Method of treating fibrosis
A new use of a cyclo(His-Pro) is disclosed. In particular, a method for treating fibrosis and/or inflammation which includes administering an effective amount of an isolated cyclo (His-Pro) to a subject in need thereof is disclosed.
1. A method for treating fibrosis comprising administering an effective amount of a composition comprising a cyclo(His-Pro) hydrate to a subject in need thereof, wherein the fibrosis is idiopathic pulmonary fibrosis.
2. The method of claim 1 , wherein the composition further comprises zinc.
3. The method of claim 2 , wherein the zinc is zinc ion, zinc metal, or a zinc salt selected from the group consisting of zinc chloride, zinc acetate, zinc gluconate, zinc stearate, zinc sulfate, zinc oxide, zinc picolinate, zinc orotate, and zinc citrate.
4. The method of claim 1 , wherein the effective amount of the cyclo(His-Pro) hydrate is in a range of about 1-10 mg/day, 10-50 mg/day, 50-100 mg/day, 100-150 mg/day, 150-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000-1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day, 1900-2000 mg/day, 2000-2100 mg/day, 2100-2200 mg/day, 2200-2300 mg/day, 2300-2400 mg/day, 2400-2500 mg/day, 2500-2600 mg/day, 2600-2700 mg/day, 2700-2800 mg/day, 2800-2900 mg/day, or 2900-3000 mg/day, as calculated in terms of anhydrous cyclo(His-Pro).
5. The method of claim 1 , wherein the effective amount of the cyclo(His-Pro) hydrate is in a range of about 0.001-0.005 mg/kg, 0.005-0.01 mg/kg, 0.01-0.02 mg/kg, 0.02-0.04 mg/kg, 0.04-0.06 mg/kg, 0.06-0.08 mg/kg, 0.08-1 mg/kg, 1-5 mg/kg, 5-6 mg/kg, 6-7 mg/kg, 7-8 mg/kg, 8-10 mg/kg, 10-15 mg/kg, 15-20 mg/kg, 20-25 mg/kg, 25-30 mg/kg, 30-35 mg/kg, 35-40 mg/kg, 40-45 mg/kg, 45-50 mg/kg, 50-100 mg/kg, 100-150 mg/kg, 150-200 mg/kg, 200-300 mg/kg, 300-400 mg/kg, 400-500 mg/kg, 500-600 mg/kg, 600-700 mg/kg, 700-800 mg/kg, 800-900 mg/kg, 900-1000 mg/kg, 1000-1100 mg/kg, 1100-1200 mg/kg, 1200-1300 mg/kg, 1300-1400 mg/kg, 1400-1500 mg/kg, 1500-1600 mg/kg, 1600-1700 mg/kg, 1700-1800 mg/kg, 1800-1900 mg/kg, 1900-2000 mg/kg, 2000-2100 mg/kg, 2100-2200 mg/kg, 2200-2300 mg/kg, 2300-2400 mg/kg, 2400-2500 mg/kg, 2500-2600 mg/kg, 2600-2700 mg/kg, 2700-2800 mg/kg, 2800-2900 mg/kg, or 2900-3000 mg/kg, as calculated in terms of anhydrous cyclo(His-Pro).
6. The method of claim 1 , wherein the composition is a solid composition that consists essentially of (i) the cyclo(His-Pro) hydrate, or (ii) the cyclo(His-Pro) hydrate and a zinc.
7. The method according to claim 1 , wherein the administering of the composition comprising a cyclo(His-Pro) hydrate as an active ingredient:
(a) reduces expression of transforming growth factor-β (TGF-β) in the lung of the target subject;
(b) reduces expression of α-smooth muscle actin (α-SMA) in the lung of the subject;
(c) reduces expression of fibronectin in the lung of the subject;
(d) reduces expression of collagen 1 in the lung of the subject;
(e) reduces expression of collagen 3 in the lung of the subject; and/or
(f) reduces expression of collagen 4 in the lung of the subject.
8. The method of claim 1 , wherein the composition is a solid composition and the cyclo(His-Pro) hydrate is a crystalline cyclo(His-Pro) hydrate.
9. The method of claim 8 , the crystalline cyclo(His-Pro) hydrate is characterized by an X-ray powder diffraction (XRPD) diffractogram comprising peaks at 2θ values of 13.7°±0.2°, 17°±0.2°, and 27.3°±0.2.
10. The method of claim 9 , wherein the XRPD diffractogram further comprises a peak at 2θ value of 10°±0.2°.
11. The method of claim 1 , which further comprises administering a zinc to the subject.
12. The method of claim 1 , wherein the zinc is administered to the subject in an amount ranging from about 0.1-1 mg/day, 1-10 mg/day, 10-50 mg/day, 50-100 mg/day, 100-150 mg/day, 150-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000-1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day, or 1900-2000 mg/day, as calculated in terms of zinc cation.
13. The method of claim 1 , wherein the zinc is zinc ion, zinc metal, or a zinc salt selected from the group consisting of zinc chloride, zinc acetate, zinc gluconate, zinc stearate, zinc sulfate, zinc oxide, zinc picolinate, zinc orotate, and zinc citrate.