Disclosed are antimicrobial vaccines comprising oligosaccharide β-(1.fwdarw.6)-glucosamine groups.

The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

The invention relates to carbohydrate ligands and moieties, respectively, mimicking glycoepitopes comprised by glycosphingolipids of the nervous system, particularly glycoepitopes comprised by glycosphingolipids of the cerebroside, the globoside-, the ganglioside- and the sulfoglucuronyl paragloboside type, which are bound by anti-glycan antibodies associated with neurological diseases. The invention further relates to the use of these carbohydrate ligands/moieties, in diagnosis as well as for the treatment of neurological diseases associated with anti-glycan antibodies. In particular, the invention relates to compounds of formula (I) and (II) and to therapeutically acceptable polymers comprising a multitude of these compounds, including polymers with loading of one compound of formula (I) or (II) or combinations of several compounds of formula (I), and/or (II). The compounds of formula (I) are defined as: ##STR00001##
wherein
R.sup.I1 is Z or ##STR00002##
wherein
R.sup.I2 is H, SO.sub.3H, or ##STR00003## ##STR00004##
wherein
R.sup.I3 is H or ##STR00005##
wherein
R.sup.I4 is H or ##STR00006##
wherein
R.sup.I5 and R.sup.I6 are independently H or ##STR00007##
wherein
R.sup.I7 is H or ##STR00008##
and compounds of formula (II) are defined as: ##STR00009##
wherein
R.sup.II1 is Z or ##STR00010##
wherein
R.sup.II2 is Z or ##STR00011##
wherein Z is —N(R.sup.a)—A—B—CH.sub.2—(CH.sub.2).sub.q—SH, wherein
R.sup.a is H, C.sub.1-C.sub.4-alky, C.sub.1-C.sub.4alkoxy, CH.sub.2C.sub.6H.sub.5, CH.sub.2CH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, or OCH.sub.2CH.sub.2C.sub.6H.sub.5;
A is C.sub.1-C.sub.7-alkylene, C.sub.1-C.sub.7-alkoxy, C.sub.1-C.sub.4-alkyl—(OCH.sub.2CH.sub.2).sub.pO—C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.7-alkoxy-R.sup.b, wherein R.sup.b is an optionally substituted aryl or an optionally substituted heteroaryl, and wherein p is 0 to 6, preferably p is 1, 2 or 3, and further preferably p is 1;
B is NHC(O), S or CH.sub.2;
q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

The invention relates to carbohydrate ligands and moieties, respectively, mimicking glycoepitopes comprised by glycosphingolipids of the nervous system, particularly glycoepitopes comprised by glycosphingolipids of the cerebroside, the globoside-, the ganglioside- and the sulfoglucuronyl paragloboside type, which are bound by anti-glycan antibodies associated with neurological diseases. The invention further relates to the use of these carbohydrate ligands/moieties, in diagnosis as well as for the treatment of neurological diseases associated with anti-glycan antibodies. In particular, the invention relates to compounds of formula (I) and (II) and to therapeutically acceptable polymers comprising a multitude of these compounds, including polymers with loading of one compound of formula (I) or (II) or combinations of several compounds of formula (I), and/or (II). The compounds of formula (I) are defined as: ##STR00001##
wherein
R.sup.I1 is Z or ##STR00002##
wherein
R.sup.I2 is H, SO.sub.3H, or ##STR00003## ##STR00004##
wherein
R.sup.I3 is H or ##STR00005##
wherein
R.sup.I4 is H or ##STR00006##
wherein
R.sup.I5 and R.sup.I6 are independently H or ##STR00007##
wherein
R.sup.I7 is H or ##STR00008##
and compounds of formula (II) are defined as: ##STR00009##
wherein
R.sup.II1 is Z or ##STR00010##
wherein
R.sup.II2 is Z or ##STR00011##
wherein Z is —N(R.sup.a)—A—B—CH.sub.2—(CH.sub.2).sub.q—SH, wherein
R.sup.a is H, C.sub.1-C.sub.4-alky, C.sub.1-C.sub.4alkoxy, CH.sub.2C.sub.6H.sub.5, CH.sub.2CH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, or OCH.sub.2CH.sub.2C.sub.6H.sub.5;
A is C.sub.1-C.sub.7-alkylene, C.sub.1-C.sub.7-alkoxy, C.sub.1-C.sub.4-alkyl—(OCH.sub.2CH.sub.2).sub.pO—C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.7-alkoxy-R.sup.b, wherein R.sup.b is an optionally substituted aryl or an optionally substituted heteroaryl, and wherein p is 0 to 6, preferably p is 1, 2 or 3, and further preferably p is 1;
B is NHC(O), S or CH.sub.2;
q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a dithiolsaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

The present invention provides a chitooligosaccharide-N-geraniol derivative and a preparation method and application thereof. The degree of substitution of a chitooligosaccharide-N-geraniol derivative is from 0.26 to 0.283. The method includes dissolving oligosaccharide in dimethyl sulfoxide, dissolving geranyl bromide in dimethylformamide, and then mixing, performing a water bath reaction and adding acetone in after the water bath reaction, performing a centrifugation and collecting precipitates, performing Soxhlet extraction and vacuum drying to obtain the chitooligosaccharide-N-geraniol derivative. The present invention has the advantages of easy preparation method, low cost, simple purification method and stable properties. The chitooligosaccharide derivative has good water solubility, antibacterial activity against Staphylococcus aureus, Escherichia coli and other bacteria, and has good application prospect in the fields of medicine, food, cosmetics, agriculture, etc.

The present invention provides a chitooligosaccharide-N-geraniol derivative and a preparation method and application thereof. The degree of substitution of a chitooligosaccharide-N-geraniol derivative is from 0.26 to 0.283. The method includes dissolving oligosaccharide in dimethyl sulfoxide, dissolving geranyl bromide in dimethylformamide, and then mixing, performing a water bath reaction and adding acetone in after the water bath reaction, performing a centrifugation and collecting precipitates, performing Soxhlet extraction and vacuum drying to obtain the chitooligosaccharide-N-geraniol derivative. The present invention has the advantages of easy preparation method, low cost, simple purification method and stable properties. The chitooligosaccharide derivative has good water solubility, antibacterial activity against Staphylococcus aureus, Escherichia coli and other bacteria, and has good application prospect in the fields of medicine, food, cosmetics, agriculture, etc.