Claims
- 1. A polysaccharide conjugate consisting essentially of:
(i) a polysaccharide having a minimum of seven saccharides and which is selected from the group consisting of β-glucans, mannans, pectic polysaccharides and 2-acetamido glucan polysaccharides; and (ii) one or more molecules having an aldehyde or ketone group; wherein said one or more molecules are the same or different, and are selected from the group consisting of aryl aldehydes, aryl ketones, heteroaryl ketones, and heteroaryl aldehydes; wherein polysaccharide (i) is attached to molecules (ii) through (iii) a direct covalent bond or covalently via a bifunctional linker in a manner that keeps the aldehyde or ketone group intact.
- 2. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group are bound to said polysaccharide via a direct covalent bond.
- 3. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group are bound to said polysaccharide via a residue of a bifunctional linker molecule.
- 4. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group are selected from the group consisting of mono- and di-substituted C6-10 arylaldehydes, C6-10 aryl(C1-4)alkylaldehydes, and mixtures thereof.
- 5. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group are phenyl or naphthyl substituted by a formyl or formyl(C1-4)alkyl substituent.
- 6. The polysaccharide conjugate of claim 5, wherein said substituted phenyl or napthyl molecules contain one or two additional substituents independently selected from the group consisting of halo, hydroxy, C1-4 alkyl, C1-4 alkoxy, trifluoromethyl, and benzyloxy.
- 7. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group are benzaldehyde or naphthaldehyde, substituted by one or two of hydroxy and halo.
- 8. The polysaccharide conjugate of claim 7, wherein said molecules having an aldehyde or ketone group is benzaldehyde.
- 9. The polysaccharide conjugate of claim 8, wherein said polysaccharide is a pectic polysaccharide or mannan.
- 10. The polysaccharide conjugate of claim 1, wherein said molecules having an aldehyde or ketone group is 3-carboxybenzaldehyde or 4-carboxybenzaldehyde.
- 11. The polysaccharide conjugate of claim 10, wherein said polysaccharide is a β-glucan.
- 12. The polysaccharide conjugate of claim 1, wherein said molecule having an aldehyde or ketone group is selected from the group consisting of 2,3-, 2,4-2,5-, and 3,4-dihydroxybenzaldehyde, 5-chloro-2-hydroxybenzaldehyde, vanillin, ethyl vanillin, naringenin, 3- and 4-hydroxybenzaldehyde, or 4-hydroxyphenylacetaldehyde; hydroxy substituted C1-4alkyl (C6-10)aryl ketones, and hydroxy substituted aryl ketones; 2-hydroxyacetophenone, 3-hydroxyacetophenone, 4-hydroxyacetophenone, and 6-hydroxy-1,2-naphthoquinone; thiophene, furan, benzothiophene, benzofuran, pyridine, quinoline, pyridazine, pyrimidine, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, isoxazole, or oxazole, each having a keto, formyl or formyl(C1-4) substituent, and optionally including an additional halo or hydroxy substituent, if these can be accommodated by available ring carbon atoms; pyridoxal, 2-thiophenecarboxaldehyde, and 3-thiophenecarboxaldehyde.
- 13. The polysaccharide conjugate of claim 1, wherein said residue of a bifunctional linker molecule is selected from the group consisting of:
H2N—(CH2)r—NH2, where r is from 2 to 12; HO—(CH2)r—NH2, where r is from 2 to 12; HS—(CH2)r—NH2, where r is from 2 to 12; amino acids that are optionally carboxy-protected; and H—(O—CH2-CH2)n—OH, where n is 1-4; ethylenediamine, 1,4-butanediamine, spermidine, 2,4-diaminobutyric acid, lysine, β-alanine, γ-aminobutyric acid, dialanine, trialanine, 3,3′-diaminodipropylamine, diaminopropionic acid, N-(2-aminoethyl)-1,3-propanediamine, and 2-(4-aminophenyl)ethylamine; —NH—(CH2)r—NH—, where r is from 2-5, —O—(CH2)r—NH—, where r is from 2-5, —NH—CH2—C(O)—, —O—CH2—CH2—O—CH2—CH2—O—, —NH—NH—C(O)—CH2—, —NH—C(CH3)2—C(O)—, —S—CH2)r—C(O)—, where r is from 1-5, —S—(CH2)r—NH—, where r is from 2-5, —S—(CH2)r—O—, where r is from 1-5, —S—(CH2)—CH(NH2)—C(O)—, —S—(CH2)—CH(COOH)—NH—, —O—CH2—CH(OH)—CH2—S—CH(CO2H)—NH—, —O—CH2—CH(OH)—CH2—S—CH(NH2)—C(O)—, —O—CH2—CH(OH)—CH2—S—CH2—CH2—NH—, —S—CH2—C(O)—NH—CH2—CH2—NH—, and —NH—O—C(O)—CH2—CH2—O—P(O2H)—.
- 14. The polysaccharide conjugate of claim 1, wherein said polysaccharide is selected from the group consisting of: β-glucans, mannans, pectic polysaccharides, chitin and its derivatives, murein, bacterial fructans, xanthans, bacterial heteropolysaccharides, flngal pullulan, and esters, sulfonates, sulfates, phosphates; ethers, and cross-linked derivatives thereof.
- 15. The polysaccharide conjugate of claim 1, wherein said polysaccharide is a β-glucan having a backbone chain of (1→3)-linked β-D-glucopyranosyl units and which has β-D-glucopyranosyl units attached by (1→6) linkages, and a molecular weight of between 5,000 to 500,000, and wherein said β-glucan is optionally modified by the addition of one or more anionic, cationic or non-ionic groups.
- 16. The polysaccharide conjugate of claim 1, wherein said polysaccharide is a β-mannan comprising (1→4) polymannose having a terminus reducing mannosyl residue, or the acetylation product thereof.
- 17. The polysaccharide conjugate of claim 1, wherein said polysaccharide is a pectic polysaccharide selected from the group consisting of homogalacturonans, rhamnogalacturonans, arabans, galactans, and arabinogalactans, and wherein said pectic polysaccharide possesses immunopotentiating activity.
- 18. A pharmaceutical composition comprising,
a polysaccharide conjugate of claim 1, and a pharmaceutically acceptable carrier or diluent.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application Ser. No. 10/114,465, filed Apr. 3, 2002, which is a divisional of U.S. patent application Ser. No. 09/165,310, filed Oct. 2, 1998, which application claims the benefit of earlier filed U.S. provisional patent application No. 60/060,768, filed Oct. 3, 1997, the contents of which are fully incorporated by reference herein.
Provisional Applications (1)
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Number |
Date |
Country |
|
60060786 |
Oct 1997 |
US |
Divisions (2)
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Number |
Date |
Country |
Parent |
10114465 |
Apr 2002 |
US |
Child |
10859577 |
Jun 2004 |
US |
Parent |
09165310 |
Oct 1998 |
US |
Child |
10114465 |
Apr 2002 |
US |