• 대한수의학회지
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• 제44권3호
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• pp.469-473
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• 2004

This study was performed to investigate the effects of calcium administration on the blood coagulation mechanism through APTT in the calf. Five male calves (70~90 kg) were used in this experiment. In the control group, heparinized normal saline (1 IU/kg/min) had been infusing into the jugular vein for 100 minutes. For the analysis of calcium effects on the APTT, the same solutions had been infusing during the first 40 minutes, subsequently the solution including calcium gluconate (3.3 mg/ml/min) had been infusing for 60 minutes. Blood samples were serially collected every 10 minutes for the APTT and platelets count and every 20 minutes for the calicum level during the infusion. In the calcium-treated group, after 70 minutes the APTT ratio (APTT heparin/APTT baseline) was higher than the therapeutic range. APTT was significantly increased at 50, 60 and 70 minutes in the calcium-treated group as compared to the control group (p<0.01). In the control group, calcium level was decreased significantly after heparin infusion (p<0.01). The platelet count was gradually decreased without significant variation in the both control and calcium-treated groups. These results suggested that APTT is slightly increased in combined heparin and calcium administration.

• Archives of Pharmacal Research
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• 제25권1호
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• pp.86-92
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• 2002

The enhancement of paracellular transport of heparin disaccharide using several absorption enhancers across Caco-2 cell monolayers was tested . The cytotoxicity of these enhancers was also examined. The enhancing effects by Quillaja saponin, diponin glycyrrhizinate, $18{\beta}-glycyrrhetinic$ acid, sodium caprate and taurine were determined by changes in transepithelial electrical resistance (TEER) and the amount of heparin disaccharide transported across Caco-2 cell monolayers. Among the absorption enhancers, $18{\beta}-glycyrrhetinic$ acid arid taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity. Our results indicate that these absorption enhancers can widen the tight junction, which is a dominant paracellular absorption route of hydrophilic compounds . It is highly possible that these absorption enhancers can be applied as pharmaceutical excipients to improve the transport of macromolecules and hydrophilic drugs having difficulty in permeability across the intestinal epithelium.

• Bulletin of the Korean Chemical Society
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• 제30권12호
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• pp.3034-3038
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• 2009

A simple, rapid, practical and sensitive spectofluorimetric method was developed for the determination of trace amount of heparin (Hep). Under the Optimum conditions, we studied the interaction between NFLX-Ce$^{3+}$-Hep complex by using absorption and fluorescence spectra. It was observed that Hep remarkably enhance the fluorescence intensity of the NFLX-Ce$^{3+}$ complex at ${\lambda}$= 356 nm in the buffer solution of pH = 7.60 and the enhancement effect is shown to relate with the concentration of Hep. The linear range and detection limit for the determination of Hep was obtained. By the Rosenthal graphic method, the association constant (K) and binding numbers (N) of Hep with probe were investigated. This method is relatively free of interference from coexisting substances and successfully applied for the determination of heparin in heparin sodium injection samples. A suitable mechanism of fluorescence enhancement between NFLX-Ce$^{3+}$ and the NFLX-Ce$^{3+}$-Hep systems were proposed and discussed.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.576-580
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• 1998

When glycosaminoglycan (GAG)-degrating enzymes were measured in normal human stool suspensions, all 5 tested different stools degraded titrable heparin and acharan sulfate. GAG-degrading bacteria were screened from the isolates of human stools. Among them, HJ-15 had the most potent activities of heparinases (GAGs-degrading enzymes). However, HJ-15 produced the enzyme even if in the media without heparin. Acharan sulfate lyase was induced by acharan sulfate and heparin. Heparinase production was also induced by these GAGs. These enzymes, acharan sulfate lyase and heparinase, were produced in exponential and stationary phase of HJ-15 growth, respectively. Optimal pHs of the acharan sulfate lyase and heparinase activities were 7.2 and 7.5 respectively. the biochemical properties of HJ-15 was similar to those of B. stercoris. However, difference from B. stercoris was utilization of raffinose. this HJ-15 also degraded chondroitin sulfates A and C.

• Journal of Chest Surgery
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• 제35권6호
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• pp.475-478
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• 2002

42세 남자환자가 내원 3개월전부터의 호흡곤란, 복부팽만 및 식욕부진으로 내원하였다. 이학적 검사상 심잡음이 청진되어 심초음파를 시행한 결과, 좌심방 혈전을 동반한 승모판협착증 및 삼첨판폐쇄부전이 진단되어 수술전 헤파린 지속 주입을 시작하였다. 내원 11일째 혈소판수치가 감소하여 시행한 항체검사 및 혈소판응괴능 검사에서 음성이 나왔지만 임상적으로 헤파린 기인성 혈소판감소증을 진단하였다. 수술중 심폐우회술시 헤파린 대체약물인 히루딘(hirudin)을 사용하였으며, ACT, aPTT를 측정하며 수술대에서 육안적으로 혈전형성여부를 확인함으로써 성공적으로 수술을 하였다, 수술 중 및 수술 후 헤파린 접촉은 없었으며, 수술 후 과다 출혈 및 전신적 혈전색전증 등의 합병증은 발생하지 않았다.

