JPS6182759A - Antithrombotic material - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of industrial application] The present invention relates to antithrombotic materials, and more particularly, to antithrombotic materials.
Anti-TFN embolism immobilized with J3 inhibitor biosynthetic enzymes is related to the family.

[i-Rice Technology] When using medical materials such as artificial organs, blood clots caused by contact with dish fluid are one of the major problems. For example, when extracorporeal blood circulation is performed, thrombus forms in surface fluid pops and artificial blood circulation circuits. 7it 1111
It is desired to develop an antithrombotic medical material with good blood compatibility that induces Pi:.

Currently, when using artificial dialysis or heart-lung machines, anticoagulants (such as heparino) are administered, but these have the disadvantage of having side effects.

Recently, the importance of platelets in in vivo thrombus formation has attracted attention. The most obvious reaction in thrombus formation is platelet adhesion. Various antiplatelet agents have been developed to suppress this drying and aggregation. Since conventional medical materials have antithrombotic properties, administration of these drugs has been essential.

[Objective of the Invention 7] An object of the present invention is to provide an anti-futi therapy that does not require the administration of drugs and has sufficient antithrombotic properties on its own.

[Construction of the Invention] The gist of the present invention resides in an antithrombotic material comprising a biosynthetic enzyme for a platelet aggregation inhibitor immobilized in a physiologically acceptable tu form.

The platelet aggregation inhibitor used in the present invention, that is, the biosynthetic enzyme for antiplatelet agents includes all enzymes that biosynthesize antiplatelet agents. Prostacyclin (PG)
It is particularly preferred that the enzyme is a biosynthetic enzyme of prostacyclin (PCI+), since lt) is a particularly potent anti-platelet agent. In addition, PCB can be used as an antiplatelet agent, and its synthetic enzyme may be immobilized.

PCII synthase is contained in bovine aorta microsomes, bovine lung microsomes, human pancreatic band vein microsomes, and the like.

For immobilization, these enzyme-containing substances can be used as they are, or
The enzyme may be separated and purified before use.

Physiologically acceptable carriers are substances that do not have a substantially negative effect on living organisms, such as artificial organs,
Refers to substances that are currently used or will be used in the future as materials for blood pumps or artificial blood circulation circuits, or as coach knob materials for these devices.

Such substances include, for example, polyhydroquinoethyl methacrylate, polyhinyl alcohol, noricone, epochino resin, polystyrene, hinyl chloride, nylon, tetron, cellophane, polyurethane, polytetrafluoroethylene, polyhinylpyroliton, polypropylene, Polyethylene, polyhinyl fluoride, polyisobutyreno, polyhinyl fluoride, polyhinyl chloride, polyethylene terephthalate, polycarna fluoride, polysulfonate, polyethylene naphthalate, polyhinyl formal, polyhinyl butyrate, acrylic resin, nitrocellulose, gelatin , cellulose, acrylamide, collagen, acetal resin, polyester, polyamide, polymethylbenteno, fibrino, polyhinyl acetate, boriamite, polyacrylonitrile, polyhenreimidazole, polyglycolic acid, and other artificial medical polymer materials or natural materials. be able to.

Copolymers consisting of these structural units and bullets of the above materials can be used.

The shape of the carrier may be planar, tubular, particulate, etc. depending on the purpose of use.
It may have a wLa shape or a mesh shape, and its surface may have any shape such as smooth, rough, porous, etc.

As the immobilization method for binding K and the 1-unit, a fixed-lifetime covalent bonding method is preferable. Examples of the coexisting bonding method include an azide bonding method, a noane bromide activation method, a carboimide activation method, an O-alkylation bonding method of an amide group, and the noane bromide activation method is particularly preferred.

1. Effects of the Invention] When the antithrombotic material of the present invention is used, for example, in parts of artificial organs that come into direct contact with blood, such as blood circulation circuits and reactors, it is possible to avoid +lu plugs caused by platelet aggregation, making it safe. Please be careful when administering treatment.

[Example] The present invention will be explained in more detail by giving examples below, or
The present invention is not limited to the examples.

Example I Surfactant Dryde: /
A 10mM linoic acid buffer solution (pH
7,4) 30+7j was added and emulsified using a Teflon (trademark) pomonizer. - Powdered Sepharose 4B activated with noane bromide (Ph
Manufactured by Armacia Fine Chemica1,
Sweden) 300119 (dry form! 2) was added to this emulsion and gently stirred at 4°C for 12-16 hours. The immobilized Sepharose 4B was collected by filtration through a glass filter, and then mixed with 0, 1 M NaHC containing 0.5 M NaC9.
After washing with O3 aqueous solution and 0.1M acetate buffer (pi-14,0) containing 0.5M NaCσ, O,l 45
Tris-HCl buffer containing M NaCQ (ptl 7
, 4) The child was kept inside.

Test Example The antithrombotic properties of anti-thrombotic calyx were evaluated using an Ablibometer (manufactured by Rika Denki Co., Ltd.) against platelet aggregation caused by the aggregating agent ADP or Tronohino.

The bare surface of the rabbit ear vein treated with citric acid was centrifuged at 150 g for 7 minutes to obtain platelet-rich plasma (PrtP). I)
RP, agglutinating substance (ΔDP or Tronch/) and ``bipodally immobilized Cephrose 413'' were placed in the cuvette of an alibometer, and the aggregation rate was measured for the immobilized Sepharose 1[3.

For comparison, the aggregation rate was also measured for only powdered Sepharose 4B, which was not immobilized.

The inhibition rate of aggregation of immobilized Sepharose 4B against Sepharose 4B alone was calculated and shown in Table 1 along with the aggregation rate.

Table 1

Claims (1)

[Scope of Claims] 1. An antithrombotic material comprising a biosynthetic enzyme for a platelet aggregation inhibitor immobilized on a physiologically acceptable carrier. 2. The antithrombotic material according to claim 1, wherein the enzyme is a prostacyclin (PGI_2) synthesizing enzyme.