Presurgical Perineural Administration of Resiniferatoxin For Reduction of Post-Operative Pain
Disclosed herein are methods, and compositions for use in such methods, of presurgical administering of resiniferatoxin (RTX) perineurally to provide peri-surgical and post-surgical benefits, including but not limited to decreasing post-surgical pain.
1 . A method of preparing a subject for surgery, comprising perineurally administering RTX to a subject in need of surgery.
2 . Resiniferatoxin (RTX) for use in a method of preparing a subject for surgery, the method comprising perineurally administering RTX to a subject in need of surgery.
3 . The method or RTX for use of claim 1 or 2 , wherein the method provides a peri-surgical or a post-surgical benefit to the subject.
4 . The method or RTX for use of any one of the preceding claims , wherein the method reduces post-surgical pain in the subject.
5 . The method or RTX for use of any one of the preceding claims , wherein the method accelerates post-surgical recovery time of the subject.
6 . The method or RTX for use of any one of the preceding claims , wherein the method reduces the amount of peri-surgical anesthetic administered to the subject.
7 . The method or RTX for use of any one of the preceding claims , wherein the method reduces the amount of post-surgical anesthetic administered to the subject.
8 . The method or RTX for use of any one of the preceding claims , wherein the method reduces inflammation caused by trauma at a surgical site.
9 . The method or RTX for use of any one of the preceding claims , wherein the method reduces cytokine release caused by trauma at a surgical site.
10 . The method or RTX for use of any one of the preceding claims , wherein nerve signaling pathways are ablated in the subject.
11 . The method or RTX for use of any one of the preceding claims , wherein the subject is being prepared for a surgical procedure.
12 . The method or RTX for use of any one of the preceding claims , wherein the subject is placed under anesthesia prior to the administration of RTX.
13 . The method or RTX for use of any one of the preceding claims , wherein the surgery occurs within 1, 2, 3, 4, 5, or 6 hours of administering RTX.
14 . The method or RTX for use of any one of the preceding claims , wherein the subject is in need of an orthopedic surgery or an amputation.
15 . The method or RTX for use of any one of the preceding claims , wherein the subject is in need of surgical intervention on a bone in the back, hand, arm or leg.
16 . The method or RTX for use of any one of the preceding claims , wherein the RTX is administered as an infiltration.
17 . The method or RTX for use of any one of the preceding claims , wherein the RTX is administered to a single site.
18 . The method or RTX for use of any one of the preceding claims , wherein the RTX is administered to a plurality of sites.
19 . The method or RTX for use of any one of the preceding claims , wherein the RTX is administered locally to a surgical site.
20 . The method or RTX for use of any one of the preceding claims , wherein RTX is administered as a nerve block.
21 . The method or RTX for use of any one of the preceding claims , wherein RTX is administered as a nerve block at the sciatic nerve and/or the femoral nerve.
22 . The method or RTX for use of any one of the preceding claims , wherein the subject is a mammal.
23 . The method or RTX for use of any one of the preceding claims , wherein the subject is a cat, dog, horse, pig, ruminant, cow, sheep, goat, or domesticated mammal.
24 . The method or RTX for use of any one of the preceding claims , wherein the subject is a human.
25 . The method or RTX for use of any one of the preceding claims , wherein the method comprises administering a dose of 0.1 μg to 100 μg of RTX, or a dose of 2 μg to 50 μg of RTX.
26 . The method or RTX for use of claim 25 wherein the dose of RTX ranges from 0.1-1 μg, 1-2 μg, 2-5 μg, 5-10 μg, 10-20 μg, 20-30 μg, 30-40 μg, 40-50 μg, 50-60 μg, 60-70 μg, 70-80 μg, 80-90 μg, or 90-100 μg.
27 . The method or RTX for use of any one of the preceding claims , wherein the method comprises administering a pharmaceutical formulation comprising the RTX and a pharmaceutically acceptable carrier.
28 . The method or RTX for use of claim 27 , wherein the pharmaceutically acceptable carrier comprises water.
29 . The method or RTX for use of claim 27 or 28 , wherein the pharmaceutically acceptable carrier comprises polysorbate 80.
30 . The method or RTX for use of any one of claims 27-29 , wherein the pharmaceutically acceptable carrier comprises polyethylene glycol.
31 . The method or RTX for use of any one of claims 27-30 , wherein the pharmaceutically acceptable carrier comprises a sugar or sugar alcohol.
32 . The method or RTX for use of claim 27-31 , wherein the pharmaceutically acceptable carrier comprises mannitol.
33 . The method or RTX for use of claim 27-32 , wherein the pharmaceutically acceptable carrier comprises dextrose.
34 . The method or RTX for use of any one of claims 27-33 , wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable buffer.
35 . The method or RTX for use of claim 27-34 , wherein the pharmaceutically acceptable carrier comprises a phosphate buffer.
36 . The method or RTX for use of any one of claims 27-35 , wherein the pharmaceutical formulation has a pH in the range of 6 to 7.6.
37 . The method or RTX for use of claim 36 , wherein the pharmaceutical formulation has a pH in the range of 6 to 6.4, 6.3 to 6.7, 6.4 to 6.8, 6.8 to 7.2, 7 to 7.4, or 7.2 to 7.6.
38 . The method or RTX for use of claim 36 , wherein the pharmaceutical formulation has a pH of 6.5 or 7.2.
39 . The method or RTX for use of any one of claims 27-38 , wherein the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable salt.
40 . The method or RTX for use of claim 39 , wherein the pharmaceutically acceptable salt is NaCl.
41 . The method or RTX for use of any one of claims 27-40 , wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.02 to 300 μg/ml.
42 . The method or RTX for use of claim 41 , wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.02-0.1 μg/ml, 0.1-1 μg/ml, 1-5 μg/ml, 5-10 μg/ml, 10-20 μg/ml, 20-50 μg/ml, 50-100 μg/ml, 100-150 μg/ml, 150-200 μg/ml, 200-250 μg/ml, or 250-300 μg/ml.
43 . The method or RTX for use of claim 41 , wherein the concentration of RTX in the pharmaceutical formulation is in the range of 150 to 250 μg/ml, or is about 200 μg/ml.
44 . The method or RTX for use of claim 41 , wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.1-200 μg/ml, optionally wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.1-50 μg/ml.
45 . The method or RTX for use of any one of the preceding claims , wherein the RTX is administered in an injection volume of 0.05-10 ml, optionally wherein the injection volume is in the range of 0.05-0.2 ml, 0.2-0.5 ml, 0.5-1 ml, 1-2 ml, 2-5 ml, or 5-10 ml.
46 . The method or RTX for use of any one of the preceding claims , wherein the method further comprises administering a local anesthetic.
47 . The method or RTX for use of claim 46 , wherein the local anesthetic is an amino-amide anesthetic.
48 . The method or RTX for use of claim 46 , wherein the local anesthetic is bupivacaine.
49 . The method or RTX for use of any one of the preceding claims , wherein the method is a method of reducing post-operative pain.
50 . The method or RTX for use any one of the preceding claims , wherein the method is a method of accelerating post-surgical recovery time of the subject.