DD252838A1 - METHOD FOR PRODUCING LATEX ARTICLES WITH ANTICOAGULATIVE DEPOT EFFECT - Google Patents

Abstract

The invention relates to a method for the production of medical latex articles with anticoagulant depot effect on the basis of NK latex and / or synthetic latex, which can find application for prostheses and implantable biomaterials. The process is characterized by a mixture of natural and / or synthetic latex, curatives, fillers, dyes and other blend ingredients to which a molecular sieve-anticoagulant adduct is added prior to vulcanization. Polyanionic compounds are used as anticoagulants.

Description

Field of application of the invention

The invention relates to a process for the preparation of medical latex articles of NK latex and / or synthetic latex types with anticoagulative depot effect, which can be used for prostheses and implantable biomaterials.

Characteristic of the known technical solution

It is known that after artificial replacement of organs in the animal and human body by intramuscular injections anticoagulant drugs are used. In the current state of the art, the production of antithrombotic latex products with substances of different active principles in the mobile phase (blood) takes place.

Current active principles are based on inhibition of blood coagulation (heparin) or dissolution of fibrin clots or deposits via indirect activation of plasminogen to plasmin (streptokinase).

It is known that fibrinolytic or coagulant drugs are used as molecular sieve adduct in the preparation of latex blends based on natural and / or synthetic latexes.

The rubber articles made from these latex mixtures have fibrinolytic or anticoagulative properties which can prevent the formation of thrombi or emboli. As anticoagulants heparin and / or heparinoids and as fibrinolytic streptokinase, urokinase and / or plasmin are used.

The disadvantages of the previous methods are that they do not support the physiological defense mechanism against thrombosis and offer no complex antithrombotic protection. Another disadvantage of a high-dose injection or infusion treatment is the occurrence of reversible thrombocytopenia. In cases of extreme alteration of the coagulation system due to overdose and possible haemorrhagic complications, the injections must be discontinued. Then again, there is the danger of the formation of thrombi, which are a frequent cause of death.

Object of the invention

The aim of the invention is to describe a process for the preparation of latex articles, which allows the production of latex articles with anticoagulant depot effect. After an artificial replacement of the organism in the animal and human body, these latex articles are used to ensure a continuous dosage of anticoagulant drugs in order to prevent the formation of thrombi or emboli.

Explanation of the essence of the invention

The object of the invention is to develop latex products with anticoagulant depot effect, which offer a complex antithrombotic protection when used in the human and animal body over known technical solutions, d. H. based on immediate support of the physiological defense mechanism against thrombi or embolisms.

It has been found that in the manufacture of latex blends based on natural and / or synthetic latex, various fillers, plasticizers, accelerators, sulfur and other blend ingredients by use with supported polyanionic compounds, latex articles having an anticoagulative depot effect and thus can be made prevent the formation of thrombi or emboli.

The molecular sieve / polyanionic compound adduct of the latex blend is added prior to vulcanization and then vulcanized at temperatures of 4O ⁰ C to 8O ⁰ C. The proportion of molecular sieve / polyanionic compound / adduct is 2 to 10% by weight, based on the total mixture, while the proportion of the polyanionic compound in the adduct should be 10 to 50% by mass.

The method described herein incorporates polyanionic compounds whose ahtithrombotic activity is based on activation of the intrinsic fibrinolysis potential of the release of extrinsic plasminogen activator which is synthesized in the intact endothal cell of the blood vessel wall and plays a crucial role in the dissolution of fibrin clots as well as in the inhibition of blood coagulation. The advantage of this method is seen in the dual antithrombotic protective function.

The latex mixtures with molecular sieve / polyanionic compounds adduct (for example mucopolysaccharides, synthetic phenol body polymers, natural humic acids, pentosan polysulphate) allow a targeted selection of substances in order to be able to ensure an increased effectiveness of the antithrombotic protective mechanism. It has been found that the anticoagulant properties of the latex articles are sufficient to prevent the development of thrombosis following artificial replacement of organs (e.g., heart, vessels, endoprostheses) in the animal and human body. In the following, an example explains the solution according to the invention without restricting it.

exemplary

The latex mixtures were produced and processed in a laboratory. All solid components were added to the latex in the form of 50% by weight aqueous dispersions. The dispersions were prepared in laboratory ball mills (meal 2 days). A nonionic surfactant is used as the dispersant

 The phys.-mechan. Vulcanizate parameters were determined according to valid TGL test specifications.

recipe

Component parts by weight

60% NK latex type LAA-TZ 167 50% sulfur dispersion 3.6

20% KOH solution 1.0

OEO ^ oigeZinkdiethylphenyldithiocarbamat-Disp. 1.8

50% zinc oxide dispersion 2.0

50% molecular sieve / polyanionic compound adduct disp. 2.0

Plates were cast and cured at 7O ⁰ C from the compound prepared according to the above recipe mixture.

The biological activity after incubation of the material was measured as follows:

Defined gum slices (10 mm, 0.250 mg) are incubated in 4 ml of human ratitate plasma at 37 ° C and the extent of thrombin time determined as a function of the incubation time.

In each case, 0.2 ml of plasma with O, 2 ml of Tris buffer (0.15 mol / l) and 0.1 ml of thrombin (5W / U / ml) are added from the whole mixture and the time until coagulation is measured (instrument KZM-W "threshold 30 ").

Tab. Biological activity after incubation of o.g. Material in whitewash plasma

incubation period It's on material min Thrombinsat% % 0 100 200 30 100 117 60 100 161 120 100 222 180 100 234 240 100 259

The elastomer material has a marked prolongation of the thrombin time in the plasma. After 4 hours of incubation, the extension of the thrombin time had increased to 257%.

Claims (3)

1. A process for the preparation of latex articles with anticoagulant Depotwirkung containing natural and / or synthetic latex, vulcanizing agents, fillers, dyes and other Mischingingredienzien and where a molecular sieve / anticoagulant adduct is added before vulcanization and the total mixture at temperatures between 40 ⁰ C. and 8O ⁰ C is vulcanized, characterized in that are used as anticoagulants polyanionic compounds. 2. The method according to item 1, characterized in that the proportion of polyanionic compounds in the adduct is 10-50 wt .-%. 3. The method according to points 1 to 2, characterized in that are used as polyanionic compounds mucopolysaccharides, synthetic phenol body polymers, natural humic acids, pentosan polysulfate.