| 摘要 |
<p>#CMT# #/CMT# An oil-in-water adjuvant emulsion comprises squalene, an aqueous solvent, a polyoxyethylene alkyl ether hydrophilic nonionic surfactant, and a hydrophobic nonionic surfactant. The emulsion is thermoreversible and 90% of the population by volume of the oil drops has a size less than 200 nm. #CMT# : #/CMT# Independent claims are also included for the following: (1) preparing an immunogenic composition comprises mixing at least one vaccine antigen with an oil-in-water emulsion, where the oil-in-water emulsion is obtained by a phase-inversion temperature process; and (2) an immunogenic composition comprising an antigen and the emulsion. #CMT#ACTIVITY : #/CMT# Immunostimulant; Virucide; Anti-HIV. #CMT#MECHANISM OF ACTION : #/CMT# Vaccine. A composition (C1) comprising: trans-acting transcription factor protein (20 mu g), squalene (5 mg), dehymuls SMO (0.75), eumulgin B1 (0.94) and mannitol (0.91 mg) was prepared. The composition (C1) was then evaluated for efficacy of immunogenicity against AIDS. Two groups of six 8-week-old female BALB/c mice were injected subcutaneously with the composition (C1) prepared, in a proportion of one dose of 200 mu l/mouse; and the injections were given on day zero and days 21. Blood samples were taken from the retro orbital sinus on days 14 in order to assess the primary response and on days 34 for the secondary response and the specific immunoglobulin 1 (IgG1) and immunoglobulin 2a (IgG2a) were determined. It was observed that the composition (C1) increased, overall, humoral response and promotes the type 1 T-helper response since the IgG2a response was increased more than the IgG1 response. #CMT#USE : #/CMT# The emulsion is useful in immunogenic composition (claimed) for viral antigen e.g. AIDS, cytomegalovirus infections and flu. #CMT#ADVANTAGE : #/CMT# The composition exhibits no sign of toxicity; provides a very large advantage from an industrial point of view; provides all the guarantees of safety and of profitability necessary for the pharmaceutical industry; is very effective even at a very low dose of antigens; allows a greater induction of antibodies; and effectively increases the immunogenicity of the flu antigens. #CMT#ORGANIC CHEMISTRY : #/CMT# Preferred Composition: The emulsion further comprises at least one alditol; alkylpolyglycoside; and cryoprotective agent. The composition comprises (%): squalene (5 - 45), polyoxyethylene alkyl ether surfactant (0.9 - 9), hydrophobic nonionic surfactant (0.7 - 7). The adjuvant emulsion comprises (%): squalene (32.5), polyoxyethylene(12) cetostearyl ether (6.18), sorbitan monooleate (4.82), and mannitol (6). In the emulsion, 90% of the population by volume of the oil drops has a size less than 160 (preferably less than 90) nm. Preferred Components: The polyoxyethylene alkyl ether is of formula CH 3-(CH 2) x-(O-CH 2-CH 2) n-OH. n : 10 - 60; and x : 11 - 17. The hydrophobic nonionic surfactant is a sorbitan ester or mannide ester surfactant. The polyoxyethylene alkyl ether surfactant is polyoxyethylene(12) cetostearyl ether. The alditol is glycerol, erythritol, xylitol, sorbitol or mannitol. The hydrophobic nonionic surfactant is sorbitan monooleate. Preferred Method: The oil-in-water emulsion is prepared by cooling a water-in-oil inverse emulsion. The water-in-oil inverse emulsion is obtained by mixing squalene, an aqueous solvent, a polyoxyethylene alkyl ether hydrophilic nonionic surfactant, and a hydrophobic nonionic surfactant to obtain a coarse oil-in-water emulsion, and then this emulsion is heated to at least the phase inversion temperature in order to obtain the inverse emulsion. The water-in-oil inverse emulsion is prepared by separately heating the aqueous phase comprising the aqueous solvent and the polyoxyethylene alkyl ether nonionic surfactant and the oily phase comprising the squalene and the hydrophobic surfactant, and mixing the pre-heated aqueous and oily phases. The aqueous and oily phases are heated, separately, to a temperature below the phase inversion temperature of the emulsion, the two phases are mixed to obtain an oil-in-water emulsion; the oil-in-water emulsion obtained is then heated to a temperature at least equal to the phase inversion temperature in order to obtain a water-in-oil inverse emulsion. The phase inversion temperature is 45 - 80 (preferably 50 - 65)[deg]C. The process involves at least one lyophilization step. #CMT#ADMINISTRATION : #/CMT# The composition is administered intramuscularly, subcutaneously, intradermally or by nasal spray. No dosage details given. #CMT#EXAMPLE : #/CMT# A composition comprising (%): squalene (32.5), polyethylene cetostearyl ether (6.18), sorbitan monooleate (4.82) and mannitol (6) was prepared.</p> |
