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1. (WO1993016719) UTILISATION DU FACTEUR DE CROISSANCE D'ORIGINE PLAQUETTAIRE DANS LA CICATRISATION DE LESIONS OPHTALMIQUES
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

We claim :

1. A method of accelerating corneal wound healing in a mammal comprising:
(a) providing an ophthalmically compatible solution of platelet-derived growth factor; and
(b) applying the solution to the cornea of a mammal at the time of or subsequent to occurrence of a corneal wound in a quantity sufficient to accelerate clinically detectable healing, the healing being
accelerated through proliferation of epithelial cells and/or keratocytes of the cornea stimulated by
application of the platelet-derived growth factor to the cornea.

2. The method of claim 1 wherein the
platelet-derived growth factor is selected from the' group consisting of the AA isoform, the AB isoform, the BB isoform, and mixtures thereof.

3. The method of claim 2 wherein the
platelet-derived growth factor is the BB isoform.

4. The method of claim 1 wherein the
concentration of platelet-derived growth factor in the solution is from about 10 μg/ml to about 1000 μg/ml.

5. The method of claim 4 wherein the
concentration of platelet-derived growth factor in the solution is from about 50 μg/ml to about 500 μg/ml.

6. The method of claim 5 wherein the
concentration of platelet-derived growth factor in the solution is about 100 μg/ml.

7. The method of claim 1 wherein the platelet-derived growth factor is a recombinantly-derived refolded B-chain homodimer of 119 amino acids, having the amino acid sequence of S-L-G-S-L-T-I-A-E-P-A-M-I-A-E-C-K-T-R-T-E-V-F-E-I-S-R-R-L-I-D-R-T-N-A-N-F-L-V-W-P-P-C-V-E-V-Q-R-C-S-G-C-C-N-N-R-N-V-Q-C-R-P-T-Q-V-Q-L-R-P-V-Q-V-R-K-I-E-I-V-R-K-K-P-I-F-K-K-A-T-V-T-L-E-D-H-L-A-C-K-C-E-T-V-A-A-A-R-P-V-T-R-S-P-G-G-S-Q-E-Q-R.

8. The method of claim 1 wherein the solution is applied once or more to the cornea subsequent to occurrence of the corneal wound.

9. The method of claim 8 wherein the solution is applied from once to three times to the cornea.

10. The method of claim 9 wherein the solution is applied at about 2 hours, at about 8 hours, and at about.24 hours after occurrence of the wound.

11. The method of claim 1 wherein the solution is applied once or more to the cornea at the time of occurrence of the corneal wound.

12. The method of claim 1 wherein the wound results from the effects of a surgical laser.

13. The method of claim 1 wherein the wound is a consequence of diabetes.

14. A method of improving the quality of wound healing of- the corneal epithelium in a mammal comprising:
(a) providing an ophthalmically compatible solution of platelet-derived growth factor; and
(b) applying the solution to the cornea of a mammal at the time of or subsequent to occurrence of a corneal wound in a quantity sufficient to improve the quality of corneal wound healing.

15. The method of claim 14 wherein the
improvement in the quality of corneal wound healing comprises at least one of a clinically detectable
decrease in epithelial sloughing and a clinically
detectable decrease in scar formation.

16. The method of claim 14 wherein the
platelet-derived growth factor is selected from the group, consisting of the AA isoform, the AB isoform, the BB isoform, and mixtures thereof.

17. The method of claim 16 wherein the
platelet-derived growth factor is the BB isoform.

18. The method of claim 14 wherein the
platelet-derived growth factor is a recombinantly-derived refolded B-chain homodimer of .119 amino acids, having the amino acid sequence of S-L-G-S-L-T-I-A-E-P-A-M-I-A-E-C-K-T-R-T-E-V-F-E-I-S-R-R-L-I-D-R-T-N-A-N-F-L-V-W-P-P-C-V-E-V-Q-R-C-S-G-C-C-N-N-R-N-V-Q-C-R-P-T-Q-V-Q-L-R-P-V-Q-V-R-K-I-E-I-V-R-K-K-P-I-F-K-K-A-T-V-T-L-E-D-H-L-A-C-K-C-E-T-V-A-A-A-R-P-V-T-R-S-P-G-G-S-Q-E-Q-R.

