Japan Chemical Research Co., Ltd.

Jcr Pharmaceuticals Co., Ltd.

Koichiro Nakanishi

Hajime Hiratani

Yoshikazu Yuki

Kazuo Kato

Hiroshi Matsumoto

Masaichi Ota

Satoshi Nishimuro

There are provided thrombolytic agents suited for oral administration. The agent comprises a proteolytic enzyme of subtilisin family, such as subtilisin BPN', subtilisin Carsberg, subtilisin amylosacchariticus, etc., produced by microorganisms belonging to genus Bacillus, such as Bacillus subtilis, Bacillus licheniformis, Bacillus amyloliquefaciens, etc. and, even when administered orally, exhibits thrombolytic activity.

Subtilisin as an oral thrombolytic agent

The thermal degradation of urokinase in an aqueous solution is suppressed by heating an aqueous solution containing urokinase in the presence of citric acid or a water-soluble salt thereof such as sodium, potassium or lithium citrate at about 60.degree. C. for about 10 hours.

Method of suppressing the thermal degradation of urokinase

Two components, trypsin and kallidinogenase, in human urine are concentrated simultaneously by allowing human urine at neutral pH, collecting bubbles thus formed to obtain the concentrate of the two components, adjusting the concentrate to weak acidity, contacting the acidified concentrate with chitosan to allow the two components to be adsorbed onto chitosan, eluting the components from the adsorbent with aqueous ammonia solution, and neutralizing and heating the eluate at about 60.degree. C. for about 10 hours to make the eluate virus-free, followed by separating the components from the eluate.

Process for concentrating and separating trypsin inhibitor and

Human urinary kallikrein is concentrated and purified by the following procedures; (a) Human urine is contacted with chitosan, a high molecular agglutinant obtained from chitin, at a pH from 4.0 to 7.0, thereby kallikrein is adsorbed on the chitosan and (b) kallikrein is eluted from the chitosan with an aqueous alkaline solution having a pH from 8.0 to 12.0.

Process for concentrating and purifying human urinary kallikrein

Human urine kallikrein dissolved in water is made heat-stable by the addition of a citric acid salt such as sodium citrate, so that an aqueous solution containing the kallikrein and the citric acid salt can be sterilized at 60.degree. to 70.degree. C.

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Ashiya, Japan

Koichiro Nakanishi