US2020230246A1PendingUtilityA1
Extended release microparticles and suspensions thereof for medical therapy
Est. expiryMay 10, 2037(~10.8 yrs left)· nominal 20-yr term from priority
A61K 31/122A61K 9/0051A61K 31/404A61K 31/5377A61K 9/5031A61K 31/216A61K 31/542A61K 31/498A61P 27/02A61K 47/54A61K 31/4155A61K 31/382
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Claims
Abstract
An improved microparticle or lyophilized or otherwise reconstitutable microparticle composition thereof for medical therapy, including ocular therapy.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . Solid aggregating biodegradable microparticles comprising a prodrug of a therapeutically active compound encapsulated in (a) poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA) and (b) poly(lactic-co-glycolic acid) conjugated to polyethylene glycol (PLGA-PEG), and a surfactant, wherein the microparticles
(i) have a mean diameter between 10 μm and 60 μm; (ii) have been surface-modified with a surface treatment agent to partially degrade surface polymer at a temperature less than about 18° C. wherein the surface treatment agent comprises an aqueous base and an organic solvent; (iii) aggregate in vivo to form at least one pellet of at least 500 μm in vivo that provide sustained drug delivery in vivo for at least three months; and (v) wherein the prodrug is selected from the formula:
or a pharmaceutically acceptable salt thereof
wherein
R 31a is hydrogen, —C(O)alkyl, aryl, alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl, polylactic acid, or polygylcolic acid;
R 106 is selected from:
R 123 is selected from:
R 311 is hydroxy, amino, A, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, or polyethylene glycol;
A is selected from H, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, and alkyloxy;
x and y are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;
x′ and y′ are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;
z is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.
2 . The solid aggregating microparticles of claim 1 , wherein R 123 is selected from
3 . The solid aggregating microparticles of claim 2 , wherein R 123 is selected from
4 . The solid aggregating microparticles of claim 1 , wherein R 106 is selected from
5 . The solid aggregating microparticles of claim 4 , wherein R 106 is selected from
6 . The solid aggregating microparticles of claim 1 , wherein R 31a is —C(O)alkyl.
7 . The solid aggregating microparticles of claim 1 , wherein x and y are independently selected from 1, 2, 3, 4, 5, and 6.
8 . The solid aggregating microparticles of claim 1 , wherein x′ and y′ are independently selected from 1, 2, 3, 4, 5, and 6.
9 . The solid aggregating microparticles of claim 1 , of the formula
or a pharmaceutically acceptable salt thereof.
10 . The solid aggregating microparticles of claim 9 , wherein y is 1, 2, 3, 4, 5, or 6 and y′ is 1, 2, 3, 4, 5, or 6.
11 . The solid aggregating microparticles of claim 9 , wherein y is 2, 3, or 4 and y′ is 2, 3, or 4.
12 . The solid aggregating microparticles of claim 9 , of the formula
or a pharmaceutically acceptable salt thereof.
13 . The solid aggregating microparticles of claim 12 , wherein y is 1, 2, 3, 4, 5, or 6 and y′ is 1, 2, 3, 4, 5, or 6.
14 . The solid aggregating microparticles of claim 12 , wherein y is 2, 3, or 4 and y′ is 2, 3, or 4.
15 . The solid aggregating microparticles of claim 12 , of the formula
or a pharmaceutically acceptable salt thereof.
16 . The solid aggregating microparticles of claim 12 , of the formula
or a pharmaceutically acceptable salt thereof.
17 . The solid aggregating microparticles of claim 12 , of the formula
or a pharmaceutically acceptable salt thereof.
18 . The solid aggregating microparticles of claim 1 , wherein the at least one pellet provides sustained drug delivery for at least 4 months.
19 . The solid aggregating microparticles of claim 1 , wherein at least one pellet provides sustained drug delivery for at least 5 months.
20 . The solid aggregating microparticles of claim 1 , wherein at least one pellet provides sustained drug delivery for at least 6 months.
21 . The solid aggregating microparticles of claim 1 , wherein the aqueous base is a hydroxide base.
22 . The solid aggregating microparticles of claim 21 , wherein the organic solvent is an alcohol.
23 . The solid aggregating microparticles of claim 22 , wherein the alcohol is ethanol.
24 . The solid aggregating microparticles of claim 1 , wherein the surface treatment agent comprises ethanol and sodium hydroxide.
25 . The solid aggregating microparticles of claim 1 , wherein the surface has been modified at a temperature not more than 16° C.
26 . The solid aggregating microparticles of claim 1 , wherein the surface has been modified at a temperature not more than 14° C.
27 . The solid aggregating microparticles of claim 1 , wherein the surface has been modified at a temperature not more than 12° C.
28 . The solid aggregating microparticles of claim 1 , wherein the surface has been modified at a temperature not more than 10° C.
29 . A pharmaceutical composition comprising the solid aggregating microparticles of claim 1 , optionally in a pharmaceutically acceptable carrier.
30 . The pharmaceutical composition of claim 29 , suitable for use as an ocular implant.
31 . The pharmaceutical composition of claim 29 suitable for a delivery route selected from the group consisting of intravitreal, intrastromal, intracameral, subtenon, sub-retinal, retrobulbar, peribulbar, suprachoroidal, subchoroidal, conjunctival, subconjunctival, episcleral, posterior juxtascleral, circumcorneal, and tear duct injections.
32 . The pharmaceutical composition of claim 31 suitable for intravitreal injection.
33 . The pharmaceutical composition of claim 31 suitable for suprachoroidal injection.
34 . A method for the treatment of an ocular disorder selected from glaucoma, wet-age related macular degeneration, dry-age related macular degeneration, a disorder related to an increase in intraocular pressure, optic nerve damage caused by high intraocular pressure, and diabetic retinopathy comprising administering an effective amount of the solid aggregating microparticles of claim 1 , optionally in a pharmaceutically acceptable carrier.
35 . The method of claim 34 for the treatment of glaucoma.
36 . The method of claim 34 for the treatment of wet-age related macular degeneration.Cited by (0)
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