Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-09-06
2000-02-15
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3152
Patent
active
060253606
DESCRIPTION:
BRIEF SUMMARY
This invention is concerned with pharmaceutical usages and compositions, particularly for the prophylaxis or treatment of asthma.
Asthma is a widespread disease, the particular mechanisms and aetiology of which have been and still are the subject of investigation and debate. Nevertheless it is generally accepted that asthma arises as the result of a specific or non-specific immune reaction within the lungs. The early bronchoconstrictive phase (Early Asthamitic Reaction, EAR) may be attributed to the release of histamine from mast cells in the lung tissue. Following this early phase the late asthmatic reaction (LAR) is characterized by infiltration of the lung with inflammatory cells comprising of eosinophils, lymphocytes, macrophages and neutrophils. In particular the eosinophil is known to directly damage lung tissue by release of cationic proteins. Attendant to this inflammatory infiltrate, are sub-epithelial changes in the bronchial airways which chronically lead to fibrosis and a reduction in the compliance of the pulmonary tissue. Orchestration of this cellular inflammation rests with the T lymphocytes which responds to specific and non-specific antigens inhaled into the lung. These antigens are absorbed on to the surface of cells such as macrophages before presentation to the T lymphocytes.
A variety of medicaments are, and have been, used in the treatment of the asthmatic condition. These can broadly be divided into those that effect a bronchodilatory change in the bronchoconstricted airways and those which effect a change in the underlying bronchial airway inflammation. An example of the first category are compounds such as salbutamol, an inhaled .beta..sub.2 agonist and an example of the latter category is "inhaled steroid" such as Beclomethasone or Budesonide.
The present invention is predicated on the unexpected finding that theophylline, a known bronchodilatory used in the treatment of asthma has an immunomodulating effect which confers on it an anti-inflammatory action making it capable of inhibiting the disease process in the asthmatic condition especially at doses lower than it is conventionally used in the treatment of asthma.
This according to the present invention we provide the use of a compound chosen from theophylline, theobromine, pharmacologically active derivatives thereof and the pharmaceutically acceptable salts thereof in the manufacture of a pharmaceutical preparation for the chronic, prophylactic, anti-inflammatory treatment of mild asthma.
Amongst the derivatives of theophyline and theobromine, and the salts suitable for use in the present invention are Acepifylline, Bamifylline, Bufylline, Cafaminol, Caffeine, Cafedrine, Cholinetheophyllinate, Diprophylline, Enprophylline, Etophylline, Heptaminolacephyllinate, Proxyphylline, Pyridofylline, Suxamidofylline, Aminophylline, Aminophyllinehydrate and Protheobromine. Preferably theophylline or a pharmaceutically acceptable salt thereof is used.
More specifically, as demonstrated in the clinical study described in detail below it has been found that the administration of theophylline on a chronic basis at surprisingly low doses has at least three distinct bit inter-related effects on the disease process. These new actions are in addition to and distinct from the bronchodilatory properties which have been known and extensively documented.
Firstly, theophylline has a specific effect on the trafficking of circulating pro-inflammatory lymphocyte and other inflammatory cell populations from the peripheral blood to the lung. In the untreated asthmatic patient during exacerbations of the asthmatic condition, lymphocytes and other inflammatory cells are activated and recruited from the peripheral blood to the lung and are responsible for the initiation of the inflammatory changes and associated tissue damage. It has been found that the administration of theophylline on a chronic basis reduces the recruitment of these pro-inflammatory cells to the lung consequently reducing the inflammatory changes in the lung. This is associated with an imp
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Court Michael
McDonald Christopher John
Miller Allan John
Euro-Celtique S.A.
Spivack Phyllis G.
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