Drug delivery from hydrogels

Patent metadata

Field	Value
Publication number	US-2016331738-A1
Application number	US-201615152739-A
Country	US
Kind code	A1
Filing date	May 12, 2016
Priority date	May 12, 2015
Publication date	Nov 17, 2016
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 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.

2 . The method of claim 1 with the agent being suspended in the hydrogel.

3 . The method of claim 1 with 50% to 100% w/w of the agent being 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.

4 . The method of claim 3 with 90% w/w of the agent being released when the hydrogel is at least 90% persistent.

5 . The method of claim 1 wherein the agent is released to provide an effective concentration of the agent in an eye over a period of time.

6 . The method of claim 5 wherein the period of time is 2-36 months.

7 . The method of claim 5 wherein, after the period of time, the hydrogel has released all of the agent and has a persistence of at least 80%.

8 . The method of claim 5 wherein, after the period of time, the hydrogel releases a further amount of the agent that is non-toxic.

9 . The method of claim 1 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.

10 . The method of claim 1 wherein the hydrogel is formed at an intravitreal site.

11 . The method of claim 1 wherein the agent is for treatment of a back of the eye disease.

12 . The method of claim 11 wherein the back of the eye disease is age-related macular degeneration (AMD) cystoid macular edema (CME), diabetic macular edema (DME), posterior uveitis, and diabetic retinopathy, or glaucoma.

13 . The method of claim 1 wherein the agent comprises anti-VEGF, blocks VEGFR1, blocks VEGFR2, blocks VEGFR3, anti-PDGF, anti-PDGF-R blocks PDGFRβ, an anti-angiogenic agent, Sunitinib, E7080, Takeda-6d, Tivozanib, Regorafenib, Sorafenib, Pazopanib, Axitinib, Nintedanib, Cediranib, Vatalanib, Motesanib, macrolides, sirolimus, everolimus, tyrosine kinase inhibitors (TKIs), Imatinibn gefinitib, toceranib, Erlotinib, Lapatinib, Nilotinib, Bosutinib Neratinib, lapatinib, Vatalanib, comprises low-soluble prostaglandin analogues for glaucoma, nepafenac, macrolides, rapamycin, sirolimus, tacrolimus, or serves to block mTOR receptors for AMD/CNV.

14 . The method of claim 1 wherein the hydrogel is formed by combining a first precursor and a second precursor that react with each other to form the hydrogel.

15 . The method of claim 14 wherein the hydrogel is formed with covalent crosslinks between the first precursor and the second precursor.

16 . The method of claim 15 wherein the first precursor and the second precursor are hydrophilic.

17 . The method of claim 1 wherein the hydrogel is essentially spherical, essentially discoidal, or essentially cylindroid.

18 . A hydrogel in an eye with a therapeutic agent dispersed in the hydrogel, the agent having a low solubility in water.

19 . The hydrogel of claim 1 with 50% to 100% w/w of the agent being 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.

20 . The hydrogel of claim 19 wherein the period of time is 2-36 months.

Assignees

• Incept Llc

Inventors

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

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• 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