Glucocorticoid combined with polyethylene glycol-modified interleukin 2 for treating respiratory disease
The present invention provides an inhalable pharmaceutical composition comprising a glucocorticoid and a polyethylene glycol (PEG)-modified interleukin-2 for treating a respiratory disease. The invention further provides an application of a PEG-modified interleukin-2 for preparing a pharmaceutical composition for enhancing the efficacy of a glucocorticoid in treating the respiratory disease. The invention also provides a method for treating the respiratory disease.
1. An inhalable pharmaceutical composition, comprising a polyethylene glycol (PEG)-modified interleukin 2 (IL-2) and a glucocorticoid, and optionally a pharmaceutically acceptable carrier and/or excipient, wherein the IL-2 is a human IL-2 and wherein the PEG modification is at a N-terminal amino acid residue of IL-2.
2. The pharmaceutical composition of claim 1 , wherein the glucocorticoid is one or more selected from the group consisting of dexamethasone (Dex), budesonide (Bud), beclomethasone dipropionate (BDP), ciclesonide, hydrocortisone, cortisone, prednison, prednisolone, methylprednisolone, triamcinolone, betamethasone, clobetasone butyrate, triamcinolone acetonide, fluocinolone acetonide, mometasone furoate, halcinonide, clobetasol propionate, halcinonide, halometasone monohydrate and diflorasone diacetate.
3. The pharmaceutical composition of claim 1 , wherein the PEG modification is a modification of IL-2 with a non-branched PEG or a branched PEG.
4. The pharmaceutical composition of claim 1 , formulated:
(1) in a form of dry powder composition, optionally comprising one or more suitable diluents or carriers; or
(2) in a form of pressurized metered dose inhalation, wherein both the PEG-modified IL-2 and the glucocorticoid are suspended or completely dissolved in a liquid propellant mixture.
5. The pharmaceutical composition of claim 1 , wherein the ratio of the PEG-modified IL-2 to the glucocorticoid is between 1,000 IU IL-2(PEG):1 μg glucocorticoid and 10,000 IU IL-2(PEG):1 μg glucocorticoid.
6. The pharmaceutical composition of claim 1 , wherein the PEG-modified IL-2 is present in the composition at a dose between 3,000 IU and 100,000 IU.
7. The pharmaceutical composition of claim 1 , wherein the PEG modification is a modification of IL-2 with a non-branched PEG or a branched PEG with a molecular weight of 2-60 KD.
8. The pharmaceutical composition of claim 1 , wherein the IL-2 is modified at its N-terminus with the PEG.
9. The pharmaceutical composition of claim 1 , wherein the glucocorticoid is Dex, and the ratio of the PEG-modified IL-2 to the Dex is 4,000 IU IL-2(PEG):1 μg Dex.
10. The pharmaceutical composition of claim 9 , wherein the PEG-modified IL-2 is present in the composition at a dose between 7,500 IU and 80,000 IU.
11. The pharmaceutical composition of claim 1 , wherein the glucocorticoid is Bud, and the ratio of the PEG-modified IL-2 to the Bud is 5,000 IU IL-2(PEG):1 μg Bud.
12. The pharmaceutical composition of claim 11 , wherein the PEG-modified IL-2 is present in the composition at a dose between 3,500 IU and 80,000 IU.
13. The pharmaceutical composition of claim 1 , wherein the glucocorticoid is BDP and the ratio of the PEG-modified IL-2 to the BDP is 5,000 IU IL-2(PEG):1 μg BDP.
14. The pharmaceutical composition of claim 13 , wherein the PEG-modified IL-2 is present in the composition at a dose between 3,500 IU and 80,000 IU.
15. The pharmaceutical composition of claim 1 , wherein the IL-2 is set forth in SEQ ID NO. 1.
16. The pharmaceutical composition of claim 1 , wherein the N-terminal amino acid residue comprises lysine, serine or threonine.
17. The pharmaceutical composition of claim 1 , wherein the PEG modification is at the N-terminal alpha-amino of IL-2.