Ophthalmic preparation for use as artificial tear

• US 5,770,628 A
• Filed: 07/21/1995
• Issued: 06/23/1998
• Est. Priority Date: 07/25/1994
• Status: Expired due to Term

• Current Assignee: Laboratoire Medidom Sa
• Original Assignee: Laboratoire Medidom Sa
• Inventors: Cantoro, Amalio
• Primary Examiner(s): Schoffer, Joseph L.
• Assistant Examiner(s): Shelborne, Kathryne E.
• Application Number:
  US08/505,095
• Time in Patent Office: 1,068 Days
• Field of Search: 424/78.04, 424/422, 424/427, 424/600, 424/601, 424/610, 424/611, 424/617, 424/677, 424/678, 424/679, 424/680, 424/681, 424/682, 514/54, 514/62, 514/777, 514/915
• US Class Current: 514/778
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions

Abstract

Ophthalmic preparation for use as artificial tear containing hyaluronate as a viscosity thickener, preferably in the form of sodic salt and having a molecular weight of 500,000 to 4,000,000 daltons, at a concentration of 0.05 to 2% by weight, as well as the following minimum quantities of ionic species: 40 mmol/l sodium ion, 12 mmol/l potassium ion, 0.4 mmol/l calcium ion, 0.4 mmol/l magnesium ion, 50 mmol/l chloride ion, 7 mmol/l phosphate ion and, preferably, 0.7 mmol/l citrate ion. The formulation, which as an osmolarity of 140 to 280 mOsm/l, is useful for the treatment of keratoconjunctivitis sicca and may be administered whenever the use of artifical tears is advisable, e.g. for the treatment of eye irritations caused by environmental conditions or contact lenses.

Claims

1. An ophthalmic aqueous preparation for use as artificial tear containing a viscosity thickener consisting of at least one hyaluronic acid salt, at a concentration of 0.05 to 2% by weight, as well as the following quantities of ionic species:

40-95 mmol/l of sodium ions, 12-28 mmol/l of potassium ions, 0.4-1,5 mmol/l of calcium ions, 0.4-1.0 mmol/l of magnesium ions, 50-100 mmol/l of chloride ions, 7-20 mmol/l of phosphate ions, 0.7-2.5 mmol/l of citrate ions, and water,

said composition having a viscosity versus shear rate, measured at 32°

C. from 10.0 to 200.0 cps at a shear rate of 2 sec^-1 and from 10 to 5 cps at a shear rate of 1000 sec^-1, and an osmolarity from 140 to 280 mOsm/l.

2. The preparation according to claim 1, further containing at least 7 mmol/l of acetate ion.

3. The preparation according to claim 1, further containing at least 5 mmol/l of bicarbonate ion.

4. The preparation according to claim 1, further containing at least 1 mmol/l of EDTA.

5. The preparation according to claim 1, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 4,000,000 daltons.

6. The preparation according to claim 1, having pH of 6.8 to 7.6.

8. A therapeutic method for the treatment of keratoconjuctivitis sicca or of eye irritations, which comprises instillation in the conjuctival sac of a subject in a need of such treatment a therapeutically effective amount of an ophtalmic preparation as claimed in claim 1.

9. The therapeutic method as claimed in claim 8, wherein eye irritations are those caused by environmental conditions or contact lenses.

10. The preparation according to claim 1, further containing dextrose.

11. The preparation according to claim 1, further containing preservatives.

12. The preparation according to claim 11, containing sodium ethylmercurithiosalicilate as a preservative.

13. The preparation according to claim 1, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 8,000,000 daltons.

14. The therapeutic method as claimed in claim 8, which comprises administering 1-2 drops per eye, from 4 to 8 times a day.

7. An ophthalmic aqueous preparation for use as artificial tear, having the following composition:

space="preserve" listing-type="tabular">______________________________________ mg/100 ml mmol/l ______________________________________ sodium hyaluronate 250 ˜

6.2 -- NaCl 279.2 47.77 KCl 103.3 13.85 Na.sub.2 HPO.sup.4.12H.sub.2 O 322.2 9.0 Na.sub.3 citrate 26.0 1.05 MgCl.sub.2.6H.sub.2 O 9.2 0.45 CaCl.sub.2.2H.sub.2 O 6.9 0.6 ______________________________________

wherein sodium hyaluronate has molecular weight 800,000-1,600,000, and the solution has pH=7.32 and osmolarity=150 mOsm/l, and a viscosity of 28 Cps at a shear rate of 2 sec^-1.

