IP Library Granted Patent US 12,702,651
Granted Patent B2
US 12,702,651 · App. 17/384,373 · Granted Aug 11, 2026

Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof

Inventors: John Scott Karolchyk (Lake Hopatcong, NJ); Mark L. Baum (San Diego, CA); Dennis Saadeh (Nashville, TN)
Assignee: Harrow IP, LLC
A61K31/137A61K9/0019A61K9/0048A61K9/0051A61K9/19A61K31/19A61K31/4409A61K45/06A61K47/02A61K47/16A61K47/183B65D25/04
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Quick Facts
Patent No.
US 12,702,651
App. No.
17/384,373
Filed
Jul 23, 2021
Granted
Aug 11, 2026
Kind
B2
Art Unit
1621
USPC
514/413
Abstract

Pharmaceutical compositions for intraocular injection are described, the compositions comprise therapeutically effective quantity of lyophilized preservative-free and sulfite-free epinephrine or adrenaline and a metal chelator. Methods for fabricating the compositions and using them for intraocular injections are also described.

Claims (27)

1 . A method of rapidly dilating a subject's pupils, the method comprising:

administering to the subject via intraocular injection a therapeutically effective amount of a composition consisting of:

a therapeutically effective quantity of phenylephrine hydrochloride;

a therapeutically effective quantity of tropicamide having a concentration in the composition of about 0.04% (w/v) to about 0.06% (w/v);

at least one metal chelator;

at least one anesthetic;

optionally, at least one tonicity adjusting agent comprising one or more chloride salts selected from the group consisting of sodium chloride, potassium chloride, and magnesium chloride;

optionally, hydrochloric acid and/or sodium hydroxide;

at least one non-steroid anti-inflammatory drug;

optionally, at least one excipient; and

a quantity of sterile water,

wherein the subject's pupils are dilated from a first diameter to a second diameter within one minute or less after administering the composition, wherein the difference between the first diameter and the second diameter is from about 5.0 mm to about 7.0 mm.

2 . The method of claim 1 wherein the subject's pupils have a diameter of at least about 1.0 mm before administration of the composition.

3 . The method of claim 1 wherein the subject's pupils have a diameter of at least about 6.0 mm after administration of the composition.

4 . The method of claim 1 wherein the subject's pupils are dilated within 40 seconds or less after administering the composition.

5 . The method of claim 4 wherein the subject's pupils are dilated within 30 seconds or less after administering the composition.

6 . The method of claim 1 , wherein the at least one metal chelator is ethylenediaminetetraacetic acid or a pharmaceutically acceptable salt thereof.

7 . The method of claim 1 , wherein the at least one non-steroid anti-inflammatory drug is diclofenac.

8 . The method of claim 1 , wherein the at least one anesthetic is lidocaine.

9 . The method of claim 1 , wherein the at least one excipient is selected from the group consisting of boric acid and polysorbate-80.

10 . The method of claim 1 , wherein the phenylephrine hydrochloride has a concentration in the composition of between about 0.02% (w/v) to about 1.5% (w/v).

11 . The method of claim 10 , wherein the phenylephrine hydrochloride has a concentration in the composition of about 1% (w/V).

12 . The method of claim 1 , wherein the tropicamide has a concentration in the composition of about 0.05% (w/v).

13 . The method of claim 7 , wherein the diclofenac has a concentration of between about 0.04% (w/v) to about 0.5% (w/v).

14 . The method of claim 13 , wherein the diclofenac has a concentration in the composition of about 0.05% (w/v).

15 . The method of claim 8 , wherein the lidocaine has a concentration of between about 0.5% (w/v) to about 1.5% (w/V).

16 . The method of claim 15 , wherein the lidocaine has a concentration in the composition of about 1% (w/V).

