Ophthalmologic irrigation solutions and method

• US 20100311705A1
• Filed: 05/05/2010
• Published: 12/09/2010
• Est. Priority Date: 07/30/2002
• Status: Active Grant

• Current Assignee: Rayner Surgical Incorporated (Rayner Surgical Group Ltd.)
• Original Assignee: Omeros Corporation
• Inventors: Demopulos, Gregory A., Palmer, Pamela Pierce, Herz, Jeffrey M.
• Granted Patent: US 8,173,707 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 27/08 Mydriatics or cycloplegics
• CPC Class Codes: A61P 27/12 : for cataracts
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Solutions for perioperative intraocular application by continuous irrigation during ophthalmologic procedures are provided. These solutions include multiple agents that act to inhibit inflammation, inhibit pain, effect mydriasis (dilation of the pupil), and/or decrease intraocular pressure, wherein the multiple agents are selected to target multiple molecular targets to achieve multiple differing physiologic functions, and are included in dilute concentrations in a balanced salt solution carrier.

Claims

1. A method for perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising irrigating intraocular tissues during an intraocular ophthalmologic procedure with a solution including at least an anti-inflammatory agent and a mydriatic agent in a liquid irrigation carrier, wherein the anti-inflammatory agent comprises ketorolac and the mydriatic agent comprises phenylephrine and each of the agents is included in a therapeutically effective amount for the inhibition of inflammation and maintenenace of mydriasis when delivered intracoularly during the intraocular ophthalmologic procedure.

2. The method of claim 1, wherein the ketorolac is included in the solution at a concentration of no more than 100,000 nanomolar and the phenylephrine is included in the solution at a concentration of no more than 500,000 nanomolar

3. The method of claim 1, wherein the solution is continuously applied to the intraocular tissues during the intraocular procedure.

4. The method of claim 1, wherein the liquid irrigation carrier further comprises an adjuvant selected from electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof

5. The method of claim 4, wherein:

the electrolytes, if selected, comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate;

the buffer, if selected, comprises bicarbonate at a concentration of from 10 to 50 millimolar;

the cellular energy source if selected, is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and

the free-radical scavenger, if selected, comprises glutathione at a concentration of from 0.05 to 5 millimolar.

6. The method of claim 1, wherein the liquid irrigation carrier further comprises electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent and a free-radical scavenger.

7. The method of claim 1, wherein the pH of the irrigation solution is between 5.5 and 8.0.

8. A method for perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising irrigating intraocular tissues during an intraocular ophthalmologic procedure with a solution including at least an anti-inflammatory agent and a mydriatic agent in a liquid irrigation carrier, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent comprises an alpha-1 adrenergic receptor agonist and each of the agents is included in a therapeutically effective amount for the inhibition of inflammation and maintenenace of mydriasis when delivered intracoularly during the intraocular ophthalmologic procedure.

9. The method of claim 8, wherein the NSAID is included in the solution at a concentration of no more than 100,000 nanomolar and the alpha-1 adrenergic receptor agonist is included in the solution at a concentration of no more than 500,000 nanomolar

10. The method of claim 8, wherein the NSAID is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen and ketorolac.

11. The method of claim 8, wherein the solution further comprises an analgesic agent selected from the group consisting of local anesthetics and opioids.

12. The method of claim 11, wherein:

the local anesthetic, if selected, is selected from the group consisting of lidocaine, tetracaine, bupivacaine, and proparacaine; and

the opioid, if selected, is selected from the group consisting of morphine, fentanyl and hydromorphone.

13. The method of claim 8, wherein:

the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline.

14. The method of claim 8, wherein the solution further comprises an agent for decreasing intraocular pressure (“

IOP reducing agent”

) selected from the group consisting of beta adrenergic receptor antagonists, carbonic anhydrase inhibitors, alpha-2 adrenergic receptor agonists, and prostaglandin agonists.

15. The method of claim 8, wherein:

the beta adrenergic receptor antagonist, if selected, is selected from the group consisting of timolol, metipranolol and levobunolol;

the carbonic anhydrase inhibitor, if selected, is selected from the group consisting of brinzolamide and dorzolamide;

the alpha-2 adrenergic receptor agonist, if selected, is selected from the group consisting of apraclonidine, brimonidine and oxymetazoline; and

the prostaglandin agonist, if selected, is selected from the group consisting of latanoprost, travoprost and bimatoprost.

16. The method of claim 8, wherein the solution is continuously applied to the intraocular tissues during the intraocular procedure.

17. The method of claim 8, wherein the liquid irrigation carrier further comprises an adjuvant selected from electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof.

18. The method of claim 17, wherein:

the electrolytes, if selected, comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate;

the buffer, if selected, comprises bicarbonate at a concentration of from 10 to 50 millimolar;

the cellular energy source if selected, is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and

the free-radical scavenger, if selected, comprises glutathione at a concentration of from 0.05 to 5 millimolar.

19. The method of claim 8, wherein the liquid irrigation carrier further comprises electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent and a free-radical scavenger.

20. The method of claim 19, wherein:

the electrolytes comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate;

the buffer comprises bicarbonate at a concentration of from 10 to 50 millimolar;

the cellular energy source is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and

the free-radical scavenger comprises glutathione at a concentration of from 0.05 to 5 millimolar.

21. The method of claim 8, wherein the pH of the irrigation solution is between 5.5 and 8.0.

22. The method of claim 8, wherein the solution comprises an NSAID and phenylephrine.

23. The method of claim 8, wherein the solution comprises an NSAID and epinephrine.

24. The method of claim 8, wherein the solution comprises oxymetazoline and an NSAID.

25. A method for perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising irrigating intraocular tissues during an intraocular ophthalmologic procedure with a solution including at least an anti-inflammatory agent and a mydriatic agent in a liquid irrigation carrier, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent is selected from the group consisting of epinephrine and phenylephrine and each of the agents is included in a therapeutically effective amount for the inhibition of inflammation and maintenenace of mydriasis when delivered intracoularly during the intraocular ophthalmologic procedure.