Pharmaceutical compositions for treating osteoarthritis
The present disclosure provides methods and compositions comprising hyaluronic acid (HA) hydrogel in combination with a saturated fatty acid for treating osteoarthritis. In some embodiments, aspects of the disclosure relate to pharmaceutical compositions comprising HA hydrogel in combination with a steroid. In some embodiments, the pharmaceutical compositions may be administrable via local, topical, and injection. In some embodiments, the pharmaceutical composition may be administrable by intra-articular injection.
1 . A pharmaceutical composition to treat osteoarthritis in a patient, consisting of:
water; and
a synergistic combination of:
a hyaluronic acid (HA) hydrogel comprising HA that has a molecular weight of at least 500 kilodaltons; and
a corticosteroid, wherein the HA and the corticosteroid are synergistically effective to reverse collagen degradation.
2 . The composition of claim 1 , wherein the corticosteroid is selected from dexamethasone or an ester thereof, wherein the esters are selected from dexamethasone acetate, dexamethasone phosphate, dexamethasone palmitate, and other fatty acid esters of dexamethasone.
3 . The composition of claim 2 , wherein the dexamethasone phosphate is present at less than 5 milligrams.
4 . The composition of claim 1 , wherein the pharmaceutical composition is administered by injection into a joint of the patient.
5 . The composition of claim 1 , wherein the HA and the corticosteroid are synergistically effective to decrease MMP13 expression.
6 . The composition of claim 2 , wherein the HA and the corticosteroid are synergistically effective to reduce inflammasome-mediated inflammation in a joint affected by osteoarthritis.
7 . The composition of claim 1 , wherein the HA and the corticosteroid are synergistically effective to decrease interleukin-1beta concentration in the patient.
8 . The composition of claim 1 , wherein the HA and the corticosteroid are synergistically effective to increase collagen, type II, alpha 1 (Col2a1) in the patient.
9 . A pharmaceutical composition for use in a method of treating inflammation, consisting of:
water; and
a synergistic combination of:
a hyaluronic acid (HA) hydrogel comprising HA that has a molecular weight of at least 500 kilodaltons; and
a corticosteroid, wherein the HA and the corticosteroid are synergistically effective to reduce inflammasome-mediated inflammation in a joint affected by osteoarthritis.
10 . The composition of claim 9 , wherein the corticosteroid is selected from dexamethasone or an ester thereof, wherein the esters are selected from dexamethasone acetate, dexamethasone phosphate, dexamethasone palmitate, and other fatty acid esters of dexamethasone.
11 . The composition of claim 10 , wherein the dexamethasone phosphate is present at less than 5 milligrams.
12 . The composition of claim 9 , wherein the HA and the corticosteroid are synergistically effective to decrease MMP13 expression.
13 . The composition of claim 9 , wherein the HA and the corticosteroid are effective to reduce progression of osteoarthritis and/or re-differentiate osteoarthritic chondrocytes.
14 . A method to treat osteoarthritis in a patient, comprising administering a therapeutically effective amount of a pharmaceutical composition to the patient, the pharmaceutical composition consisting of:
water, and
a synergistic combination of:
a hyaluronic acid (HA) hydrogel comprising HA that has a molecular weight of at least 500 kilodaltons; and
a corticosteroid.
15 . The method of claim 14 , wherein the corticosteroid is selected from dexamethasone or an ester thereof, wherein the esters are selected from dexamethasone acetate, dexamethasone phosphate, dexamethasone palmitate, and other fatty acid esters of dexamethasone.
16 . The method of claim 15 , wherein the dexamethasone phosphate is present at less than 5 milligrams.
17 . The method of claim 14 , comprising injecting the pharmaceutical composition into a joint of the patient.
18 . The method of claim 14 , wherein the HA and the corticosteroid are synergistically effective to decrease MMP13 expression.
19 . The method of claim 14 , wherein the HA and the corticosteroid are effective to reduce progression of osteoarthritis and/or re-differentiate osteoarthritic chondrocytes.
20 . The method of claim 14 , wherein the HA and the corticosteroid are synergistically effective to decrease interleukin-1beta concentration in the patient.