Assignments (6)
SECURITY INTEREST Recorded Sep 26, 2025
From: HARROW, INC.; HARROW IP, LLC
To: FIFTH THIRD BANK, NATIONAL ASSOCIATION, AS AGENT
Reel/Frame 072384/0781 →
RELEASE OF SECURITY INTEREST Recorded Sep 18, 2025
From: OAKTREE FUND ADMINISTRATION, LLC, AS ADMINISTRATIVE AGENT
To: HARROW IP, LLC
Reel/Frame 072299/0911 →
PATENT SECURITY AGREEMENT Recorded Mar 30, 2023
From: HARROW IP, LLC
To: OAKTREE FUND ADMINISTRATION, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 063205/0708 →
TERMINATION AND RELEASE OF SECURITY INTEREST IN INTELLECTUAL PROPERTY AT REEL/FRAME NO. 62105/0556 Recorded Mar 30, 2023
From: B. RILEY COMMERCIAL CAPITAL, LLC, AS ADMINISTRATIVE AGENT
To: HARROW HEALTH, INC.; HARROW EYE, LLC; HARROW IP, LLC; IMPRIMISRX, LLC; IMPRIMIS NJOF, LLC; IMPRIMISRX NJ, LLC; VISIONOLOGY EQUITY, LLC; VISIONOLOGY, INC.; VISIONOLOGY MSO, INC.
Reel/Frame 063205/0889 →
SECURITY INTEREST Recorded Dec 15, 2022
From: HARROW HEALTH, INC.; HARROW EYE, LLC; HARROW IP, LLC; IMPRIMISRX, LLC; IMPRIMIS NJOF, LLC; IMPRIMISRX NJ, LLC; VISIONOLOGY EQUITY, LLC; VISIONOLOGY, INC.; VISIONOLOGY MSO, INC.
To: B. RILEY COMMERCIAL CAPITAL, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 062105/0556 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: BAUM, MARK L.; SAADEH, DENNIS
To: HARROW IP, LLC
Reel/Frame 057701/0889 →
Continuity (7)
Continuation In Part 17330023 · May 25, 2021
Continuation 15247524 · Aug 25, 2016
Continuation In Part 14506120 · Oct 3, 2014
Provisional Application 61947778 · Mar 4, 2014
Provisional Application 61892872 · Oct 18, 2013
Provisional Application 61886269 · Oct 3, 2013
Related Publication 20210346318A1 · Nov 11, 2021
References Cited (76)
US 3808317A · Hecht et al. · 1974 [cited by applicant]
US 4525346A · Stark · 1985 [cited by applicant]
US 4550022A · Garabedian et al. · 1985 [cited by applicant]
US 4590210A · Langham · 1986 [cited by applicant]
US 5654337A · Roentsch et al. · 1997 [cited by applicant]
US 5709852A · Gopalkrishnan et al. · 1998 [cited by applicant]
US 6562002B1 · Taylor · 2003 [cited by applicant]
US 9301936B2 · Buderer et al. · 2016 [cited by applicant]
US 10285957B2 · Karolchyk · 2019 [cited by applicant]
US 10993921B2 · Karolchyk et al. · 2021 [cited by applicant]
US 20020146375A1 · Schreiber et al. · 2002 [cited by applicant]
US 20030216413A1 · Root-Bernstein et al. · 2003 [cited by applicant]
US 20040072809A1 · Demopulos et al. · 2004 [cited by applicant]
US 20040076588A1 · Batycky et al. · 2004 [cited by applicant]
US 20050074414A1 · Tamarkin et al. · 2005 [cited by applicant]
US 20050118231A1 · El Meski · 2005 [cited by applicant]
US 20050176823A1 · Diaz · 2005 [cited by applicant]
US 20070060877A1 · Bassarab · 2007 [cited by applicant]
US 20070196324A1 · Keefe et al. · 2007 [cited by applicant]
US 20080269347A1 · Bruss · 2008 [cited by applicant]
US 20090017120A1 · Trimble et al. · 2009 [cited by applicant]
US 20100311705A1 · Demopulos · 2010 [cited by applicant]
US 20110237681A1 · Batycky et al. · 2011 [cited by applicant]
US 20120129944A1 · Baillie et al. · 2012 [cited by applicant]
US 20120220637A1 · Khatib · 2012 [cited by examiner]
US 20130210840A1 · Grasela et al. · 2013 [cited by applicant]
US 20140235691A1 · Demopulos · 2014 [cited by examiner]
US 20150017151A1 · Buderer · 2015 [cited by applicant]
US 20150119440A1 · Karolchyk et al. · 2015 [cited by applicant]
US 20160354308A1 · Karolchyk et al. · 2016 [cited by applicant]
CA 2002643A1 · 1990 [cited by applicant]
EP 2246045A1 · 2010 [cited by applicant]
FR 2779061A1 · 1999 [cited by applicant]
JP 07502544A · 1995 [cited by applicant]
JP 2004509920A · 2004 [cited by applicant]
JP 2006504661A · 2006 [cited by applicant]
JP 2016532723A · 2016 [cited by applicant]
WO 1994008602A1 · 1994 [cited by applicant]
WO 199803641A1 · 1998 [cited by applicant]
WO 2002026223A2 · 2002 [cited by applicant]
WO 2004010894A2 · 2004 [cited by applicant]
WO WO2007122580A2 · 2007 [cited by examiner]
WO 2009111083A2 · 2009 [cited by applicant]
WO 2010057007A1 · 2010 [cited by applicant]
West (Journal of Pharmacy and Pharmacology vol. 12 pp. 113T-115T published 1960), (Year: 1960). [cited by examiner]
