Formulations for treating a fibrotic disease
The present invention provides formulations for the treatment of fibrotic diseases and disorders. In some embodiments, the formulation comprises a microparticle that includes an antifibrotic.
1. A formulation comprising microparticles comprising an aliphatic polyester and an antifibrotic agent, wherein (i) said microparticles have a diameter of 1-100 μm; (ii) the antifibrotic agent is relaxin and is present in an amount that is 0.01-33% of total mass; (iii) said aliphatic polyester is of molecular weight 10,000-200,000 Daltons; or (iv) the microparticles further comprise a vinyl polymer.
2. The formulation of claim 1 , wherein said antifibrotic agent is an agonist of the receptor RXFP1.
3. The formulation of claim 1 , wherein said antifibrotic agent is human relaxin-2 or an analog or variant.
4. The formulation of claim 1 , wherein the aliphatic polyester is poly-lactide-co-glycolide or polycaprolactone.
5. The formulation of claim 1 , wherein said aliphatic polyester is terminated by an ester functional group, an alkyl-ester functional group or a carboxylic acid functional group.
6. The formulation of claim 1 , wherein said formulation comprises a vinyl polymer that is poly(vinyl alcohol) or poly(pyrrolidone).
7. The formulation of claim 1 , wherein said formulation comprises a vinyl polymer that is of molecular weight 10,000-200,000 Daltons.
8. The formulation of claim 1 , wherein the diameter of said microparticles is 1-75 μm; or 1-50 μm; or 5-50 μm; or 25-50 μm; or 30-50 μm; or 40-50 μm.
9. The formulation of claim 1 , wherein said aliphatic polyester is poly-lactide-co-glycolide with a molar ratio of 15:85-25:75, lactide:glycolide.
10. The formulation of claim 1 , wherein the formulation comprises the vinyl polymer in an amount of 0.01-0.1% of total mass.
11. The formulation of claim 1 , wherein said antifibrotic agent is 0.005-5% of the total formulation mass.
12. The formulation of claim 1 , wherein said formulation comprises microparticles suspended in a sodium chloride liquid solution or a sodium carboxymethylcellulose solution.
13. The formulation of claim 1 , wherein said formulation is a sustained release formulation.
14. The formulation of claim 1 , wherein the formulation is formulated for administration via inhalation as an aerosol, administration via intra-articular injection or administration via intramuscular injection.
15. The formulation of claim 1 , wherein the formulation is administered to the subject such that the antifibrotic agent is administered to a subject at a dose between 1-2000 μg/kg body weight.
16. The formulation of claim 1 , wherein said formulation is a sustained release formulation wherein the antifibrotic agent is released over an extended period time selected from the group consisting of between 1-5 days; between 2-5 days; between 1-2 days; between 2-3 days; between 3-4 days; between 4-5 days; between 3-10 days; between 1-15 weeks; between 2-10 weeks; between 4-8 weeks; and between 8-15 weeks.