• Archives of Pharmacal Research
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• v.21 no.3
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• pp.248-252
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• 1998

To prolong the biological half-life of streptokinase, a thrombolytic agent, streptokinase-bearing liposome with and distearolyphosphatidyl ethanolamine-N-poly (ethylene glycol) 2000 (DSPEPEG 2000) was prepared and evaluated. Streptokinase-bearing liposomes composed of distearolyphosphatidylcholine (DSPC), cholesterol and cholesterol-3-sulfate with DSPE-PEG 2000 was prepared by the freeze-thawing method and administered via femoral vein to rats (15000 IU/kg). The activity of streptokinase in plasma was determined by the method based on the amidolytic activity of streptokinase-plasminogen complex. Pharmacokinetic parameters of streptokinase incorporated in liposomes were compared with those of streptokinase alone. The $T_{1/2}$ and $AUC_\infty$ streptokinase incorporated in DSPC-PEG liposome increased 16.3- and 6.1-fold, respectively, compared with those of streptokinase alone. Streptokinase-bearing long-circulating liposome could increase the circulation time of streptokinase in blood and expect longer thrombolytic activity compared with streptokinase alone.

• Microbiology and Biotechnology Letters
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• v.31 no.3
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• pp.307-310
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• 2003

A gene encoding streptodornase(sdc) from Streptococcus equisimilis H46A was expressed in S. equisimilis H64H sdc under the control of the streptokinase gene promoter. Secretion of the streptodornase was directed by the signal sequences of streptokinase or streptodornase. The expressed streptodornase activity from S. equisimilis H46A sdc transformant with streptokinase promoter - streptodornase coding sequence fusion vector was 2.3 fold higher than that from wild type. Construct of signal sequence region replaced by streptokinase ones was similarly expressed as a wild type. But constructs of skc or lrp core regions of streptokinase promoter streptodornase fusion were similarly expressed as in sdc mutant. In conclusion, improved expression of streptodornase by use of streptokinase promoter required the full length of promoter.

• Journal of Pharmaceutical Investigation
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• v.29 no.3
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• pp.211-216
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• 1999

To evaluate the thrombolytic activity of streptokinase-dextran conjugate, a rat model of arterial thrombosis was used. Briefly, the femoral artery was exposed and a filter paper saturated with 70% $FeCl_3$ solution was placed around the femoral artery in order to stop the blood flow. Six minutes after the stop of the blood flow in the femoral artery, streptokinase $(10000{\sim}30000\;units\;per\;rat)$ or streptokinase-dextran conjugate $(5000{\sim}17000\;units\;per\;rat)$ was administered by i.v. bolus injection through the femoral vein. Then the blood flow in the femoral artery was monitored using a Doppler laser flow meter. The i.v. bolus administration of streptokinase could not restore the blood flow in the femoral artery in the dose range of $10000{\sim}30000$ units per rat. The i.v. bolus administration of streptokinase-dextran conjugate could restore the blood flow in the femoral artery in the dose range of $5000{\sim}17000$ units per rat. A good correlation between the dose of streptokinase-dextran conjugate and the total thrombolytic effect was observed. In addition, the lag time between the injection of streptokinase-dextran conjugate and the restoring of the blood flow was decreased as the i.v. dose of streptokinase dextran conjugate increased. These results show the superior beneficial effect of streptokinase-dextran conjugate compared with the unconjugated streptokinase with respect to the elongation of thrombolytic activity, the administration method (single injection versus continuous infusion), and the reduced dose necessary for a equivalent thrombolytic effect.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.13-19
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• 2000

$Stealth^{\circledR}$ liposomes entrapped with streptokinase were prepared to improve the physical stability of conventional liposomes. The particle size distribution, dissolution rate and entrapping efficiency of the $Stealth^{\circledR}$ liposomes were studied. The entrapping efficiency of streptokinase into conventional liposomes was proportional to the total lipid and cholesterol amounts. In $Stealth^{\circledR}$ liposomes, the entrapping efficiency of streptokinase was increased with the increase of DPPE-PEG(5,000) amount. The particle size of $Stealth^{\circledR}$ liposomes decreased with the increase of DPPE-PEG(5,000) amount. The dissolution rate of streptokinase from conventional liposomes was decreased by addition of cholesterol. The dissolution rate of streptokinase from the $Stealth^{\circledR}$ liposomes was also decreased by addition of DPPE-PEG(5,000).

