Emulsified composition for dilution and cancer vaccine composition
View Patent ↗Provided is an emulsified composition for diluting a cancer antigen peptide or a dimer thereof. Also provided is a novel cancer vaccine composition or specific CTL inducer that efficiently induces CTL irrespective of the type of cancer antigen peptide when mixing the emulsified composition for dilution and a water phase comprising a cancer antigen peptide or a dimer thereof. The present invention relates to an emulsified composition for diluting a cancer antigen peptide or a dimer thereof, comprising a particular ester, a particular surfactant, a particular emulsifier, and a water phase. The present invention also relates to a cancer vaccine composition or specific CTL inducer obtained by freshly diluting and mixing a water phase comprising a cancer antigen peptide or a dimer thereof with the emulsified composition for dilution.
1. An emulsified composition for diluting a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof, comprising:
(A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C) 1 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D) 5 to 20% by weight water.
2. An emulsified composition for diluting a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof, comprising:
(A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D) 5 to 20% by weight water,
wherein the average particle diameter of the dispersion phase of the emulsified composition for dilution is 50 to 500 nm.
3. The emulsified composition for dilution of claim 2 , wherein the fatty acid of (A) is oleic acid, myristic acid or 2-ethylhexanoic acid.
4. The emulsified composition for dilution of claim 2 , wherein the ester of (A) is ethyl oleate, octyldodecyl myristate or cetyl 2-ethylhexanoate.
5. The emulsified composition for dilution of claim 2 , wherein the hydroxy fatty acid triglyceride of (B) is castor oil or hardened castor oil.
6. A method of preparing a cancer vaccine composition, comprising diluting 0.25 to 1 part by volume of a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof with 1 part by volume of an emulsified composition for dilution comprising (A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C., (B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide, (C) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and (D) 5 to 20% by weight water.
7. A method of preparing a cancer vaccine composition, comprising diluting 0.25 to 1 part by volume of a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof with 1 part by volume of the emulsified composition for dilution of claim 2 .
8. The emulsified composition for dilution of claim 2 , wherein the nonionic surfactant of (B) consists of a hydroxy fatty acid triglyceride adduct with 10 to 20 mol of ethylene oxide.
9. The emulsified composition for dilution of claim 2 , comprising the emulsifier of (C) at 1 to 20% by weight.
10. A cancer vaccine composition comprising:
(A) 30 to 80% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the solidification point of the ester being not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C) 1 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C.,
(D) 10 to 60% by weight water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof,
wherein the composition is a W/O emulsion.
11. The cancer vaccine composition of claim 10 , comprising
(A′) 40 to 60% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the solidification point of the ester being not more than 10° C.,
(B′) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C′) 5.0 to 10.0% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D′) 30 to 50% by weight water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof.
12. The cancer vaccine composition of claim 10 obtained by diluting 0.25 to 1 part by volume of a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof with 1 part by volume of an emulsified composition for dilution, wherein the emulsified composition comprises:
(A′) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B′) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C′) 1 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D′) 5 to 20% by weight water.
13. A method of inducing a cancer antigen-specific cytotoxic T cell comprising administering to a subject a cancer vaccine composition comprising:
(A) 30 to 80% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the solidification point of the ester being not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride with 5 to 20 mol of ethylene oxide added thereto,
(C) 1 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D) 10 to 60% by weight water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof,
wherein the composition is a W/O emulsion.
14. The method of claim 13 , wherein the composition comprises
(A′) 40 to 60% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the solidification point of the ester being not more than 10° C.,
(B′) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C′) 5.0 to 10.0% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D′) 30 to 50% by weight water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof.
15. The method of claim 13 , wherein the cancer vaccine composition is obtained by diluting 0.25 to 1 part by volume of a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof with 1 part by volume of an emulsified composition for dilution, wherein the emulsified composition comprises:
(A′) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B′) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C′) 1 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D′) 5 to 20% by weight water.
16. The method of claim 15 , wherein the average particle diameter of the dispersion phase of the emulsified composition for dilution is 50 to 500 nm.
17. A kit for freshly preparing a cancer vaccine composition, comprising a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof, and an emulsified composition for dilution for diluting the water phase, wherein the emulsified composition for dilution comprises (A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C., (B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide, (C) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and (D) 5 to 20% by weight water.
18. An emulsified composition for diluting a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof, consisting essentially of:
(A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D) 5 to 20% by weight water,
wherein the average particle diameter of the dispersion phase of the emulsified composition for dilution is 50 to 500 nm.
19. An emulsified composition for diluting a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof, consisting of:
(A) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D) 5 to 20% by weight water,
wherein the average particle diameter of the dispersion phase of the emulsified composition for dilution is 50 to 500 nm.
20. A cancer vaccine composition obtained by diluting 0.25 to 1 part by volume of a water phase comprising a cancer antigen peptide having 8 to 12 amino acids or a dimer thereof with 1 part by volume of an emulsified composition for dilution,
wherein the emulsified composition comprises:
(A′) 50 to 90% by weight ester of a fatty acid having 8 to 22 carbon atoms and an alcohol having 2 to 24 carbon atoms, the ester having a solidification point of not more than 10° C.,
(B′) 0.5 to 20% by weight nonionic surfactant consisting of a hydroxy fatty acid triglyceride adduct with 5 to 20 mol of ethylene oxide,
(C′) 0 to 20% by weight emulsifier that is a partial ester of a polyhydric alcohol and a fatty acid, the partial ester being liquid at 40° C., and
(D′) 5 to 20% by weight water, and
wherein the average particle diameter of the dispersion phase of the emulsified composition for dilution is 50 to 500 nm.