Mono-and disaccharide derivatives

Abstract

The present invention relates to a novel family of monosaccharide derivatives and disaccharide derivatives and to a method of preparation thereof. A mono- and disaccharide derivatives according to the invention comprises at least one fatty acid ester and may further comprise one or more anionic groups and are useful for, inter alia, medical, pharmaceutical, cosmetic and food applications.

1 . A mono- or disaccharide derivative, said derivative having at least one but not more than N−1 fatty acid esters groups, wherein N is the number of hydroxyl groups of the mono- or disaccharide from which the derivative is derived.  
     
     
         2 . A mono- or disaccharide derivative according to  claim 1 , further comprising at least one but no more than N−1 anionic groups, wherein the combined number of fatty acid esters and anionic groups does not exceed N.  
     
     
         3 . A mono- or disaccharide derivative according to  claim 2 , having at least 2, preferably at least 3, but not more than N−1 fatty acid esters groups and at least 1 but no more than N−2, preferably no more than N−3 anionic groups.  
     
     
         4 . Mono- or disaccharide derivative according to  claim 3 , having at least 4, but no more than N−1 fatty acid esters groups and at least 1 but no more than N−3, preferably no more than N−4 anionic groups.  
     
     
         5 . A derivatised monosaccharide according to any of the preceding claims, having at least one anionic group and at least two fatty acid esters, wherein the total sum of anionic groups and fatty acid esters is in the range of 3-5.  
     
     
         6 . A derivatised disaccharide according to any of the claims  1 - 4 , having at least one anionic group, preferably one or four anionic groups, and at least one fatty acid ester, wherein the total sum of anionic groups and fatty acid esters is in the range of 6-9, preferably 7 or 8.  
     
     
         7 . A monosaccharide derivative according to any of the claims  1 - 5 , derived from a pentose with the general formula C 5 H 10 O 5  or a hexose with the general formula C 6 H 12 O 6 .  
     
     
         8 . A monosaccharide derivative according to any of the claims  1 - 5  or  7 , wherein the monosaccharide derivative is derived from a monosaccharide with N being 3 or 4.  
     
     
         9 . A disaccharide derivative according to any of the claims  1 - 4 , or  6 , derived from a disaccharide with the general formula C 12 H 22 O 10 .  
     
     
         10 . A mono- or disaccharide derivative according to any of the preceding claims derived from allolose, altriose, fructose, galactose, glucose, gulose, inositol, mannose, sorbose, saccharose, maltose, lactose, lactulose, arabinose, xylose, ribose, cellobiose, gentiobiose, sucrose, turanose, melibiose.  
     
     
         11 . A mono- or disaccharide derivative according to any of claims  2 - 10 , wherein at least one anionic group is a sulphate ester having the general formula —SO 2 —OR, or a phosphate ester having the general formula —PO 2 —(OR) 2 , wherein R is a monovalent cation.  
     
     
         12 . A mono- or disaccharide derivative according to  claim 14 , wherein any R is independently selected from the group consisting of H+, K +  Na + , Li +  and NH 4   + .  
     
     
         13 . A mono- or disaccharide derivative according to any of the preceding claims, wherein each of the fatty acid ester groups are represented by a general formula of-O—C(═O)—(CH 2 ) x —CH 3 , wherein x is at least 4, by —OC(═O)—(CH 2 ) x —CH═CH—(CH 2 ) y —CH 3 , wherein x+y is at least 4 and preferably not more than 24. —O—(C═O)—(CH 2 ) x —CH═CH—(CH 2 ) y —CH═CH—(CH 2 ) z —CH 3 , wherein x+y+z is between 2 and 20.  
     
     
         14 . A mono- or disaccharide derivative according to  claim 13 , wherein each of the fatty acid ester groups is represented by a general formula of —OC(═O)—(CH 2 ) x —CH 3 , wherein x is between 6 and 14.  
     
     
         15 . A mono- or disaccharide derivative according to  claim 13 , wherein each fatty acid ester group is represented by a general formula of —OC(═O)—(CH 2 ) x —CH 3 , wherein x is 6 or 8 or 10 or 12.  
     
     
         16 . Use of a mono- or disaccharide derivative according to any of the preceding claims as an adjuvant.  
     
     
         17 . Adjuvant formulation comprising a mono- or disaccharide derivative (I) according to any of claims  1 - 15 , a water-immiscible liquid phase (II), an emulsifier or stabilizer (III) and optionally an aqueous phase (IV).  
     
     
         18 . Adjuvant formulation according to  claim 17 , wherein the water-immiscible phase (II) is an oil.  
     
     
         19 . Adjuvant formulation according to  claim 17  or  18 , wherein the water-immiscible phase (II) is squalane, squalene, a mineral oil, a plant oil, hexadecane, a fluorocarbon or a silicon oil.  
     
     
         20 . Adjuvant formulation according to any of the claims  17 - 19 , wherein the emulsifyer or stabilizer (III) 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.  
     
     
         21 . Adjuvant formulation according to any of the claims  17 - 20 , wherein the emulsifier or stabilizer (III) is a mono- or disaccharide derivative, according to any of the claims  1 - 15 .  
     
     
         22 . Adjuvant formulation containing a mono- or disaccharide derivative (I) according to any of the claims  1 - 15 , a water-immiscible solid phase (V) and optionally and an aqueous phase (IV).  
     
     
         23 . Adjuvant formulation according to  claim 22 , wherein the water-immiscible solid phase (V) is an insoluble salt.  
     
     
         24 . Adjuvant formulation according to  claim 23 , wherein the insoluble salt is a aluminum or calcium salt, preferably an aluminum hydroxide, aluminum phosphate, calcium phosphate, silica or a mixture thereof.  
     
     
         25 . A vaccine comprising a mono- or disaccharide derivative of any of the claims  1 - 15  or an adjuvant formulation according to any of the claims  17 - 24 , further comprising an antigenic component.  
     
     
         26 . A process for the preparation of a mono- or disaccharide derivative according to any of the claims  1 - 15 , wherein the monosaccharide or disaccharide is subsequently or simultaneously reacted with acoylchloride and sulphonating agent.  
     
     
         27 . A proces according to  claim 26  wherein the mono- or disaccharide is first reacted with acoylchloride and with sulphonating agent at ambient temperature and subsequently the temperature of a mixture of the mono- or disaccharide, acoylchloride and sulphonating agent is brought to about 50-70° C.  
     
     
         28 . A process according to  claim 26  or  27 , wherein said acoylchloride is hexanoylchloride, octanoylchloride, decanoylchloride, dodecanoylchloride, tetradecanoylchloride, hexadecanoylchloride, octadecanoylchloride, oleoylchloride or a mixture thereof.  
     
     
         29 . A process according to any of the claims  26 - 28 , wherein the sulphonating agent is chosen from the group consisting of gaseous SO 3 , HClSO 3 , SO 3 -pyridine, SO 3 -2-methylpyridine, SO 3 -2,6-dimethylpyridine, SO 3 -dimethylformamide, SO 3 -trimethylamine, SO 3 -triethylamine, SO 3 -dimethylanaline, SO 3 -N-ethylmorpholine, SO 3 -diethylanaline, SO 3 -dioxane or a mixture thereof.  
     
     
         30 . Use of a mono- or disaccharide derivative according to any of the claims  1 - 15  as an emulsifyer.