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1. (WO1996010394) PROCEDE DE LIAISON DE SUBSTANCES DE RECONNAISSANCE A DES LIPOSOMES
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS
I CLAIM:
1. A process for producing bioadhesive liposomes comprising the steps of:
(a) providing a reaction vessel containing a liposome having phosphatidylethanolamine;
(b) admixing a recognizing substance component to the reaction vessel to form a reaction mixture with the liposome;
(c) buffering the reaction mixture;
(d) admixing a crosslinking reagent to the buffered reaction mixture; and,
(e) incubating the buffered reaction mixture and reagent for a period of time sufficient to form the bioadhesive liposomes .

2. The process of Claim 1 wherein the liposome is selected from the group consisting of multilamellar vesicles and unilamellar vesicles.

3. The process of Claim 2 wherein the
unilamellar vesicles include microemulsified liposomes and large unilamellar liposomes.

4. The process of Claim 1 wherein the
recognizing substance component is selected from the group consisting of collagen, gelatin and a growth factor.

5. The process of Claim 4 wherein the growth factor is epidermal growth factor.

6. The process of Claim 4 wherein the growth factor is urogastrone.

7. The process of Claim 1 wherein the
crosslinking reagent is glutaraldehyde .

8. The process of Claim 1 wherein the
crosslinking reagent is a bifunctional oxirane.

9. The process of Claim 1 where in the
crosslinking reagent is ethylene glycol diglycidyl ether.

10. A bioadhesive liposome produced according to the method of Claim 1.

11. A process for creating a bioadhesive liposome formed by covalently bonding a recognizing substance to a liposome creating a bioadhesive liposome comprising the steps of:
(a) providing a reaction vessel
containing a liposome having phosphatidylethanolamine;
(b) admixing a recognizing substance
selected from the group consisting of collagen, gelatin and growth factor to the reaction vessel to form a reaction mixture with the liposome;
(c) buffering the reaction mixture;
(d) admixing a crosslinking reagent to the buffered reaction mixture;
(e) incubating the buffered reaction
mixture and reagent for a period of time sufficient to form the covalent bonding of amine residues of the recognizing substance and liposome to create a
bioadhesive liposome; and,
(f) separating and removing of excess unreacted and noncovalently bound materials from the bioadhesive liposome.

12. The process of Claim 11 wherein the
liposome is selected from the group consisting of
multilamellar vesicles and unilamellar vesicles.

13. The process of Claim 12 wherein the
unilamellar vesicles include microemulsified liposomes and large unilamellar vesicles.

14. The process of Claim 11 wherein the growth factor is epidermal growth factor.

15. The process of Claim 11 wherein the growth factor is urogastrone.

16. The process of Claim 11 wherein the
crosslinking reagent is glutaraldehyde.

17. The process of Claim 11 wherein the
crosslinking reagent is a bifunctional oxirane.

18. The process of Claim 11 where in the crosslinking reagent is ethylene glycol diglycidyl ether.

19. A bioadhesive liposome produced according to the method of Claim 11.

20. A process for covalently bonding a
recognizing substance which is hyaluronic acid to a liposome creating a bioadhesive liposome comprising the steps of:
(a) providing a reaction vessel containing a liposome having phosphatidylethanolamine;
(b) activating the hyaluronic acid by pre-incubation in acidic pH with a crosslinker;

(c) admixing the activated hyaluronic acid to the reaction vessel;
(d) buffering the reaction mixture of the liposome and the activated hyaluronic acid to a basic pH;
(e) incubating the buffered reaction mixture for a period of time sufficient for the bioadhesive liposome to form.

21. The process of Claim 20 wherein the
hyaluronic acid may be activated with a mixture
consisting of DMSO and acetic anyhdride at an acidic pH.

22. A bioadhesive liposome produced from the process of Claim 20.

23. A bioadhesive liposome comprising a
liposome covalently linked to a recognizing substance by a crosslinking reagent.

24. The bioadhesive liposome of Claim 23 wherein the liposome includes phosphatidylethanolamine.

25. The bioadhesive liposome of Claim 23 wherein the liposome is selected from the group
consisting of multilamellar vesicles and unilamellar vesicles including microemulsified liposomes and large unilamellar liposomes.

26. The bioadhesive liposome of Claim 23 wherein the recognizing substance is selected from the group consisting of collagen, gelatin, hyaluronic acid and epidermal growth factor.

27. The bioadhesive liposome of Claim 26 wherein the recognizing substance component is
urogastrone.

28. The bioadhesive liposome of Claim 23 wherein the crosslinking reagent is glutaraldehyde.

29. The bioadhesive liposome of Claim 23 wherein the crosslinking reagent is a bifunctional oxirane.

30. The bioadhesive liposome of Claim 22 wherein the crosslinking reagent is ethylene glycol diglycidyl ether.

31. A bioadhesive liposome designed for the sustained release of a therapeutic substance comprising a liposome component, the theraptic substance encapsulated by the liposome component, and a recognizing substance component bonded to the liposomai surface.

32. The bioadhesive liposome of Claim 31 wherein the recognizing substance component confers to the liposome component target specificity for and
retention at a designated biological target site for release of the therapeutic substance.

33. The bioadhesive liposome of Claim 32 wherein the recognizing substance component confers to the liposome component target specificity for and
retention at the designated biological target site for release of the therapeutic substance from the liposome component without interference from the attachment of the recognizing substance.

34. The bioadhesive liposome of Claim 31 wherein the recognizing substance component is selected from the group consisting of gelatin, collagen, hyaluronic acid and epidermal growth factor.