Mucosal administration of substances to mammals

• US 6,096,291 A
• Filed: 12/27/1996
• Issued: 08/01/2000
• Est. Priority Date: 12/27/1996
• Status: Expired due to Fees

• Current Assignee: Biovector Therapeutics S.A.
• Original Assignee: Biovector Therapeutics S.A.
• Inventors: de Miguel, Ignacio, Kravtzoff, Roger, Betbeder, Didier, Major, Michel, Etienne, Alain
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US08/774,920
• Time in Patent Office: 1,313 Days
• Field of Search: 424/1.11, 424/1.53, 424/1.65, 424/1.69, 424/1.73, 424/9.1, 424/9.2, 424/184.1, 424/201.1, 424/204.1, 424/450
• US Class Current: 424/1.69
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/783 Organic host/matrix, e.g. lipid
• CPC Class Codes: Y10S 977/788 Of specified organic or carbon-based composition
• CPC Class Codes: Y10S 977/795 Composed of biological material
• CPC Class Codes: Y10S 977/798 having internalized material
• CPC Class Codes: Y10S 977/80 Nucleic acid, e.g. DNA or RNA
• CPC Class Codes: Y10S 977/801 Drug
• CPC Class Codes: Y10S 977/83 Inorganic core or cluster coated with organic or biological shell
• CPC Class Codes: Y10S 977/917 Vaccine

Abstract

A novel method for the mucosal administration of a substance to a mammal is provided. The method comprises contacting a mucosal surface of the mammal with the substance in combination with a Biovector. The Biovector has a core that comprises a natural polymer, or a derivative or a hydrolysate of a natural polymer, or a mixture thereof. A preferred natural polymer is a polysaccharide or an oligosaccharide. The core is optionally coated with an amphiphilic compound, such as a lipid.

Claims

1. A method for the mucosal administration of a vaccine against a pathogen to a mammal, the method comprising contacting a mucosal surface of the mammal with an antigen in combination with a Biovector core, wherein the Biovector core comprises a natural polymer, or a derivative or a hydrolysate of a natural polymer, or a mixture thereof, and wherein the core is uncoated, or is partially or completely coated with no more than one layer, the layer comprising a lipid compound covalently bonded to the core, or an amphiphilic compound.

2. The method of claim 1, wherein the natural polymer is selected from the group consisting of a cross-linked polysaccharide, a cross-linked oligosaccharide, a derivative or hydrolysate of a cross-linked polysaccharidec or a cross-linked oligosaccharide, and a mixture thereof.

3. The method of claim 2, wherein the cross-linked polysaccharide and cross-linked oligosaccharide are selected from the group consisting of starch, dextran, dextrin, and maltodextrin.

4. The method of claim 2, wherein 0 to 2 milliequivalents of ionic charge per gram is grafted to the cross-linked polysaccharide or cross-linked oligosaccharide.

5. The method of claim 4, wherein the ionic charge is a positive charge.

6. The method of claim 5, wherein the positive charge is due to the presence of a cationic or basic group selected from the group consisting of a quaternary ammonium group, a primary amine, a secondary amine, and a tertiary amine.

7. The method of claim 5, wherein the positive charge is due to the presence of a quaternary ammonium group.

8. The method of claim 5, wherein the positive charge is due to the presence of a ligand selected from the group consisting of choline, 2-hydroxypropyltrimethylammonium, 2-dimethylaminoethanol, 2-diethylarninoethanol, 2-dimethylaminoethylamine, and 2-diethylaminoethylamine and an amino acid.

9. The method of claim 4, wherein the ionic charge is a negative charge.

10. The method of claim 9, wherein the negative charge is due to the presence of a an anionic or acidic group selected from phosphate, a sulfate, and carboxylate.

11. The method of claim 9, wherein the negative charge is due to the presence of a phosphate group.

12. The method of claim 2, wherein the cross-linked polysaccharide or cross-linked oligosaccharide is coated partially or completely with a layer of an amphiphilic compound.

13. The method of claim 12 wherein the amphiphilic compound is a phospholipid or a ceramide.

14. The method of claim 13 wherein the phospholipid is selectcd from the group consisting of phosphatidyl choline, phosphatidyl hydroxycholine, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl glycerol.

15. The method of claim 1, wherein the diameter of the Biovector is 20-200 nm.

16. The method of claim 1, wherein the diameter of the Biovector is 20-100 nm.

17. The method of claim 1, wherein the cross-linked polysaccharide or cross-linked oligosaccharide binds non-specifically to the mucosal surface.

18. The method of claim 1 wherein the Biovector is dispersed.

19. The method of claim 1, wherein the Biovector is dried.

20. The method of claim 19, wherein the dried Biovector is resuspended.

21. The method of claim 1, wherein the pathogen is selected from the group consisting of a virus, a bacterium, a yeast, and a fungus.

22. The method of claim 21, wherein the virus is selected from the group consisting of an influenza virus, a cytomegalovirus, HIV, a papilloma virus, a respiratory syncytial virus, a poliomyelitis virus, a pox virus, a measles virus, an arbor virus, a Coxsackie virus, a herpes virus, a hantavirus, a hepatitis virus, a lyme disease virus, a mumps virus, and a rotavirus.

23. The method of claim 22, wherein the virus is an influenza virus.

24. The method of claim 22, wherein the virus is HIV.

25. The method of claim 21, wherein the bacterium is selected from the group consisting of a member of the genus Neisseria, Aerobacter, Pseudomonas, Porphyromonas, Salmonella, Escherichia, Pasteurella, Shigella, Bacillus, Helibacter, Corynebacterium, Clostridium, Mycobacterium, Yersinia, Staphylococcus;

Bordetelia, Brucelia, Vibrio, and Streptococcus.

26. The method of claim 21, wherein the pathogen is a member of a genus selected from the group consisting of Plasmodium, Schisostoma, and Candida.

27. The method of claim 1, wherein the antigen is a biological molecule.

28. The method of claim 27, wherein the biological molecule is selected from the group consisting of an amino acid, an oligopeptide, a peptide, a protein, a glycoprotein, and a lipoprotein.

29. The method of claim 1, wherein more than one antigen is administered in combination with the Biovector.

30. The method of claim 2, wherein the antigen is located in the inner core of the cross-linked polysaccharide or cross-linked oligosaccharide.

31. The method of claim 2, wherein the antigen is located at the outer surface of the cross-linked polysaccharide or cross-linked oligosaccharide.

32. The method of claim 12, wherein the antigen is located in the inner core of the amphiphilic compound layer.

33. The method of claim 12, wherein the antigen is located at the outer surface of the layer.

34. The method of claim 1, wherein the antigen is added to the Biovector prior to administration to the mammal.

35. The method of claim 1, wherein the antigen and the Biovector are mixed together at the time of administration to the mammal.

36. The method of claim 1, wherein the mucosal surface is selected from the group consisting of a nasal, buccal, oral, vaginal, ocular, auditory, pulmonary tract, urethral, digestive tract, and rectal surface.

37. The method of claim 36, wherein the mucosal surface is selected from the group consisting of a nasal, vaginal, and ocular surface.