Swelling behavior of calcium ion-crosslinked sodium alginate in an in vitro hemostatic tamponade model.

Various types of hemostatic agents are used to manage bleeding in surgery. Many such agents are animal products, which carry the risk of secondary infection. The aim of this study is to develop a novel hemostatic agent from a non-animal source that quickly stops bleeding, is easy to use, and has no risk of infection. In this study, we synthesized calcium ion-crosslinked sodium alginate (Alg-Na/Ca) by partial substitution of Ca ions for Na ions in sodium alginate. We prepared 12 kinds of Alg-Na/Ca powders with different Ca mass ratios, molecular weights, M/G ratios and particle size distributions and measured their swelling ratio and the burst pressure generated. We found that Alg-Na/Ca began to swell immediately after contact with saline, especially Alg-Na/Ca at Ca mass ratios of 74.1-77.0 % showed a high swelling ratio after 2 min and a high burst pressure, over 200 % and 500 mmHg respectively. Also, there is a correlation between the swelling ratio after 2 min and the burst pressure. Our results suggest that, by optimizing the composition conditions, Alg-Na/Ca may be an effective hemostatic agent that could act as a tamponade by absorbing and swelling at a bleeding site to quickly achieve primary hemostasis.

Randomized controlled trial of new hemostatic material "sodium calcium alginate" in a preclinical model.

BACKGROUND: The demand for nonbiological hemostatic materials has increased in surgical practice; however, few have sufficient hemostatic efficacy. This study investigated whether optimizing the composition of sodium calcium alginate, which forms a stable gel, improves hemostatic efficacy. METHODS: The sodium calcium alginate was changed for each composition, including powder size, calcium substitution rate, molecular weight, and mannuronic/guluronic acid ratio. The hemostasis in liver punch-out injury and bleeding was evaluated using swine. For the study, sodium calcium alginate with different compositions was randomly applied to bleeding sites. Previous hemostatic materials, including cellulose and sodium alginate, were used as a control. We investigated hemostasis at 2 and 5 minutes after application. RESULTS: Each powder size (53-150 µm, 150-250 µm, 53-250 µm) had a similar hemostatic effect. However, the hemostatic rate was significantly higher in sodium calcium alginate than in previous hemostatic materials (P value < .01). A 74.1% calcium substitution rate had the highest hemostasis at 2 and 5 minutes after application (2 minutes: 100%, 5 minutes: 95.2%). Regarding molecular weight, the hemostatic rate was significantly higher in 333,000 than in 50,000 (2 minutes: 95% vs 70%, 5 minutes: 95% vs 70%, P = .038). Moreover, a 1.9 mannuronic/guluronic acid ratio had the highest hemostasis compared with the 0.4 mannuronic/guluronic acid ratio (2 minutes: 58.8% vs 11.8%, 5 minutes: 58.8% vs 0%, P = .033) CONCLUSION: The composition of sodium calcium alginate with a high hemostatic effect was optimized. This new hemostatic material demonstrated potential usefulness for bleeding during surgery.

Sodium alginate ameliorates indomethacin-induced gastrointestinal mucosal injury via inhibiting translocation in rats.

AIM: To investigate the effects of sodium alginate (AL-Na) on indomethacin-induced small intestinal lesions in rats. METHODS: Gastric injury was assessed by measuring ulcerated legions 4 h after indomethacin (25 mg/kg) administration. Small intestinal injury was assessed by measuring ulcerated legions 24 h after indomethacin (10 mg/kg) administration. AL-Na and rebamipide were orally administered. Myeloperoxidase activity in the stomach and intestine were measured. Microvascular permeability, superoxide dismutase content, glutathione peroxidase activity, catalase activity, red blood cell count, white blood cell count, mucin content and enterobacterial count in the small intestine were measured. RESULTS: AL-Na significantly reduced indomethacin-induced ulcer size and myeloperoxidase activity in the stomach and small intestine. AL-Na prevented increases in microvascular permeability, superoxide dismutase content, glutathione peroxidase activity and catalase activity in small intestinal injury induced by indomethacin. AL-Na also prevented decreases in red blood cells and white blood cells in small intestinal injury induced by indomethacin. Moreover, AL-Na suppressed mucin depletion by indomethacin and inhibited infiltration of enterobacteria into the small intestine. CONCLUSION: These results indicate that AL-Na ameliorates non-steroidal anti-inflammatory drug-induced small intestinal enteritis via bacterial translocation.

Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

Effect of sodium alginate on dextran sulfate sodium- and 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis in mice.

We evaluated the effects of sodium alginate (AL-Na) on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. DSS was added to the drinking water for 7 days. In another experiment, DSS was added to the drinking water for 5 days and DSS-free water was provided thereafter. In a separated study, colitis was induced by intrarectally administered TNBS. AL-Na, 5-aminosalicylic acid, or prednisolone was orally administered. These colitis models exhibited colonic damage and produced noticeable inflammatory responses and aggravated goblet cell damage. AL-Na significantly ameliorated DSS- and TNBS-induced experimental colitis and prevented goblet cell damage. Prednisolone also suppressed colitis but caused loss of body and spleen weight. In contrast, AL-Na did not provoke these symptoms. These data suggest that AL-Na may be a possible therapeutic agent for the treatment of inflammatory bowel disease.