AK-Dilate 2.5% phenylephrine hydrochloride ophthalmic solution Product page from Falcon Pharmaceuticals and Alcon Laboratories (Year: 2014). [cited by examiner]
AK-Dilate from Falcon Pharmaceuticals and Alcon Laboratories (Year: 2012). [cited by examiner]
Saettone (J. Pharm. Pharmacol. vol. 32 pp. 519-521 published 1980) (Year: 1980). [cited by examiner]
AK-Dilate product page (Year: 2014). [cited by examiner]
Dubois (BMC Ophthalmology vol. 6 Issue 36 pp. 1-4, published 2006). (Year: 2006). [cited by examiner]
West, G.B., Journal of Pharmacy and Pharmacology, vol. 12, p. 113T-115T, Published 1960. [cited by applicant]
Das Gupta, V., J. Clin. Hop Pharm, vol. 11, pp. 449-452, 1986. [cited by applicant]
Slack, American Journal of Ophthalmology, vol. 110, p. 77-82, 1990. [cited by applicant]
Shugar et al., “Use of epinephrine for IFIS prophylaxis,” Journal of Cataract & Refractive Surgery, 2006, 32(7):1074-1075. [cited by applicant]
Sinnott et al., “On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve block,” The Journal of American Society of Anesthesiologists, 2003, 98(1):181-188. [cited by applicant]
International Search Report with Written Opinion corresponding to International Patent Application No. PCT/US2014/059077, dated Jan. 26, 2015. [cited by applicant]
Overgaard, “How to Make Sterile Water and Sterile Saline,” Phoenix Children's Hospital, 2006. [cited by applicant]
Non-FInal Rejection corresponding to U.S. Appl. No. 14/506,120, dated Oct. 5, 2017, 28 pages. [cited by applicant]
Shugar, J.K., “Intracameral Epinephrine for IFIS Prophylaxis,” Cataract & Refractive Surgery Today, 2006, pp. 1-13. [cited by applicant]
BSS Product Page, Alcon Laboratories, Inc., 2012. [cited by applicant]
Verhoff, F. et al., Ulmann's Encyclopedia of Industrial Chemistry: Citric Acid, Wiley-VCH GMBH & Co. KGaA, Weinheim, pp. 1-9, 2015. [cited by applicant]
Schulze Jr., Richard, “EPI-Shugarcaine With Plain Balanced Salt Solution for Prophylaxis of Intraoperative Floppy-Iris Syndrome,” Journal of Cataract Surgery, 2010, 35:523. [cited by applicant]
Stewart, R., et al., “Efficacy and safety profile of ketorolac 0.5% ophthalmic solution in the prevention of surgically induced miosis during cataract surgery,” Clinical Therapeutics, 1999, 21:723-732. [cited by applicant]
Grubstein, B., et al., “Stabilization of Epinephrine local anesthetic injectable solution using reduced levels of Sodium Metabisulfite and EDTA” Drug Development and Industrial Pharmacy, 1992, 18:1549-1566. [cited by applicant]
PH, Encyclopedia Brittanica, published online, 1998, https://britannica.com/science/pH. [cited by applicant]
Zhang, et al., “Study of mixed micelles and interaction parameters for polymeric nonionic and normal surfactants,” Journal of Nanoscience and Nanotechnology, 2006. [cited by applicant]
United States Pharmacopoeia 21st Review, National Formulary 16th Review, 1985, pp. 1651, 592-596, 1662, 571-572, 827-830, 883-884. [cited by applicant]
PCT/US2014/059077, filed Oct. 3, 2014, John Scott Karolchyk. [cited by applicant]
U.S. Appl. No. 15/241,958, filed Aug. 19, 2016, John Scott Karolchyk. [cited by applicant]
U.S. Appl. No. 14/506,120, filed Oct. 3, 2014, John Scott Karolchyk. [cited by applicant]
Remington, The Science and Practice of Pharmacy, 21st Edition, 2005, pp. 828-829. [cited by applicant]
American Reagent Laboratories, Inc., MSDS of Epinephrine Injection from Lutipold Pharmaceuticals, 1998, 4 pages. [cited by applicant]
Lorenzetti, “Dose-dependent Influence of Topically Instilled Adrenergic Agents on Intraocular Pressure and Outflow Facility in the Rabbit”, Exp Eye Res, 1971, 12:80-87. [cited by applicant]
Roscoe et al., “Chelating Agents as Color Stabilizers for Epinephrine Hydrochloride Solutions”, Journal of American Pharmaceutical Association, 1956, 45(7): 464-470. [cited by applicant]
Office Action in U.S. Appl. No. 17/330,023 dated Feb. 1, 2023, 19 pages. [cited by applicant]
Lorente, et al. “Intracameral Phenylephrine 1.5% for Prophylaxis against Intraoperative Floppy Iris Syndrome: Prospective, Randomized Fellow Eye Study”, Ophthalmology 2012; 119:2053-2058. [cited by applicant]