Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Reexamination Certificate
2000-08-25
2002-02-26
Fay, Zohren (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
C514S563000, C514S912000
Reexamination Certificate
active
06350781
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of Invention
The current invention concerns a method for ophthalmic analgesia achieved with nontoxic subanesthetic concentration of multiple doses of topically administered lidocaine. In particular, the invention concerns administration of diluted topical lidocaine preparation comprising about and up to about 0.4% (4000 &mgr;g/ml) of lidocaine and a topical ophthalmic preparation for corneal analgesia having a fast onset of pain relief and extended duration of the corneal analgesia. The lidocaine preparation may be administered for several months without accompanying toxic symptoms.
2. Background Art and Related Art Disclosures
Trauma to the eye, particularly corneal injury and abrasion, tends to be excruciatingly painful. While many anesthetic agents such as proparacaine, cocaine, procaine, tetracaine, hexylcaine, bupivacaine, lidocaine, benoxinate, mepivacaine, prilocaine and etidocaine, to name a few, are well known to attain temporary anesthesia and suppression of pain, concentrations of these agents needed to achieve corneal anesthesia are between 0.25% and 4%. At these concentrations, these agents can only be administered for a very short period of time necessary to achieve local anesthesia and permit performance of ophthalmic procedures such as examination of a painful eye, measurement of intraocular pressure, gonioscopic examination, removal of foreign bodies and sutures from the cornea, diagnostic conjunctival and corneal scrapings, radial keratotomy, and other surgical procedures. The onset of the anesthesia is very rapid, typically under 15 seconds, and typically lasts for about 10-30 minutes.
Unfortunately, application of local anesthetics to the cornea at these concentrations causes the development of temporary superficial corneal epithelial lesions. Upon repeated application for prolonged anesthesia, these lesions progress to extensive erosions of the corneal epithelium and grayish infiltrates of the corneal stroma which can lead to permanent scarring and loss of vision. Prolonged application, of local anesthetics is further associated with delayed corneal reepithelialization after wounding, altered lacrimation and tear film stability, corneal swelling, and disruption of epithelial cell mitosis and migration.
It is therefore clear that the use of local anesthetics in their normal and intended manner is limited to short-term anesthesia and cannot be safely utilized for sustained decrease or elimination of pain over several hours or days.
Anesthesia, which is a partial or total loss of the sense of pain, temperature, and touch, is very different from analgesia, a state in which the individual does not feel pain but feels other sensations, such as touch or temperature.
Sustained ophthalmic analgesia is very difficult to achieve. This is particularly true with respect to corneal analgesia. The cornea is the clear dome-shaped window in the front of the eye. The cornea serves two functions. First, it forms the front part of the eye's outer wall and thus protects structures inside the eye. Second, with its curved shape, the cornea acts like a camera lens to transmit light and focus images on the retina at the back of the eye. The epithelium (outermost layer) of the cornea is heavily enervated. Therefore, the cornea is very sensitive, and any damage to the surface epithelium can cause severe pain.
A common cause of such pain is a break in the corneal epithelium. Such epithelial defects can be caused by corneal drying, infection and inflammation which damage epithelial cells, by corneal dystrophies with loosely adherent epithelium, or by mechanical removal of the corneal epithelium in traumatic abrasions or surgical procedures. In most cases, the pain persists until the epithelial defect has healed.
At present, in order to provide immediate but short-term alleviation of the severe pain experienced by patients suffering from corneal epithelial defects, commercially available local anesthetics can be applied topically to the eye, providing rapid onset of short-acting corneal anesthesia. Two commonly used topical anesthetics are proparacaine in a concentration of 0.5% (5,000 &mgr;g/ml) and tetracaine 0.5% (5,000 &mgr;g/ml). Lidocaine 4.0% (
40,000 &mgr;g/ml) is also occasionally used.
While short-term relief from pain accompanies the application of these anesthetics, there are conditions of the cornea where such short term relief from pain is not sufficient and where prolonged analgesia is necessary and desirable. This is especially true for relief of pain associated with corneal epithelial defects. In these instances, the toxicity associated with repeated use of topical anesthetics for achieving sustained corneal analgesia has been well documented. In
Ocular Pharmacology,
Fifth Edition, CV Mosby, St. Louis, pages 75-76 (1983), the repeated use of anesthetic concentrations of topical anesthetics was found to be detrimental to the cornea, and the article states that the repeated use of anesthetics is prohibited because of their toxicity. Thus, the toxicity of these anesthetic agents precludes their repeated use for prolonged corneal analgesia. At this time, therefore, acceptable methods for long-term relief of corneal pain are limited to patching and oral analgesics.
Patching provides partial pain relief in some patients by reducing eyelid movement over the corneal surface and limiting exposure to the outside environment. However, patching has many disadvantages. It is difficult for the patient to reapply the patch properly when it becomes loose or soiled. Patching restricts the frequent use of topical medications. It raises the temperature of the eye surface and thus supports the growth of microorganisms. Finally, many patients are uncomfortable with an eye patched. While patching with a bandage soft contact lens may overcome some of these problems, patching provides incomplete pain relief in most patients and is no substitute for sustained analgesia in patients suffering from corneal epithelial defects, where the pain can persist for several days to several weeks or months.
Oral agents are reasonably effective in reducing corneal pain. However, onset of action is gradual and slow rather than immediate. Doses adequate for corneal analgesia are high and usually cause significant generalized sedation, occasionally accompanied by nausea and vomiting and rarely by life-threatening allergic reactions.
It would therefore be highly desirable and advantageous to have available a method for treatment of acute and chronic corneal pain without exposing a patient to the undesirable side effects of currently available oral analgesics, to the inadequate analgesia and inconvenience associated with patching, or to the toxic effects of repeated doses of currently available concentrations of topical anesthetics.
It is therefore the primary object of this invention to provide a method for achieving sustained and extended corneal analgesia by administration of analgesic concentrations of lidocaine formulated in topical ophthalmic analgesic solutions or ophthalmic analgesic preparations.
SUMMARY
One aspect of the current invention is a topical ophthalmic preparation for sustained corneal analgesia comprising diluted lidocaine.
Another aspect of the current invention is a topical ophthalmic preparation comprising diluted lidocaine for relief of corneal pain formulated as an ointment, cream, suspension, solution, gel or a sustained release vehicle comprising lidocaine of about and up to about 0.4%.
Still yet another aspect of the current invention is a method for safe alleviation of corneal pain by administration of an ophthalmic analgesic solution or preparation comprising diluted lidocaine administered on an as needed basis decided by the patient, as often and for as long as necessary.
DEFINITIONS
As used herein:
“Local anesthetics” means lidocaine.
“Dose” means a measurable amount of the ophthalmic analgesic for proper dosage containing from about and up to 0.4% of lidocaine.
“Microsystem” means a microdose or microdrop system wherein a topical lido
Fay Zohren
Verny, Esq. Hana
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