Photokinetic ocular drug delivery methods and apparatus

• US 8,948,863 B2
• Filed: 10/12/2010
• Issued: 02/03/2015
• Est. Priority Date: 10/09/2009
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kraft, Edward R., Kulp, Gabriela A., Godley, Bernard F., Koutrouvelis, Aristides P.
• Primary Examiner(s): Bosworth, Kami A
• Assistant Examiner(s): HAYMAN, IMANI N
• Application Number:
  US12/903,126
• Publication Number:
  US 20110125076A1
• Time in Patent Office: 1,575 Days
• Field of Search: 604 20- 22, 435/173.1, 607/53, 607/88, 607/141
• US Class Current: 604/20
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/0079 using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves
• 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 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7042 Compounds having saccharide radicals and heterocyclic rings
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/16 containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61N 2005/0651 Diodes
• CPC Class Codes: A61N 2005/0656 Chemical light sources
• CPC Class Codes: A61N 2005/0659 : infrared
• CPC Class Codes: A61N 2005/0661 : ultraviolet
• CPC Class Codes: A61N 2005/0662 : Visible light
• CPC Class Codes: A61N 5/062 : Photodynamic therapy, i.e. excitation of an agent

Abstract

The present invention relates generally to transscleral, transcorneal, and transocular delivery of biologically active substances through the tissues, blood vessels and cellular membranes of the eyes of patients without causing damage to the cellular surface, tissue or membrane. The invention provides compositions and methods for enhanced transscleral, transcorneal and transocular delivery of biologically active substances using pulsed incoherent light, and particularly the transcleral, transcorneal or transocular delivery of high molecular weight biologically active substances to a patient using pulsed incoherent light. The invention further provides a device for the application of the pulsed incoherent light to cellular surfaces and membranes of the eye of a subject using those compositions and methods.

Claims

1. A device for photokinetic transscleral ocular drug delivery, the device comprising:

a generator that provides an oscillating electrical pulse in electrical communication with at least one light emitting diode (LED) that is mounted on a photokinetic patch adapted and dimensioned to be inserted under an eyelid and fit against an external ocular surface of an eye of a patient, the photokinetic patch including a drug layer, wherein the at least one LED receives the oscillating electrical pulse and responds by providing an incoherent light directed through the drug layer and towards an interior of the eye of the patient at a wavelength selected to induce a photokinetic transocular translocation of a drug loaded in the drug layer.

2. The device according to claim 1, wherein the generator is a repeat cycle square wave pulse generator.

3. The device according to claim 1, wherein the photokinetic patch further comprises a light pad that includes the at least one LED.

4. The device according to claim 3, wherein the light pad is comprised of an optically clear material.

5. The device according to claim 4, wherein the optically clear material is poly(methylmethacrylate) or silicone rubber.

6. The device according to claim 1, wherein the at least one LED is a discrete wavelength LED characterized by a peak emitting wavelength at a 50% radiance output that is ±

10 nm of the wavelengths selected from the group consisting of 350 nm, 370 nm, 390 nm, 405 nm and 450 nm.

7. The device according to claim 1, wherein the drug layer comprises a biologically active substance and a solvent.

8. The device according to claim 7, wherein the drug layer further comprises at least one gelling agent.

9. The device according to claim 8, wherein the at least one gelling agent is selected from one or more of hydroxyethyl cellulose, pectines, agar, alginic acid and its salts, guar gum, pectin, polyvinyl alcohol, polyethylene oxide, cellulose and its derivatives, propylene carbonate, polyethylene glycol, hexylene glycol sodium carboxymethylcellulose, polyacrylates, polyoxyethylene-polyoxypropylene block copolymers, pluronics, wood wax alcohols, and tyloxapol.

10. The device according to claim 7, wherein the biologically active substance is selected from one or more anesthetics, anti-infectives, antibiotics, antifungals, antivirals, antineoplastics, anti-VEGFs, antineovasculars, steroids, anti-inflammatories (including NSAIDS), immunomodulators, gases, antioxidants, nanoparticles, genes, cytokines, peptides, antithrombotics, nucleotides, RNAs, anti-compliment medications, compliment modulating medications, peptides, immunoglobulins, antibodies, antigens, anti-glaucoma medications, hormones, vitamins, amino acids, silicone liquids, heavy liquid tamponades, cellular nutrients, anti-apoptotic agents, anticoagulants, tissue adhesives, cofactors, coenzymes, enzymes and combinations thereof.

11. The device according to claim 1, wherein the at least one LED emits light at a wavelength from about 350 nm to about 700 nm.

12. The device according to claim 1, wherein the at least one LED is an infrared light emitting diode (ILED).

13. The device according to claim 3, wherein the light pad is coated on at least one surface with a reflective coating or layer.

14. The device according to claim 1, wherein the generator is a pulse generator that induces delivery of pulsed incoherent light.

15. The device according to claim 14, wherein the pulsed incoherent light is at a pulse rate between 1.7 cycles per second (cps) and 120 cps.

16. The device according to claim 14, wherein the pulsed incoherent light is applied at a duty cycle between 50% and 75%.

17. The device according to claim 1, wherein the generator is adapted and configured for mounting on an ear of the patient proximate to the external ocular surface.

18. The device according to claim 1, wherein the generator is mounted on a headband that is adapted and dimensioned to be fit over a head of the patient undergoing the photokinetic transscleral ocular drug delivery.

19. The device according to claim 1, wherein the device is supplied with the drug layer preloaded with the drug.

20. The device according to claim 1, wherein the drug layer is loaded with the drug at the time the photokinetic patch is inserted onto and fit against the external ocular surface of the patient.

21. The device according to claim 1, wherein the drug layer is loaded with a large molecule drug having a molecular weight of over 10,000 Daltons.

22. The device according to claim 1, wherein the drug layer is loaded with a large molecule drug having a molecular weight of over 100,000 Daltons.