Liquid purification or separation – Processes – Ion exchange or selective sorption
Reexamination Certificate
1999-10-19
2001-11-13
Cintins, Ivars (Department: 1724)
Liquid purification or separation
Processes
Ion exchange or selective sorption
C210S691000
Reexamination Certificate
active
06315907
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an adsorbent for toxic shock syndrome toxin 1, a method for removing the toxin by adsorption, an adsorber comprising the adsorbent packed, and use of the adsorbent.
BACKGROUND ART
The toxic shock syndrome toxin 1 (hereinafter referred to as “TSST-1”) is an exotoxin composed of a soluble protein having a molecular weight of about 20-30 kDa produced by
Staphylococcus aureus,
and is a representative superantigen.
Sepsis refers to a state that an infection exists somewhere in a body, whereby a systemic inflammatory response has occurred. If this inflammatory symptom accelerates, a shock symptom (septic shock) occurs, and organopathy (organ failure) occurs, further falling into such a grave state as multi-organ failures. The source of that infection is mainly bacteria, and the bacteria is roughly classified into Gram-positive bacteria and Gram-negative bacteria.
If infected with
Staphylococcus aureus
which is a sort of Gram-positive bacteria, TSST-1 produced by the infecting
Staphylococcus aureus
propagates and activates T-cells to cause sepsis. Recently, infection with methicillin resistant
Staphylococcus aureus
(MRSA) and septic shock accompanied thereby attract attention as an important prophlogistic bacteria of nosocomial infection and have come a large social problem for the last several years (Tomoyuki Kawamata et al., Intensive & Critical Care Medicine, Vol. 7, page 631, 1995).
On the other hand, if infected with Gram-negative bacteria, endotoxin present in the cell wall of the bacteria enters into blood to cause sepsis. Further, in recent years, it is reported that since TSST-1 activates immune system as a superantigen to enhance the toxicity of endotoxin to several thousands times, sepsis is caused even by the presence of such a low concentration of endotoxin that cannot clinically cause sepsis. Thus, in case of mixed infection with both Gram-positive bacteria and Gram-negative bacteria, a possibility of causing sepsis becomes very high.
Antibiotics as a countermeasure for infection and &ggr;-globulin to activate the resistance to infection have been used for the treatment of sepsis, but the mortality is still high. For the reason, it has been desired from the medical point of view to remove TSST-1 and endotoxin which become a cause of sepsis from body fluids.
As to endotoxin, adsorbents to remove it from body fluids are known. For example, Japanese Patent Publication Kokoku No. 1-16389 discloses an adsorbent wherein polymyxin known as an antidote to endotoxin is immobilized on a suitable carrier. Also, the present inventors disclose in Japanese Patent Publication Kokai No. 8-173803 that endotoxin can be adsorbed by a sulfo group-introduced styrene-divinyl benzene copolymer. These adsorbents are expected to produce a fairly large effect against infection with Gram-negative bacteria. However, in case that both TSST-1 and endotoxin coexist as a result of mixed infection with Gram-positive bacteria and Gram-negative bacteria, the effect lowers. Further, in case that a person is infected with only Gram-positive bacteria and TSST-1 enters a body fluid, no effect is expected. Various adsorbents for endotoxin are known, but no adsorbent for TSST-1 has been known. Thus, development of adsorbent for TSST-1 has been strongly desired.
An object of the present invention is to provide an adsorbent capable of efficiently removing TSST-1 present in body fluids, a method and an adsorber for removing TSST-1 in body fluids by adsorption with the adsorbent, and use of the adsorbent.
DISCLOSURE OF INVENTION
The present inventors made an intensive study on adsorbents capable of efficiently removing TSST-1 present in body fluids. As a result, the present inventors have found that an adsorbent comprising a water-insoluble carrier and a compound having a log P value of at least 2.50 immobilized on the carrier can efficiently adsorb and remove TSST-1 present in body fluids, thus they have accomplished the present invention.
That is to say, the present invention relates to (1) an adsorbent for TSST-1 comprising a water-insoble carrier and a compound having a log P value of at least 2.50 wherein P is a partition coefficient in an octanol-water system, the compound being immobilized on the carrier.
Further, the present invention relates to (2) the adsorbent mentioned in (1), wherein the water-insoluble carrier is a water-insoluble porous carrier.
Further, the present invention relates to (3) the adsorbent mentioned in (2), wherein the water-insoluble carrier has an exclusion limit for globular protein of from 1×10
4
to 60×10
4
.
Further, the present invention relates to (4) a method for removing TSST-1 in body fluid, characterized by bringing a body fluid containing TSST-1 into contact with the adsorbent mentioned in (1).
Further, the present invention relates to (5) an adsorber for TSST-1 comprising a container having an inlet and an outlet for a body fluid and a means for preventing an adsorbent from flowing out of the container, and the adsorbent mentioned in (1) which is packed in the container.
Further, the present invention relates to (6) use of an adsorbent comprising a water-insoluble carrier and a compound having a log P value of at least 2.50 and immobilized on the carrier, wherein P is a partition coefficient in an octanol-water system, for the manufacture of an adsorbent for toxic shock syndrome toxin-1.
REFERENCES:
patent: 4814077 (1989-03-01), Furuyoshi et al.
patent: 5279821 (1994-01-01), Hirayama et al.
patent: 5919898 (1999-07-01), Nakatani et al.
patent: 0 247 592 A2 (1987-12-01), None
patent: 0 723 794 A1 (1996-07-01), None
patent: 0 743 067 A2 (1996-11-01), None
patent: 5-253479 (1993-10-01), None
Patric M. et al., “Identification and Characterization of an Exotoxin fromStafpylococcus aureusAssociated with Toxic-shock Syndrome,”,The Journal of Infection Diseases, vol. 143 (No. 4), pp. 509-516 (1981).
Igarashi H. et al., “Purification and Characterization ofStafpylococcus aureusFRI1169 and 587 Toxic Shock Syndrome Exotoxins”,Infection and Immunity, vol. 44 (No. 1), pp. 175-181 (1984).
European Search Report dated Feb. 4, 2000.
Asahi Takashi
Hirai Fumiyasu
Maruyama Hiroyuki
Ogino Eiji
Sakogawa Takayuki
Armstrong Westerman Hattori McLeland & Naughton LLP
Cintins Ivars
Kaneka Corporation
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