Mono- and disaccharide derivatives
The present invention includes a formulation comprising a physiological salt solution, or an oil-in-water emulsion, or a water immiscible solid phase, and an adjuvant comprising one or more disaccharide derivatives derived from cellobiose, gentiobiose, lactose, lactulose, maltose, melibiose, sucrose or turanose, wherein at least four of the free hydroxyl groups of the disaccharide molecule have been modified such that the disaccharide derivative has: (i) at least 3, but not more than N-1, fatty acid ester groups, wherein each of the fatty acid ester groups is represented by a general formula of —O—C(═O)—(CH 2 ) x CH 3 wherein x is between 6 and 14, and (ii) at least one, but no more than N-1 anionic groups, wherein N is the number of hydroxyl groups of the disaccharide from which the derivative is derived and wherein the combined number of fatty acid esters and anionic groups does not exceed N.
1. An adjuvant formulation comprising a physiological salt solution, or an oil-in-water emulsion, or a water immiscible solid phase, and optionally an aqueous phase, and comprising, as an adjuvant, one or more disaccharide derivatives of formula:
wherein
(i) at least 3, but not more than N-1, of the groups R are represented by: —C(═O)—(CH 2 ) x CH 3 — groups, wherein x is between 6 and 14, and
(ii) at least one, but no more than N-1, of the groups R are anionic —SO 2 —OR 1 groups, wherein R 1 is a monovalent cation,
wherein N is the number of groups R of the disaccharide derivative and wherein the combined number of —C(═O)—(CH 2 ) x CH 3 groups and anionic —SO 2 —OR 1 groups does not exceed N and the remaining groups R are hydrogen.
2. An adjuvant formulation according to claim 1 , wherein said disaccharide derivative has no more than N-2, or no more than N-3, anionic —SO 2 —OR 1 groups.
3. An adjuvant formulation according to claim 1 , wherein said disaccharide derivative has at least 4, but no more than N-1, —C(═O)—(CH 2 ) x CH 3 groups and no more than N-3, or no more than N-4, anionic SO 2 —OR 1 groups.
4. An adjuvant formulation according to claim 1 , wherein said disaccharide derivative has two, three or four anionic —SO 2 —OR 1 groups, and at least three —C(═O)—(CH 2 ) x CH 3 groups, wherein the total sum of anionic —SO 2 —OR 1 groups and —C(═O)—(CH 2 ) x CH 3 groups is in the range of 6 or 7.
5. An adjuvant formulation according to claim 1 , wherein the monovalent cation is independently selected from the group consisting of H + , K + Na + , Li + and NH 4 + .
6. An adjuvant formulation according to claim 1 which comprises an oil in water emulsion, wherein said oil-in-water emulsion comprises a water-immiscible liquid phase which is squalane, a mineral oil, a plant oil, hexadecane, a fluorocarbon or a silicon oil.
7. An adjuvant formulation according to claim 1 , further comprising an emulsifier or stabilizer.
8. An adjuvant formulation according to claim 7 , wherein the emulsifier or stabilizer is a non-ionic detergent with a hydrophilic-lipophilic balance value of more than 10, a sugar fatty acid ester, or an anionic detergent with a hydrophilic-lipophilic balance value of more than 10.
9. An adjuvant formulation according to claim 7 , wherein the emulsifier or stabilizer is a disaccharide derivative.
10. An adjuvant formulation according to claim 1 , wherein the water immiscible solid phase is an insoluble salt.
11. An adjuvant formulation according to claim 10 , wherein the insoluble salt is an aluminum or calcium salt, preferably an aluminum hydroxide, aluminum phosphate, calcium phosphate, silica or a mixture thereof.
12. A vaccine comprising an adjuvant formulation according to claim 1 , said vaccine further comprising an antigenic component.