• 보건의료기술평가
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• 제6권2호
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• pp.133-141
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• 2018

Objectives: In the past, the pharmaceutical drug heparin was mostly used as the anticoagulant for continuous renal replacement therapy (CRRT), but the duration time is long to have the risk of a bleeding adverse effect, and in that case the drug therapy Nafamostat mesilate was utilized instead, as it is more safe in this case, with a short half-life and is increasing in use to permit lower concerns for bleeding incidents. However, there are insufficient number of large-scale studies on the comparison of Nafamostat mesilate and heparin. Methods: In this study, a systematic review are used to compare the bleeding risk of Nafamostat mesilate and Heparin, as subjected to patients and procedures for measuring risks performed with a CRRT, and the filter life span is to be evaluated as well in this patients. Results: As a result of literature review search, a total of 6 studies were included in systematic review. The reducing risk of bleeding and filter life span was analyzed. The retrospective cohort studies confirm that Nafamostat mesilate is less at risk of bleeding than heparin. And a cohort study confirms that Nafamostat mesilate is longer filter lifespan than heparin and randomized controlled trial studies show that Nafamostat mesilate is longer filter lifespan than not using the anticoagulants. Conclusion: Nafamostat mesilate is considered to be a good therapeutic option because it has a longer filter life span as well as the advantage of reducing bleeding.

• Journal of Chest Surgery
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• 제31권9호
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• pp.867-872
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• 1998

배경: 심폐바이패스에 의한 개심술시 적절한 항응고요법은 수술 관련 혈액응고장애를 최소화한다 는 점에서 중요하다. 심폐바이패스시 헤파린 및 프로타민 투여량을 결정하는데에는 활성화응고시간을 이 용한 고정용량법이 용량반응 곡선을 이용한 방법과 함께 보편적으로 사용되고 있다. 대상 및 방법: 저자들은 고정용량법에 대한 전향적 연구를 통해 고정용량 투여후 헤파린 및 프로 타민의 추가 투여 빈도, 헤파린 저항및 헤파린 유발성 혈소판감소증 빈도, 심폐바이패스시 활성화응고시 간 변화 양상, 그리고 아프로티닌 사용시 활성화응고시간 변화등을 분석하였다. 심폐바이패스 시작전 헤 파린 300 unit/kg를 투여하고 5분후 그리고 심폐바이패스 시작후 10분, 30분, 60분(이후 30분 간격)의 활성화응고시간을 측정하여 400초 이하인 경우 100 unit/kg 헤파린을 추가 투여하였다. 프로타민 중화는 사용 헤파린 100 unit당 1 mg을 투여한후 30분에 측정한 활성화응고시간이 130초 이상 또는 130초 미만이 라도 명백한 응고장애가 있을 경우 0.5mg/kg 추가 투여하였다. 결과: 서울대병원에서 개심술을 받은 환자중 80명(성인 50명, 소아 30명)을 대상으로 하였다. 수 술전 활성화응고시간은 성인에서 114.3$\pm$19.3초, 소아에서 119.5$\pm$18.2초로 나이, 체중, 체표면적 및 성 별에 따른 유의한 차이는 발견되지 않았다. 과거 개심술 병력도 수술전 활성화응고시간에 영향이 없었다. 고정용량법 투여후 헤린 추가 투여가 필요하였던 경우는 성인 환자 10례(20%), 소아 환자 3례(10%)였다. 프로타민 추가투여가 필요하였던 경우는 성인에서 9례(18%), 소아에서 10례(33%)였다. 심폐바이패스 시간 과 프로타민 추가 투여 사이에는 상관관계를 찾을수 없었다. 헤파린저항을 보였던 경우는 성인에서만 2명 (4%)이었고 소아는 없었다. 헤파린 유발성 혈소판감소증은 성인에서 2례(4%), 소아에서 1례(3.3%) 관찰되 었다. 심폐바이패스 운용중 활성화응고시간은 시간경과에 따라 길어지는 양상을 보였다. 성인환자에서 저 용량 아프로티닌이 12례(24%)에서 사용되었는데, 이들에서는 심폐바이패스중 활성화응고시간(celite를 활 성물질로 사용)이 비사용군에 비해 높았고, 활성 물질로 kaolin을 사용했을 때의 활성화응고시간은 celite ACT에 비하여 낮게 나타났다. 결론: 결론적으로 헤파린 및 프로타민 고정 용량 투여법은 큰 문제 없이 운용될 수있으나 추가 용량 투여 빈도의 측면에서는 만족할만한 수준은 되지 못하였다.

• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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• pp.48-49
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• 2006

The incorporation of heparin to biomaterials has been widely studied to improve the biocompatibility (blood and cell) of biomaterials surfaces. In our laboratory, various kinds of heparinized polymers including heparinized thermosensitive polymers ($Tetronic^{(R)}$-PLA(PCL)-heparin copolymers) and star-shaped PLA-heparin copolymers have been developed as a novel blood/cell compatible material. These heparinized polymers have demonstrated their unique properties due to bound heparin, resulting in improved biocompatibility. These heparinized bioactive polymers can be applied as blood and tissue compatible biodegradable materials in variable medical application such as tissue engineering and drug delivery system.

• 대한수의학회지
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• 제43권4호
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• pp.703-708
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• 2003

This study was carried out to compare the efficacy of carboxymethyl chitosan fabric (CMCF) with that of the combination of low molecular weight heparin (LMWH) and CMCF for the prevention of postoperative adhesions in the rat. Adhesions were induced by suturing both the ileal serosa and peritoneum scraped until petechial bleeding occurred. CMCF were sutured between two surfaces, and LMWH were instilled intraperitoneally immediately before closure of the peritoneomuscular layer. The adhesions were blindly assessed 2 weeks later by using a tensiometer. The mean tensile strength(Newton) of formed adhesions was $2.59{\pm}0.85$ in control group, $2.10{\pm}0.75$ in the CMCF group and $1.53{\pm}0.44$ in the CMCF+LMWH group. The most favorable prevention against adhesion was achieved in the CMCF+LMWH group. Therefore, we could conclude that CMCF+LMWH were effective in prevention against postoperative adhesion in the rat.

• Journal of Chest Surgery
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• 제51권2호
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.