United States Patent:  6,013,634

Assignee:  Synsorb Biotech, Inc. (Calgary, CA)

Filed:  April 2, 1998

Disclosed are novel solid support matrices having a toxin-binding oligosaccharide covalently attached to a solid support through a linking arm which has at least 5 atoms separating the oligosaccharide from the solid support. The disclosed solid support matrices are useful for neutralizing toxins from disease-causing microorganisms.

SUMMARY OF THE INVENTION

This invention provides for novel solid support matrices which are useful for diagnosing or neutralizing various toxins from disease-causing microorganisms. The solid support matrices of this invention are characterized both by the relative ease of synthesis and the broad range of linking arms which can be prepared.

Accordingly, in one of its composition aspects, this invention is directed to a solid support matrix represented by the formula: 

wherein SS is a solid support; R¹ is selected from the group consisting of a covalent bond and a hydrocarbylene group having from 1 to about 20 carbon atoms;

R² is a hydrocarbylene group of from 2 to 20 carbon atoms;

each X' is independently selected from the group consisting of --O-- and >NR⁴ wherein each R⁴ is independently selected from hydrogen, --R² NH₂ or --R² NR³ Z wherein R² is as defined above;

R³ is selected from the group consisting of hydrogen and --C(O)R⁵ wherein R⁵ is selected from the group consisting of hydrogen and hydrocarbyl of from 1 to 20 carbon atoms;

W is selected from oxygen or sulfur;

X is selected from the group consisting of --NH--, --O-- and --S--;

Y is selected from the group consisting of --NH--, --O-- and --S--;

Z is toxin-binding oligosaccharide;

p is an integer of from 0 to 50 or more; and

n is an integer such that the matrix has a loading level of the toxin-binding oligosaccharide of from about 0.001 to about 2000 .mu.mols per gram of solid support

wherein the total number of atoms in separating the solid support from the toxin-binding oligosaccharide is at least 5.

Particularly preferred matrices of this invention include those where X and Y are NH, W is oxygen, p is 0 and R² is an alkylene group of from 4 to 10 carbon atoms. Such preferred matrices are represented by the formula: 

wherein SS, R¹, R³, Z and n are as defined above and R⁶ is an alkylene group of from 4 to 10 carbon atoms.

In another aspect, the invention provides a pharmaceutical composition useful for in vivo treatment of a toxin-mediated disease in a mammal, which composition comprises a solid support matrix described above and a pharmaceutically acceptable carrier suitable for oral administration, wherein the matrix is capable of being eliminated from the gastrointestinal tract.

Claim 1 of 10 Claims

1. A solid support matrix of the formula:

wherein SS is a solid support; R¹ is selected from the group consisting of a covalent bond and a hydrocarbylene group having from 1 to about 20 carbon atoms;

R² is a hydrocarbylene group of from 2 to 20 carbon atoms;

each X' is independently selected from the group consisting of --O-- and >NR⁴ wherein each R⁴ is independently selected from hydrogen, R² NH₂ or R² NR³ Z wherein R² is as defined above;

R³ is selected from the group consisting of hydrogen and --C(O)R⁵ wherein R⁵ is selected from the group consisting of hydrogen and hydrocarbyl of from 1 to 20 carbon atoms;

W is selected from oxygen or sulfur;

X is selected from the group consisting of --NH--, --O-- and --S--;

Y is selected from the group consisting of --NH--, --O-- and --S--;

Z is toxin-binding oligosacchlaride;

p is an integer from 0 to 50; and

n is an integer such that the matrix has a loading level of the toxin-binding oligosaccharide of from about 0.001 to about 2000 .mu.moles per grain of solid support

wherein the total number of atoms separating the solid support from the toxin-binding, oligosaccharide is at least 6.

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