Salt of a pyrimido[6,1-A]isoquinolin-4-one compound
The present invention relates to a pharmaceutically acceptable acid addition salt of: (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554); and (ii) ethane-1,2-disulfonic acid, ethanesulfonic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid.
1. A pharmaceutically acceptable acid addition salt of:
(i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554); and
(ii) ethane-1,2-disulfonic acid.
2. A pharmaceutically acceptable acid addition salt according to claim 1 , which is RPL554 ethane-1,2-disulfonate.
3. A pharmaceutical composition comprising:
(a) a pharmaceutically acceptable acid addition salt of (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) and (ii) ethane-1,2-disulfonic acid; and
(b) a pharmaceutically acceptable excipient, carrier or diluent.
4. A pharmaceutical composition according to claim 3 , which is formulated for administration by inhalation.
5. A pharmaceutical composition according to claim 3 , which is a dry powder.
6. A pharmaceutical composition according to claim 3 , which is produced by dissolving a pharmaceutically acceptable acid addition salt of (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) and (ii) ethane-1,2-disulfonic acid.
7. A pharmaceutical composition according to claim 6 , wherein the aqueous solution is a buffered aqueous solution.
8. A pharmaceutical composition according to claim 7 , wherein the buffered aqueous solution comprises a phosphate buffer, a citrate buffer or a citro-phosphate buffer.
9. A pharmaceutical composition according to claim 6 , wherein the pH of the pharmaceutical composition is greater than or equal to about 2.5.
10. A pharmaceutical composition according to claim 6 , wherein the pharmaceutically acceptable acid addition salt is present at a concentration of greater than or equal to about 1.0 mg/ml.
11. A method of treating or preventing a disease or condition selected from asthma, allergic asthma, hay fever, allergic rhinitis, bronchitis, emphysema, bronchiectasis, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), steroid resistant asthma, severe asthma, paediatric asthma, cystic fibrosis, lung fibrosis, pulmonary fibrosis, interstitial lung disease, skin disorders, atopic dermatitis, psoriasis, ocular inflammation, cerebral ischaemia, inflammatory diseases and auto-immune diseases in a subject, which method comprises administering to said subject an effective amount of a pharmaceutically acceptable acid addition salt of (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) and (ii) ethane-1,2-disulfonic acid.
12. A method of treating or preventing a disease or condition according to claim 11 , wherein the disease or condition is chronic obstructive pulmonary disease (COPD).