Drug delivery from hydrogels

Patent metadata

Field	Value
Publication number	US-2022370419-A1
Application number	US-202217830968-A
Country	US
Kind code	A1
Filing date	Jun 2, 2022
Priority date	May 12, 2015
Publication date	Nov 24, 2022
Grant date	—

Abstract

Drug delivery involving hydrogels as used for various medical conditions, and includes hydrogels formed in an eye with extended drug release times. An embodiment of the invention is a method of delivering a therapeutic agent to a tissue comprising forming a hydrogel in situ in an eye with a therapeutic agent dispersed in the hydrogel, the agent having a low solubility in water. The agent may be essentially insoluble in water. The hydrogel may be made so that 50% to 100% w/w of the agent is released when the hydrogel is from 100% to 50% persistent, with the persistence being a measure of the dry weight of the hydrogel relative to an initial dry weight of the hydrogel.

First claim

1 . A hydrogel implant with a therapeutic agent in the hydrogel, the agent having a low solubility or a very low solubility in water, wherein the hydrogel is water-degradable, as measurable by the hydrogel being dissolvable in vitro in an excess of water by degradation of water-degradable groups.

2 . The hydrogel of claim 1 wherein the hydrogel essentially persists until the agent is essentially released.

3 . The hydrogel of claim 1 wherein 50% to 100% w/w of the agent being released when the hydrogel is from 100% to 90% persistent.

4 . The hydrogel of claim 1 wherein the hydrogel delivers the agent at a therapeutically effective concentration for a period of time that is in a range of 1-36 months after formation of the hydrogel in situ.

5 . The hydrogel of claim 1 wherein the hydrogel is no more than 10% degraded for a time that is in a range of 1-36 months after formation of the hydrogel in situ.

6 . The hydrogel of claim 1 wherein 50% w/w, of the agent delivered is at time that is in a range of 1-20 months after formation of the hydrogel in situ.

7 . The hydrogel of claim 1 wherein the tissue and/or the site of formation of the hydrogel is an eye, intracanalicular, sub-tenons, intracameral, intravitreal, intrasceleral, choroidal, suprachoroidal, a retina, subretinal, a lens, a tissue, lumen, void, potential space, inside an animal, on a surface of an animal, iatrogenic site, site where tissue is removed, surgical site, cancer tissue, at or near cancer tissue, dental tissue, gums, periodontal, sinus, brain, intravascular, aneurysm, or site of a pathology.

8 . The hydrogel of claim 1 wherein the agent is for treatment of a back of the eye disease.

9 . The hydrogel of claim 8 wherein the back of the eye disease is age-related macular degeneration (AMD) cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, diabetic retinopathy, retinal vein occlusion, or glaucoma.

10 . The hydrogel of claim 1 wherein the agent comprises anti-VEGF, blocks VEGFR1, blocks VEGFR2, blocks VEGFR3, anti-PDGF, anti-PDGF-R blocks PDGFRβ, anti-angiogenesis, Sunitinib, E7080, Takeda-6d, Tivozanib, Regorafenib, Sorafenib, Pazopanib, Axitinib, Nintedanib, Cediranib, Vatalanib, Motesanib, macrolides, sirolimus, everolimus, tyrosine kinase inhibitors (TKIs), Imatinib (GLEEVAC) gefinitib (IRESSA), toceranib (PALLADIA), Erlotinib (TARCEVA), Lapatinib (TYKERB) Nilotinib Bosutinib Neratinib, lapatinib, or Vatalanib. Also wherein the agent is a steroid, nonsteroidal antiflammatory drug, antibiotic, or pain killer.

11 . The hydrogel of claim 1 wherein the agent comprises low-soluble prostaglandin analogues.

12 . The hydrogel of claim 1 wherein the agent is a suspension in the hydrogel.

13 . The hydrogel of claim 1 wherein the hydrogel is a first hydrogel, the hydrogel further comprising forming a second hydrogel in situ with a second agent in the second hydrogel, the second agent having a low solubility in water.

14 . The hydrogel of claim 13 wherein the first agent and the second agent have the same active ingredient.

15 . The hydrogel of claim 13 wherein the first agent and the second agent comprise different enantiomers, salts, or free bases.

16 . The hydrogel of claim 13 wherein the first agent and the second agent have identical chemical structures.

17 . The hydrogel of claim 13 , with the first hydrogel releasing the agent more quickly than the second hydrogel.

18 . The hydrogel of claim 13 with the first hydrogel having a larger surface area than the second hydrogel.

19 . The hydrogel of claim 13 wherein the hydrogel is formed by combining a first precursor and a second precursor that react with each other to form the hydrogel.

20 . The hydrogel of claim 19 wherein the hydrogel is formed without covalent crosslinks between the first precursor and the second precursor.

Assignees

• Incept Llc

Inventors

• Jarrett Peter
• El-Hayek Rami
• Jarrett Timothy S
• Blizzard Charles D
• Sawhney Amarpreet S

Classifications

• A61K31/56

  Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids · CPC title

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title