OPHTHALMOLOGIC IRRIGATION SOLUTIONS AND METHOD

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 composition for use in perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising an anti-inflammatory agent and a mydriatic agent in a physiologic irrigation solution for intraocular delivery, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent comprises an alpha-1 adrenergic receptor agonist, wherein the NSAID and the alpha-1 adrenergic receptor agonist are included at concentrations less than that used for conventional topical or systemic delivery and in a therapeutically effective amount for the maintenance of mydriasis during the procedure and the reduction of postoperative pain when delivered intraocularly during the intraocular ophthalmologic procedure.

2. The composition of claim 1, wherein the NSAID is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen, ketorolac, indomethacin, naproxen, ibuprofen.

3. The composition of claim 1, wherein the NSAID is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen and ketorolac.

4. The composition of claim 2, wherein the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline.

5. The composition of claim 1, wherein the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline.

6. The composition of claim 1, wherein the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine and epinephrine.

7. The composition of claim 1, 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.

8. The composition of claim 1, wherein the physiologic solution comprises a balanced salt solution liquid irrigation.

9. The composition of claim 8, wherein the balanced salt solution liquid irrigation carrier further comprises an adjuvant selected from a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof.

10. The composition of claim 1, wherein the solution further comprises an analgesic agent selected from the group consisting of local anesthetics and opioids.

11. The composition of claim 10, 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.

12. A composition for use in perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising an anti-inflammatory agent and a mydriatic agent in a physiologic irrigation solution for intraocular delivery, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent comprises an alpha-1 adrenergic receptor agonist, wherein the NSAID and the alpha-1 adrenergic receptor agonist are included at concentrations less than that used for conventional topical or systemic delivery and in a therapeutically effective amount for the maintenance of pupil dilation and inhibition of miosis during the procedure and the reduction of postoperative pain when delivered intraocularly during the intraocular ophthalmologic procedure.

Description

VII. EXAMPLES

[0094] The following are exemplary formulations in accordance with the present invention suitable for ophthalmologic procedures.

Example 1

[0095] Exemplary ophthalmologic solutions of the present invention for use during cataract removal surgery are described in Tables 20, 21 and 22. This solution, and the following solutions of Tables 23-25, are provided by way of example only, and are not intended to limit the invention. Anti-inflammatories are believed to be particularly useful in cataract solutions of the invention, to potentially reduce the post-operative incidence of, or hasten resolution of, cystoid macular edema (CME). These exemplary solutions and the other exemplary ophthalmologic irrigation solutions described herein below are provided in terms of the concentration of each agent included in the previously described preferred balanced-salt solution. The solution may suitably be supplied in 500 ml bags, this being the quantity of irrigation solution typically applied during a procedure, by way of non-limiting example.

TABLE-US-00020 TABLE 20 Exemplary Cataract Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred anti- flurbiprofen 10-1,000,000 100-100,000 1,000-10,000 inflammatory IOP red. agent timolol 10-1,000,000 100-100,000 1,000-10,000 mydriatic phenylephrine 50-500,000.sup.  500-100,000 1,000-10,000

TABLE-US-00021 TABLE 21 Alternate Exemplary Cataract Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred anti- ketoprofen 10-1,000,000 100-100,000 1,000-10,000 inflammatory IOP red. agent timolol 10-1,000,000 100-100,000 1,000-10,000 mydriatic tropicamide 10-1,000,000 100-100,000 1,000-10,000

TABLE-US-00022 TABLE 22 Alternate Exemplary Cataract Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred mydriatic, IOP oxymetazoline 10-1,000,000 100-100,000 1,000-10,000 red. agent anti- flurbiprofen 10-1,000,000 100-100,000 1,000-10,000 inflammtory

Example 2

[0096] A similar irrigation solution including multiple agents for effective reduction of inflammation and to provide mydriasis for invasive ophthalmologic surgery, such as a trabeculectomy, is provided in Table 23.

TABLE-US-00023 TABLE 23 Exemplary Trabeculectomy Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred anti- prednisolone 10-1,000,000 100-100,000 1,000-10,000 inflammatory anti- flurbiprofen 10-1,000,000 100-100,000 1,000-10,000 inflammatory IOP red. agent timolol 10-1,000,000 100-100,000 1,000-10,000 mydriatic phenylephrine 50-500,000.sup.  500-100,000 1,000-10,000

Example 3

[0097] Irrigation solutions suitably used for extensive ophthalmologic surgery or posterior ocular chamber procedures, such as vitrectomy, provide increased analgesia by the addition of a local anesthetic. Such solutions of the present invention including a local anesthetic are provided in Tables 24 and 25.

TABLE-US-00024 TABLE 24 Exemplary Local Anesthetic Ophthalmologic Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred IOP red. agent timolol 10-1,000,000 100-100,000 1,000-10,000 anti- flurbiprofen 10-1,000,000 100-100,000 1,000-10,000 inflammatory mydriatic tropicamide 10-1,000,000 100-100,000 1,000-10,000 analgesic lidocaine 1,000-100,000,000  10,000-10,000,000  100,000-1,000,000

TABLE-US-00025 TABLE 25 Alternate Exemplary Local Anesthetic Ophthalmologic Solution Class of Agent Concentration (Nanomolar): Most Drug Therapeutic Preferred Preferred IOP red. agent timolol 10-1,000,000 100-100,000 1,000-10,000 anti- flurbiprofen 10-1,000,000 100-100,000 1,000-10,000 inflammatory mydriatic tropicamide 10-1,000,000 100-100,000 1,000-10,000 analgesic bupivacaine 125-400,000   1,000-300,000.sup.  225,000-275,000 

[0098] While the preferred embodiment of the invention has been illustrated and described, it will be appreciated that various changes to the disclosed solutions and methods can be made therein without departing from the spirit and scope of the invention. For example, alternate pain inhibitors, inflammation inhibitors, IOP reducing agents and mydriatic agents may be discovered that may augment or replace the disclosed agents in accordance with the disclosure contained herein. It is therefore intended that the scope of letters patent granted hereon be limited only by the definitions of the appended claims.