Method of treating urolithiasis
The present disclosure provides phospholipid-containing compounds, pharmaceutical compositions and microspheres that exhibit high affinity for mineralized metals. The present disclosure also provides strategies for using said compounds, compositions and microspheres in the treatment of nephrolithiasis or kidney stone disease, and methods of manufacturing and preparing said compounds and compositions.
1. A method of treating an abnormal or obstructive mass, the method comprising:
administering to a subject with the abnormal or obstructive mass an effective amount of a microsphere composition comprising microspheres containing fluid, so as to bring the microspheres into contact with the abnormal or obstructive mass within the subject, and
directionally applying an energy to the abnormal or obstructive mass at a frequency that excites the fluid within the microspheres;
wherein the microsphere composition comprises:
a compound of Formula I
or a salt, isomer, or salt of an isomer thereof;
wherein:
n is from 10 to 30;
m is from 1 to 100; and
X is selected from the group consisting of: hydrogen, silyl, acyl, aminoacyl, thioacyl, aminocarbonyl, aminoacyl carbonyloxy, aminothiocarbonyl, aminosulfonyl, amidino, substituted sulfonyl, substituted sulfinyl, carboxy ester, phthalimido, OH, SO 3 H and PO 3 H; and
a pharmaceutically acceptable excipient, wherein the abnormal or obstructive mass is a urinary stone or a kidney stone.
2. The method of claim 1 , wherein the microsphere composition is a reconstituted microsphere solution.
3. The method of claim 2 , wherein the reconstituted microsphere solution is administered into a ureter of the subject through a urinary catheter.
4. The method of claim 1 , wherein the energy is in a form of ultrasonic, electromagnetic, acoustic, microwave, laser or photonic energy.
5. The method of claim 4 , wherein the energy is ultrasonic.
6. The method of claim 5 , wherein the ultrasonic energy is in a frequency range from 100 kilohertz (kHz) to 2 megahertz (MHz).
7. The method of claim 5 , wherein the ultrasonic energy is associated with peak pressures in a range from 0.1 MPa to 10 MPa.
8. The method of claim 1 , wherein the energy is applied for a sufficient amount of time to fragment the abnormal or obstructive mass.
9. The method of claim 8 , wherein the amount of time is no more than 100 minutes, no more than 90 minutes, no more than 80 minutes, more than 70 minutes, no more than 60 minutes, no more than 50 minutes, no more than 40 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, or no more than 10 minutes.
10. The method of claim 1 , wherein the applied energy causes a change in volume of the microspheres or causes other cavitation effects of the microspheres.
11. The method of claim 10 , wherein the cavitation of the microspheres causes pressure gradient changes and other mechanical effects in the abnormal or obstructive mass around the microspheres.
12. The method of claim 1 , wherein the applied energy causes fragmentation of the abnormal or obstructive mass.
13. The method of claim 1 , wherein the subject is human.
14. The method of claim 1 , wherein the microsphere composition further comprises:
i. a compound of Formula II
or a salt, isomer, or salt of an isomer thereof; and
ii. a compound of Formula III
or a salt, isomer, or salt of an isomer thereof;
wherein:
t is from 10 to 30;
y is from 1 to 100; and
z is from 10 to 30.
15. The method of claim 1 , wherein the abnormal or obstructive mass is a urinary stone.
16. The method of claim 1 , wherein the energy is in a form of laser.