• Journal of Microbiology and Biotechnology
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• v.7 no.2
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• pp.101-106
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• 1997

Strain improvement for the enhanced production of streptokinase and streptodornase in Streptococcus sp. ATCC 12449 was performed. Strain UB111, a hyperproductive mutant which was isolated by use of nitrosoguanidine and selection of colonies with large clear zones on DNase test agar plates supplemented with $1{\%}$ glucose and $0.5{\%}$ ammonium chloride, produced about 3 fold more streptokinase and streptodornase than the wild type when tested in shake flask fermentations. The enhanced production of both streptokinase and streptodornase was achieved by cultivating the mutant in a pH-controlled fermentor containing fermentation medium enriched with yeast extract ($2.1{\%}$). Under these conditions, the mutant produced 7300 units/ml of streptokinase and 800 units/ml of streptodornase.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.5
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• pp.326-331
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• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.

• Journal of Microbiology and Biotechnology
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• v.20 no.1
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• pp.132-137
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• 2010

The skc gene encoding streptokinase (SK) with a molecular mass of approximately 47.4 kDa was cloned from Streptococcus equisimilis ATCC 9542 and heterologously overexpressed in Streptomyces lividans TK24 and E. coli using various strong promoters. When the promoter for sprT [Streptomyces griseus trypsin (SGT)] was used in the host S. lividans TK24, a 47.4-kDa protein was detected along with a smaller hydrolyzed protein (44 kDa), suggesting that posttranslational hydrolysis had occurred as has been reported in other expression systems. The casein/plasminogen plate assay revealed that the plasmid construct containing the SGT signal peptide was superior to that containing the SK signal peptide in terms of SK production. Maximal production of SK was calculated to be about 0.25 unit/ml of culture broth, a value that was five times higher than that obtained with other expression systems using ermE and tipA promoters in the same host. When the skc gene was expressed in E. coli BL21(${\Delta}DE3$)pLys under the control of the T7 promoter, a relatively large amount of SK was expressed in soluble form without hydrolysis. SK activity in E. coli/pET28a-$T7_pSK_m$ was more than 2 units/ml of culture broth, even though about half of the expressed protein formed an inactive inclusion body.

• Journal of Chest Surgery
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• v.27 no.10
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• pp.858-861
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• 1994

Prosthetic valve thrombosis is rare but it is one of fatal complication after heart valve surgery. Improvements of the valve design and the material have decreased the frequency of thrombosis but have not eliminated completely. And some cases of prosthetic valve thrombosis during pregnancy were reported inspite of adequate anticoagulation therapy.Urgent surgical intervention is indicated for prosthetic valve thrombosis but it is associated with high operative risk, therefore medical thrombolytic therapy such as urokinase or streptokinase therapy is regarded as an alternative therapy. This is a case report of the successful thrombolytic therapy for valve thrombosis in a pregnant patient after mechanical mitral valve replacement.

• Tuberculosis and Respiratory Diseases
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• v.55 no.3
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• pp.297-302
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• 2003

Background : Airway obstruction due to blood clot occurs unusually but in a variety of clinical settings. Initial efforts for removal of the endobronchial blood clot involve flexible bronchoscopic evaluation with saline lavage and suctioning and then forceps extraction. If unsuccessful, further options include rigid bronchoscopy, Fogarty catheter dislogement of the clot, and topical thrombolytic agents. The several successful uses of endobronchial streptokinase or urokinase to dissolve an endobronchial blood clot have been previously reported, but not yet in Korea. Herein we describe a 51-year old man with superior vena cava thrombosis secondary to Behcet's disease who experienced life threatening airway obstruction after hemoptysis due to a large organized blood clot in left main bronchus. Urokinase(260,000 U), injected through a fiberoptic bronchoscope, totally dissolved the clot. No complications occurred.

• Journal of Pharmaceutical Investigation
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• v.8 no.1
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• pp.1-5
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• 1978

Drug interaction of a new antibiotic, methampicillin lysinate (MAL) with nine drugs were investigated using four species of gram positive and gram negative bacteria. The experimental results were as follows: 1. MIC of MAL were found to be decreased against E. coil when combined with mefenamic acid, probenecid, aluminium hydroxide gel or corticosteroids. The other drugs did not affect MIC of MAL against the same bacteria. 2. MIC of MAL were found to be increased against Staphylococcus aureus ATCC 6538-P, 9441 when combined with mefenamic acid, aluminum hydroxide gel or dexamethasone acetate. The other drugs did not affect MIC of MAL against the same bacteria. 3. MIC of MAL were found to be increased against Shigella dysenteriae when either of the nine drugs was combined. 4. MIC of MAL were found to be increased approximately 2.5 times when combined with Streptokinase-Streptodornase or hydrocortisone and to be decreased approximately 2 times when combined with probenecid or dexamethasone against Salmonella typhi(type 2). It seems the other drugs do not affect the MIC of MAL against the same bacteria.