Medicaments for Treating Chronic Respiratory Disease
There is provided the use of a methylxanthine compound and a steroid in a synergistic combination for the treatment of a respiratory disease, wherein the methylxanthine compound is administered at a dose, which, in isolation, is not effective to treat said disease.
1 . A method of treating a chronic respiratory disease in a subject in need thereof, comprising the administration of a methylxanthine compound and a steroid, wherein the methylxanthine compound is administered at a dose which, in isolation, is not effective in treating said respiratory disease.
2 . The method of claim 1 , wherein the steroid is administered at a dose which, in isolation, is not effective in reducing the inflammation associated with the respiratory disease.
3 . The method of claim 2 , wherein the steroid is administered at a dose which, in isolation, has minimal efficacy with respect to improvements in lung function and inflammation in treating said respiratory disease.
4 . The method of claim 1 , wherein the methylxanthine compound and the steroid act synergistically to treat inflammation in said respiratory disease.
5 . The method of claim 1 , wherein the methylxanthine compound and/or the steroid are administered by a route selected from the group consisting of inhalation, injection, oral administration and by means of long-term releasing implants.
6 . The method of claim 4 , wherein the methylxanthine compound and the steroid are administered by the same route.
7 . A pharmaceutical composition in unit dosage form, comprising a methylxanthine compound at a dose which is insufficient to be effective in treating a respiratory disease if administered to a subject independently, and a steroid.
8 . A pharmaceutical composition according to claim 7 , wherein the steroid is provided at a dose which is insufficient to demonstrate anti-inflammatory activity in treating a respiratory disease if administered independently.
9 . A pharmaceutical composition according to claim 7 , wherein the treatment is the reduction of inflammation in a respiratory disease whereby the anti-inflammatory effect may result in an improvement in health status of the patient.
10 . A kit for the treatment of a respiratory disease, comprising a methylxanthine compound and a steroid in unit dosage form, wherein the methylxanthine compound is provided at a dose which is insufficient to be effective in treating a respiratory disease if administered independently.
11 . The kit according to claim 10 , wherein the steroid is provided at a dose which is insufficient to demonstrate anti-inflammatory activity in treating a respiratory disease if administered independently.
12 . A methylxanthine compound and a steroid in unit dosage form, wherein the methylxanthine compound is provided at a dose which is insufficient to be effective in treating a respiratory disease if administered independently, for simultaneous, simultaneous separate or sequential use in the treatment of a respiratory disease.
13 . The methylxanthine compound and a steroid in unit dosage form of claim 12 , wherein the methylxanthine compound and the steroid are provided at doses which are insufficient to demonstrate anti-inflammatory activity in treating a respiratory disease if administered independently, for simultaneous, simultaneous separate or sequential use in the treatment of a respiratory disease.
14 . The method of claim 1 , wherein the dose of methylxanthine compound used achieves plasma levels that are lower than that required for clinical efficacy (<5 mg/L).
15 . The method of claim 1 , wherein the dose of methylxanthine compound is administered by inhalation and is less than those required for clinical efficacy (30 mg to 500 mg).
16 . The method of claim 1 , wherein the dose of steroid is one that is used clinically which is either sub optimal or fails to demonstrate anti-inflammatory activity.
17 . The method of claim 16 , wherein the steroid is budesonide, either given alone or in combination with bronchodilators, and is administered twice daily at a dose of 400 μg or 800 μg respectively.
18 . The method of claim 1 , wherein the treatment of the respiratory disease is assessed by counting cells in or by bronchoalveolar lavage, induced sputum or bronchial biopsies.
19 . The method of claim 18 , wherein the cells are selected from the group consisting of macrophages, epithelial cells, neutrophils, eosinophils and lymphocytes.
20 . The method of claim 18 , wherein the cell count is reduced by 50% or more upon administration of a methylxanthine compound and a steroid.
21 . The method of claim 20 , wherein the cell count is reduced by 70% or more upon administration of a methylxanthine compound and a steroid.
22 . The pharmaceutical composition of claim 7 , wherein the amount of methylxanthine compound administered to the subject produces plasma levels that are insufficient for alleviating symptoms associated with a chronic respiratory disease.
23 . The pharmaceutical composition of claim 22 , wherein the methylxanthine compound plasma levels are less than 5 mg/L.
24 . The pharmaceutical composition of claim 7 , wherein the composition is formulated for administration by inhalation.
25 . The pharmaceutical composition of claim 24 , wherein the amount of methylxanthine compound administered by inhalation to the subject is between 30 mg to 500 mg.
26 . The pharmaceutical composition of claim 7 , wherein the steroid is present in an amount that is either sub-optimal or insufficient to alleviate inflammatory activity when administered to the subject.
27 . The pharmaceutical composition of claim 7 , wherein the steroid is budesonide.
28 . The pharmaceutical composition of claim 27 , wherein the amount of budesonide is 400 μg.
29 . The pharmaceutical of claim 27 , wherein budesonide is administered in combination with one or more bronchodilators.