Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-03-01
2001-02-20
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S078310, C424S078320, C424S078330, C424S078350, C424S078360, C424S078370, C424S078380, C424S406000, C514S055000
Reexamination Certificate
active
06190688
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a material for detoxification or elimination of super antigens such as staphylococcal enterotoxin and streptococcal exotoxin. This material binds with super antigens existing in a protein solution at a high concentration such as in the human blood etc., it is preferably used as an (antidote) medicine for reducing or eliminating toxic activity of super antigens, as in a purification column for eliminating super antigen or as wound dressing material.
DESCRIPTION OF THE RELEVANT ART
Super antigens are a group of proteins which can directly bind with a major histocompatibility antigen class II proteins (hereinbelow it is called “MHC class II” in some cases) on an antigen presentins cell without passing through processing in the antigen presenting cell. Super antigens are different from conventional antigens and furthermore, stimulate a T-cell by forming a complex of this MHC class II and the T cell. Several restrictions exist in binding the T-cell for the conventional antigens, and number of T-cells reacting with conventional antigens is usually at most one per ten thousand, but as the super antigen binds only to the variable region of the &bgr;-chain of the T-cell receptor, certain kinds of super antigens stimulate one T-cell among five T-cells. As the result, it is thought that super antigens stimulate extraordinarily the immune system to generate fevers, rash and hypotension during sepsis and vomiting during food posioning or autoimmune diseases (D. L. Murray et al, American Society of Microbiology News. 61(5) p229 (1995)). As the super antigens, staphylococcal enterotoxin, Streptococcal exotoxin, Yersinial exotoxin, certain virus proteins and heat shock proteins have been confirmed and it is possible that other super antigens will be found in the future.
Up to this time, as those substances which have affinity with these super antigens, antibodies to these super antigens have been described (P. M. Rosten et al. Journal of Clinical Microbiology 25(2) p327 (1987)), major histocompatibility antigen class II proteins and fragments thereof (J. K. Russell et al. Biochemical and Biophysical Research Communications, 168, p696 (1990)), ion exchange resins (H. Igarashi etc., Infection and Immunity 44(1) p175 (1984)) etc., are known and they have been used as binding substances for adsorbing super antigens in blood and culture supernatant. However, most of these binding subtances are proteins and peptides and they are easily deactivated by sterilization. In addition, affinity between ion exchange resins and super antigens is easily reduced by the influence of pH of the solution; specificity is decreased in the neutral region. Therefore, they are not suitable as a material having sufficient affinity for super antigens in solutions having a high protein concentration as blood, foods etc., where the pH should be kept neutral.
OBJECT OF THE INVENTION
The present invention has as its objective, to solve the disadvantages of the conventional technologies by providing a material with excellent selective affinity for super antigens even in a highly concentrated protein solution at a pH in the neutral region, possessing residual activity after sterilization and are also inexpensive. Namely, the material of the present invention has a high affinity for super antigens and it can bind with super antigens existing in body fluids such as blood and urine, foods, drinks and medicines. It is possible by these bindings that the toxin-like activities of the super antigens can be eliminated (detoxification) by changing such properties of the super antigens as their conformations or by shielding the binding sites with MHC class II or/and T-cells. Namely, when the material of the present invention is used as a medicine, it is possible to effectively treat the effects of food poisoning, sepsis and autoimmune diseases or to prevent them from occurring. In addition, if this material is water-insoluble, it becomes possible to eliminate super antigens from body fluids such as blood and urine, foods, drinks and medicines to treat the effects of food poisoning, sepsis and autoimmune diseases and to prevent them from occurring. Especially, it is suitable as a body fluid purifying column for eliminating super antigens or as a super antigen-adsorbing wound dressing material. In addition, it may be used as a quantitative measuring material, making it possible to diagnose food poisoning, sepsis and autoimmune diseases. The present invention provides a material which enables diagnosis and therapy of these diseases and to prevent them from occurring.
SUMMARY OF THE INVENTION
We found that a material containing a urea bond or a thiourea bond has an affinity with staphylococcal enterotoxin and Streptococcal exotoxin. That is, the first aspect of the present invention is a material for eliminating or detoxifying super antigens wherein said material comprises a urea bond or a thiourea bond. The material preferably comprises a group capable of forming a hydrogen bond and an aromatic substituent.
A second aspect of the present invention is a urea or thiourea compound of the following formula:
which compound contains a group capable of forming a hydrogen bond and an aromatic substituent, and
X is O or S;
k is 0 or a positive integer;
each of R
1
, R
2
, R
3
, may be the same or different, is any one of a group capable of forming a hydrogen bond or an aromatic substituent.
Where k≧2, it is preferable that a unit having a group capble of forming a hydrogen bond and a unit having an aromatic substituent are alternatively appeared.
As a group capable of forming a hydrogen bond, an amino group or a hydroxyl group; particularly, a secondary amino group or a tertiary amino group is preferable.
The third aspect of the present invention is a body fluid purifying column comprising the above mentioned material.
The fourth aspect of the present invention is a wound dressing material comprising the above mentioned material.
DETAILED DESCRIPTION OF THE INVENTION
There are no special limitations as the substituent of the urea bond or the thiourea bond and aliphatic compounds such as a hexyl group, octyl group and dodecyl group and alicyclic compounds such as cyclohexane and cyclopentane are used, but aromatic compounds such as a phenyl group, naphthyl group and anthranyl group are more preferably used. In addition, derivatives such derivatives as aminohexyl group, monomethylaminohexyl group, dimethylaminohexyl group, aminooctyl group, aminododecyl group and tolyl group, chlorophenyl group, nitrophenyl group, diphenylmethyl group and aminodiphenylmethyl group are also preferably used. In addition, compounds containing a group capable of forming hydrogen bonds such as amino group, hydroxyl group, carboxyl group and mercapto group are preferably used as substituents. For example, such compounds as having hydroxyl group, hydroxypropane, 1,3-diamino-2-hydroxypropane, hydroxybutanone, hydroxybutyric acid and hydroxypyrimidine and glucides such as monosaccharides, oligosaccharides and polysaccharides such as glucose, glucosamine, galactosamine, maltose, cellobiose, sucrose, agarose, cellulose, chitin, chitosan and derivatives thereof, and such compounds as having amino group, diethylenetriamine, triethylenetetramine, tetraethylepentamine, dipropylenetriamine, polyethyleneimine, N-methyl-2,2′-diaminodiethylamine are preferably used. The material of the present invention can have most preferably both an aromatic compound and a group capable of forming a hydrogen bond such as an amino group or a hydroxyl group-containing compound (including glucides or their derivatives) as substituents of a urea bond or a thiourea bond.
In addition, as either monomers, oligomers or polymers can be used as the material of the present invention, such compounds as polymerized compounds of the above described substituents or a part thereof are also in the range of materials of the present invention. Namely, as the above described substituents or a part thereof, a repeating unit of synthetic polymers such as
Fukuyama Mayumi
Ishikawa Kazuo
Miwa Keishi
Ghaa Isis
Nixon & Vanderhye
Page Thurman K.
Toray Industries Inc.
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