15. An ophthalmic aqueous preparation for use as artificial tear in the treatment of a disease selected from the group consisting of dry eye syndrome and a state of eye irritation, containing a viscosity thickener consisting of at least one hyaluronic acid salt, at a concentration of 0.05 to 2% by weight, as well as the following quantities of ionic species:

49-95 mmol/l of sodium ions, 12-28 mmol/l of potassium ions, 0.4-1,5 mmol/l of calcium ions, 0.4-1.0 mmol/l of magnesium ions, 50-100 mmol/l of chloride ions, 7-20 mmol/l of phosphate ions, 0.7-2.5 mmol/l of citrate ions, and water,

said composition having a viscosity versus shear rate, measured at 32°

C., from 10.0 to 200.0 cps at a shear rate of 2 sec^-1 and from 10 to 5 cps at a shear rate of 1000 sec^-1, and an osmolarity from 140 to 280 mOsm/l.

16. The preparation according to claim 15, wherein the eye irritations are those caused by environmental conditions or contact lenses.

17. The preparation according to claim 15, further containing at least one additional ingredient selected from the group consisting of:

at least 7 mmol/l of acetate ion, at least 5 mmol/l of bicarbonate ion and at least 1 mmol/l of EDTA.

18. The preparation according to claim 15, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 8,000,000 daltons.

19. The preparation according to claim 15, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 4,000,000 daltons.

20. The preparation as claimed in claim 15, which has a pH from 6.8 to 7.6.

21. A therapeutic method for the treatment of keratoconjuctivitis sicca or of eye irritations, which comprises instilling in the conjuctival sac of a subject in a need of such treatment a therapeutically effective amount of an ophthalmic preparation as claimed in claim 15.

22. The therapeutic method as claimed in claim 21, wherein eye irritations are those caused by environmental conditions or contact lenses.

23. The therapeutic method as claimed in claim 21, which comprises administering 1-2 drops per eye, from 4 to 8 times a day.

31. A therapeutic method for the treatment of keratoconjuctivitis sicca or of eye irritations, which comprises instilling in the conjuctival sac of a subject in need of such treatment a therapeutically effective amount of an ophthalmic preparation as claimed in claim 15.

32. The therapeutic method as claimed in claim 31, wherein eye irritations are those caused by environmental conditions or contact lenses.

33. The therapeutic method as claimed in claim 31, which comprises administering 1-2 drops per eye, from 4 to 8 times a day.

24. An ophthalmic aqueous preparation for use as artificial tear consisting essentially of at least one hyaluronic acid salt, at a concentration of 0.05 to 2% by weight, as well as the following quantities of ionic species:

40-95 mmol/l of sodium ions, 12-28 mmol/l of potassium ions, 0.4-1,5 mmol/l of calcium ions, 0.4-1.0 mmol/l of magnesium ions, 50-100 mmol/l of chloride ions, 7-20 mmol/l of phosphate ions, 0.7-2.5 mmol/l of citrate ions, and water,

said composition having a viscosity versus shear rate, measured at 32°

C., from 10.0 to 200.0 cps at a shear rate of 2 sec^-1 and from 10 to 5 cps at a shear rate of 1000 sec^-1, and an osmolarity from 140 to 280 mOsm/l.

25. The preparation as claimed in claim 24, for use in the treatment of an eye irritation state selected from the group consisting of dry eye syndrome and of eye irritations.

26. The preparation according to claim 24, wherein the eye irritations are those caused by environmental conditions or contact lenses.

27. The preparation as claimed in claim 24, which has a pH from 6.8 to 7.6.

28. The preparation according to claim 24, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 8,000,000 daltons.

29. The preparation according to claim 24, wherein said hyaluronic acid salt is sodium hyaluronate having molecular weight of 500,000 to 4,000,000 daltons.

30. The preparation according to claim 24, further containing at least one additional ingredient selected from the group consisting of at least 7 mmol/l of acetate ion, at least 5 mmol/l of bicarbonate ion and at least 1 mmol/l of EDTA.