Methods of treating and preventing gastrointestinal motility disorders using aminosterols
This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminoserol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias , or derivatives thereof, to a subject in need.
1. A method of treating a gastrointestinal motility disorder in a subject in need thereof, comprising orally administering to the subject a composition comprising a pharmaceutically acceptable grade of at least one aminosterol, or a pharmaceutically acceptable salt or derivative thereof, in an amount sufficient to produce a beneficial effect,
wherein the disorder or condition is selected from the group consisting of chronic idiopathic constipation, Irritable bowel syndrome, Opioid-induced constipation, and Inflammatory Bowel Disease, and
wherein the at least one aminosterol is selected from Compounds 1-6 and 8 below:
2. The method of claim 1 , wherein the disorder or condition is chronic idiopathic constipation.
3. The method of claim 1 , wherein the condition or disorder is Irritable bowel syndrome.
4. The method of claim 1 , wherein the condition or disorder is Opioid-induced constipation.
5. The method of claim 1 , wherein the condition or disorder is Inflammatory Bowel Disease.
6. The method of claim 1 , wherein the aminosterol comprises Compound 1.
7. The method of claim 1 , wherein the aminosterol comprises Compound 2.
8. The method of claim 1 , wherein the aminosterol comprises Compound 3.
9. The method of claim 1 , wherein the aminosterol is Compound 4.
10. The method of claim 1 , where the aminosterol comprises Compound 5.
11. The method of claim 1 , wherein the aminosterol comprises Compound 6.
12. The method of claim 1 , wherein the at least one aminosterol comprises squalamine.
13. The method of claim 1 , wherein the effective daily dosing amount is about 0.1 to about 20 mg/kg body weight.
14. The method of claim 1 , wherein the effective dose is established by defining the initial dose required to induce an Aminosterol-Induced GI Response, which is the initial dose required to stimulate a change in bowel activity, nausea, secretory diarrhea, or any combination thereof.
15. The method of claim 1 , wherein the aminosterol is administered in combination with at least one additional active agent to achieve either an additive or synergistic effect.
16. The method of claim 15 , wherein the additional active agent is administered via a method selected from the group consisting of
(a) concomitantly;
(b) as an admixture;
(c) separately and simultaneously or concurrently; and
(d) separately and sequentially.
17. The method of claim 1 , wherein the oral dosage form is a liquid, capsule, or tablet designed to disintegrate in either the stomach, upper small intestine, or more distal portions of the intestine.
18. The method of claim 1 , wherein less than about 10 ng/ml of the administered aminosterol is detected in the blood stream of the subject about 1 to about 12 hours following oral administration.
19. The method of claim 1 , wherein the composition further comprises at least one pharmaceutically acceptable carrier.
20. The method of claim 1 , wherein the subject is human.
21. The method of claim 1 , wherein colonic motility is increased in the subject.
22. The method of claim 1 , wherein an amount sufficient to produce a beneficial effect is an amount sufficient to stimulate the intrinsic primary afferent neurons (IPANs) in the colon of the subject.