19. A method of accelerating clinically
detectable re-innervation of the corneal epithelium after occurrence of a corneal wound that denervates at least a portion of the corneal epithelium in a mammal comprising:
(a) providing an ophthalmically compatible solution of platelet-derived growth factor; and
(b) applying the solution to the cornea of a mammal at the time of or subsequent to occurrence of a corneal wound that denervates at least a portion of the corneal epithelium in a quantity sufficient to accelerate clinically detectable re-innervation of the corneal epithelium.

20. The method of claim 19 wherein the
platelet-derived growth factor is selected from the group consisting of the AA isoform, the AB isoform, the BB isoform, and mixtures thereof.

21. The method of claim 20 wherein the
platelet-derived growth factor is the BB isoform.

22. The method of claim 14 wherein the
platelet-derived growth factor is a recombinantly-derived refolded B-chain homodimer of 119 amino acids , having the amino acid sequence of S-L-G-S-L-T-I-A-E-P-A-M-I-A-E-C-K-T_R»T_E_v_F_E_I_s_R-_R_L_I_D_R_T_N_A_N_F_L_v_w_p_p_c_v^

V-Q-R-C-S-G-C-C-N-N-R-N-V-Q-C-R-P-T-Q-V-Q-L-R-P-V-Q-V-R-K-I-E-I-V-R-K-K-P-I-F-K-K-A-T-V-T-L-E-D-H-L-A-C-K-C-E-T-V-A-A-A-R-P-V-T-R-S-P-G-G-S-Q-E-Q-R.

23. A pharmaceutical composition for
application to the cornea of a mammal for accelerating corneal wound healing comprising:
(a) water;
(b) an ophthalmically" compatible solution of platelet-derived growth factor comprising at least about 10 μg/ml of platelet-derived growth factor; and
(b) buffer to adjust the pH to within a range of from about 5 to about 8.

24. The composition of claim 23 wherein the platelet-derived growth factor is selected from the group consisting of the AA isoform, the AB isoform, the BB isoform, and mixtures thereof.

25. The composition of claim 24 wherein the platelet-derived growth factor is the BB isoform.

26. The composition of claim 24 wherein the concentration of platelet-derived growth factor in the solution is from about 10 μg/ml to about 1000 μg/ml.

27. The composition of claim 26 wherein the concentration of platelet-derived growth factor in the solution is from about 50 μg/ml to about 500 μg/ml.

28. The composition of claim 27 wherein the concentration of platelet-derived growth factor in the solution is about 100 μg/ml.

29. The composition of claim 23 wherein the platelet-derived growth factor is a recombinantly-derived refolded B-chain homodimer of 119 amino acids, having the amino acid sequence of S-L-G-S-L-T-I-A-E-P-A-M-I-A-E-C-K-T-R-T-E-V-F-E-I-S-R-R-L-I-D-R-T-N-A-N-F-L-V-W-P-P-C-V-E-V-Q-R-C-S-G-C-C-N-N-R-N-V-Q-C-R-P-T-Q-V-Q-L-R-P-V-Q-V-R-K-I-E-I-V-R-K-K-P-I-F-K-K-A-T-V-T-L-E-D-H-L-A-C-K-C-E-T-V-A-A-A-R-P-V-T-R-S-P-G-G-S-Q-E-Q-R.

30. The composition of claim 23 wherein the composition is in dosage unit form.

31. A tablet for preparation of a
pharmaceutical composition for application to the cornea of a mammal for accelerating corneal wound healing comprising:
(a) a quantity of platelet-derived growth factor sufficient to accelerate wound healing; and
(b) non-toxic ophthalmically-acceptable excipients which are suitable for the manufacture of tablets.

32. The tablet of claim 31 wherein the platelet-derived growth factor is in the BB isoform.