Artificial tear replacement solution

• US 7,001,607 B1
• Filed: 06/30/2000
• Issued: 02/21/2006
• Est. Priority Date: 08/14/1999
• Status: Expired due to Fees

• Current Assignee: Pharm Pur GmbH
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Menz, Dirk-Henning, Winter, Martin, Dresp, Joachim
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US10/049,558
• Time in Patent Office: 2,062 Days
• Field of Search: 424/78.02, 424/427, 514/755, 514/756, 514/832, 514/743, 514/772.4, 514/914, 514/944
• US Class Current: 424/427
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 31/03 aromatic
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/695 Silicon compounds
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions

Abstract

A tear replacement solution that contains at least one water-soluble fluorosurfactant, water and a non-polar component, preferably in gel form, and a method for the external treatment for the eye of an mammal by applying the tear replacement solution to the eye, preferably by placing in the conjunctival sac.

Claims

1. Method for the treatment of an eye of a mammal, the eye having a conjunctival sac comprising the steps of:

a. preparing a sterile polyaphron gel comprising at least one water-soluble fluorinated surfactant in a concentration lower than critical micellae formation, water and one homopolar component in an amount greater than 60% by weight selected from the group consisting of partially fluorinated fluorocarbon compounds of the general formula R_FR_H, R_FR_HR_F, fluorocarbon oligomers of the type (R_F)_XR_H, silicone oil, and mixtures thereof;

b. introducing the sterile polyaphron gel into the conjunctival sac of the eye to form a gel-like reservoir whereupon at each blink of the eye, a portion of the sterile polyaphron gel irreversibly liquefies under the effect of the shear forces caused by the blink, extrudes from the conjunctival sac and spreads over the cornea of the eye as a thin liquid film functioning as a tear substitute.

2. Method in accordance with claim 1, wherein the fluorinated surfactant is of the general formula

R_F—

R_POL

whereby R_F is a linear or branched perfluoroalkyl group having more than 5 carbon atoms and Rpol is a polar hydrogen residue comprising at least one functional group selected from the series CO—

NH(R), CO—

NH(R)₂, COO—

, COOR, SO₃, SO₂—

N(R)₂, CH₂—

O—

R, PO₂H, PO₃H whereby R is an alkyl.

3. Method in accordance with claim 1, wherein the molecular mass of the fluorinated surfactant is greater than 400/lmol, and the surface tension of the fluorinated surfactant in aqueous solution is less than 30 m/Nm.

4. Method in accordance with claim 1, wherein the concentration of the fluorinated surfactant is lower than 0.1% and the concentration of fluorocarbons is greater than 90 weight percent.

5. Method in accordance with claim 1, wherein the water-soluble fluorinated surfactant has at least 6 fully fluoridated carbon atoms.

6. Method in accordance with claim 1, wherein the sterile polyaphron gel has a refraction index of 1.334 to 1.338.

7. Method in accordance with claim 1, wherein the sum of the surface tension of the sterile polyaphron gel and the interfacial tension between the sterile polyaphron gel and the surface of the eye is smaller than the surface tension of the surface of the eye.

8. A sterile polyaphron gel comprising at least one water-soluble fluorinated surfactant in a concentration lower than critical micellae formation, water and one homopolar component in an amount greater than 60% by weight selected from the group consisting of partially fluorinated fluorocarbon compounds of the general formula R_FR_H, R_FR_HR_F, fluorocarbon oligomers of the type (R_F)_XR_H, silicone oil, and mixtures thereof;

said sterile polyaphron gel being adapted for introduction into the conjunctival sac of an eye of a mammal to form a gel-like reservoir whereupon at each blink of the eye, a portion of the sterile polyaphron gel will liquefy irreversibly under the effect of the shear forces caused by the blink, extrude from the conjunctival sac and spread over the cornea of the eye as a thin liquid film functioning as a tear substitute.

9. A sterile polyaphron gel in accordance with claim 8, wherein the fluorinated surfactant is of the general formula

R_F—

R_POL

whereby R_F is a linear or branched perfluoroalkyl group having more than 5 carbon atoms and Rpol is a polar hydrogen residue comprising at least one functional group selected from the series CO—

NH(R), CO—

NH(R)₂, COO—

, COOR, SO₃, SO₂—

N(R)₂, CH₂—

O—

R, PO₂H, PO₃H whereby R is an alkyl.

10. A sterile polyaphron gel in accordance with claim 8, wherein the molecular mass of the fluorinated surfactant is greater than 400/lmol, and the surface tension of the fluorinated surfactant in aqueous solution is less than 30 m/Nm.

11. A sterile polyaphron gel in accordance with claim 8, wherein the concentration of the fluorinated surfactant is lower than 0.1% and the concentration of fluorocarbons is greater than 90 weight percent.

12. A sterile polyaphron gel in accordance with claim 8, wherein the water-soluble fluorinated surfactant has at least 6 fully fluoridated carbon atoms.

13. A sterile polyaphron gel in accordance with claim 8, wherein the sterile polyaphron gel has a refraction index of 1.334 to 1.338.

14. A sterile polyaphron gel in accordance with claim 8, wherein the surface tension of the sterile polyaphron gel is adjusted such that the sum of the surface tension of the sterile polyaphron gel and the interfacial tension between the sterile polyaphron gel and the surface of the eye is smaller than the surface tension of the surface of the eye.