EP0231266A1 - Composition de traitement d'affections pulmonairesobstructives chroniques - Google Patents

Composition de traitement d'affections pulmonairesobstructives chroniques

Info

Publication number
EP0231266A1
EP0231266A1 EP86904627A EP86904627A EP0231266A1 EP 0231266 A1 EP0231266 A1 EP 0231266A1 EP 86904627 A EP86904627 A EP 86904627A EP 86904627 A EP86904627 A EP 86904627A EP 0231266 A1 EP0231266 A1 EP 0231266A1
Authority
EP
European Patent Office
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
EP86904627A
Other languages
German (de)
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
Publication of EP0231266A1 publication Critical patent/EP0231266A1/fr
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)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Otolaryngology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (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.
EP86904627A 1985-07-02 1986-07-01 Composition de traitement d'affections pulmonairesobstructives chroniques Ceased EP0231266A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US75111485A 1985-07-02 1985-07-02
US751114 1985-07-02

Publications (1)

Publication Number Publication Date
EP0231266A1 true EP0231266A1 (fr) 1987-08-12

Family

ID=25020531

Family Applications (1)

Application Number Title Priority Date Filing Date
EP86904627A Ceased EP0231266A1 (fr) 1985-07-02 1986-07-01 Composition de traitement d'affections pulmonairesobstructives 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)

Families Citing this family (3)

* 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
CA3013734C (fr) * 2009-12-03 2020-01-14 Dr. Kenneth Adams Medicine Professional Corporation Methode et composition destinees au traitement et a la prevention d'une vaste gamme d'affections virales
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 (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8700047A1 *

Also Published As

Publication number Publication date
AU601695B2 (en) 1990-09-20
DK103087D0 (da) 1987-02-27
FI870731A (fi) 1987-02-20
WO1987000047A1 (fr) 1987-01-15
MY100519A (en) 1990-10-30
DK103087A (da) 1987-02-27
KR890004691B1 (ko) 1989-11-25
AU6141486A (en) 1987-01-30
JPS63500243A (ja) 1988-01-28
KR870700349A (ko) 1987-12-28
FI870731A0 (fi) 1987-02-20

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Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19870224

AK Designated contracting states

Kind code of ref document: A1

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

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: KEY PHARMACEUTICALS, INC.

17Q First examination report despatched

Effective date: 19890113

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 19910425

RIN1 Information on inventor provided before grant (corrected)

Inventor name: SACKNER, MARVIN

Inventor name: AHMED, TAHIR