaskulären und cerebralen Wirkungen
US20120245145A1 (en) * 2009-12-03 2012-09-27 Adams Kenneth W Method and compositions for treatment and prevention of broad spectrum virus ailments comprising a calcium channel blocker or a calmodulin blocker

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR201007251A2 (tr) * 2010-09-01 2012-03-21 Bi̇lgi̇ç Mahmut Kalsiyum kanal blokörü formülasyonu.

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3440881A1 (de) * 1984-11-06 1986-05-15 Schering AG, Berlin und Bergkamen, 1000 Berlin Pharmazeutische zusammensetzung, ihre herstellung und verwendung

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 85, No. 15, 11 October 1976 (Columbus, Ohio, US) H. BOBBAERS et al.: "Action of Isoprenaline on the Mechanical Properties of Lungs and Airways in Healthy People and Patients with Obstructive Lung Diseases", see page 64, Abstract No. 104169h, & Bull. Eur. Physiopathol. Respir. 1976, 12(4), 515-31 *
CHEMICAL ABSTRACTS, Vol. 88, No. 17, 24 April 1978 (Columbus, Ohio, US) M.A. SACKNER et al.: "The Pulmonary Hemodynamic Effects of Aerosols of Isoproterenol and Ipratropium in Normal Subjects and Patients with Reversible Airway Obstruction", see page 56, Abstract No. 115427d, & Am. Rev. Respir. Dis. 1977, 116(6), 1013-22 *
CHEMICAL ABSTRACTS, Vol. 97, No. 11, 13 September 1982 (Columbus, Ohio, US) P. EYRE et al.: "Equine Influenza Virus Enhances Responsiveness of Quinea Pig Tracheal Muscle to Isoprenaline", see page 564, Abstract No. 89884q, & Res. Commun. Chem. Pathol. Pharmacol. 1982, 37(1), 3-10 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4430128A1 (de) * 1994-08-25 1996-02-29 Hoechst Ag Kombinationspräparat mit immunsuppressiven, kardiovaskulären und cerebralen Wirkungen
US20120245145A1 (en) * 2009-12-03 2012-09-27 Adams Kenneth W Method and compositions for treatment and prevention of broad spectrum virus ailments comprising a calcium channel blocker or a calmodulin blocker
US10350190B2 (en) * 2009-12-03 2019-07-16 Dr. Kenneth Adams Medicine Professional Corporation Method and compositions for treatment and prevention of broad spectrum virus ailments comprising a calcium channel blocker or a calmodulin blocker
US10888541B2 (en) 2009-12-03 2021-01-12 Dr. Kenneth Adams Medicine Professional Corporation Method and compositions for treatment and prevention of broad spectrum virus ailments comprising a calcium channel blocker or a calmodulin blocker

Also Published As

Publication number Publication date
FI870731L (fi) 1987-02-20
KR890004691B1 (ko) 1989-11-25
DK103087D0 (da) 1987-02-27
FI870731A7 (fi) 1987-02-20
EP0231266A1 (fr) 1987-08-12
JPS63500243A (ja) 1988-01-28
DK103087A (da) 1987-02-27
FI870731A0 (fi) 1987-02-20
AU6141486A (en) 1987-01-30
KR870700349A (ko) 1987-12-28
AU601695B2 (en) 1990-09-20
MY100519A (en) 1990-10-30

Similar Documents

Publication Publication Date Title
CA2359813C (fr) Vaporisateur de nicotine pour les muqueuses
EP1446119B1 (fr) Compositions comprenant d'ipatropium et de xylometazoline pour traiter le rhume
KR20010015807A (ko) 9-데옥시-2',9-알파-메타노-3-옥사-4,5,6-트리노르-3,7-(1',3'-인터페닐렌)-13,14-디하이드로-프로스타글란딘에프1을 이용한 말초 혈관 질환의 치료
EP0409662B1 (fr) Préparation atomisées à base de zinc
US6284800B1 (en) Methods and compositions for treatment of asthma
WO1987000047A1 (fr) Procede et composition de traitement d'affections pulmonaires obstructives chroniques
EA010886B1 (ru) Фармацевтическая композиция, способ ее получения и ее применение для лечения респираторных заболеваний, фармацевтический продукт и его применение, набор
EP0245366A1 (fr) Procede et composition pour bloquer des reactions allergiques provoquees par des antigenes
EA009935B1 (ru) Новая синергетическая комбинация, включающая рофлумиласт и формотерол
EP0881218A4 (fr) Composes de prevention/traitement s'appliquant aux complications de diabetes
IE59327B1 (en) Prazosin-pirbuterol combination for bronchodilation
US4689213A (en) Method and composition for treating bronchospastic airway diseases
WO2001012192A2 (fr) Compositions pharmaceutiques
EP1567140B1 (fr) Combinaison synergique comprenant du roflumilast et du (r,r)-formoterol
US4829068A (en) Treatment of disorders of the gastro-intestinal tract
KR101644286B1 (ko) 레이노 증후군의 치료를 위한 방법들 및 조성물들
JPS63500307A (ja) 気管支痙攣性気道疾患を治療するための方法および組成物
Boothe Plugs, bugs and drugs: treating the respiratory tract.
HK1067984B (en) Compositions comprising ipatropium and xylometazoline for treatment of the common cold
HK1081862B (en) Synergistic combination comprising roflumilast and (r,r)-formoterol
MXPA97004579A (en) Pharmaceutical composition comprising mirtazapine and one or more selective seroton reabsorption inhibitors
KR890003399A (ko) 약리적 활성 화합물 및 용도

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU DK FI JP KR NO

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1986904627

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1986904627

Country of ref document: EP

WWR Wipo information: refused in national office

Ref document number: 1986904627

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1986904627

Country of ref document: EP